Miracle-dz/UniFAR-FTUs huggingface dataset:
On the Role of Eddy Mixing in the Subtropical Ocean Circulation

Most of the classic wind-driven circulation theories based on Sverdrup balance have neglected the profound influence of eddy mixing on the large-scale potential vorticity (PV) distribution, thus failing to explain some prominent features of the observed circulation. In this study, using a series of numerical experiments based on the MITgcm, we diagnose the PV balance to quantify the effect of eddy mixing on the subtropical gyre. Four horizontal grid-spacings of 1°, 1/3.2°, 1/10°, and 1/32° are selected to compare the structure of the upper-ocean circulation to examine the effect of different eddy influences. In the 1° grid case, the thermocline structure is as predicted by the Sverdrup dynamics, with its maximum depth located in the subtropical interior where the wind stress curl is strongest. With increasing resolution, however, this maximum depth is displaced towards the subtropical front, which more closely resembles the observed thermocline. From 1° to 1/32°, the enhanced eddy mixing tends to homogenize the macroscopic PV in the subtropical gyre and reduces the meridional PV range by about 75% of the non-eddy (1°) solution; and the region where Sverdrup balance holds is relegated to isolated patches, with its area reduced by about 60%. Furthermore, sensitivity experiments show that the observed thermocline structure is well reproduced in eddy-resolving runs, indicating that the PV mixing provides a reasonable explanation of the subtropical circulation. Our results suggest that the Sverdrup relationship should be treated carefully in the eddy-rich region, even in the subtropical interior.
Effects of Branched Chain Amino Acids on digestive enzymes secretion from pancreas of dairy cows

Background : The limited ability of ruminant to digest starch in the small intestine may be attributed to insufficient digestive enzyme activity secreted by the pancreas. The purpose of this study was to investigate effects of leucine (Leu), isoleucine (Ile) and valine (Val) on digestive enzymes secretion from pancreas collected of Holstein dairy cows by tissue incubation in vitro. Methods: Two experiments were designed in the present study. In experiment 1, Five Holstein dairy cows were slaughtered and pancreatic tissue was removed immediately, rinsed with ice-cold normal saline (0.9% Nacl) and cut into small segments (approximately 2 × 2 mm), which were placed in oxygenated Krebs Ringer bicarbonate buffer (KRB) containing no amino acid (control), leu, Ile or Val (2.62, 5.24 or 10.48 mg/mL). Each treatment was repeated for five times and incubated in a 39°C shaker. KRB and pancreatic tissue samples were collected at 60, 120 and 180 min after the incubation. In experiment 2, Five Holstein dairy cows were slaughtered and the pancreatic tissue was immediately removed and treated, which were placed in KRB containing no amino acid (control), leu, Ile or Val (5.24 mg/mL) for incubation 60 min. Results : In experiment 1, The activity of pancreatic α-amylase were increased by Leu ( P < 0.01), Ile ( P < 0.01) or Val ( P = 0.06). Compared with the control group, Leu ( P < 0.05) or Ile ( P < 0.05) could linearly increase the activity of trypsin, but Val ( P > 0.05) had no effect on the trypsin activity. Neither Leu or Val had no influence on the activity of chymotrypsin ( P > 0.05). However, chymotrypsin activity decreased linearly with the increase of the Ile concentration at incubation time 180 min ( P < 0.01). Lipase activity were reduced linearly by Val ( P < 0.05 ). In experiment 2, Leu and Val markedly increased α-amylase activity ( P < 0.05), decreased lipase activity ( P < 0.05). The activities of trypsin and chymotrypsin were not affected by the three amino acids ( P > 0.05), and there was no interaction among them ( P > 0.05). Conclusion: This study demonstrated that Leu, Ile and Val can stimulate the secretion of pancreatic enzymes in vitro, especially α-amylase. There was no interaction between the three amino acids on the activities of α-amylase, trypsin and chymotrypsin.
'I Think I Made The Right Decision … I Hope I'm Not Wrong'. Vaccine hesitancy, commitment and trust among parents of young children.

During the last decade, public health research has emphasised the growing public disaffection with vaccination. This contemporary vaccine hesitation (VH) refers to a delay in acceptance or refusal of vaccines, as well as agreement despite doubt and reluctance. We investigated VH among French parents of young children, with an emphasis on two key features of VH: trust towards physicians and commitment to vaccination issues. We targeted two populations with contrasting socioeconomic profiles, using in-depth interviews (n = 25). Most parents exhibited some kind of VH, with differentiated attitudes across vaccines, including acceptance despite enduring doubts, especially for vaccines already provided to older siblings ('vaccine inertia'). Despite the rise of the Internet and social media, our participants still strongly relied on face-to-face interactions with peers and significant others. Most participants trusted their own physician but this was the result of a selection process: they had engaged resources to find a physician they could trust. Participants with contrasted socioeconomic profiles struggled with the same dilemmas, and they committed themselves to the same quest to find the 'right' physician. Nevertheless, parents with a higher socioeconomic status were able to engage more resources and use a wider repertoire of actions, and they also displayed greater health literacy.
Cytochrome P450 family members are associated with fast-growing hepatocellular carcinoma and patient survival: An integrated analysis of gene expression profiles

Background/Aims: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study. Materials and Methods: In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets. Results: From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754–0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716–0.995, P = 0.033). Conclusions: In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence.
Urolithin A‐activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo

Mitochondrial autophagy (mitophagy) clears damaged mitochondria and attenuates ischemic neuronal injury. Urolithin A (Uro‐A) activates mitophagy in mammal cells and Caenorhabditis elegans. We explored neuroprotection of Uro‐A against ischemic neuronal injury.
GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients

Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.
Resistance to visceral obesity is associated with increased locomotion in mice expressing an endothelial cell‐specific fibroblast growth factor 1 transgene

Overdevelopment of visceral adipose is positively correlated with the etiology of obesity‐associated pathologies including cardiovascular disease and insulin resistance. However, identification of genetic, molecular, and physiological factors regulating adipose development and function in response to nutritional stress is incomplete. Fibroblast Growth Factor 1 (FGF1) is a cytokine expressed and released by both adipocytes and endothelial cells under hypoxia, thermal, and oxidative stress. Expression of Fibroblast Growth Factor 1 (FGF1) in adipose is required for normal depot development and remodeling. Loss of FGF1 leads to deleterious changes in adipose morphology, metabolism, and insulin resistance. Conversely, diabetic and obese mice injected with recombinant FGF1 display improvements in insulin sensitivity and a reduction in adiposity. We report in this novel, in vivo study that transgenic mice expressing an endothelial‐specific FGF1 transgene (FGF1‐Tek) are resistant to high‐fat diet‐induced abdominal adipose accretion and are more glucose‐tolerant than wild‐type control animals. Metabolic chamber analyses indicate that suppression of the development of visceral adiposity and insulin resistance was not associated with alterations in appetite or resting metabolic rate in the FGF1‐Tek strain. Instead, FGF1‐Tek mice display increased locomotor activity that likely promotes the utilization of dietary fatty acids before they can accumulate in adipose and liver. This study provides insight into the impact that genetic differences dictating the production of FGF1 has on the risk for developing obesity‐related metabolic disease in response to nutritional stress.
Large-Area Biomolecule Nanopatterns on Diblock Copolymer Surfaces for Cell Adhesion Studies

Cell membrane receptors bind to extracellular ligands, triggering intracellular signal transduction pathways that result in specific cell function. Some receptors require to be associated forming clusters for effective signaling. Increasing evidences suggest that receptor clustering is subjected to spatially controlled ligand distribution at the nanoscale. Herein we present a method to produce in an easy, straightforward process, nanopatterns of biomolecular ligands to study ligand–receptor processes involving multivalent interactions. We based our platform in self-assembled diblock copolymers composed of poly(styrene) (PS) and poly(methyl methacrylate) (PMMA) that form PMMA nanodomains in a closed-packed hexagonal arrangement. Upon PMMA selective functionalization, biomolecular nanopatterns over large areas are produced. Nanopattern size and spacing can be controlled by the composition of the block-copolymer selected. Nanopatterns of cell adhesive peptides of different size and spacing were produced, and their impact in integrin receptor clustering and the formation of cell focal adhesions was studied. Cells on ligand nanopatterns showed an increased number of focal contacts, which were, in turn, more matured than those found in cells cultured on randomly presenting ligands. These findings suggest that our methodology is a suitable, versatile tool to study and control receptor clustering signaling and downstream cell behavior through a surface-based ligand patterning technique.
Hepatocellular Carcinoma.

Presenting the most up-to-date knowledge of hepatocellular carcinoma, it covers all topics — including those more controversial ones — in this rapidly advancing field, from epidemiology to prevention, from molecular biology to gross pathology, from screening to atypical presentation, from diagnosis to treatment, and from assessment to choice of appropriate treatment. This volume is therefore an important contribution to the field of hepatocellular carcinoma.
PARP Inhibitor Protects Against Chronic Hypoxia/Reoxygenation-Induced Retinal Injury by Regulation of MAPKs, HIF1α, Nrf2, and NFκB.

Purpose In the eye, chronic hypoxia/reoxygenation (H/R) contributes to the development of a number of ocular disorders. H/R induces the production of reactive oxygen species (ROS), leading to poly(ADP-ribose) polymerase-1 (PARP1) activation that promotes inflammation, cell death, and disease progression. Here, we analyzed the protective effects of the PARP1 inhibitor olaparib in H/R-induced retina injury and investigated the signaling mechanisms involved. Methods A rat retinal H/R model was used to detect histologic and biochemical changes in the retina. Results H/R induced reductions in the thickness of most retinal layers, which were prevented by olaparib. Furthermore, H/R caused increased levels of Akt and glycogen synthase kinase-3β phosphorylation, which were further increased by olaparib, contributing to retina protection. By contrast, H/R-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinases (MAPK) phosphorylation and activation were reduced by olaparib, via mitogen-activated protein kinase phosphatase 1 (MKP-1) expression. In addition, H/R-induced hypoxia-inducible factor 1α (HIF1α) levels were decreased by olaparib, which possibly contributed to reduced VEGF expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression was slightly increased by H/R and was further activated by olaparib. Nuclear factor-κB (NFκB) was also activated by H/R through phosphorylation (Ser536) and acetylation (Lys310) of the p65 subunit, although this was significantly reduced by olaparib. Conclusions Olaparib reduced H/R-induced degenerative changes in retinal morphology. The protective mechanisms of olaparib most probably involved Nrf2 activation and ROS reduction, as well as normalization of HIF1α and related VEGF expression. In addition, olaparib reduced inflammation by NFκB dephosphorylation/inactivation, possibly via the PARP1 inhibition-MKP-1 activation-p38 MAPK inhibition pathway. PARP inhibitors represent potential therapeutics in H/R-induced retinal disease.
Synthetic and genetic dimers as quantification ruler for single-molecule counting with PALM

How membrane proteins oligomerize determines their function. Superresolution microscopy can report on protein clustering and extract quantitative molecular information. Here, we evaluate the blinking kinetics of four photoactivatable fluorescent proteins for quantitative single-molecule microscopy. We identified mEos3.2 and mMaple3 to be suitable for molecular quantification through blinking histogram analysis. We designed synthetic and genetic dimers of mEos3.2 as well as fusion proteins of monomeric and dimeric membrane proteins as reference structures, and we demonstrate their versatile use for quantitative superresolution imaging in vitro and in situ. We further found that the blinking behavior of mEos3.2 and mMaple3 is modified by a reducing agent, offering the possibility to adjust blinking parameters according to experimental needs.
Distributed Dynamic Event-Triggered Control for Cooperative Output Regulation of Linear Multiagent Systems

This paper investigates the cooperative output regulation problem for heterogeneous linear multiagent systems under fixed communication graphs via event-triggered control. A fully distributed event-triggered dynamic output feedback control law is proposed based on the feedforward design approach. At the same time, a fully distributed dynamic event-triggering mechanism is designed so that each agent can determine when to broadcast its information to its neighbors. Compared with existing related results, both the control law and the event-triggering mechanism in this paper are independent of any global information. It is shown that with the proposed dynamic event-triggered control strategy, the cooperative output regulation problem can be solved in a fully distributed manner by intermittent communication. Moreover, Zeno behavior can be strictly ruled out for each agent. Finally, the effectiveness of the proposed dynamic event-triggered control strategy is validated by a numerical example.
The Transformation of Data Marketing: How an Ethical Lens on Consumer Data Collection Shapes the Future of Marketing

With a mass of customer data at our fingertips and the ability to use it to individualize promotion strategies, marketing communications, and product offerings, marketing activities are becoming more and more tailored to the individual customer. However, as concerns about online privacy and the handling of personal data take on an ever-increasing significance, marketers must increasingly evaluate and adapt their personalization and data collection methods. As a result, there is an increasing demand to take a critical look at the collection of data for personalization processes from an ethical perspective and to consider implications for further initiatives to maintain consumers’ trust. This research study utilizes a systematic literature review approach to investigate the current state of knowledge on the tradeoff between personalization and customer privacy by synthesizing and integrating extant knowledge. From the results of the present study’s search process, 20 articles were selected and analyzed for this review. Findings emphasize the importance of strengthening consumer relationships by increasing consumer trust, loyalty, confidence, and emotional attachment through specific organizational activities. The adaptation of marketing-related activities can thereby create a competitive advantage for data-collecting companies, as consumer backlash and privacy concerns decrease, and the willingness to disclose data increases. The current research contributes to the field of marketing by reviewing the issue of increasing personalization at the cost of customer privacy and explores how the resulting ethical considerations may affect the future of marketing practices. It thereby serves to help marketeers to implement effective strategies to ensure customer relationships and the resulting willingness to disclose personal data for personalization processes.
Stabilization of amyloidogenic immunoglobulin light chains by small molecules

Significance Light-chain amyloidosis (AL) is a progressive and often fatal degenerative disease caused by conformational changes within Ig light chains that generally lead to aggregation. Current chemotherapy treatments aim to eliminate the clonal plasma cells that secrete full-length light chains; however, complete eradication is achieved in only 30–40% of the patients. The kinetic stabilizer strategy introduced herein does not require an understanding of the nonnative light-chain structure–proteotoxicity relationships driving organ degeneration in AL to be successful at stopping disease progression because it stops light-chain conformational excursions at the beginning of the aggregation cascade. The small-molecule kinetic stabilizers identified bind to conserved residues at the variable-domain–variable-domain interface in the native dimer, stabilizing this putative nontoxic structure. In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs. NMR and X-ray crystallographic data demonstrate that at least one structural family of hits bind at the LC–LC dimerization interface within full-length LCs, utilizing variable-domain residues that are highly conserved in most AL patients. Stopping the amyloidogenesis cascade at the beginning is a proven strategy to ameliorate postmitotic tissue degeneration.
FIRST LANGUAGE IN ENGLISH FOREIGN LANGUAGE CLASSES: IS IT NECESSARY?

To maintain the class alive, language choice used in the classroom plays an important role. So far, some English teachers have thought that they have to use English in the classroom during the learning process because it will encourage the learners to think and speak in English. In contrast, some research shows that the use of first language (L1) in the classroom will give positive benefits in the learners’ understanding to the subject learnt and responds during the discussion. This paper is intended to describe the positive effect and benefits of using L1 in the EFL classroom.