Miracle-dz/UniFAR-FTUs huggingface dataset:
27-Hydroxycholesterol Binds GPER and Induces Progression of Estrogen Receptor-Negative Breast Cancer

Simple Summary Breast cancer is the most common cancer in women, and there is a known link between high cholesterol levels and breast cancer. However, how cholesterol impacts breast cancer is poorly understood, particularly in the case of an aggressive form of cancer known as estrogen receptor negative breast cancer. Using cells in culture and models of breast tumors in mice, we have determined that an abundant metabolite of cholesterol known as 27-hydroxycholesterol stimulates estrogen receptor negative breast cancer growth. We have also determined how 27-hydroxycholesterol stimulates the growth, identifying a new mechanism of action of 27-hydroxycholesterol. These new findings may explain the link between high cholesterol and estrogen receptor negative breast cancer, and they may lead to the development of new therapies for a type of breast cancer that presently lacks specific treatments. Abstract Cholesterol affects the proliferation of breast cancer (BC) and in particular of estrogen receptor-negative (ER−) BC. Cholesterol is converted to 27-hydroxycholesterol (27HC), which promotes the growth of ER+ BC. Potentially, 27HC can be involved in cholesterol-dependent ER− BC proliferation. Stable MDA-MB-231 silenced clones for CYP7B1 (27HC metabolizing enzyme) show an increased basal proliferation rate, which is not observed in the presence of lipoprotein-deprived serum. Furthermore, the treatment of SKBR3, MDA-MB-231 and MDA-MB-468 with 27HC increased cell proliferation that was prevented by G15, a selective G Protein-Coupled Estrogen Receptor (GPER) inhibitor, suggested this receptor to be a potential 27HC target. Binding experiments demonstrate that 27HC is a new ligand for GPER. We show that ERK1/2 and NFκB are part of the 27HC/GPER pathway. The stable silencing of GPER prevents NFκB activation and reduces basal and 27HC-dependent tumor growth. Additionally, conditioned medium from ER− BC cells treated with 27HC promotes tube formation, which does not occur with CM from GPER silenced cells. Collectively, these data demonstrate that cholesterol conversion into 27HC promotes ER− BC growth and progression, and the expression of GPER is required for its effects.
Medication-Related Osteonecrosis of the Jaw: A Reflection of Current Preventative and Therapeutic Guidelines: A Review

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of bisphosphonates, denosumab, and antiangiogenic drugs. Although the literature is rich with research work discussing MRONJ, the pathogenesis of this devastating condition has not been adequately understood yet. Roles of infection, immunity and genetic predisposition have been extremely unclear. Moreover, many controversies have been governing risk assessment and management guidelines. In 2003, 36 cases of osteonecrosis of the jaw (ONJ) associated with the use of either pamidronate or zoledronate were reported. Furthermore, in 2014, the American Association of Oral and Maxillofacial Surgeons (AAOMS) suggested the term “medication-related osteonecrosis of the jaw” (MRONJ) to describe jaw osteonecrosis related to the use of medications. This review sheds the light on recent research work discussing the pathogenesis of MRONJ. Moreover, it suggests possible guidelines for risk assessment and management based on information gathered from different research papers found in the literature.
Prioritizing Scheduling Parameters in the Automotive Industry Using Fuzzy TOPSIS-DEMATEL Model

The Automotive industry is one of the biggest emerging sectors in terms of revenue. Every automotive industry has an indispensable need for optimum manufacturing scheduling systems for generating good revenues and profits. This need can be pulled off by identifying and prioritizing the scheduling parameters. Multi-criteria decision making (MCDM) is one of the best techniques of operation research in selecting the best parameters or factors among the various alternatives. This study includes the identification and prioritization of the various important scheduling parameters (SPs) in the Indian automotive industry. The twelve scheduling parameters have been identified in this study and these parameters are prioritized by the fuzzy- Technique for order preference by similarity to ideal solution (TOPSIS) and Decision Making Trial and Evaluation Laboratory Model (DEMATEL). The expert’s views are gathered from the five automobile industries. Makespan, energy consumption, due date, and travel time are the crucial parameters obtained using Fuzzy TOPSIS. The least important parameters obtained using Fuzzy TOPSIS are work in process, flow time, and release date. The most influential parameters identified using the DEMATEL method are completion time and processing time. This study is valuable for every industry and research organization in the field of the automobile industry.
The Flipped Learning Strategy’s Effect on Developing Gifted Female Students’ Achievement in Grammar Course in the Southern Region in Jordan

This study ultimately intended to manifest the strategy of flipped learning strategy along with its effect on developing gifted female students’ achievement in grammar course at King Abdullah II Schools for Excellence, in the southern region of Jordan. To achieve this study’s objectives and answer its question, the quasi-experimental approach was used. Moreover, the study tools included: the teacher's guide for flipped learning and a test of the grammar course content for the eighth-grade female students. Besides, the study sample ultimately included (30) female students. They were ultimately divided equally into a control and an experimental group. The study found that there are obvious differences with statistical significance, at the significance level of (α≤0.005), between the scores concerning the members of both the experimental group and the control group, in the post-test scale, on the achievement test. Such differences were for the experimental group. Moreover, it also concluded that there are no obvious statistically significant differences, at the significance level of (α≤0.005), concerning the mean scores related to the experimental group’s members, in the post-test scale as well as the follow-up on the achievement test. Therefore, with reference to this study’s results, the researchers recommended that it is important to employ e-learning and integrated learning environments, which are based on technological innovations, in the process of education.
Transfer-Learning-Based SVM Method for Seismic Phase Picking With Insufficient Training Samples

Efficient seismic phase picking is fundamental to seismic signal processing. Phase picking methods based on neural networks show great potential in accurately picking signals with a low signal-to-noise ratio but require large training datasets. We present a transductive transfer-learning-based support vector machine (TTL-SVM) algorithm for seismic phase picking when the seismic dataset possesses insufficient training samples. An objective function of TTL-SVM, which is incorporated with a pretraining classification process in the source domain that possesses an adequate training dataset and quality labeling, is proposed for phase picking in the target domain with no quality labeling. Seismic compressional (<inline-formula> <tex-math notation="LaTeX">$P$ </tex-math></inline-formula>-) and shear (<inline-formula> <tex-math notation="LaTeX">$S$ </tex-math></inline-formula>-) phase picking is performed using two TTL-SVM processing steps: seismic phase and noise classification, and then <inline-formula> <tex-math notation="LaTeX">$P$ </tex-math></inline-formula>- and <inline-formula> <tex-math notation="LaTeX">$S$ </tex-math></inline-formula>-phase classification from the picking phases. Experiments are performed to test the algorithm using a simulated dataset and two earthquake datasets from Jiuzaigou in China and New Zealand. The TTL-SVM results are remarkable compared with those obtained through traditional automatic and manual picking approaches. This algorithm provides an alternative approach for seismic phase picking when the dataset possesses insufficient training samples.
Reviving käthe seidel’s legacy to University of Minho

In the 80’s Prof. Kathe Seidel was in Portugal by invitation of the University of Minho (UM). The relationship established led to the donation of Seidel’s laboratory to UM, to create a Limnological Laboratory. Some institutional and personal reasons rendered this unviable and until now, Seidel’s legacy at UM is resumed to some German bibliography, equipment and unpublished work. Prof. Kickuth was Seidels’ disciple. His technology is based on a rooted emergent macrophyte system of horizontal subsurface flow that relied on optimized substrate planted with Phragmites. Aiming to determine the efficiency of Kickuth’s process and to understand the role of the biotic communities presented on these optimized substrates, mensal sampling campaigns were made in a Constructed Wetland (CW) located in the North of Portugal. The sampling campaigns began on January 2005. Inlet (IN) and outlet (OUT) wastewater simple samples and substrate samples were taken from one of the two CW’s beds. In situ determinations of temperature, pH and redox potential were recorded, and IN and OUT wastewater samples were analysed for BOD5, COD and TSS; estimated densities of some microbiological communities were assessed by the recovery of colony formed units (CFU/ml) on solid culture media, using the spread technique. The results obtained show a very good efficiency on organic load removal (values of 80-90%) accompanied by higher values in percent removal of the estimated heterotrofics CFU/ml. The total and fecal coliforms removal was also high (90-100%). The substrate’s biodiversity characterized by optical microscopy allowed the identification of both protozoa and metazoa (mainly nematodes and annelids). The sampling and quantification methodologies of the biota taxa aren’t optimized. As the knowledge of this “black box” effective function may contribute to increase the credibility of these sustainable systems, it seems pertinent to proceed with these studies.
Novel Perspectives in Immune Checkpoint Inhibitors and the Management of Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma

Simple Summary Hepatocellular carcinoma (HCC) is a huge worldwide healthcare burden. The incidence of non-viral causes of hepatocellular carcinoma, such as non-alcoholic steatohepatitis (NASH), is rising. The introduction of immune checkpoint inhibitors (ICI) has led to a paradigm shift in the systemic treatment of HCC. However, not all patients can benefit from ICI. Recent studies have suggested that the response to ICI may allude to the underlying aetiology of HCC, such as NASH. Our review aims to summarise the latest evidence of ICI in advanced HCC, elaborates on the controversy surrounding the use of ICI in NASH-HCC, and discusses potential biomarkers that can be used to predict responses to ICI in advanced HCC. Abstract Immune checkpoint inhibitors have revolutionised the systemic treatment of advanced hepatocellular carcinoma. Although phase III trials, testing single agent nivolumab and pembrolizumab, failed to meet their primary endpoints, the combination of atezolizumab and bevacizumab has demonstrated a remarkable objective response and unprecedented survival benefits, replacing sorafenib as the standard first-line treatment for advanced hepatocellular carcinoma. Despite these successes observed in immune checkpoint inhibitors in the management of advanced hepatocellular carcinoma, not all patients responded to treatment, which has led to the search of risk factors and biomarkers that could predict the response to immune checkpoint inhibitors. Recent translational studies have begun to shed light on the impact of an underlying liver disease, namely NASH, which might affect the response to immune checkpoint inhibitors. In addition, antidrug-antibody and gene expression assays have demonstrated promises in predicting the response to immune checkpoint inhibitors. In this article, we will provide an overview of the use of ICI in the management of advanced HCC, review the evidence that surrounds the recent controversy regarding NASH-HCC, and discuss potential biomarkers that predict the response to immune checkpoint inhibitors.
Dynamic performance of a 140m SES in simulations, model tests and sea trial: an introduction to recent development of the Techno Super Liner

Abstract This paper introduces the dynamic performance of a 140m Surface Effect Ship in simulations, sea trials and model tests, which Mitsui Engineering & Shipbuilding Co. Ltd. carried out as part of the recent development of the Techno Super Liner (TSL). The paper presents some examples of the motion simulation, stopping simulation, model experiment, and sea trial in relation to operational and safety performance. The motion simulation is based on 3DOF motion (heave/pitch/roll) and air cushion dynamics. It was performed for both model and full-scale ship in various headings relative to the sea. In the model tests, towing tests were conducted in both regular and irregular waves. The model was equipped with lift fans and all the tests were carried out with on-cushion conditions. The results from the simulations and model tests are compared. The scale effects between model and full-scale ship are considered with the results of simulations. A brief introduction to the results of the sea trial is also presented in this paper.
Behaviour of Precast Prestressed Hollow Core Slabs with and without FRP Strengthening

Hollow core slabs are Prestressed precast floor/roof elements which have longitudinal cores running along the span and are primarily used floor slab elements in building construction. Structural eficiency and increased exural capacity of prestressed precast hollow core (PPHC) slabs allows larger spans to be built leading to cost savings. Strengthening of these slabs may be required for several reasons to maintain their structural integrity. The main reasons include, material degradation, increased dead or live loads, architectural modifications, installation of heavy machinery and openings in slabs.
Stability analysis and test for cutting chatter of a slender shaft

To study the stability of chatter while cutting a slender shaft,based on chatter mechanism studying of cutting a slender shaft,the analysis model of regenerative chatter was established,for a two-DOF coupled vibration system of a tool and a slender shaft.The stability of the dynamic equations with time delay was analyzed using an analytical method to get a stability cutting limit figure between cutting width and rotational speed.The figure showed that the limit cutting width of the two-DOF system is reduced by 28.6% compared to that of single-DOF system.This result could provide theoretical cutting parameters for highly effective and stable processing of flexible workpieces.The cutting chatter tests of a slender shaft were done in a turn-milling center.Compared with the stability cutting limit figure,the test results agreed well with the theoretical ones.The varying laws of the vibration features of the tool and the shaft during chatter were summarized.They were the important recognition indices when monitoring and early-warning cutting chatters.
AMPK Activation Is Indispensable for the Protective Effects of Caloric Restriction on Left Ventricular Function in Postinfarct Myocardium

Simple Summary Impaired coronary blood flow induces cardiac ischemia and can lead to myocardial infarction. Although revascularization therapy and medical treatment potentially restore cardiac function in ischemic hearts, loss of cardiomyocytes and replacement of the dead myocardium by a scar can lead to ischemic heart disease with impaired cardiac output, a condition called heart failure. Medical treatment of heart failure includes drugs such as ACE-inhibitors, beta-blockers, diuretics, mineralocorticoid receptor antagonists, and SGLT (sodium-glucose cotransporter) 2 inhibitors. In addition, dietary interventions may provide further benefits to slow down disease progression. Caloric restriction, the decrease in calorie intake without malnutrition, is a strategy for improving health and increasing lifespan. Caloric restriction reduces the risk factors for cardiovascular diseases, and it improves heart function in animals and humans. Our study investigated the impact of caloric restriction on heart failure progression in mice and rats with myocardial infarction. We show that caloric restriction inhibits progressive loss of heart function, even when started after heart failure is already established. Together, the findings help to deepen our understanding of the complex mechanisms involved in the cardioprotective effects of caloric restriction and how they could be therapeutically utilized to prevent disease progression. Abstract Background: Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury. Here, we investigated the role of AMP-activated protein kinase (AMPK) in mediating the cardioprotective CR effects in failing, postinfarct myocardium. Methods: Ligation of the left coronary artery or sham operation was performed in rats and mice. Four weeks after surgery, left ventricular (LV) function was analyzed by echocardiography, and animals were assigned to different feeding groups (control diet or 40% CR, 8 weeks) as matched pairs. The role of AMPK was investigated with an AMPK inhibitor in rats or the use of alpha 2 AMPK knock-out mice. Results: CR resulted in a significant improvement in LV function, compared to postinfarct animals receiving control diet in both species. The improvement in LV function was accompanied by a reduction in serum BNP, decrease in LV proapoptotic activation, and increase in mitochondrial biogenesis in the LV. Inhibition or loss of AMPK prevented most of these changes. Conclusions: The failing, postischemic heart is protected from progressive loss of LV systolic function by CR. AMPK activation is indispensable for these protective effects.
The use of information and communication technology in pedagogical documentation: an investigation of early childhood education in China

ABSTRACT Pedagogical documentation has been regarded as an important practice in early childhood education (ECE) settings because it provides an opportunity to observe children’s learning and help teachers plan for learning experiences. This article focuses on teachers’ use of information and communication technology (ICT) in pedagogical documentation in an under-researched context. A qualitative study was conducted in three kindergartens in Nanjing, China, over five months. The Technological Pedagogical and Content Knowledge (TPACK) model was adopted to understand participants’ decision-making about pedagogical documentation. Findings indicate that ICT-supported pedagogical documentation aimed to help children learn from peers’ experiences and reflect on their own learning. Participants considered pedagogical documentation as a tool for initiating discussion with children, though few used it to plan for future learning experiences. A gap between practice and policy in relation to pedagogical documentation was found in the study, and implications for both areas are discussed.
Cultural Transformation in Healthcare: How Well Does the Veterans Health Administration Vision for Whole Person Care Fit the Needs of Patients at an Academic Rehabilitation Center?

Background The Veterans Health Administration is undergoing a cultural transformation toward person-driven care referred to as the Whole Health System of Care. Objective This pilot study evaluated whether the Whole Health model resonates with patients of a large public university rehabilitation clinic. Methods Thirty participants completed the Veterans Health Administration’s Personal Health Inventory (PHI), and six attended the course “Taking Charge of My Life and Health. ” Researchers analyzed PHI responses and post-course focus group transcripts. A short post-PHI survey and post-course evaluation were collected. Results Participants agreed the PHI is a simple, useful tool. The course, while well attended, did not meet participants’ expectations. Participants wanted access to integrative therapies and opportunities to contribute to healthcare transformation. Conclusion Rehabilitation patients resonated with the Whole Health vision. They expressed enthusiasm for the cultural transformation represented by the model along with frustration that standard healthcare experiences fall short of this vision.
‘You just get sucked into it’: extending the immersion process model to virtual gameplay experiences in managed visitor attractions

ABSTRACT This study investigates the immersion process in virtual visitor experiences in the context of a managed visitor attraction. It validates and extends previously developed models of the immersion process from tourism and proposes an underlying structure with four mechanisms driving the immersion process forward. Data was collected through semi-structured in-depth interviews with visitors participating in virtual gameplay at a commercial gaming centre in Oslo, Norway. Findings indicate that the immersion process is comparable across ‘real world’ and virtual visitor experiences and that the process consists of three stages (engagement, engrossment, and transcending involvement), corresponding with involvement triggers, involvement worlds, and the state of immersion. The study extends previous models of the immersion process by identifying the influence of pre-existing involvement as an ‘involvement booster’ enhancing the individual visitor’s immersion process. The findings have implications for how the underlying structure and components of the immersion process can be understood and offers practical implications for experience designers working in the intersection between virtual and ‘real world’ visitor experiences.
High-Performance Self-Aligned Top-Gate Amorphous InGaZnO TFTs With 4 nm-Thick Atomic-Layer-Deposited AlOx Insulator

Electrical characteristics of self-aligned top-gate (SATG) amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs) with 4 nm-thick atomic-layer-deposited (ALD) AlO<sub>x</sub> gate insulator (GI) are investigated. It is demonstrated that the SATG a-IGZO TFTs present high-performance metrics including a near-ideal subthreshold swing (<italic>SS</italic>) of 60.9 mV/dec, a low off-state current below 10<sup>−12</sup> A, a positive <inline-formula> <tex-math notation="LaTeX">${V}_{\text{th}}$ </tex-math></inline-formula> of 0.1 V, and a decent mobility of 14.1 cm<sup>2</sup>/<inline-formula> <tex-math notation="LaTeX">$\text{V}\,\cdot $ </tex-math></inline-formula>s. In addition, the TFTs exhibit negligible <inline-formula> <tex-math notation="LaTeX">${V}_{\text{th}}$ </tex-math></inline-formula> shifts less than 0.02 V against electrical bias stresses. Both high performance and excellent stability are thus simultaneously achieved for the ultrathin GI of amorphous oxide semiconductor (AOS) TFTs.