Miracle-dz/UniFAR-FTUs huggingface dataset:
δ-Catenin Increases the Stability of EGFR by Decreasing c-Cbl Interaction and Enhances EGFR/Erk1/2 Signaling in Prostate Cancer

δ-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that δ-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind δ-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that δ-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase. c-Cbl monoubiquitinates EGFR and thus facilitates its internalization, followed by lysosomal degradation. We observed that δ-catenin plays a key role in EGFR stability and downstream signaling. δ-Catenin competes with c-Cbl for EGFR binding, which results in a reduction of binding between c-Cbl and EGFR and thus decreases the ubiquitination of EGFR. This in turn increases the expression of membrane bound EGFR and enhances EGFR/Erk1/2 signaling. Our findings add a new perspective on the role of δ-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.
Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis

AIM To investigate the protective effects of Ampelopsis grossedentata (AMP) on dextran sulfate sodium (DSS)-induced colitis in mice based on systems pharmacology approach. METHODS Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis (UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSS-induced colitis model in C57BL/6 mice (n = 10/group) was constructed and treated with 5-aminosalicylic acid (100 mg/kg/d) and AMP (400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry. RESULTS The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8. CONCLUSION AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.
The Relationship between Impulsivity and Internet Gaming Disorder in Young Adults: Mediating Effects of Interpersonal Relationships and Depression

Background: This study aimed to explore relationships between impulsivity, interpersonal relationships, depression, and Internet Gaming Disorder (IGD) symptoms. Methods: A total of 118 young adults participated in this study: 67 IGD patients who met five or more of the DSM-5 diagnostic criteria for IGD and 56 healthy controls. We administered questionnaires to assess IGD symptoms (Young’s Internet Addiction Test; Y-IAT), impulsivity (Barratt Impulsiveness Scale; BIS-11), interpersonal relationship (Relationship Change Scale; RCS), and depression (Beck Depression Inventory; BDI). We used PROCESS macro in SPSS to perform mediation analysis. Results: IGD symptom was positively related to depression and impulsivity, and negatively related to the quality of interpersonal relationships. Mediation analysis revealed full mediation effects of interpersonal relationships and depression on the association between impulsivity and IGD symptoms in the IGD group. Specifically, even after adjusting for gender as a covariate, high impulsivity was associated with greater difficulty with interpersonal relationships; which further affected depression and increased the risk of IGD. Conclusions: These results demonstrate the importance of early intervention in IGD patients, particularly in young adults with high impulsivity. When intervening in adults’ IGD, we should consider not only individual factors (e.g., depression) but also socioenvironmental factors (e.g., interpersonal relationships).
Mechanism of Striation in Dielectric Barrier Discharge

在在纯氖的绝缘的障碍分泌物的有条纹或刻痕之状态的机制被二维的 particle-in-cell/Monte Carlo 碰撞(PIC-MCC ) 学习模型。 有条纹或刻痕之状态在源于电离和否定的墙费用的血浆背景，和不一致的电场出现，这被显示出在阳极上面出现在绝缘的层上。 有条纹或刻痕之状态的 Thesustainment 是无弹性的影响与中立气体控制的一个成层的领域里的电子的非局部的运动效果。 在短暂绝缘的障碍分泌物的有条纹或刻痕之状态类似于在 dc 的那些积极的列分泌物。
Genetic diversity of Bartonella genotypes found in the striped field mouse (Apodemus agrarius) in Central Europe

SUMMARY We investigated the diversity of Bartonella in Apodemus agrarius, an important rodent of peri-domestic habitats, which has spread into Europe in the past 1000 years. Spleen samples of 344 A. agrarius from Eastern Slovakia were screened for the presence of Bartonella spp. using 16S–23S rRNA internal transcribed spacer region and bacteria were detected in 9% of rodents. Based on sequencing of three housekeeping genes (gltA, rpoB and groEL) Bartonella genotypes were ascribed to the species typical for mice and voles: B. grahamii, B. taylorii and B. birtlesii. However, the study also confirmed presence of genotypes belonging to the B. clarridgeiae/B. rochalimae clade, and the B. elizabethae/B. tribocorum clade, which are not commonly found in woodland rodents. In addition, a potential recombination event between these two genotypes was noted, which highlights an important role of A. agrarius in shaping Bartonella diversity and evolution.
Identifying actionable variants using next generation sequencing in patients with a historical diagnosis of undifferentiated pleomorphic sarcoma

There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re‐evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons). In total, 95 patients initially classified with UPS were identified. Following pathology re‐review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N = 44); UPS(N = 18); and Others (N = 27; including undifferentiated spindle cell sarcoma (N = 15) and dedifferentiated liposarcoma (N = 6)). Seven cases were excluded from further analysis for other reasons. Baseline demographics of the finalized cohort (N = 88) showed a median age of 66 years (32–95), primarily with stage I–III disease (92%) and high‐grade (86%) lesions. Somatic mutations were identified in 31 cases (35%)(Total mutations = 36: solitary mutation(n = 27); two mutations( =n = 3); three mutations(n = 1)). The most commonly identified mutations were in TP53 (n = 24), ATM (n = 3) and PIK3CA (n = 2). Three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations, mainly related to biomarkers of prediction of response; however few had targetable driver mutations. Somatic mutation status did not influence disease free or overall survival. Based on the small number of clinically relevant mutations, these data do not support the routine use of targeted NGS panels outside of research protocols in UPS.
Tissue-Engineered Small Diameter Arterial Vascular Grafts from Cell-Free Nanofiber PCL/Chitosan Scaffolds in a Sheep Model

Tissue engineered vascular grafts (TEVGs) have the potential to overcome the issues faced by existing small diameter prosthetic grafts by providing a biodegradable scaffold where the patient’s own cells can engraft and form functional neotissue. However, applying classical approaches to create arterial TEVGs using slow degrading materials with supraphysiological mechanical properties, typically results in limited host cell infiltration, poor remodeling, stenosis, and calcification. The purpose of this study is to evaluate the feasibility of novel small diameter arterial TEVGs created using fast degrading material. A 1.0mm and 5.0mm diameter TEVGs were fabricated with electrospun polycaprolactone (PCL) and chitosan (CS) blend nanofibers. The 1.0mm TEVGs were implanted in mice (n = 3) as an unseeded infrarenal abdominal aorta interposition conduit. , The 5.0mm TEVGs were implanted in sheep (n = 6) as an unseeded carotid artery (CA) interposition conduit. Mice were followed with ultrasound and sacrificed at 6 months. All 1.0mm TEVGs remained patent without evidence of thrombosis or aneurysm formation. Based on small animal outcomes, sheep were followed with ultrasound and sacrificed at 6 months for histological and mechanical analysis. There was no aneurysm formation or calcification in the TEVGs. 4 out of 6 grafts (67%) were patent. After 6 months in vivo, 9.1 ± 5.4% remained of the original scaffold. Histological analysis of patent grafts demonstrated deposition of extracellular matrix constituents including elastin and collagen production, as well as endothelialization and organized contractile smooth muscle cells, similar to that of native CA. The mechanical properties of TEVGs were comparable to native CA. There was a significant positive correlation between TEVG wall thickness and CD68+ macrophage infiltration into the scaffold (R2 = 0.95, p = 0.001). The fast degradation of CS in our novel TEVG promoted excellent cellular infiltration and neotissue formation without calcification or aneurysm. Modulating host macrophage infiltration into the scaffold is a key to reducing excessive neotissue formation and stenosis.
Kinesin rotates unidirectionally and generates torque while walking on microtubules

Significance Given the importance of cytoskeletal motor proteins, we asked whether translational motors rotate while walking along their tracks. Using an optical tweezers-based approach, we simultaneously measured translation, force, rotation, and torque of a kinesin motor with molecular resolution. We found that the gait followed a rotary stepping mechanism that generates torque and spins cargo. Thus, during walking, the motor “tail (and organelle) will tend to wind up like the rubber band of a toy airplane,” as Joe Howard hypothesized in 1996. To determine the overall motor efficiency, our measurements also point to the importance of accounting for rotational work. Apart from other cytoskeletal motors, the technique may be applied to molecular machines such as DNA motors and rotary engines like the ATP synthase. Cytoskeletal motors drive many essential cellular processes. For example, kinesin-1 transports cargo in a step-wise manner along microtubules. To resolve rotations during stepping, we used optical tweezers combined with an optical microprotractor and torsion balance using highly birefringent microspheres to directly and simultaneously measure the translocation, rotation, force, and torque generated by individual kinesin-1 motors. While, at low adenosine 5′-triphosphate (ATP) concentrations, motors did not generate torque, we found that motors translocating along microtubules at saturating ATP concentrations rotated unidirectionally, producing significant torque on the probes. Accounting for the rotational work makes kinesin a highly efficient machine. These results imply that the motor’s gait follows a rotary hand-over-hand mechanism. Our method is generally applicable to study rotational and linear motion of molecular machines, and our findings have implications for kinesin-driven cellular processes.
ELMO and Sponge specify subapical restriction of Canoe and formation of the subapical domain in early Drosophila embryos

ABSTRACT Canoe/Afadin and the GTPase Rap1 specify the subapical domain during cellularization in Drosophila embryos. The timing of domain formation is unclear. The subapical domain might gradually mature or emerge synchronously with the basal and lateral domains. The potential mechanism for activation of Rap1 by guanyl nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs) is unknown. Here, we retraced the emergence of the subapical domain at the onset of cellularization by in vivo imaging with CanoeYFP in comparison to the lateral and basal markers ScribbledGFP and CherrySlam. CanoeYFP accumulates at a subapical position at about the same time as the lateral marker ScribbledGFP but a few minutes prior to basal CherrySlam. Furthermore, we show that the unconventional GEF complex ELMO-Sponge is subapically enriched and is required for subapical restriction of Canoe. The localization dynamics of ELMO-Sponge suggests a patterning mechanism for positioning the subapical region adjacent to the apical region. While marking the disc-like apical regions before cellularization, ELMO-Sponge redistributes to a ring-like pattern surrounding the apical region at the onset of cellularization. Highlighted Article: GEF complex ELMO-Sponge, which redistributes from a disc-like to ring-like pattern during onset of cellularization, determines Cno accumulation independently of Scribbled and Slam to specify the subapical cortical domain, which emerges together with the basal and lateral domains.
Berberine Inhibits Uterine Leiomyoma Cell Proliferation via Downregulation of Cyclooxygenase 2 and Pituitary Tumor-Transforming Gene 1

We previously demonstrated that berberine (BBR) inhibits cell proliferation and induces apoptosis in a human uterine leiomyoma (UtLM) cell line but does not demonstrate a significant cytotoxic effect in a normal human uterine smooth muscle (UtSM) cell line. However, the mechanisms of this inhibition are unclear. Of note, cyclooxygenase 2 (COX2) and pituitary tumor-transforming gene 1 (PTTG1) are overexpressed in human uterine leiomyomata and are involved in the pathogenesis of uterine fibroids (UFs). We found that COX2 and PTTG1 were overexpressed in UtLM and that BBR decreased COX2 and PTTG1 expression in UtLM cells. Our data support that UtLM and UtSM are immortalized cell lines without phenotypic alterations from parental cell types and suggest that COX2 and PTTG1 are molecular targets for BBR. However, studies in these cell lines may not reveal all activities of BBR in vivo, and we therefore proceeded to test in this report the antitumor effects of BBR in an UF nude mouse xenograft model. When UF nude mice were killed at 7 weeks, tumor weight in controls was 45 ± 7 mg versus 20 ± 3 mg (P < .05) in the low-dose (5 mg/kg) and 7 ± 3 mg (P < .01) in the high-dose (10 mg/kg) BBR groups, respectively. Expression of proliferation markers, cell cycle–related genes, and UF-related genes was downregulated in tumors. No unusual behavioral changes and no signs of kidney or liver damage were observed in the animals with BBR treatment. In conclusion, our data suggests that (a) COX2 and PTTG1 are molecular targets for BBR and (b) BBR is potentially an effective and safe anti-UF agent.
Dapagliflozin in patients with type 1 diabetes: A post hoc analysis of the effect of insulin dose adjustments on 24‐hour continuously monitored mean glucose and fasting β‐hydroxybutyrate levels in a phase IIa pilot study

To investigate the effects of total daily insulin dose (TDD) reductions on 24‐hour continuously monitored mean glucose and fasting β‐hydroxybutyrate (a marker for diabetic ketosis/ketoacidosis [DKA]) levels, using patient‐level data from a 14‐day, pilot study of dapagliflozin in type 1 diabetes (T1DM).
Yuanfudao at SemEval-2018 Task 11: Three-way Attention and Relational Knowledge for Commonsense Machine Comprehension

This paper describes our system for SemEval-2018 Task 11: Machine Comprehension using Commonsense Knowledge. We use Three-way Attentive Networks (TriAN) to model interactions between the passage, question and answers. To incorporate commonsense knowledge, we augment the input with relation embedding from the graph of general knowledge ConceptNet. As a result, our system achieves state-of-the-art performance with 83.95% accuracy on the official test data. Code is publicly available at https://github.com/intfloat/commonsense-rc.
The CAPIO 2017 Conversational Speech Recognition System

In this paper we show how we have achieved the state-of-the-art performance on the industry-standard NIST 2000 Hub5 English evaluation set. We explore densely connected LSTMs, inspired by the densely connected convolutional networks recently introduced for image classification tasks. We also propose an acoustic model adaptation scheme that simply averages the parameters of a seed neural network acoustic model and its adapted version. This method was applied with the CallHome training corpus and improved individual system performances by on average 6.1% (relative) against the CallHome portion of the evaluation set with no performance loss on the Switchboard portion. With RNN-LM rescoring and lattice combination on the 5 systems trained across three different phone sets, our 2017 speech recognition system has obtained 5.0% and 9.1% on Switchboard and CallHome, respectively, both of which are the best word error rates reported thus far. According to IBM in their latest work to compare human and machine transcriptions, our reported Switchboard word error rate can be considered to surpass the human parity (5.1%) of transcribing conversational telephone speech.
Vacuum Far-infrared Drying of Foods and Agricultural Materials

Infrared radiation drying has the unique characteristics of energy transfer mechanism. During Infrared radiation, the energy in the form of electromagnetic wave is absorbed directly by the product without loss to the environment, leading to considerable energy savings. For drying under vacuum (or vacuum drying), moisture within the product being dried evaporates at lower temperatures (lower than 100 o C) giving better product quality, especially in the cases of foods or agricultural products, which are heat-sensitive in nature. When the advantages of the two dying methods are combined, energy efficiency of the drying process is enhanced and degradation of dried product quality is also reduced. The objective of this paper is to review the results obtained from the drying system combining the concept of infrared radiation drying and drying under vacuum. In this paper the possible combined drying system is introduced. The effects of several parameters on the drying kinetics and dried product quality are mentioned. Comparison is also made with similar sets of data obtained from other drying systems.
Platelet activation and clotting cascade activation by dialyzers designed for high volume online hemodiafiltration

Introduction: Hemodialysis patients are pro‐thrombotic. Higher volume online postdilutional hemodiafiltration (OL‐HDF), with increasing hematocrit increases the risk of clotting in the extracorporeal circuit (ECC). We wished to determine whether OL‐HDF increased platelet activation and ECC clotting.
The effects of orthodontic force application upon the tissues of the human dental pulp

Aims: To investigate the effects of orthodontic force application on pulpal tissues. Materials and methods: Sixteen patients were scheduled for bilateral upper premolar removal followed by fixed appliance treatment. Each had a sectional fixed appliance placed in order to extrude one premolar only for a period of 14 days. The contralateral premolar was used as a control. After 14 days both premolars were extracted and processed for MMA or paraffin embedding, and sectioning. The pulpal morphology of both control and test tissues were examined under a light microscope, and fibroblast numbers, together with blood vessel number and area, analysed on serial sections. Immunohistochemical staining for Von Willebrand’s factor and CD31 was undertaken to assess angiogenesis. Results: No statistically significant difference was found in fibroblast numbers, blood vessel number or angiogenic activity and no morphological differences were observed between the control and test tissues after the 14-day period. However the overall blood vessel area was greater (p<0.05) in the test tissues. Conclusions: A 2-week application of 50g extrusive force leads to significant blood vessel dilation, but does not give rise to any significant changes in overall pulpal morphology, fibroblast number, blood vessel number, or angiogenesis.
Understanding Web Archiving Services and Their (Mis)Use on Social Media

Web archiving services play an increasingly important role in today's information ecosystem, by ensuring the continuing availability of information, or by deliberately caching content that might get deleted or removed.Among these, the Wayback Machine has been proactively archiving, since 2001, versions of a large number of Web pages, while newer services like archive.is allow users to create on-demand snapshots of specific Web pages, which serve as time capsules that can be shared across the Web. In this paper, we present a large-scale analysis of Web archiving services and their use on social media, shedding light on the actors involved in this ecosystem, the content that gets archived, and how it is shared. We crawl and study: 1) 21M URLs from archive.is, spanning almost two years; and 2) 356K archive.is plus 391K Wayback Machine URLs that were shared on four social networks: Reddit, Twitter, Gab, and 4chan's Politically Incorrect board (/pol/) over 14 months. We observe that news and social media posts are the most common types of content archived, likely due to their perceived ephemeral and/or controversial nature. Moreover, URLs of archiving services are extensively shared on "fringe" communities within Reddit and 4chan to preserve possibly contentious content. Lastly, we find evidence of moderators nudging or even forcing users to use archives, instead of direct links, for news sources with opposing ideologies, potentially depriving them of ad revenue.
Fast physics-based electromigration assessment by efficient solution of linear time-invariant (LTI) systems

Electromigration (EM) is a key reliability concern in chip power/ ground (p/g) grids, which has been exacerbated by the high current levels and narrow metal lines in modern grids. EM checking is expensive due to the large sizes of modern p/g grids and is also inherently difficult due to the complex nature of the EM phenomenon. Traditional EM checking, based on empirical models, cannot capture the complexity of EM and better models are needed for accurate prediction. Thus, recent physics-based EM models have been proposed, which remain computationally expensive because they require solution of a system of partial differential equations (PDEs). In this paper, we propose a fast and scalable methodology for power grid EM verification, building on previous physics-based models. We first convert the PDE system to a succession of homogeneous linear time invariant (LTI) systems. Because these systems are found to be stiff, we numerically integrate them using optimized variable-step backward differentiation formulas (BDFs). Our method, for a number of IBM power grids and internal benchmarks, achieves an average speed-up of over 20x as compared to previously published work and has a runtime of only about 8 minutes for a 4 million node grid.