Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca²⁺ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.

The abstract should be a total of about 250 words and structured to contain the following headings: Background/Objectives, Methods, Results, Conclusions. Background/Objectives: Place the question addressed in a broad context and highlight the purpose of the study; Methods: Describe briefly the main methods or treatments applied. Include any relevant preregistration numbers, and species and strains of any animals used; Results: Summarize the article’s main findings; Conclusions: Indicate the main conclusions or interpretations. The abstract should be an objective representation of the article: it must not contain results which are not presented and substantiated in the main text and should not exaggerate the main conclusions. Clinical trial abstracts should include items that the CONSORT group has identified as essential.

As a new plant slope protection technology, living stumps can effectively improve slope stability. The current study attemptes to investigate the mechanical characteristics of the root system of living stumps and their reinforcement mechanism on slopes by carrying out a three-dimensional living stump slope modeling test. Using ABS materials, a 3D model of a living elm stump was created by 3D printing and a slope model test was carried out. The reinforcement mechanism of the living stump was studied through a combination of model testing and numerical simulation. The results indicate that, due to the presence of living stumps in the lower and middle parts of the slope, the maximum shear stress area of the soil moved to a deeper direction. The stress state of the soil around the living stump was effectively improved due to the existence of the lateral root system.Living stumps in the lower part of the slope cross the potential sliding surface and transferred the soil shear stress gradually to the root system through root-soil interaction. Moreover, the tap roots and lateral roots of living stumps form a robust spatial structure that bears the shear stress of soil together, thus increasing the stability of the slope.

The dynamics of many complex systems can be classified as ordered, chaotic, or critical. Order offers stability and robustness, while chaos allows for change and adaptability. Criticality, then, is often seen as a balance required by living systems at different scales. In classical models, however, criticality is only found near phase transitions, restricting the parameter space (and thus the likelihood) of critical dynamics, as most parameters yield ``undesirable'' solutions. Here we show that this limitation is due to the homogeneity built-in these models, i.e., all elements sharing parameter values. By exploring heterogeneous versions of archetypal models in physics and computer science, we observe critical dynamics in a broader range of parameters, and thus could be more common than previously thought.

Hyperspectral imaging, a rapidly evolving technique, furnishes exhaustive information on Earth's surface reflectance over an extensive spectrum of wavelengths. We have developed a more precise method for analyzing spectral data by meticulously selecting plant leaf pixels and employing a relative reference approach. This enhanced technique correlates camera pixel values with light intensity, bypassing the need for complex equations and thereby providing clearer insights into vegetation vitality. The findings of this study not only enhance the precision of hyperspectral imaging but also bolster our capability for ecological monitoring and understanding environmental health. A novel algorithm based on the red-edge slope was established to classify images, exploiting the spectral reflectance data gleaned from the hyperspectral Liquid Crystal Tunable Filter (LCTF) camera. Compared with conventional SVM and K-means algorithms, our novel algorithm demonstrated commendable performance, achieving an overall accuracy of 90% with a Kappa Coefficient of 0.86. This comparison highlights the novel algorithm's relative strength and potential for large-scale satellite and drone imagery analysis applications. The advancements facilitated by this research are instrumental in ecological assessments, conservation efforts, and resource management strategies, signaling a leap forward in the era of environmental monitoring and analysis.

In view of the fact that the field monitoring information can more intuitively and accurately reflect the stability state of slopes, this paper takes the warning threshold of slope deformation rate monitoring as the slope stability evaluation standard, and puts forward a method for solving the safety coefficient of rocky slopes. The discrete element method 3DEC, which is suitable for rocky slopes, is selected as the numerical calculation tool, and the convergence criterion of its strength reduction method is modified to the slope deformation rate threshold, and the method is realized by the bifurcation method through its built-in FISH programming language. The results of the classical case show that, by selecting the slope deformation rate threshold in the appropriate interval, the results of this paper's method are very close to those of the finite unit stress method and the limit equilibrium method, which verifies the reliability of this paper's method. Further, the method of this paper is applied to an open-pit mine slope project, based on the slope deformation on-site monitoring data, through the time series prediction method to determine the slope deformation rate warning threshold, using the threshold as an evaluation criterion to solve the slope's coefficient of safety, the calculation results show that: the slope's coefficient of safety in natural working conditions is 1.086, basically stable, suffered from continuous rainfall, the slope body is gradually saturated, the slope's coefficient of safety is reduced to 0.987, the slope's safety is reduced to 0.987. After continuous rainfall and gradual saturation of the slope, the coefficient of safety decreased to 0.987, destabilizing and destroying, which is consistent with the site conditions.

This paper focuses on the physical attributes of land that intrinsically limit land use and possibly affect land values. In particular, we investigate if the slope of a land does decrease its price and investigate the role of land slope in forming more reliable constant-quality land price indices and aggregate house price indices. We find that, while land slopes do decrease the land price per unit, they have a small effect on the quality-adjusted land price indices in selected neighborhoods in Auckland, New Zealand, where sloped terrain is common.

Urban air pollution is a critical global environmental issue, necessitating an understanding of the spatiotemporal characteristics and driving factors for effective environmental protection and urban planning. This study introduced an advanced air quality assessment system that integrates environmental, socio-economic, and urban layout factors, addressing gaps in traditional models that often overlook the impact of urban spatial structures. Analyzing air quality data from Beijing's main urban area (2016-2020) alongside multi-source geographic data, the research develops a comprehensive evaluation system, incorporating 14 key driving factors. Employing Geographically Weighted Regression (GWR) and Multi-scale Geographically Weighted Regression (MGWR), the study quantitatively assessed the influence and spatial heterogeneity of these factors. Findings revealed an annual improvement in air quality, with a U-shaped seasonal pattern and significant spatial clustering (Global Moran’s I = 0.922). The MGWR model, in particular, provided a superior fit over GWR, effectively capturing the spatial variability of factors. Variables such as NDVI), economic output (GDP), and humidity space adjustment capability (HSAC) showed significant positive spatial impacts on air quality, while population density (POP), temperature (TEMP), and road density (RD) exhibited negative effects. These insights enhance the understanding of air pollution dynamics and aid in refining urban planning strategies.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to form different cell types and provide paracrine signals to the developing heart. Despite its quiescent state during adulthood, in response to cardiac injury, adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis supporting cardiac tissue remodeling. Thus, the epicardium has been considered as a crucial source of cell progenitors with important contribution to developing and injured heart. Although several studies have provided evidence about cell fate determination in the epicardium, to date it is unclear whether epicardial-derived cells (EPDCs) come from specific, and previously predetermined, epicardial cell subpopulations or if they are derived from a common progenitor. In recent years, different approaches have been used to study cell heterogeneity within the epicardial layer by using different experimental models. However, generated data are still insufficient to understand the complexity of this epithelial layer. In this review, we summarize the previous works supporting the cellular composition, molecular signatures and diversity within the developing and adult epicardium.

According the JKR theory of adhesive contact, changes of the contact configuration after formation of the adhesive neck and before detaching are completely reversible. This means, that after formation of the initial contact, the force-distance dependencies should coincide, independently on the direction of the process (indentation or pull-off). In the majority of real systems, this invariance is not observed. The reasons for this may be either plastic deformation in the contacting bodies or surface roughness. One further mechanism of irreversibility (and corresponding energy dissipation) may be chemical heterogeneity of the contact interface leading to the spatial dependence of the specific work of adhesion. In the present paper, this "chemical" mechanism is analyzed on a simple example of an axisymmetric contact (with axisymmetric heterogeneity). It is shown that in the asymptotic case of a "microscopic heterogeneity", the system follows, during both indentation and pull-off, JKR curves, however, corresponding to different specific surface energies. After the turning point of the movement, the contact area first does not change and the transition from one JKR curve to the other occurs via a linear dependency of the force on indentation depth. The macroscopic behavior is not sensitive to the absolute and relative widths of the regions with different surface energy but depends mainly on the values of the specific surface energy.

Intratumor heterogeneity (ITH) is associated with therapeutic resistance and poor prognosis in cancer patients, and attributed to genetic, epigenetic, and microenvironmental factors. We developed a new computational platform, GATHER, for geostatistical modeling of single cell RNA-seq data to synthesize high-resolution and continuous gene expression landscapes of a given tumor sample. Such landscapes allow GATHER to map the enriched regions of pathways of interest in the tumor space and identify genes that have spatial differential expressions at locations representing specific phenotypic contexts using measures based on optimal transport. GATHER provides new applications of spatial entropy measures for quantification and objective characterization of ITH. It includes new tools for insightful visualization of spatial transcriptomic phenomena. We illustrate the capabilities of GATHER using real data from breast cancer tumor to study hallmarks of cancer in the phenotypic contexts defined by cancer associated fibroblasts.

Water resources provided by alpine glaciers are an important pillar for people living in the arid regions in the west of China. In this study, the HBV (Hydrologiska Byrans Vattenavdelning) light model was applied to simulate glacier mass balance and runoff in the Koxkar River Basin (KRB) on the south slope of Mt. Tumur, western Tianshan Mts.. Daily temperature and precipitation were calculated by multiple linear regressions and gradient-inverse distance weighting, respectively, based on in-situ observed data by automatic weather stations (AWSs) in the basin (2007–2009) and at four meteorological stations neighbering the basin (1959–2009). Observed daily air temperature and precipitation were taken as input data for the HBV model, which was calibrated using runoff in 2007/08 and 2009/10, and validated in 2008/09 and 2010/11. Generally, the model could simulate runoff very well. The annual glacier mass balance and runoff were calculated using the HBV model driven by interpolated meteorological data for the period of 1959–2009. The simulated glacier mass balance were reasonable when compared with those observed values at nearby glaciers, indicating a decrease trend of mass balance in the basin with an average value of –370.4 mm a^-1 since 1959. The annual runoff showed a slight increase trend (5.51 mm a^-1). Futher analysis indicated that the runoff is more sensitive to temperature than precipitation amuont in the Koxkar river basin.

Oral squamous cell carcinoma (OSCC) remains an under-studied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential pro-tumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors. CAFs present a heterogeneity both in phenotype as well as functions, leading to the suggestion of different CAF subtypes in several cancer forms. The task to subtype CAFs in OSCC has however just begun and there is today no united way of subtyping CAFs in this disease. This review aims to define the features of CAFs and to summarize CAF subtype research in OSCC including aspects as disease prognosis and therapeutic opportunities.

Colorectal cancer is a high-incidence tumor that has a high mortality rate due to its frequent metastasis to the liver. The difference in genes, proteins, and immune microenvironment between the primary and metastatic sites causes them to show different responses to treatment. Colorectal cancer liver metastasis patients also tend to show poorer treatment response and prognosis. Therefore, in this paper, we summarize the heterogeneity exhibited after colorectal cancer liver metastasis from five aspects (gene, transcriptome, protein, metabolism, and immunity), and we found that except for the genetic heterogeneity, the other four aspects exhibite significant heterogeneity, which might serve as a new therapeutic direction and a prognostic marker for patients with liver metastasis. Finally, the therapeutic modalities regarding tumors are rapidly evolving, and we have also summarize the new clinical therapeutic modalities currently proposed based on these heterogeneities, aiming to provide new therapeutic ideas for the clinical treatment of patients with colorectal cancer liver metastases.

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

Analyzing the impacts of urban landscape patterns on the thermal environment has become one of the key research areas in addressing urban heat islands (UHI) and improving the living environment. A case study was carried out in Fuzhou, Fujian Province of China, to quantify the spatial patterns of urban landscape and land surface temperature (LST) in different development areas. The contribution of the thermal environment and the factors influencing the heterogeneity of LST were analyzed and discussed. In this study, bi-temporal Landsat imagery was selected to calculate LST, percent impervious surface area (ISA), and fractional vegetation cover (FVC). The urban area was further divided into three concentric urban zones, ranging from the city center to the urban periphery, based on urban development densities. The spatial pattern of LST and its variance were analyzed and compared between different zones and different dates. The thermal environment contribution of different zones was also quantified to indicate the change in urban landscape pattern resulting from urban expansion in different zones. Furthermore, Geodetector was used to explore the single factors and interaction factors controlling the spatial patterns of LST in each zone. The results showed that (ⅰ) Urban expansion primarily increased in zone 2 and zone 3, and the areal proportion of high and sub-high LST areas increased from 56.11% and 21.08% to 62.03% and 32.49% in zone 2 and zone 3, respectively, from 2004 to 2021; (ⅱ) The heat effect contribution of zones 2 and 3 reached from 75.16% in 2004 to 89.40% in 2021, indicating that the increase of ISA with >LSTmean was more pronounced in zone 3 and zone 2 during the period; (ⅲ) The driving factors of LST spatial distribution were regionally different because of the different landscape patterns, and the explanatory power for the heterogeneity of LST in zone 1 was weaker than that in zone 2 and zone 3 in the study area; (ⅳ) The interaction of different factors had a higher explanatory power on the spatial distribution of LST than a single factor in each zone because the distributions of land cover types are heterogeneous in urban area. The results of the study can be used to improve urban planning for urban ecology and UHI mitigation.

High-precision ground point cloud data has a wide range of applications in various fields, and the separation of ground points from non-ground points is a crucial preprocessing step. Therefore, designing an efficient, accurate, and stable ground extraction algorithm is of great significance for improving the processing efficiency and analysis accuracy of point cloud data. The study area in this article was a Park in Guilin, Guangxi, China. The point cloud was obtained by utilizing the UAV platform. In order to improve the stability and accuracy of the Filter algorithm, this article proposed a triangular grid filter based on Slope Filter, found violation points by the spatial position relationship within each point in the triangulation network, improved KD-Tree-Based Euclidean Clustering, and applied it to the non-ground points extraction, this method has good accuracy, stability and achieves good results in separating ground points from non-ground points. At first, using Slope Filter to remove some non-ground points, to reduce the error of taking ground points as non-ground points; Secondly, established a triangular grid based on the triangular relationship between each point, the violation-triangle can determin through the grid, and then the corresponding violation points were found in the violation-triangle; Thirdly, according to the three-point collinear method to extract the regular points, used these points to extract the regular landmarks by KD-Tree-Based Euclidean Clustering and Convex Hull Algorithm; Finally, removed disperse points and irregular landmarks by Clustering Algorithm. In order to confirm the superiority of this algorithm, this article compared the filter effects of various algorithms on the study area and filtered the 15 sample data provided by ISPRS, and obtained an average error of 3. 46%. The results showed that the algorithm in this article have a high processing efficiency and accuracy, which can greatly improve the processing efficiency of point cloud data in practical applications.

Purpose - Soil aggregates are of great significance to soil and water conservation and ecological environment construction in arid area of northwest district．Methods - Exploring the effects of different vegetation includes types and land use methods on the stability of soil aggregates in the Loess Plateau, and provide reference for the rational use and management of land, also the improvement of soil structure in the region. Select 9 types of samples of 0-30 cm of typical soil plots as the research objects, compare and analyze the particle size index, stability differences and anti-erodibility of soil aggregates under various vegetation cover. Results - The results show that P value, MWD value, GMD value, D value, and AI value of the 0-10cm surface soil all show the maximum value. As the depth increases, the size distribution of the above index values of each soil sample in the 10-20cm and 20-30cm layers is different; P value in the 0-30cm depth layer is linearly positively correlated with the AI value and MWD value, and linearly negatively correlated with the D value. The correlation coefficient R between each variable is in the range of 0.78-0.97, and the D value reflects the Loess Plateau area stability and erosion resistance of soil aggregates better. GMD and MWD value show an exponential relationship, the correlation coefficient R value of 10-20cm height layer is 0.46; AI and MWD value in 0-10cm, 20-30cm height layer have a power function relationship, 10-20cm height layer has a polynomial function, the correlation coefficient R value is 0.97. The scour coefficient of different soil samples has a high degree of dispersion, the maximum CV value is 1.92, and the minimum value is 0.49. Conclusions - The results of this study can provide a theoretical basis for the ecological and hydrological benefit evaluation of slope erosion control and vegetation restoration on the Loess Plateau.

We propose an asynchronous acoustic chirp slope keying to map bit sequences on single or multiple bands without preamble or error correction coding on the physical layer. Details of the implementation are disclosed and discussed, the performance verified on laboratory scale in a pool measurement, as well as simulated for a channel containing Rayleigh fading and Additive White Gaussian Noise. For time-bandwidth products of 50 in single band mode, a raw data rate of 100~bit/s is simulated to achieve bit error rates below 0.001 for signal-to-noise ratios above -6~dB. In dual-band mode and a data rate of 200~bit/s, this bit error level was achieved for signal-to-noise ratios above 0~dB for time-bandwidth product of 25. The packet error rates follow this behavior with an offset of 1~dB.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. AML with mutated Nucleophosmin1 (NPM1-mut) is the largest of the genetically defined groups, involving about 30% of adult AMLs and is currently recognized as a distinct entity in the actual AML classifications. NPM1-mut AML usually occurs in de novo AML and is associated predominantly with a normal karyotype and relatively favorable prognosis. However, NPM1-mut AMLs are genetically, transcriptionally, and phenotypically heterogeneous. Furthermore, NPM1-mut is a clinically heterogenous group. Recent studies have in part clarified the consistent heterogeneities of these AMLs and have strongly supported the need for an additional stratification aiming to improve the therapeutic response of the different subgroups of NPM1-mut AML patients.

The effects of heterogeneity of cooperative membership on cooperative and collective action sustainability has been previously discussed. However, despite the importance of membership heterogeneity in recent theoretical frameworks, empirical examinations have been limited. We determine the effect of changes to cooperative member heterogeneity on cooperative sustainability and discuss changes to heterogeneity overtime that can advance our understanding to cooperative sustainability long-term. This study uses USDA Agricultural Management Resource Survey data, coupled with USDA-Rural Development cooperative financial data at the state level, to quantify effects of cooperative member heterogeneity to sustainability of U.S. farmer cooperatives. We use random forest regression to interpret the significance of heterogeneity with cooperative sustainability at an aggregate level. The findings of this empirical study narrowly reconciles the theoretical understanding of the emergence of intra-cooperative issues while providing consistent empirical evidence and expectations for the sustainability of cooperatives in the near term.

Accurate detection and quantification of regional vegetation trends is essential for understanding the dynamics of landscape ecology and vegetation distribution. We applied a comprehensive trend analysis to satellite data to describe geo-spatial changes in vegetation along the Pacific slope of Peru and northern Chile, from sea level to the continental divide, a region characterised by biologically unique and highly sensitive arid and semi-arid environments. Our statistical analyses show broad regional patterns of positive trends in EVI, called “greening” alongside patterns of “browning” where trends are negative between 2000 and 2020. The coastal plain and foothills, up 1000m, contain notable greening of the coastal Lomas and newly irrigated agricultural lands occurring alongside browning trends related to changes in land use practices and urban development. Strikingly, the precordilleras show a distinct ’greening strip’ which extends from approximately 6°S to 22°S, with an altitudinal trend; ascending from the tropical lowlands (170-780 m) in northern Peru, to the subtropics (1000-2800 m) in central Peru, and temperate zone (2600-4300 m) in southern Peru and northern Chile. We find that the geographical characteristics of the greening strip do not match climate zones previously established by Köppen and Geiger. Greening and browning trends in the coastal deserts and the high Andes lie within well defined climatic and life zones, producing variable but identifiable trends. However, the distinct Pacific slope greening presents an unexpected distribution with respect to the regional Köppen-Geiger climate and life zones. This work provides insights on understanding the effects of climate change on Peru’s diverse ecosystems in highly sensitive, biologically rich arid and semi-arid environments on the Pacific slope.

On the basis of the force and safety factor analysis of traditional retaining wall, a new analytical method of force and displacement of slope is suggested, the numerical theoretical solution of the stress distribution of the sliding body can be obtained under the conditions, which the stresses distribution are satisfied with the differential equilibrium equations, the boundary conditions, the compatibility equation and the macroscopic equilibrium equations. The interface stresses between the sliding body and the retaining wall are continuous, the theoretical solution of retaining wall stress distributions can be gotten, while the stress differential equilibrium equation, the compatibility equation, macroscopic force and moment balance equations are satisfied. The strain and displacement solutions can be obtained by using Duncan Chang and Hooke constitutive equations for the slope and the retaining wall respectively. The transfer station of landfill in the Guandukou Town of Badong County is taken as an example, the results of the sliding body and retaining wall analysis show: The stress and strain solutions of a slope and a retaining wall can be obtained by the proposed method, the forces between the retaining wall and the sliding body include shear stress and normal stress, and the stress distributions change with the deformation of the sliding body, the shape and material of retaining wall can be optimized according to the calculation results，it is feasible for the proposed analysis method of slope with retaining wall design to be run many years.

Permeable asphalt pavement refers to an asphalt mixture layer with an air void content of more than 18% and internal water permeability and drainage capabilities, which can quickly drain away water on the road surface, improve rainy day travel safety and ride comfort. This paper aims to explore the optimal asphalt mixture mix design for long longitudinal slope roads. By using CT scanning technology to analyze the air void content of different rotated and compacted asphalt mixture specimens, and extensively testing and evaluating the performance of permeable pavement mixtures, the following conclusions are drawn: Based on the research philosophy of functional integration, a new asphalt mixture gradation suitable for long longitudinal slope roads is proposed, with the optimal key factor composition being: 0.075mm passing rate of 7%, 2.36mm passing rate of 20%, 9.5mm passing rate of 55%, and oil-stone ratio of 4.8%. The FAM mixture was divided into three parts for air void analysis, with the upper part having a slightly higher air void content than the lower part. The air void distribution diagram of the FAM mixture is concave, with higher air void rate curves on both sides and a lower middle curve. Compared with laboratory dry measurement method, CT scanning test showed slightly higher air void content in specimens. Through dynamic modulus testing, the strength requirement for road asphalt mixture in pavement structure design was evaluated. It was found that at high temperature conditions (50℃), the minimum dynamic modulus value of the FAM mixture was 323 MPa, with a peak value of 22746MPa at a temperature of -10℃ and a frequency of 25HZ. The dynamic modulus value at high temperature conditions is lower than at low temperature conditions, while the dynamic modulus value at high frequency conditions is higher than at low frequency conditions. This study provides useful information and experimental data for the design of new asphalt mixtures for long longitudinal slope roads, and has conducted in-depth research on the air void distribution and performance of the mixture, providing strong support for related research fields and practical applications.

The entry and exit method is a simple and practical method to determine the critical slip surface of slope. However, it has the drawback of sacrificing computational efficiency to improve search accuracy. To solve this problem, this paper proposes an improved entry and exit method to search for the critical slip surface. Based on the random fields generated by using Karhunen–Loève expansion method, the simplified Bishop’s method combined with the improved entry and exit method is used to determine the critical slip surface and its corresponding minimum factor of safety. Then, the failure probability is calculated by conducting Monte Carlo simulation. Two examples are reanalyzed to verify the accuracy and efficiency of the proposed method. Meaningful comparisons are made to demonstrate the calculating accuracy and calculating efficiency of the improved entry and exit method in searching for the minimum safety factor of slope, based on which the effect of the reduced searching range on slope reliability was explored. The results indicate that the proposed method provides a practical tool for evaluating the reliability of slopes in spatially variable soils. It can greatly improve the computational efficiency in relatively high-computational accuracy of slope reliability analysis.

The load on the top of a slope is an important cause of slope failure, and it is of great significance to study the relationship between the load and the stability of the slope. This paper uses elastic theory and Moore Coulomb's theory as transformation conditions to obtain the slope stability coefficient expression under slope top load based on the Swedish slice method. In view of the actual engineering, the corresponding slope model structure was established, and 5 sliding surfaces were set with the crack on the top of the slope as the shear outlet. According to the slope stability coefficient expression, the stability coefficient of the set sliding surface is solved. The result shows that the slope is unstable under the load. The judgment result is consistent with the GEO-STUDIO check calculation result. This method can provide reference for theory and engineering practice.

Chromosomal instability (CIN), defined by variations in the number or structure of chromosomes from cell to cell, is recognized as a distinctive characteristic of cancer, associated with the ability of tumors to adapt to challenging environments. CIN has been recognized as a source of genetic variation that leads to clonal heterogeneity (CH). Recent findings suggest a potential association between CIN and CH with the prognosis of BC patients, particularly in tumors expressing the epidermal growth factor receptor 2 (HER2+). In fact, information on the role of CIN in other BC subtypes, including luminal B BC, is limited. Additionally, it remains unknown whether CIN in luminal B BC tumors, above a specific threshold, could have a detrimental effect on the growth of human tumors, or if low or intermediate CIN levels could be linked to a more favorable BC patient prognosis when contrasted with elevated levels. Clarifying these relationships could have a substantial impact on risk stratification and the development of future therapeutic strategies aimed at targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples from ten patients with luminal B BC, and compared them with established clinicopathological parameters. The results of our study show that luminal B BC patients exhibit intermediate CIN and stable aneuploidy, both of which correlated with lymphovascular invasion. These findings suggest that evaluating CIN, CH and aneuploidy could improve risk stratification, the prediction of clinical outcomes and future therapeutic approaches in luminal B BC patients.

Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.

The fixed and random effects models are popular methods for identifying the causal effects of treatment. First, I introduce the two-way fixed effects model and show a class of the estimators for the random effects models. Misidentification may occur in these models due to the treatment effect heterogeneity. Then, I propose the differential error component models to address such problems while the models exclude the fixed effects of units and time periods and consider the random effects of units and time periods. Meanwhile, I present a simulation of a staggered design and revisit the application in (De Chaisemartin and D'Haultfoeuille, 2020). The results demonstrate that one additional newspaper increases the 0.31% average effect of the presidential turnout and the 1.05% average effect when the newspapers’ changes are non-negative, where the proposed estimators are robust and efficient.

This paper presents a statistical approach to identify the underlying roughness characteristics in synthetic aperture radar (SAR) intensity data. The physical modeling of this kind of data allows the use of the Gamma distribution in the presence of fully-developed speckle, i.e., when there are infinitely many independent backscatterers per resolution cell, and none dominates the return. Such areas are often called ``homogeneous'' or ``textureless'' regions. The GI0 distribution is also a widely accepted law for heterogeneous and extremely heterogeneous regions, i.e., areas where the fully-developed speckle hypotheses do not hold. We propose three test statistics to distinguish between homogeneous and inhomogeneous regions, i.e., between gamma and GI0 distributed data, both with a known number of looks. The first test statistic uses a bootstrapped non-parametric estimator of Shannon entropy, providing a robust assessment in uncertain distributional assumptions. The second test uses the classical coefficient of variation (CV). The third test uses an alternative form of estimating the CV based on the ratio of the mean absolute deviation from the median to the median. We apply our test statistic to create maps of \(p\)-values for the homogeneity hypothesis. Finally, we show that our proposal, the entropy-based test, outperforms existing methods, such as the classical CV and its alternative variant, in identifying heterogeneity when applied to both simulated and actual data.

Among the impacts of climate change in West Africa, coastal erosion is the most threatening disaster apart from floods and the increase in temperature. The southern coast of the Dakar region, as part of the most threatened coastal zones in West Africa, records the most current coastal damages in Dakar due to its coastline dynamics and low-lying area. This study was conducted in three littoral cells (Mbao, Bargny and Toubab Dialaw) and aims to investigate if there is a relationship between the coastline dynamic, topographic and slope and the contribution of the geomorphology along the southern coast of Dakar. It helps to understand better the role which plays the topography, Slope and geomorphology in coastal dynamics using remote sensing, cartographic tools and statistical methods. The Modified Normalized Different Water index (MNDWI) was employed to delineate the coastlines before computing the dynamic rate of the coastline using the Digital Shoreline Analysis System (DSAS) software. After that, Topography and Slope were determined using Digital Elevation Model (DEM). Then, the correlation between the coastline dynamic, topography and slope was analyzed through the coefficient of correlation and multiple linear regression model. High dynamic rates were noted in the littoral cells, where the topography and slope are low. In Mbao, there is a significant relationship between the coastline dynamic, topography and slope with a coefficient of correlation of about 0.63. In Bargny, the relationship is also significant, with a coefficient of 0.87. The relationship is not significant in Toubab Dialaw, where topography and Slope are high, with a coefficient of 0.15. We conclude that topography, slope and soil properties play an important role in the study area.

Within the spectrum of a natural image, the amplitude of modulation decreases with spatial frequency. The speed of such an amplitude decrease, or the amplitude spectrum slope, of an image affects the perceived aesthetic value. Additionally, a human observer would consider a symmetric image more appealing than they do an asymmetric one. We investigated how these two factors jointly affect aesthetic preferences by manipulating both the amplitude spectrum slope and the symmetric level of images to assess their effects on aesthetic preference on a 6-point Likert scale. Our results showed that the preference ratings increased with the symmetry level but had an inverted U-shape relation to amplitude spectrum slope. In addition, a strong interaction existed between symmetry level and amplitude spectrum slope on preference rating, in that symmetry can amplify the amplitude spectrum slope’s effects. Such effects can be described by a quadratic function of the spectrum slope. That is, preference is an inverted U-shape function of spectrum slope whose intercept is determined by the number of symmetry axis. In addition, the interaction between the two factors is manifested as the modulation depth of the quadratic function.

Tumor heterogeneity is a major obstacle to achieving consistent outcomes in cancer therapy. We offer a novel perspective on tumor heterogeneity, informed by an advanced understanding of tumor evolution. We understand any cells, or any organism, will inherently respond with specific capacities when faced with adversity. Our concepts, which extend beyond canonical views, posit that tumor evolution is driven by cellular responses to survival challenges. The disease is driven by a rudimentary action taken by any organism when confronted with adversity - a cellular response to generate specific capacities to overcome the threat - the responses that utilize advantageous genetic mutations and other cellular contents to attain these capacities and further drive the disease. The disease is initiated by a cellular response to survival challenges and the ongoing development of hallmark cancer capabilities, as cells endeavor to obtain a competitive advantage, results in increased molecular disarray, observed as tumor heterogeneity. When the evolutionary drive for survival is impeded by therapeutic inhibition of critical genes, cell death occurs, a phenomenon termed oncogene addiction. Drawing from the same idea that cells responding to survival challenges, we recognize the increasing primitiveness of cancer during its progress stems from the innate cellular response to the demand for regeneration under sustained cellular damage. This necessitates a regression to a more primitive state purposed to renew progeny, unleashing a hitherto undiscerned cellular capacity. Taken together, the ideas explored herein pave the way for novel cancer therapies and the betterment of human health.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS through additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events and aberrant expression of CRLF2, JAK2 mutations, and RAS pathway activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

Bare slope instability is a prevalent concern. The root system of, herbaceous vegetation enhances the shear strength of shallow–slope soil. Indoor experiments were conducted on rootless undisturbed soil (RUS) and undisturbed soil with a root system (USRS) using a triaxial compression apparatus to analyze the slope stability of composite soil with a Tagetes erecta root system. Significance tests and correlation analysis of the factors affecting shear performance were conducted using R software. The slope reinforcement, effect by the plant root system was simulated under 24 working conditions using the MIDAS finite element method. The results revealed the influence of the–root content (RC), moisture content (MC), and stress on the shear strength of USRS, the contribution degree, and the variables’ influences on slope stability. Both RUS and USRS exhibited strain hardening during shearing. The internal friction angle (φ) and cohesion (c) of USRS were negatively and positively correlated with the RC and MC (root burial depth), respectively, and a good fit was obtained for the relationship. The maximum deviatoric stress during shear failure was 1.29 times higher for USRS than for RUS. The RC (root depth) was positively correlated with the slope safety coefficient and the slope of the line under different working conditions, whereas the slope gradient was negatively correlated with the slope safety coefficient. The reinforcement effect by the root system resulted in a 13.2% increase in the safety coefficient and improved stability of slopes with a gradient larger than 1.5%. This article investigated the mechanism of the root–soil system and, the effects of different influencing factors on the shear strength of the soil, and slope stability. The findings provide new insights into shallow slope stability in practical slope protection projects.

Understanding the spatiotemporal characteristics of merging behavior is crucial for the ad-vancement of autonomous driving technology. This study aims to analyze on-ramp vehicle merg-ing patterns, and investigate how various factors, such as merging scenarios and vehicle types, in-fluence driving behavior. Initially, a framework based on High-Definition (HD) Map is devel-oped to extract trajectory information in a meticulous manner. Subsequently, eight distinct merg-ing patterns (Pattern A to H) are identified, with a thorough examination of their behavioral characteristics from both temporal and spatial perspectives. Merging behaviors are examined temporally, encompassing the sequence of events from approaching the on-ramp to completing the merge. This study specifically analyzes the target lane's spatial characteristics, evaluates the merging distance (ratio), investigates merging speed distributions, compares merging patterns and identifying high-risk situations. Our novel findings reveal that Patterns C and F, with Time-to-Collision (TTC) values less than 2.5 seconds, pose a significantly higher risk than other patterns. In traffic simulations, Patterns B and E can be integrated, as they show negligible differences in speed, distance traveled, and duration. Additionally, the practice of truck platooning has a signif-icant impact on vehicle merging behavior. This study enhances the understanding of merging be-havior, facilitating autonomous vehicles' ability to comprehend and adapt to merging scenarios. Furthermore, this research is significant in improving driving safety, optimizing traffic manage-ment, and enabling the effective integration of autonomous driving systems with human drivers.

Intratumoral heterogeneity associates with more aggressive disease progression and worse patient outcomes. Understanding the reasons enabling the emergence of such heterogeneity remains incomplete, which restricts our ability to manage it from a therapeutic perspective. Technological advancements such as high-throughput molecular imaging, single-cell omics and spatial transcriptomics now allow recording the patterns of spatiotemporal heterogeneity in a longitudinal manner, thus offering insights into the multi-scale dynamics of its evolution. Here, we review latest technological trends and biological insights from molecular diagnostics as well as spatial transcriptomics, both of which have witnessed a burgeoning growth in recent past in terms of mapping heterogeneity within tumor cell types as well as stromal constitution. We also discuss ongoing challenges, indicating possible ways to integrate insights across these methods to have a systems-level spatiotemporal map of heterogeneity in each tumor, and a more systematic investigation of implications of heterogeneity for the patient outcomes.

About 50% of colorectal cancer patients develop liver metastases. Patients with metastatic colorectal cancer have 5-year survival rates below 20% despite new therapeutic regimens. Tumor heterogeneity has been linked with poor treatment response and clinical outcome, but was so far mainly studied via bulk genomic analyses. In this study we performed spatial proteomics via MALDI mass spectrometry imaging on six patient-matched CRC primary tumor and liver metastases to characterize interpatient, intertumor and intratumor hetereogeneity. We found several peptide features that were enriched in vital tumor areas of primary tumors and liver metastasis and tentatively derived from tumor cell specific proteins such as annexin A4 and prelamin A/C. Liver metastases of colorectal cancer showed higher heterogeneity between patients than primary tumors while within patients both entities show similar intratumor heterogeneity sometimes organized in zonal pattern. Together our findings give new insights into the spatial proteomic heterogeneity of primary CRC and patient-matched liver metastases.

The triple-negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and still remains as an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically heterogeneous cell populations within a tumor plays a crucial role in chemoresistance, tumor progression and metastasis. Increased understanding of the molecular regulators of intratumoral heterogeneity will enable the development of effective therapeutic strategies in TNBC. We have identified a molecular mediator involved in intratumoral heterogeneity in breast cancer using an unbiased approach. We isolated two heterogeneous tumor cell populations from the 4T1 TNBC tumor model and phenotypic characterization revealed that the cells are distinct in terms of their morphology, proliferation and self-renewal ability in vitro; as well as primary tumor formation and metastatic potential in vivo. Further, RNA sequencing on both cell populations was performed to identify the molecular mediators underlying this heterogeneity. Bioinformatic analysis performed on the differentially expressed genes along with the Kaplan-Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as the top candidate gene mediating the aggressive phenotype. The role of Macc1 in regulating the proliferative phenotype was validated using siRNA mediated gene knockdown. The role of Macc1 in the aggressive cancer cell phenotypes and disease progression is being studied further using a small molecule transcriptional inhibitor of Macc1 in cell line and animal models, thus increasing our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to the improvement in the treatment of women currently living with the highly aggressive TNBC subtype.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric problem with a few core symptoms: weaknesses in social behavior, verbal impairments, repetitive behavior and restricted interests. Beyond the core symptoms, autism has strong association with other disorders such as intellectual disability, epilepsy, schizophrenia among many others. This paper outlines a theory of ASD with capacity to connect heterogeneous ‘core’ symptoms, medical and psychiatric comorbidities as well as other etiological theories of autism in a unifying cognitive framework rooted in neuroscience and genetics. Cognition is embedded into an ever-developing structure modified by experiences, including the outcomes of environment influencing behaviors. We introduce the hypothesis that autism is caused by deficits in component-based cognition and the internal learning reinforcing machinery. Specifically, we outline our Cartesian Factor forming autoencoder like model that supports cognition by breaking combinatorial explosion and discuss the cognitive and neural processes behind our model. The high dimensionality of sensory information poses serious problems, since the brain can handle only 7±2 relevant variables at a time making processes, such as the extraction and encoding of the relevant variables and their efficient manipulation critical. These processes are influenced by previous experiences and the internal reward system. In addition, large delays of distributed information processing should be counteracted by learned predictive models to synchronize sensory, proprioceptive, and cognitive signals and have timely and accurate model-based actions. Impairments in any of these aspects may disrupt learning and execution. Combinations of small impairments may allow the solving of low complexity tasks but may become visible if learned variables and the related metric are improper and imprecise, respectively, especially if their number is large. We claim that social interactions are amongst the most challenging cognitive tasks in terms of the number of variables involved. In turn, they are highly susceptible to combinations of small impairments. We consider impairments as the basic colors of autism, whereas the combinations of diverse impairments make the palette of autism. In turn, social processes can be spoiled in many ways and can lead to diverse comorbidities.

With the development of free trade port in Hainan Island, the construction of tourist roads around the island is also in full swing. Under the weather conditions of strong typhoon and rainstorm in Hainan, the highway cutting slope built on the coastal weak sandy terraces has strong sand loss and is easy to be scour by rainfall. MICP green spray irrigation solidification technology is used to strengthen the sandy cutting, and pore water pressure monitoring is carried out on the slope model during MICP solidification and rainfall scour. Combined with the model pore water pressure and flow slip failure pattern, dynamic analysis was carried out. The results show that MICP sprinkler irrigation technology can solidified the surface of the slope model in a short time, and the cementation depth of the model reaches 4cm after three sets of rotation reinforcement. The surface reinforcement effect is good, and the sand samples are closely connected. Under the erosion effect of simulated rainfall intensity, the sand loss of the slope is weakened, and no sand binding damage occurs, and the integrity is enhanced. Due to the cementation between sand grains, most of the rainfall was converted into runoff, and the slope slid after 150s. When the slope began to slip, the leading edge of the slope model lost sand and unloaded, and the failure mode was graded creep slip failure. Finally, the slope was divided into several blocks due to the continuous expansion of cracks after the slope failure. The erosion stability of the sandy slope under heavy rains is optimized and the sand loss is prevented effectively. In this study, a new method of MICP remediation techniques is proposed, which provides a new test basis for the application of MICP technology in practical engineering.

The feet cannot perform tasks as quickly and with as much dexterity as the hands. However, due to the heavy workload placed on the hands, there is potential for the feet to replace or assist the hands. In order to use the feet more effectively, this study aims to find ways to increase the speed and accuracy of directly touching a touchpad with the feet while in a seated position. The study investigates the effects of three factors: the slope of the touchpad, the direction of foot movement, and the touch area of the foot used. Regarding the direction of foot movement, the study found that the most effective direction for both accuracy and speed was at a 30-degree angle to the right when the front of the right foot was set at 0 degrees. The 0-degree and 60-degree angles showed similar efficiencies, but were lower than the 30-degree angle. The study also found that using the big toe as the touch area resulted in the best speed, accuracy, and subjective satisfaction. The index toe was the second-best option, while using the ball of the foot was the least accurate and slowest option. Lastly, using an slope angle of 15 degrees for the touchpad was found to increase work efficiency compared to using a 7-degree slope angle. These findings can serve as guidelines for designing foot interfaces.

Power converters with coupled inductors are very promising due to the high efficiency and high voltage gain. Apart from the aforementioned advantages, the boost-flyback converter reduces the voltage stress on the semiconductors. However, to obtain good performance with high voltage gains, the controller must include two control loops (current and voltage), and a compensation ramp. One of the most used control techniques for power converters is the peak current-mode control with compensation ramp. However, in the case of a boost-flyback converter there is no mathematical expression in the literature, to compute the slope of the compensation ramp. In this paper, a formula to compute the slope of the compensation ramp is proposed in such a way that a stable period-1 orbit is obtained. This formula is based on the values of the circuit parameters, such as inductances, capacitances, input voltage, switching frequency and includes some assumptions related to internal resistances, output voltages, and some other electrical properties related with the physical construction of the circuit. The formula is verified numerically using the saltation matrix and experimentally using a test circuit.

By installing FBG sensors on the geogrids, smart geogrids can both reinforce and monitor the stability for geogrid-reinforced slopes. In this paper, a geogrid-reinforced sand slope model test was conducted in the laboratory and fiber Bragg grating (FBG) sensing technology is used to measure the strain distribution of the geogrid. Based on the model test, the performance of the reinforced soil slope is simulated by finite element software Midas-GTS, and the stability of the reinforced soil slope is analyzed by strength reduction method. The relationship between the geogrid strain and safety factor is set up. The results indicate that the measured strain and calculated results agree very well. The geogrid strain measured by FBG sensor can be applied to evaluate the stability of geogrid-reinforced sand slopes.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

The present study aimed to investigate influence of genotypic differences to zinc and iron agronomic biofortification responses among yield of finger millet. A field experiment was conducted over two seasons in farmers’ fields in Ethiopia (2019, 2020). The experimental design had 15 treatment combinations comprising 3 finger millet varieties and application of different combinations of zinc and iron mineral fertilizers. 5 soil-applied fertilizer treatments (20 kg h-1 FeSO4 + 25 kg h-1 ZnSO4 + NPKS, 25 kg h-1 ZnSO4 + NPKS, 20 kg h-1 FeSO4 + NPKS, NPKS, and 30% NPKS), at 2 locations (Gojjam and Arsi Negelle, Ethiopia), and two 2 slope positions (Foot and hill), replicated four times in a randomized complete block design. Grain yield and biomass were evaluated on plot basis. Plant height, total and productive tiller number, finger length of the longest spike and number of fingers per main ear were measured at maturity stage. The combined soil application of FeSO47H2O and ZnSO47H2O increased yield to Meba variety by 51.6%. Also, ZnSO47H2O fertilizer application increased yield to Urji variety by 27.6%. About 18.3% of yield enhancement of Diga-01 variety was achieved due to the FeSO47H2O fertilizers application. The findings of the present study suggests that the influence of Zn and Fe agronomic biofortification on yield of finger millet could be affected by genotype differences and environmental conditions.

Landslides are serious geological hazards that become a disaster worldwide, causing a large number of casualties and economic losses every year. There are many factors affecting landslide susceptibility, such as rainfall, soil and slope. Each of them has an important role in the process of slope losing stability. In this paper, the effects of rainfall intensity, rainfall pattern, slope gradient and soil type on landslide susceptibility are studied. In the process of rainfall-induced landslide, the relevant physical quantities of soil changes continuously. Their values and processes are closely related to the time of landslide occurrence. Hence, the variation of soil volumetric water content, matrix suction, pore water pressure and total stress throughout the rainfall are measured. As the results, soil type, slope gradient and rainfall intensity have a large influence on landslide susceptibility. The occurrence of landslides has a prerequisite that the slope is greater than or equal to 15°. The rainfall intensity needs to be not less than 80 mm/h. The difference of rainfall pattern also affects the landslide susceptibility. The rainfall pattern with rainfall intensity peak at the later stage is more likely to induce landslide. Coarser soils with gravels are prone to landslides when other conditions are the same. Steeper slopes, stronger rainfall, and coarser soils can all increase the amount of sediment yield.

The Soil Conservation Service - Curve Number (SCS-CN) method is extensively used to calculate the runoff from rainfall over a large catchment over the world. Slope is an important criterion for runoff but a very few attempts have been made to evaluate the effect of slope on the CN with runoff potential. The objective of this paper is to summarise the historical review on the effects of slope on CN and runoff potential in various regions by the hydrologists. This paper also depicts that how the various researchers proved the importance of consideration of slope for CN and runoff estimation. In addition, paper highlights the key features of research in future like to classify the watersheds on slope based CN, accurate Antecedent Moisture Condition (AMC) and proper initial abstraction in the various regions etc. Considering these parameters an accurate runoff estimation can be predicted and managed properly in the urban watersheds.

Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β⁺/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β⁺). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.

In this study, UAV (Unmanned Aerial Vehicle) photogrammetry was used to monitor the ground displacement on the slope below a coal waste-rock stockyard, and to investigate the role of rainfall on this displacement. The study area is a mountainous region in Korea, where coal mining continues, and coal waste-rock is stored on the slopes of the mountain. In this area, ma-terial removal work was undertaken to reduce the steepness of the slope and driving forces in order to prevent disasters, but the strategy requires continuous monitoring to confirm the stabilization of the slope. For slope monitoring, a total of six UAV photogrammetry campaigns were conducted between April 2019 and August 2020. As a result of data processing, an orthoimage and DSM (Digital Surface Model) were generated. The ground displacement was estimated through four ways: slope extraction, displacement area evaluation, horizontal displacement, and vertical displacement analysis. During the study period, the maximum vertical displacement was 3.3 m and the maxi-mum horizontal displacement was 3.5 m. The horizontal displacement was effectively evaluated through the measurement of the movement of the drainage system using orthoimages that captured with a periodic survey. The effects of rainfall on ground displacement were also investigated. A very clear linear relationship between rainfall intensity higher than 20mm/d and ground displacement was identified. Accumulated amount of rainfall also showed good correlation with slope movement, but the frequency of rainfall intensity below 20 mm/d showed relatively low correlation with ground dis-placements.

Hydraulic fracturing for oil-gas and geothermal reservoir stimulation is closely related to the generation and propagation of Mode I crack. Nonlinear deformation due to rock heterogeneity occurs at such crack tip, which causes the fracture process zone (FPZ) to form before the crack propagates unsteadily. However, the relationship between the FPZ characteristics and rock heterogeneity still remain elusive. We used three rock types common in reservoir for experimental investigation, and each of them includes two subtypes with different heterogeneity due to grain size or microstructural characteristics. Drawing on the experiment results, we calculated the FPZ size in each cracked chevron notched Brazilian disk, and we reproduced the formation process of the FPZ in marble by discrete element method. We showed that strong heterogeneity is favorable to large FPZ size, can enhance the ability of crack generation and complicate crack morphology. Coupling the Weibull distribution with fracture mechanics, the dependence of the FPZ size on heterogeneity degree can be theoretically explained, which suggests that inherent heterogeneity of rocks set physical foundation for formation of FPZ. These findings can improve our recognition to formation mechanism of the Mode I crack and provide useful guidelines for evaluating reservoir fracability.

The way Norway is spearheading electrification in the transport sector is of global interest, and details of its policies and emission impacts represent a reference. We used the NERVE model, a bottom-up high-resolution traffic emission model, to calculate all exhaust emissions in Norway (2009-2020). This allows us to evaluate the co-benefit of policies to target climate change mitigation and air quality. We have analyzed local municipal data with regards to traffic growth, road network influences, vehicle composition, emissions and energy consumption. Light vehicle CO2 emissions per kilometre have been reduced by 22% since 2009, mainly driven by an increaseing bio-fuel mixing and BEV share. BEVs are mostly located in and around the main cities, areas with young vehicle fleets, and strong local incentives. Beneficiaries of all BEVs incentives have been a subset of the population with strong economic indicators. The incentivized growth in the share of diesel-fuelled passenger vehicle has been turned, and together with Euro6 emission standards, light vehicle NOx emissions have been halved since peaking in 2014. BEV represent an investment in emission reductions in years to come and current sales set up for an accelerated decline in emissions despite growth in traffic.

Is human capital heterogeneity a decisive factor for Chinese enterprises to invest in Africa? Based on the Outward Foreign Direct Investment (OFDI） data of Chinese enterprises in 37 African countries from 2007 to 2017, this paper using the FGLS model, is the empirical analysis of the mechanism and effect of the human capital heterogeneity of host countries on OFDI location selection. The human capital heterogeneity can be divided into four dimensions: scale, quality, cost and structure, which can be measured by health level, education level, wage level, child dependency ratio and old-age dependency ratio. The results show that: (1) the host country's human capital scale and child dependency ratio structure have a significant positive impact on decision-making for OFDI; (2) the cost of human capital and the structure of old-age dependency ratio are negatively correlated with the inflow of OFDI; (3) different from the existing conclusions, the quality of human capital will inhibit the inflow of OFDI in the sample period; (4) the extended test shows that the quality of human capital has a significant positive impact on OFDI decision-making. The results of robustness test are reliable. Finally, according to the conclusion of this paper, policy recommendations are put forward.

Karst peaks and depressions are scattered in karst zones with strong spatial heterogeneity and fragile ecological environments and are crucial for determining the degree of karst geomorphologic development. However, realizing automatic depiction and extracting depressions with high accuracy is difficult because of their complex morphology. Herein, based on 12.5-m resolution DEM data, six typical karst peaks from depressions in southwest China were selected as the study areas and a revised terrain openness index method based on slope mutation points (ROBSMPs) was used to determine the degree of karst geomorphologic development and the boundary of karst depressions. The extent of depressions extracted by ROBSMPs and the terrain openness index method with the extent of depressions hand-drawn based on remote sensing images was compared and analyzed. The results show that compared with the topographic openness index method, the overall accuracy of karst depression extracted by ROBSMPs was improved and the perimeter, area, and raster displacement error indexes were reduced. ROBSMPs realized high-precision extraction of depressions, thereby strengthening the applicability of the topographic openness index method to karst peak zones. This study offers a new perspective and path toward the expansion of digital terrain analysis technology in karst mountainous areas and is expected to play a vital role in the extraction of similar geomorphic units in karst zones.

This article introduces the design and analysis of a slope detection circuit tailored for on-chip sensing of the load current in DC-DC converters. The novel indirect sensing approach is grounded in measuring the output voltage slope across the filtering capacitor during discharge phases. Consequently, this slope data can be effectively harnessed to control the converter switches. The slope detector circuit was designed in standard 65 nm CMOS technology using the nominal supply voltage of 1.2 V and can be used for current sensing within the range from one to hundreds of mA. Since the proposed circuit has mainly digital character, the robustness to process, temperature and supply voltage variations can be ensured rather conveniently.

Municipal solid waste management is a growing worldwide challenge. Landfill mining is a promising technique to reduce MSW landfills. In the present study, arbitrary embankments made of different MSW fractions are analyzed to find the safety factor of their slopes. Properties of Municipal solid waste fines (MSWF), Shredded MSW, MSW Incineration Ash, and MSW having particles less than 35 mm are used in the analysis. For doing the same, finite element-based application 'Plaxis-2D' is used. The safety of slopes is assessed while the water table is inserted, and a uniform load is applied to the embankment to establish how well they will perform in critical situations. It was found that the slope made of shredded MSW is most safe due to its low density and high friction angle, while the least safe slope is made of MSW having less than 35 mm fractions.

Predictive simulation of concurrent debris flow using only pre-disaster information has proven to be difficult as a result of problems in predicting the location of debris-flow initiation (i.e., slope failure). However, because catchment topography has concave characteristics, with all channels in a catchment joining each other as they flow downstream, it is possible to predict damage to downstream area using relatively inaccurate initiation points. Based on this, this paper presents methodologies employing debris-flow initiation points generated randomly using statistical slope failure prediction. A many-case simulation across numerous initiation points was performed to quantify the effect of slope-failure location in terms of deviations in the predicted water level and terrain deformation. It was found that the relative standard deviation diminished as the points approached the downstream area, indicating a location-based predictability effect.

Hillslope and mountain roads are often the source of erosion, which in turn can lead to larger landslides and other types of mass-movements. For this reason, low-cost repeat surveys that can be done by practitioners and not solely scientists and engineers is essential. To solve this issue the present contribution shows the testing and applicability of a mix of SfM-MVS and low-cost SLAM technology to provide erosion information. The low-cost SLAM generated between 300 ~ 900 points per square meter, while SfM-MVS created between ~11,000 to 900,000 points. The density is however a trade-off against a spatially varying error, although the variability at the road-cut scale only ranges from 2 cm vertically to 2.5 cm in x,y,z based on the C2C algorithm. Furthermore, this error tends to be more important in the higher section of the cutout (further away from the sensor and at a flatter angle). It is thus possible to measure small-scale roadside change, providing that the change is in the range of >5 cm (adding the maximum potential error twice) and providing that the road-cut is such that the sensors can be brought close to the surface (camera or sensor on a pole). The authors suggest that it can be a solution for state and agencies with limited funding and that cannot afford regular laser or for roadside that are difficult to access.

Human arteries show structural and functional peculiarities according to the nutrient and oxygen needs of a specific vascular district. This architectural heterogeneity is reflected in the pathological setting of cardiovascular diseases (CVDs). Indeed, the responsiveness to cardiovascular risk factors, the morphological and molecular patterns are discriminating factors among CVDs affecting different vascular beds. Micro-RNAs (miRNAs) are endogenous regulators of gene expression and fine tuners of vascular cell differentiation, thus these non-coding RNAs can modulate the arterial heterogeneity. The identification of a miRNA signature artery-specific would be promising in the therapy of CVDs, especially in frail elderly patients. In the present review we will provide a concise description of the arterial tree heterogeneity on structural and cellular basis, mainly in the pathological context. Secondly, we will address the miRNA potential as crucial mediators of arterial heterogeneity focusing on abdominal aorta and femoral artery, with the final goal of strengthening the search of more targeted therapies in CVDs and stratification approaches in frail elderly patients.

Slope failures pose a substantial threat to mining activity due to their destructive potential and high probability of occurrence on steep slopes close to limit equilibrium conditions, often found both in open pits and in waste and tailing disposal facilities. The development of slope monitoring and modeling programs usually entails the exploitation of in situ and remote sensing data together with the application of numerical modeling, and it plays an important role in the definition of prevention and mitigation measures aimed at minimizing the impact of slope failures in mining areas. Here we present a new methodology combining satellite radar interferometry and 2D finite element modeling for slope stability analysis at a regional scale, applied within slope unit polygons. We studied a former mining area in southeast Spain, and the method proved useful in detecting and characterizing a considerably large number of unstable slopes. Out of 1,959 slope units used for the spatial analysis of the radar interferometry data, 43 were unstable, with varying values of safety factor and landslide size. Out of the 43 active slope units, 21 exhibited line of sight velocities greater than the maximum error obtained through the validation analysis (2.5 cm/year). Eventually, this work discusses the possibility of using the results of the proposed approach to devise a proxy for landslide hazard. The proposed methodology can help to provide non-expert final users with intelligible, clear and easily comparable information to analyze slope instabilities in different settings, not limited to mining areas.

Arsenic (As) contamination of groundwater is a common problem in BDP. The alkaline pH of the groundwater provides favourable condition for geomicrobiochemical processes, where organic matter also plays an important role in mobilization of As. The total arsenic content (AsT) of the groundwater is in the range of 69-178 µgL-1 with mean value of 118.58 µgL-1. The groundwater quality of monitored drinking water wells are related to local land–use pattern and rural sanitation installation and practices (which can have a strong influence on microbial contamination). The study indicates that As heterogeneity, probably a consequence of microbial heterogeneity is a feature of the study area. The excessive total and fecal coliform (TC and FC) count of the ponds possibly suggest uncontrolled surface run offs and sewage leakage, notably from nearby pit-latrine, which increased the microbial contamination in these water sources. The tube wells located in close proximity (~ 2-3 m) of the surveyed ponds are also contaminated with high TC and FC values, due to faulty water supply system, pond water infiltration and cracked tube well platforms. Coliforms may influence geomicrobiological processes in groundwater and thereby, contribute in As release and mobilization. The TC and FC values of monitored tube wells and ponds show seasonal variation, with high TC and FC values during wet season. Attempt has been made to focus on sanitation risk of the monitored wells (based on sanitation and fecal coliform scores) which is usually less explored. The sanitary risk score reveal the need of immediate attention to all the sites, as 25.0 %, 58.3 %, 11.1 % and 5 % of tube wells of the six sites fell under very high risk (sanitary risk score ≥ 9), high risk (sanitary risk score 6-8), intermediate risk (sanitary risk score 3-5) and low risk category (sanitary risk score 0-2), respectively. Fecal coliform score classified all the sites under intermediate risk category (FC count 10-100 per 100 ml of water). The predominance of As heterogeneity particularly in areas under high risk category (showing high TC and FC contamination) is observed along with the similar sinusoidal pattern of TC, FC and AsT content. Finally, this study shed light on the factors responsible for unsafe nature of monitored tube wells and the influence of anthropogenic activities on the microenvironment of the groundwater, which could be a probable reason behind the As heterogeneity in the groundwater of the study area.

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Soil erosion is the major factor that has contributed to the reduction of soil fertility in the highlands of Ethiopia. This factor was reduced by soil and water conservation (SWC) practices. Hence, the study evaluated the effects of SWC practices and slope gradient on soil physicochemical properties in the Agemi watershed of northwestern Ethiopia. Farmland treated by SWC such as stone-faced soil bund (SFSB) and soil bund (SB), untreated farmland and slope gradient were identified in the study area. About 27 soil samples were collected from the treated farmland and untreated farmland with three slope classes, including lower (5-10%), middle (10-15%) and upper slopes (>15%). The soil physicochemical properties were analyzed by two ways analysis of variance (ANOVA) using SAS 9.2. The results of the study showed that the content of sand, clay, total porosity, pH, soil organic matter (SOM), total nitrogen (TN), available phosphorus (AP), exchangeable cations such as Ca²⁺, Mg²⁺, K⁺ and cation exchange capacity (CEC) were significantly affected (p<0.01) by SWC practices and untreated farmland with slope gradients. However, the content of silt, percent of base saturation (PBS) and exchangeable Na were statistically insignificant (p>0.05). Farmland treated with SFSB confirmed higher mean values of soil physicochemical properties than SB and untreated farmland. Moreover, the lower total porosity (TP) and higher bulk density (BD) were recorded on untreated farmland and upper slopes. This study concludes that farmland treated with SFSB improved soil physicochemical properties than farmland treated with SB followed by untreated farmland. Therefore, SFSB should be implemented on farmland to improve soil fertility in the study area.

With more and more transportation tunnels have been and will be constructed in loess areas in Northwest China with high earthquake potential, the overall stability of portal section under earthquakes actions and the related aseismic countermeasures attracted the attentions from both the scholars and engineers, especially the tunnels in the upper slope connecting the high bridges crossing rivers or valleys. In order to study the dynamic response characteristics and damage evolution of steep loess slope with a tunnel under the earthquake actions, a large-scale shaking table tests were performed on steep loess slope with a tunnel. Wenchuan-tangyu (WT) wave and El Centro (El) wave records were applied on the model to investigate the displacement response and acceleration response of loess slope with a tunnel under the horizontal (X) and the combined action of horizontal and vertical (X-Z) seismic loads, respectively. In particular, three-dimensional non-contact optical measurement techniques were used to obtain the slope surface displacements. The results showed that the main deformation pattern of the slope was horizontal movement and settlement when the seismic wave input was in the X and X-Z directions, respectively. However, the X direction seismic wave had a greater impact on the deformation of the slope, and the tunnel portal slope was destroyed under the action of a large horizontal seismic acceleration finally. Slope failure ahead of a tunnel could be divided into four stages, i.e. elastic deformation stage, plastic deformation accumulation stage, local failure stage, and overall failure stage. The peak ground displacement of X direction (PGDX) and peak ground displacement of Z direction (PGDZ) of the slope surface increased with the increasing of the input peak ground acceleration (PGA) when the input wave was same waveform and same direction. The existence of the tunnel had a great influence on the PGA and the PGA amplification factor (PGAAF) of the soil mass surrounding it. This was because the seismic waves encounter a tunnel surface with clear differences in the physical properties of the medium during their propagation in the slope, thereby forming a strong reflection and refraction effect, and the amplitude changed significantly. Numerical simulation results were basically consistent with the experimental results.

The development of forecasting models for the evaluation of potential slope instability after rainfall event represents an important issue for the scientific community. This topic has received considerable impetus due to climate change effect on the territory [1, 2] as several studies demonstrate that the increase in global warming can significantly influence the landslide activity and stability conditions of natural and artificial slopes [3]. A consolidated approach in evaluating rainfall induced landslide hazard is based on the integration of rainfall forecasts and physically based (PB) predictive models through deterministic laws. However, considering the complex nature of the processes and the high variability of the random quantities involved, probabilistic approaches are recommended in order to obtain reliable predictions. A crucial aspect of the stochastic approach is represented by the definition of appropriate probability density functions (pdfs) to model the uncertainty of the input variables as this may have an important effect on the evaluation of the probability of failure (PoF). The role of the pdf definition on reliability analysis is discussed through a comparison of PoF maps generated using Monte Carlo (MC) simulations performed over a study area located in the Umbria Region of central Italy.

The paper presents a three-dimensional slope stability limit equilibrium solution for translational, planar failure modes. The proposed solution uses Bishop’s average skeleton stress combined with the Mohr – Coulomb failure criterion to describe soil strength evolution under unsaturated conditions while its formulation ensures a natural and smooth transition from the unsaturated to the saturated regime and vice versa. The proposed analytical solution is evaluated by comparing its predictions with the results of the Ruedlingen slope failure experiment [1]. The comparison suggests that despite its relative simplicity the analytical solution can capture well the experimentally observed behaviour and highlights the importance of lateral resistance consideration together with a realistic interplay between mechanical parameters (cohesion) and hydraulic (pore water pressure) conditions.

In this paper, a new approach to the sliding-mode control of single-phase inverters under linear and non-linear loads is introduced. The main idea behind this approach is to utilize a non-linear, flexible and multi-slope function in controller structure. This non-linear function makes the controller possible to control the inverter by a non-linear multi-slope sliding surface. In general, this sliding surface has two parts with different slopes in each part and the flexibility of the sliding surface makes the multi-slope sliding-mode controller (MSSMC) possible to reduce the total harmonic distortion, to improve the tracking accuracy, and to prevent overshoots leading to undesirable transient-states in output voltage which are occurred when the load current sharply rises. In order to improve the tracking accuracy and to reduce the steady-state error, an integral term of the multi-slope function is also added to the sliding surface. The improved performance of the proposed controller is confirmed by simulations and finally, the results of the proposed approach are compared with a conventional SMC and a SRFPI controller.

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

Calcium (Ca) is an essential element constituting sedimentary carbonate in subducting sediments. Ca isotopic characteristics of subduction-related rocks could provide insight into the behavior and budget of carbonate and carbon cycles in subduction zones, due to the distinctive δ^44/40Ca ranges of sedimentary carbonate with respect to the mantle. Here, we studied the Ca isotopic compositions of arc magmas from the Northern Luzon arc (NLA), which are evolved from a depleted mantle metasomatized by slab-derived fluids and sediment melts. The δ^44/40Ca values range from 0.76 ± 0.04‰ to 1.01 ± 0.03‰ and cover the typical ranges for bulk silica earth (BSE, ~ 0.94‰) and fresh mid-ocean ridge basalt (MORB, ~ 0.83‰). The Ca isotopes of NLA volcanics are not dominantly determined by the effects of mantle partial melting or fractional crystallization, nor significantly modified by secondary alteration. Instead, the δ^44/40Ca values of NLA volcanics are controlled by the subduction-related metasomatism. The metasomatism by slab-derived fluids (mainly expelled from altered oceanic crust, AOC) dramatically elevated the contents of fluid-mobile elements (e.g., Ba and Pb) with respect to fluid-immobile elements (e.g., Ce). This process, however, rarely modified the Ca isotopes, possibly ascribed to the δ^44/40Ca similarity between AOC and the depleted mantle. The δ^44/40Ca values significantly correlated with subduction indicators (e.g., Sr-Nd isotopes, Ba/Nb, Ce/Pb, and Nb/La), demonstrating the Ca isotopes of NLA volcanics are mainly controlled by the metasomatism of sediment melts subducting from the South China Sea (SCS). Based on the thermal structures and chemical compositions of sediments subducting into global trenches, we propose that carbonate Ca isotopic signals can only be observed in the arcs with high sedimentary Ca fluxes and temperature-pressure conditions well beyond the solidus of H₂O-saturated sediment melting, e.g., NLA, Nicaragua, Guatemala, Colombia, Peru, South Chile, North Vanuatu, New Zealand, and Kermadec. The absence of such signals in other arcs suggests either limited sedimentary fluxes or much of the subducting sedimentary carbonate has been survived during plate subduction to enter the deep mantle.

We propose a theory of ASD as a condition of comorbid cognitive impairments that corrupt the learning, encoding, and manipulation of episodic and semantic memories. We consider (i) episodic and semantic memory functions of the entorhinal-hippocampal complex, (ii) constraints on the transfer and encoding of these memory components into neocortical areas, and (iii) the demands of cognitively manipulating memories in distributed computations being necessary for goal oriented interactions. In ASD, learning and cognitive challenges manifest in diverse ways but especially in high-complexity model predictive control tasks with latent variables. ASD impairments in social interactions represent a prototypical example. Social interactions are at the high end of complexity and require processes (i)–(iii) to work in a concerted fashion due to the need for the learning and estimation of many, sometimes latent, parameters, including emotions, intention, physical and mental capabilities as well as the predictive modeling of these parameters for decision making and timed-action series. We put forth the idea that autism is a result of an arbitrary combination of otherwise not prominent corruptions in processes (i)–(iii). Together, these corruptions may severely impair intelligence and slow down learning, especially in high complexity learning tasks. Over time, slow learning may spare the spontaneous learning-by-doing method - namely, repetitive behavioral patterns, whereas behavioral failures related to complex tasks can restrict interest in such task, thus inducing a fear of novelty; conversely, the fear of novelty restricts interest and can slow learning down. We embed our thoughts into a predictive autoencoding, goal-oriented model of a deterministic world. We compare this model to others, such as the noisy brain model, the Bayesian prior theory, the mirror neuron theory and the weak central coherence theory. We argue that the predictive autoencoder model of the deterministic world harmonizes with these other models and embraces them in a straightforward way.

This article reveals a best possible design for hybrid dispersion compensating fiber (HyDCF) with high birefringence established on modified broadband compensating structure through S, C and L telecommunication bands. The simulation outcome exhibits relatively higher birefringence of 3.76×10-2 at wavelength of 1550 nm. The suggested fiber also has dispersion compensation characteristics in an inclusive series of wavelengths which covers 1400-1625 nm. The reported design can achieve dispersion quantity of – 606 ps/ (nm.km) at 1550 nm effective wavelength. The reported fiber design matches the relative dispersion slope (RDS) 0.003694 nm-1 similar to single mode fiber at 1550 nm operating wavelength. This fiber demonstrates negatively flattened effective dispersion of – 2.703 ± 0.734 ps/ (nm.km) within 180 nm flat band ranging from 1460-1640 nm wavelength. It is also convenient to optical high bit rate communication systems. The low confinement loss is found 3.756×10-10 dB/m at the operating wavelength. This design also achieves highly nonlinear coefficient of 50.34 W-1km-1. In some cases, it can also be used in sensing applications.

Recently L-shaped tunneling field-effect-transistor (LTFET) has been introduced to overcome the thermal subthreshold limit of conventional metal-oxide-semiconductor field-effect-transistors (MOSFET). In this work, shortcoming of LTFET was investigated. It was found that corner effect present in LTFET effectively degrades its subthreshold slope. To get rid of corner effect a new type of device with dual material gates is presented. The new device termed as DG-LTFET gets rid of the corner effect and results in a significantly improved subthreshold slope of less than 10 mV/dec, and an improved ON/OFF current ratio over LTFET. In this work DG-LTFET was evaluated for different device parameters, and bench-marked against LTFET. This work presents an optimum configuration of DG-LTFET in terms of device dimensions and doping levels, to get the best subthreshold, ON current and ambipolar performance from the DG-LTFET.

Glioblastoma is a highly malignant brain tumor consisting of heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be well adapted to limitations in the variety and number of substrates imported into the brain parenchyma and present it their microenvironment. Additionally, the phenotypic heterogeneity of cancer cells could promote the variations among their metabolic capabilities regarding the utilization of available substrates and release of metabolic intermediates. With the aim to identify the putative metabolic footprint of different types of glioblastoma cells, we exploited the possibility for separation of polar and ionic molecules present in culture media or cell lysates by hydrophilic interaction liquid chromatography (HILIC). The mass spectrometry (MS) was then used to identify and quantify the eluted compounds. The introduced method allows the detection and quantification of more than 150 polar and ionic metabolites in single run, those may be present either in culture media or cell lysates and provide data for polaromic studies within metabolomics. The method was applied to analyze the culture media and cell lysates derived from two types of glioblastoma cells, T98G and U118. The analysis revealed that even the both types of glioblastoma cells share several common metabolic aspects, they also exhibit differences in their metabolic capability. This finding agrees with the hypothesis about metabolic heterogeneity of glioblastoma cells. Furthermore, the combination of both analytical methods, HILIC-MS, provides a valuable tool for metabolomic studies based on the simultaneous identification and quantification of a wide range of polar and ionic metabolites - polaromics.

The increasing residential space differentiation is an important practical problem for Chinese cities. The different choice of living space for urban residents is a concrete reflection of social class divide, which reflects the differences in the choices and demands of different social groups for urban housing. Taking Wuhan, an important city in central China, as an example, this research divides the residential space based on the social resource structure, and analyzes and compares the spatial differentiation and influencing factors of different residential areas and houses with different prices in Wuhan by spatial differentiation indicators and geographic detector. The results show clear differences in resource structure among residential areas, and there are few high-quality residential areas with a concentrated distribution. The spatial differentiation levels of different residential areas are distinct, and the pursuit of high-quality and scarce resources is the key to the residential space differentiation of most large cities in China. In addition, residential space differentiation can lead to inter-generational problems such as housing wealth inequality, resource deprivation and solidified class identity. Exploring the mechanisms and social effect of residential space differentiation in most large cities in China can provide some reference for China's urban space planning and real estate market regulation in the new era.

Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen frequently associated with acute diarrhea in children and travelers to endemic regions. EAEC was found the most prevalent bacterial diarrheal pathogen from hospitalized Bolivian children less than five years of age with acute diarrhea from 2007 to 2010. Here, we further characterized the epidemiology of EAEC infection, virulence genes, and antimicrobial susceptibility of EAEC isolated from 414 diarrheal and 74 non-diarrheal cases. EAEC isolates were collected and subjected to a PCR-based virulence gene screening of seven virulence genes and a phenotypic resistance test to nine different antimicrobials. Our results showed that atypical EAEC (a-EAEC, AggR-negative) was significantly associated with diarrhea (OR, 1.62, 95% CI, 1.25 to 2.09, P < 0.001) in contrast to typical EAEC (t-EAEC, AggR-positive). EAEC infection was most prevalent among children between 7 - 12 months of age. The number of cases exhibited a biannual cycle with a major peak during the transition from warm to cold season (April – June). Both typical and a-EAEC infections were graded as equally severe; however, t-EAEC harbored more virulence genes. aap, irp2, and pic were the most prevalent genes. Surprisingly, we detected 60% and 52.6% of multidrug resistance (MDR) EAEC among diarrheal and non-diarrheal cases. Resistance to ampicillin, sulfonamides, and tetracyclines was most common, being the corresponding antibiotics, the ones that are frequently used in Bolivia. Our work is the first study that provides comprehensive information on the high heterogenicity of virulence genes in t-EAEC and a- EAEC and the large prevalence of MDR EAEC in Bolivia.

Wave is a common environmental load that often causes serious damages to offshore structures. In addition, the stability for the submarine artificial slope is also affected by the wave loading. Although the landslide of submarine slopes induced by the waves has received wide attention, the research on the influence of solitary-wave is rare. In this study, a 2-D integrated numerical model is developed to investigate the stability of the foundation trench under the solitary wave loading. The Reynolds-Averaged-Stokes (RANS) equations are used to simulate the propagation of a solitary wave, while the current is realized by setting boundary inlet/outlet velocity. The pore pressure induced by the solitary wave is calculated by Darcy’s law and the seabed is characterized by Mohr-Coulomb constitutive model. Firstly, the wave model is validated through the comparison between analytical solution and experimental data. The initial consolidation state of slope under hydrostatic pressure is achieved as the initial state. Then, the factor of stability (FOS) for the slope corresponding to different distance between wave crest and slope top is calculated with the strength reduction method. The minimum of FOS is defined as the stability index for the slope with specific slope ratio during the process of dynamic wave loading. The parametric study is conducted to examine the effects of soil strength parameters, slope ratio and current direction. At last, the influence of upper slope ratio in a two-stage slope is also discussed.

Overcoming terrain obstacles presents a major problem for people with disabilities or with limited mobility who are dependent on wheelchairs. An engineering solution designed to facilitate the use of wheelchairs are assisted propulsion systems. The objective of the research described in this article is to analyse the impact of the hybrid manual-electric wheelchair propulsion system on the kinematics of the anthropotechnical system when climbing hills. The tests were carried out on a wheelchair ramp with an incline degree of 4°, using a prototype wheelchair with a hybrid manual-electric propulsion system in accordance with the patent application P.427855. The test subjects were three people whose task was to propel the wheelchair in two assistance modes supporting manual propulsion. The first mode is hill climbing assistance, while the second one is assistance with propulsion torque in the propulsive phase. During the tests, a number of kinematic parameters of the wheelchair were monitored. An in-depth analysis was performed for the amplitude of speed during a hill climb and the number of propulsive cycles performed on a hill. The tests performed showed that when propelling the wheelchair only using the hand rims, the subject needed an average of 13 pushes on the uphill slope, and their speed amplitude was 1.8 km/h with an average speed of 1.73 km/h. The climbing assistance mode reduced the speed amplitude to 0.76 km/h, while the torque assisted mode in the propulsive phase reduced the number of cycles required to climb the hill from 13 to 6. The tests were carried out at various values of assistance and assistance amplification coefficient, and the most optimally selected parameters of this coefficient were presented in the results. The tests proved that electric propulsion assistance has a beneficial and significant impact on the kinematics of manual wheelchair propulsion when compared to a classic manual propulsion system when overcoming hills. In addition, assistance and assistance amplification coefficient were proved to be correlated to operating conditions and the user's individual characteristics.

Strata and surface movement induced by mining under open-pit final slope is a huge threat to mine safety. Physical model test is an important method to study mining-induced strata and surface movement laws. Because of rock joints predominantly control rock mass deformation and failure, thus physical model test leaving out of consideration of rock joints is difficult to reflect the influence of rock joints on rock mass deformation. Therefore, this paper presents a three-dimensional physical model test considering simplified dominant rock joints. This test process includes the design of testing equipment, the construction of physical model with dominant rock joint sets, conduction of mining and deformation monitoring. And mining under eastern final slope of Yanqianshan iron mine was selected as a case to study the behavior of mining-induced strata and surface movement.

Real estate industry is related to the national economy and people's livelihood，characterized by a high degree of financial intensity. The enterprises in this industry need certain financial ability and large shareholder controlling ability to support their survival. However，due to the multiple adverse impacts of current state policies，banks and private capital，the credit crunch，the sudden decrease in withdrawn funds and the limitation of internal financing，the problem of capital restraint of real estate enterprises has become more and more serious. From the perspective of corporate governance，this paper studies the interaction among financial constraints，ownership concentration and corporate performance under different shareholding states by analyzing the quantitative characteristics of equity structure，and looks for the appropriate range of the largest shareholder holding ratio，which has considered the financial performance and risk. It is found that raising the ownership concentration can effectively ease the financing constraints and improve the performance of enterprises，both of which are significant under the state of high ownership concentration， while the financial constraints play a significant intermediary effect under the State of absolute holding， while in the decentralized state of ownership，there is a significant regulatory effect，and the interaction of the three will be different due to the size of the enterprise.

This research examines how rainfall and mining affect the slope damage resulting from the transition from open-pit mining to underground mining. Using unmanned aerial vehicle (UAV), the Huangniu slope of Dexing Copper Mine was fully characterized, and experiments were conducted on rock samples from appropriate sites. First, the mechanical properties of the samples were measured. Then, the parameters of the similarity simulation experiments were derived based on the similarity theory. Subsequently, the rainfall, rock slope, data acquisition and monitoring systems were designed. Finally, the rock mass failure with different slope angles was analyzed, and the deformation and damage patterns under the coupling effect were obtained. The results show that rainfall increases pore water pressure and moisture content. Rainfall and slope-slip water have more impact on the open-pit platform. The pore water pressure values on the upper rock mass rise faster than inside. In the open-pit mining stage, the rock mass shifts slightly to the upper left. In the room mining stage, vertical fractures and goaf sinking occur. The fractures above the mine room form a semi-ellipse. In the pillar mining stage, the overlying rock displacement is evident, and fractures persist. In the continuous pillar mining stage, the overlying rock collapses massively. The 65° slope model is the most damaged, while the 55° slope model is the least damaged. The results also suggest that the UAV guides sample selection.

In recent years, the genesis of natural gas and the definition of major gas source rocks in the Baiyun Sag of the Pearl River Mouth Basin have attracted extensive attention from scholars. There is still considerable controversy over the genesis and the main gas source rocks of natural gas. In this study, the chemical kinetics method of natural gas generation and carbon isotope fractionation was used to study the generation history and isotope evolution history of Paleogene natural gas in the Y5 well area located on the north slope of Baiyun Sag. And other geochemical discriminant methods were applied simultaneously to determine the type and source rocks of natural gas. The results show that the natural gas in the Y5 well area on the northern slope of Baiyun Sag is mainly kerogen degradation gas, mixed with a small amount of oil cracking gas. The mixture of kerogen degradation gas and a small amount of crude oil cracking gas caused the inversion of the carbon isotope sequence of ethane and propane. The natural gas in the Y5 well area mainly comes from delta–shallow lacustrine facies source rock. The high–quality reservoirs in the shallower strata accumulate natural gas generated in the early stage, and the tight reservoirs in the deeper strata mainly accumulate natural gas generated in the late stage.

Digital Elevation Models (DEMs) are widely used in geographic and environmental studies. In the current work, the fusion of multi-source DEMs is investigated to improve the overall accuracy of public domain DEMs. Multi-scale decomposition is an important analytical method in data fusion. Three multi-scale decomposition methods – the wavelet transform (WT), bidimensional empirical mode decomposition (BEMD) and nonlinear adaptive multi-scale decomposition (N-AMD) - are applied to the 1-arc-second Shuttle Radar Topography Mission Global digital elevation model (SRTM-1 DEM) and the Advanced Land Observing Satellite World 3D – 30 m digital surface model (AW3D30 DSM) in China. Of these, the WT and BEMD are popular image fusion methods. A new approach for DEM fusion is developed using N-AMD (which is originally invented to remove the cycle from sunspots). Subsequently, a window-based rule is proposed for the fusion of corresponding frequency components obtained by these methods. Quantitative results show that N-AMD is more suitable for multi-scale fusion of multi-source DEMs, taking the ice cloud and land elevation satellite (ICESat) global land surface altimetry data as a reference. The vertical accuracy of the fused DEM shows significant improvements of 29.6% and 19.3% in a mountainous region and 27.4% and 15.5% in a low-relief region, compared to the SRTM-1 and AW3D30 respectively. Furthermore, a slope position-based linear regression method is developed to calibrate the fused DEM for different slope position classes, by investigating the distribution of the fused DEM error with topography. The results indicate that the accuracy of the DEM calibrated by this method is improved by 16% and 13.6%, compared to the fused DEM in the mountainous region and low-relief region respectively, proving that it is a practical and simple means of further increasing the accuracy of the fused DEM.

Astrocytes are morphological intricate cells and actively modulate the function of the brain. Through the numerous fine processes, astrocytes contact with neurons, blood vessels and other glia cells. Emerging evidence have shown that astrocytes exhibit brain-regional diversity in the morphology, transcriptome, calcium signaling and functions. However, little is known about the brain regional heterogeneity of astrocyte-astrocyte structural interaction. So far, the visualization and characterization of the morphological features for the adjacent astrocytes with high resolution has been difficult, and as a result, it is still well accepted that astrocytes in the adult brain share non-overlapped territory. In contrast, by using an approach that combines sparse viral labeling with dual-fluorescent dyes, which allows for efficient and specific labeling of adjacent astrocytes, thus enabling a comprehensive visualization of their fine processes and the degree of their territorial overlap. Our study in the hypothalamic regions revealed a marked spatial overlap among adjacent astrocytes. Additionally, we revealed the heterogeneity of astrocyte-neuron ratio across brain regions, and conducted an assessment of the photostability and labeling efficiency of fluorescent dyes used for labeling adjacent astrocytes. Our study here provides new insights for studying the morphological heterogeneity of astrocytes across the central nervous system.

Tourism sustainability is a significant approach to forming a synergistic model of industry and ecology in ecologically vulnerable areas. Scientifically detecting the effect mechanism of tourism development (TDI) on eco-environment resilience (ERI) is important in achieving regional social-ecological system sustainability. Empirical exploration is conducted on the levels of TDI and ERI in the Yangtze River Economic Belt (YREB) to study the spatiotemporal heterogeneity of TDI's effect on ERI. The results indicate a significant growth in TDI in the YREB, with the formation of tourist clusters around Shanghai and Chongqing as the core. Although ERI typically exhibits a declining trend, the rate of decline has notably slowed, forming a "high at the sides and low in the middle" spatial pattern. TDI and ERI are spatially dependent in the YREB, with predominantly high-high (HH) and low-high (LH) clusters in Shanghai, Zhejiang, and Jiangsu. Conversely, upstream regions with strong eco-environmental foundations exhibit low-low (LL) and high-low (HL) clusters. In general, TDI promotes ERI, but there is significant spatiotemporal heterogeneity in the YREB. Positive impact regions are expanding, while negative impact regions are shrinking. These results could provide scientific evidence for differentiated classification and control policies in the YREB.

The sustainability of grazing lands lies in the nexus of human consumption behavior, livestock productivity, and environmental sustainability. Due to fast growing global food demands, many grazing lands have suffered from overgrazing, leading to soil degradation, air and water pollution, and biodiversity losses. Multidisciplinary efforts are required to understand how grazing lands can be better monitored, assessed and managed to attain predictable outcomes of optimal benefit to society. This paper synthesizes our understanding based on previous work done on impacts of grazing on ecosystem goods and services, identifies current knowledge gaps, and formulates a plan forward. We review the impacts of two contrasting grazing systems, continuous and multi-paddock rotational grazing, on soil carbon (C), nutrient cycling and greenhouse gas emissions (GHGs). We then extend our review to explore challenges of incorporating spatial heterogeneity and temporal variability into monitoring and modelling C and nutrient cycling in grazing lands. We revisit two process-based models (i.e., DNDC and DayCent) and two watershed models (i.e., SWAT and VIC) widely used to simulate C, nutrient and water cycles of these lands. Finally we identify research directions for improving the knowledge base which is essential to conserve grazing lands and maintain their ecosystem goods and services.

Rapid draw-down in an earthfill dam has serious implications for dam safety regarding slope stability. The evaluation of reservoir draw-down impact on slope stability was carried out considering the case study of 8 hours of rapid draw-down of the Middle Marsyangdi Hydroelectric Power Project (MMHPP) rock-fill dam using the Limit Equilibrium Method (LEM) and stress-based Finite Element Method (FEM). The time-dependent factor of safety (FOS) was evaluated and found that the 8 hours of rapid draw-down undertaken in October 2012 for reservoir flushing was unsafe with a draw-down rate of 1.91m/h. The resulting FOS of 1.28 and 1.27 using LEM and FEM was classified as unsafe as per the US Army Corps of Engineers’ guideline, the minimum required factors of safety should be greater than 1.3. The minimum safe allowable draw-down rate of 0.76m/h for 20 hours was identified. Applying three layers of horizontal filter materials and increasing the upstream dam’s permeability provided adequate FOS results for all cases by increasing seepage discharge to reduce the destabilizing excess pore water pressure. Several gradual draw-down rates were also tested and found that FOS increases with decreased draw-down rates, as it reduces the excess pore water pressure controlled with stabilizing existing water load.

In Ethiopia, land degradation in the form of gully development and soil nutrient depletion is a very serious issue. The goal of this study is to determine how different types of land management practices and slope positions affect particular soil physico-chemical characteristics in the Agamssa watershed. Using systematic sampling techniques, soil samples were taken using a sampling quadrat (15 * 15 m) that was placed 50 m apart from one another. A total of 54 quadrats were planted at three slope positions: upper (>15%), middle (10–15%), and foot (3–10%) slope respectively. 18 composite soil samples were then. A two-way ANOVA was used to analyze the data, and the Least Significant Difference (LSD) test was used to separate the means at p ≤ 0.05. According to the study's findings, the value of most soil physical and chemical characteristics was higher in closed area than on open grazing land, as well as at foot slope position compared to middle and upper slope positions. The higher mean value (7.3 ppm) was recorded at the foot slope, while the lower mean value (4.9 ppm) was found at the upper slope position. The exchangeable cations such as Mg+2, K+, and Na+ were significantly (p≤ 0.01) affected by the main effect of land-use types. The higher mean values of Mg+2 (9.70 mq/100g), K+ (0.38 mq/100 g), and Na+ (0.035 mq/100 g) were found at area closure, whereas the lower mean values of Mg+2 (7.33 mq/100g), K+ (0.30 mq/100 g), and Na+ (0.027 mq/100g) were recorded at open grazing land. It was able to conclude this study that area closure enhances the physical and chemical qualities of soil and recovers woody plant species. Therefore, converting open grazing land into a closure area is advised.

The determination and classification of seafloor sediment types are crucial for the exploitation of marine resources, construction of marine engineering, and maintenance of marine ecological en-vironments. Automatic classification of seafloor sediment based on acoustic telemetry data is an important method to quickly understand the type of a large range of sediment. Currently, most studies on sediment classification are based on multi-beam backscattering intensity data, which is a relatively single data type. Besides, the low-dimensional details of standard U-Net gradually weaken in the propagation process, limiting the accuracy of sediment classification. Therefore, this study proposes an automatic classification method of seafloor sediment types based on an im-proved U-Net and K-means clustering algorithm, using multi-beam water depth, sub-bottom profile, and sample test data in the Northern Slope of the South China Sea. Six sediment types, including gravelly muddy sand, sand, silty sand, less muddy silt, muddy silt, and silty mud, were identified in the study area. Additionally, the study area was divided into four sedimentary en-vironment zones, including the shelf sedimentary area, the upper shelf slope break sedimentary area, the lower shelf slope break mixed sedimentary area, and the slope deposition area, based on the results of sediment classification and geological background. The sedimentary environment zones were found to be distributed along the trend of the shelf slope break line. The results of this study not only provide an important supplement to the existing classification methods of seafloor sediments but also contribute to the understanding of the sedimentary environment and process of the Northern Slope of the South China Sea.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Life is supported by metabolism, a vital physiological activity. It guarantees enough energy available to power every cellular activity. The primary cellular substrate, glucose, is where the majority of the energy needed by the cell to support all other life activities and the growth of living creatures is derived. The quality of life is greatly impacted by any disease or flaw that alters the metabolism of glucose. There is no known cure for the metabolic illness known as diabetes. As diabetes is so varied, the only effective treatments would be based on precision medicine and a molecular strategy. This review covers a wide range of topics, including the ability to recognize the various forms of diabetes, the anthropogenic and genetic influence of the cause of diabetes, the severity of the various forms of diabetes, its potential existential risk, the disease burden, and clinical methods for diagnosing them. The most recent research goes on to recommend ways to ameliorate the disease, including diet-based management, biotherapies, and other individual lifestyle choices. Futuristic therapy using molecular biology approach was suggested. Recent research found a direct correlation between an individual's lifestyle and the rate of gene mutation in diabetes. There is an existential risk associated with the sickness as the rate of the spread of the disease among population globally is faster than the world's population growth rate. It is possible to think of diabetes as a silent pandemic.

Flow cytometric detection of intracellular (IC) signaling proteins and transcription factors (TFs) will help elucidate the regulation of B cell survival, proliferation and differentiation. However, simultaneous detection of signaling proteins or TFs, with membrane markers (MM) can be challenging as required fixation and permeabilization procedures can affect functionality of conjugated antibodies. Here, a phosphoflow method is presented for detection of activated NF-κB p65 and phosphorylated STAT1, STAT3, STAT5 and STAT6 together with B cell differentiation MM CD19, CD27 and CD38. Additionally, a TF-flow method is presented that allows detection of B cell TFs; PAX5, c-MYC, BCL6, AID and antibody-secreting cell (ASC) TFs BLIMP1 and XBP-1s together with MM. Applying these methods on in vitro induced human B cell differentiation cultures showed significantly different steady-state levels, and responses to stimulation, of phosphorylated signaling proteins in CD27-expressing B cell and ASC populations. The TF-flow protocol and UMAP analysis revealed heterogeneity in TF-expression within stimulated CD27 or CD38-expressing B cell subsets. The methods presented here allow for sensitive analysis of STAT and NF-κB p65 signaling and TFs together with B cell differentiation MM at single-cell resolution. This will aid further investigation of B cell responses in both health and disease.

In the last years, the development of low-cost GNSS sensors allowed monitoring in a continuous way movement related to natural processes like landslides with increasing accuracy and limited efforts. In this work, we present the first results of an experimental low-cost GNSS continuous monitoring applied to the unstable slope affecting the Madonna del Sasso Sanctuary (NW Italy). The courtyard of Sanctuary is built of two unstable blocks delimited by high cliff. Previous studies and non-continuous monitoring showed that blocks suffer a seasonal cycle of thermal expansion and long-term trend to downslope of few millimeters per year. The presence of continuous monitoring solution, could be an essential help to better understand the kinematics of unstable slope and to recognize the beginning of a possible paroxysm phase that could end with a failure of the unstable area. We tested the accuracy of the instruments and the first year of experimental measurements are presented. We also propose a methodological approach that considers the use of automatized procedures for the identification of anomalous trends and a risk communication strategy based on monitoring data.

Due to the special terrain of Urumqi (in the valley area), which often triggers strong foehn weather, and causes huge losses to local people's lives and social economy. This study uses in-situ surface meteorological variables (including the hourly temperature, pressure, humidity, wind, etc.) from the Urumqi Meteorological Station (downstream station, DS) and the Dabancheng Meteorological Station (upstream station, US) in the Middle Tianshan Valley and NCEP/NCAR reanalysis data from 2008 to 2022. A dataset of the foehn weather process at DS in the past 15 years is established and the variation patterns of each meteorological variable during the process of foehn is analyzed. Based on the physical mechanism of the occurrence of foehn, a three-element identification standard for foehn in Urumqi is established by comparing and analyzing the variation of wind direction (WD), wind speed (WS), and the difference of potential temperature (Δθ) between DS and US during the period of foehn and non-foehn from 2013 to 2022, namely: 94°≤ 2-minute average WD ≤168°, 2-minute average WS ≥2.0 m/s, and Δθ between DS and US ≥ 0.29 K. According to the test and evaluation, the three-element identification standard has an accuracy of 82.96%, and a hit rate of 89.50% for the occurrence of foehn in Urumqi from 2008 to 2012. Moreover, the hit rate of foehn identification is 100% for strong wind or above (i.e., 2-minute average WS ≥10.8 m/s) WS. In addition, combined with two predictors of sea-level pressure difference (ΔP) and Δθ between DS and US, forecasting foehn can be more accurately predicted than a single forecasting factor. When ΔP ≤ -12 hPa and Δθ≥5 K, the probability of the occurrence of foehn is more than 90%. This study provides certain reference and application value for the weather forecasting operation of foehn.

Cancer stem cells play a crucial role in tumor initiation, metastasis and therapy resistance. Cellular heterogeneity and plasticity challenge the isolation of cancer stem cells. The impact of intratumoral cellular heterogeneity in the context of treatment resistance using a label-free approach remains understudied. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three cell subpopulations sorted by SdFFF exhibits cancer stem cell traits, including high tumorigenicity in vivo, and a higher frequency of tumor-initiating cells compared to the other subpopulations. In vitro two- and three-dimensional chemosensitivity assays emphasize the therapeutic relevance of this cancer stem cell-like subpopulation due to its chemoresistance. Therefore, our findings highlight a label-free cell sorting approach to reveal intratumoral cellular heterogeneity and its implication in therapy resistance. This approach enables the study of the individualized response of each sorted cell subpopulation by breaking down the tumor, thus offering new perspectives for personalized therapy.

Fire regimes in mountain landscapes of southern Europe have been shifting from their baselines due to rural abandonment and fire exclusion policies. Understanding the effects of fire on biodiversity is paramount to implement adequate management. Herein, we evaluated the relative role of burn severity and heterogeneity on bird abundance in an abandoned mountain range located in the biogeographic transition between the Eurosiberian and Mediterranean region (the Natural Park ‘Baixa Limia–Serra do Xurés’). We surveyed the bird community in 206 census plots distributed across the Natural Park, both inside and outside areas affected by wildfires over the last 11 years (from 2010 to 2020). We used satellite images of Sentinel 2 and Landsat missions to quantify the burn severity and heterogeneity of each fire within each surveyed plot. We also accounted for the past land use (forestry or agropastoral use) by using a land cover information for year 2010 derived from satellite image classification. We recorded 1,735 contacts from 28 bird species. Our models, fitted by using GLMs with Poisson error distribution (pseudo-R²_-average of 0.22 ± 0.13), showed that up to 71% of the modelled species were linearly correlated with at least one attribute of the fire regime. The spatiotemporal variation in burnt area and severity were relevant factors for explaining the local abundance of our target species (39% of the species; Akaike weights > 0.75). We also found a quadratic effect of at least one fire regime attribute on bird abundance for 60% of the modeled species. The past land use, and its legacy after 10 years, was critical to understand the role of fire (Akaike weights > 0.75). Our findings confirm the importance of incorporating remotely sensed indicators of burn severity into the toolkit of decision makers to accurately anticipate the response of birds to fire management.

In order to understand the impact of lithologic heterogeneity of continental mixed fine-grained sedimentary rocks on reservoir brittleness in western Qaidam basin, the mechanical properties of the rocks and their correlation with mineral composition and petrographic characteristics were studied by measns of mineralogy, petrography and triaxial stress test. The results show that the reservoir rocks can be divided into 5 different types according to the mechanical properties of the reservoir (characteristics of stress-strain curves), among them Type I and III belong to similar elastoplastic failure model, type II shows a special pulse failure mode for plastic material, type IV shows a failure mode of mixed characteristics, and type V exhibits a typical plastic failure model. The correlation between minerals and mechanical properties indicates that quartz and feldspar, which are often considered brittle minerals, do not contribute much to the brittleness of continental fine-grained sedimentary rocks. The main minerals affecting reservoir brittleness are dolomite and clay minerals, and their contributions to reservoir brittleness are positive and negative, respectively. The petrographic analysis results prove that the abnormal correlation between rock mechanical properties and quartz and feldspar is caused by the different rock fabrics. When dolomite forms a rock skeleton, it typically exhibits greater strength, brittleness and physical properties than other minerals. Based on the results, a brittleness evaluation standard for continental fine-grained sedimentary rock reservoir is proposed, and the validity of the standard is verified by the spatial correlation between the lithology probability model and the micro-seismic monitoring data, indicating that the spatial heterogeneity of dolomite-rich rock is the main controlling factor for the development of ‘sweet spot’ in the Cenozoic continental fine-grained sedimentary rock reservoir in the Western Qaidam Basin.

The Lac Fallère area, located in the upper Clusellaz Valley (tributary of the middle Aosta Valley), is shaped in micaschist and gneiss referred to as the Mont Fort Unit (Middle Penninic) near the tectonic contact with calcschist and marble of the Aouilletta Unit (Combin Zone). Lac Fallère exibits an elongated shape and is hosted in a WSW–ENE trending depression, according to slope direction. This lake also shows a semi-submerged WSW–ENE rocky ridge, that longitudinally divides the lake. This evidence, in addition to the extremely fractured rocks, indicates the presence of a wide deep-seated gravitational slope deformation (DSGSD), even if this area is not yet included within the regional landslide inventory of the Aosta Valley Region. The Lac Fallère area also shows reliefs involved by glacial erosion (roche moutonnée), a wide cover of subglacial sediments and many moraines essentially referred to as Lateglacial. The DSGSD evolution in a glacial environment produced, as observed in other areas, significant effects both on the facies of Quaternary sediments and the formation of numerous and wide moraines. Glacial slope sectors and lateral moraines displaced by minor scarps and counterscarps and glaciers using trenches forming several arched moraines suggest an interplay between glacial and gravitational processes, which shared part of their evolution history.

The active debate about the processes governing the organic-rich sediment deposition generally involves the relative roles of elevated primary productivity and enhanced preservation related to anoxia. However, other less spotlighted factors could have a strong impact on such deposits: e.g. residence time into the water column (bathymetry), sedimentation rate, transport behavior of organo-mineral floccules on the sea floor. They are all strongly interrelated and may be obscured in the current conceptual models inspired from most representative modern analogues (i.e. upwelling zones and stratified basins). To improve our comprehension of organic matter distribution and heterogeneities, we conducted a sensitivity analysis on the processes involved in organic matter production and preservation which have been simulated within a 3D stratigraphic forward model. The Lower-Middle Toarcian of the Paris Basin was chosen as a case study as it represents one of the best documented example of marine organic matter accumulation. The relative influence of the critical parameters (bathymetry, diffusive transport, oxygen mixing rate and primary production) on the output parameters (Total Organic Carbon, and oxygen level), determined performing a Global Sensitivity Analysis, shows that, in the context of a shallow epicontinental basin, a moderate primary productivity (> 175 gC.m^-².yr^-1) can led to local anoxia and organic matter accumulation. We argue that, regarding all the processes involved, the presence and distribution of organic-rich intervals is linked as a first-order parameter to the morphology of the basin (e.g. ramp slope, bottom topography). These interpretations are supported by very specific ranges of critical parameters which allowed to obtain output parameter values in accordance with the data. This quantitative approach and its conclusions open new perspectives about the understanding of global distribution and preservation of organic-rich sediments.