Miracle-dz/UniFAR-FTUs huggingface dataset:
LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting the miR‐346/KLF14 axis

Long non‐coding RNAs (lncRNAs) are a class of regulatory noncoding RNAs. Emerging evidence highlights the critical roles of lncRNAs in the progression of hepatocellular carcinoma (HCC). Although many lncRNAs have been identified in the development of HCC, the association between DiGeorge syndrome critical region gene 5 (DGCR5) and HCC remains unclear. In the current study, we focused on the biological role of DGCR5 in HCC. We observed that DGCR5 was decreased in HCC cells, including SMCC7721, Hep3B, HepG2, MHCC‐97L, MHCC‐97H, and SNU449 hepatocellular carcinoma cells, compared with the normal human liver cell line THLE‐3 normal human liver cells. In addition, DGCR5 overexpression could repress HCC cell growth, migration, and invasion considerably. Increasing studies have indicated the interactions between lncRNAs and microRNAs. MicroRNAs are endogenous small noncoding RNAs and they can play important roles in tumorigenesis. MicroRNA 346 (miR‐346) has been demonstrated in various human cancer types, including HCC. MiR‐346 was found to be increased in HCC cells and DGCR5 can act as a sponge of miR‐346 to modulate the progression of HCC. The binding correlation between DGCR5 and miR‐346 was validated in our research. Subsequently, Krüppel‐like factor 14 (KLF14) was predicted as a downstream target of miR‐346 and miR‐346 can induce the development of HCC by inhibiting KLF14. Finally, we proved that DGCR5 can rescue the inhibited levels of KLF14 repressed by miR‐346 mimics in MHCC‐97H and Hep3B cells. Taken together, it was indicated in our study that DGCR5 can restrain the progression of HCC through sponging miR‐346 and modulating KLF14 in vitro.
Vision-only egomotion estimation in 6DOF using a sky compass

SUMMARY A novel pure-vision egomotion estimation algorithm is presented, with extensions to Unmanned Aerial Systems (UAS) navigation through visual odometry. Our proposed method computes egomotion in two stages using panoramic images segmented into sky and ground regions. Rotations (in 3DOF) are estimated by using a customised algorithm to measure the motion of the sky image, which is affected only by the rotation of the aircraft, and not by its translation. The rotation estimate is then used to derotate the optic flow field generated by the ground, from which the translation of the aircraft (in 3DOF) is estimated by another customised, iterative algorithm. Segmentation of the rotation and translation estimations allows for a partial relaxation of the planar ground assumption, inherently increasing the robustness of the approach. The translation vectors are scaled using stereo-based height to compute the current UAS position through path integration for closed-loop navigation. Outdoor field tests of our approach in a small quadrotor UAS suggest that the technique is comparable to the performance of existing state-of-the-art vision-based navigation algorithms, whilst also removing all dependence on additional sensors, such as an IMU or global positioning system (GPS).
PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of Mismatch Repair Deficiency–Mediated Acquired Resistance to Temozolomide

Mismatch repair (MMR) deficiency through MSH6 inactivation has been identified in up to 30% of recurrent high-grade gliomas, and represents a key molecular mechanism underlying the acquired resistance to the alkylating agent temozolomide (TMZ). To develop a therapeutic strategy that could be effective in these TMZ-refractory gliomas, we first screened 13 DNA damage response modulators for their ability to suppress viability of MSH6-inactivated, TMZ-resistant glioma cells. We identified a PLK1 selective inhibitor, Volasertib, as the most potent in inhibiting proliferation of glioblastoma cells. PLK1 inhibition induced mitotic catastrophe, G2–M cell-cycle arrest, and DNA damage, leading to caspase-mediated apoptosis in glioblastoma cells. Importantly, therapeutic effects of PLK1 inhibitors were not influenced by MSH6 knockdown, indicating that their action is independent of MMR status of the cells. Systemic treatment with Volasertib potently inhibited tumor growth in an MMR-deficient, TMZ-resistant glioblastoma xenograft model. Further in vitro testing in established and patient-derived cell line panels revealed an association of PLK1 inhibitor efficacy with cellular Myc expression status. We found that cells with deregulated Myc are vulnerable to PLK1 inhibition, as Myc overexpression sensitizes, whereas its silencing desensitizes, glioblastoma cells to PLK1 inhibitors. This discovery is clinically relevant as glioma progression post-TMZ treatment is frequently accompanied by MYC genomic amplification and/or pathway activation. In conclusion, PLK inhibitor represents a novel therapeutic option for recurrent gliomas, including those TMZ-resistant from MMR deficiency. Genomic MYC alteration may serve as a biomarker for PLK inhibitor sensitivity, as Myc-driven tumors demonstrated pronounced responses.
A small‐sample kernel association test for correlated data with application to microbiome association studies

Recent research has highlighted the importance of the human microbiome in many human disease and health conditions. Most current microbiome association analyses focus on unrelated samples; such methods are not appropriate for analysis of data collected from more advanced study designs such as longitudinal and pedigree studies, where outcomes can be correlated. Ignoring such correlations can sometimes lead to suboptimal results or even possibly biased conclusions. Thus, new methods to handle correlated outcome data in microbiome association studies are needed. In this paper, we propose the correlated sequence kernel association test (CSKAT) to address such correlations using the linear mixed model. Specifically, random effects are used to account for the outcome correlations and a variance component test is used to examine the microbiome effect. Compared to existing genetic association tests for longitudinal and family samples, we implement a correction procedure to better calibrate the null distribution of the score test statistic to accommodate the small sample size nature of data collected from a typical microbiome study. Comprehensive simulation studies are conducted to demonstrate the validity and efficiency of our method, and we show that CSKAT achieves a higher power than existing methods while correctly controlling the Type I error rate. We also apply our method to a microbiome data set collected from a UK twin study to illustrate its potential usefulness. A free implementation of our method in R software is available at https://github.com/jchen1981/SSKAT.
Dual-layer transposon repression in heads of Drosophila melanogaster

piRNA-mediated repression of transposable elements (TE) in the germline limits the accumulation of heritable mutations caused by their transposition in the genome. It is not clear whether the piRNA pathway plays a functional role in adult, non-gonadal tissues in Drosophila melanogaster. To address this question, we first analyzed the small RNA content of adult Drosophila melanogaster heads. We found that varying amount of piRNA-sized, ping-pong positive molecules in heads correlates with contamination by gonadal tissue during RNA extraction, suggesting that most of piRNAs detected in head sequencing libraries originate from gonads. We next sequenced the heads of wild type and piwi mutants to address whether piwi loss of function would affect the low amount of piRNA-sized, ping-pong negative molecules that are still detected in heads hand-checked to avoid gonadal contamination. We find that loss of piwi does not affect significantly these 24-28 RNA molecules. Instead, we observe increased siRNA levels against the majority of Drosophila transposable element families. To determine the effect of this siRNA level change on transposon expression, we sequenced the transcriptome of wild type, piwi, dicer-2 and piwi, dicer-2 double-mutant fly heads. We find that RNA expression levels of the majority of TE families in piwi or dicer-2 mutants remain unchanged and that TE transcript abundance increases significantly only in piwi, dicer-2 double-mutants. These results lead us to suggest a dual-layer model for TE repression in adult somatic tissues. Piwi-mediated transcriptional gene silencing (TGS) established during embryogenesis constitutes the first layer of TE repression whereas Dicer-2-dependent siRNA-mediated post-transcriptional gene silencing (PTGS) provide a backup mechanism to repress TEs that escape silencing by piwi-mediated TGS.
Long-term Survival of Locally Advanced Stage III Non-small Cell Lung Cancer Patients Treated with Chemoradiotherapy and Perspectives for The Treatment with Immunotherapy

Abstract Background Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.
The binding of Class II sRNA MgrR to two different sites on matchmaker protein Hfq enables efficient competition for Hfq and annealing to regulated mRNAs

MgrR is an Hfq-dependent sRNA, whose transcription is controlled by the level of Mg2+ ions in Escherichia coli. MgrR belongs to Class II sRNAs because its stability in the cell is affected by mutations in Hfq differently than canonical, Class I sRNAs. Here, we examined the effect of mutations in RNA binding sites of Hfq on the kinetics of the annealing of MgrR to two different target mRNAs, eptB and ygdQ, by global data fitting of the reaction kinetics monitored by gel electrophoresis of intermediates and products. The data showed that the mutation on the rim of the Hfq ring trapped MgrR on Hfq preventing the annealing of MgrR to either mRNA. The mutation in the distal face slowed the ternary complex formation and affected the release of MgrR-mRNA complexes from Hfq, while the mutation in the proximal face weakened the MgrR binding to Hfq and in this way affected the annealing. Moreover, competition assays established that MgrR bound to both faces of Hfq and competed against other sRNAs. Further studies showed that uridine-rich sequences located in less structurally stable regions served as Hfq binding sites in each mRNA. Overall, the data show that the binding of MgrR sRNA to both faces of the Hfq ring enables it to efficiently anneal to target mRNAs. It also confers on MgrR a competitive advantage over other sRNAs, which could contribute to efficient cellular response to changes in magnesium homeostasis.
Pressure/Temperature Sensing Bimodal Electronic Skin with Stimulus Discriminability and Linear Sensitivity

Human skin imperfectly discriminates between pressure and temperature stimuli under mixed stimulation, and exhibits nonlinear sensitivity to each stimulus. Despite great advances in the field of electronic skin (E‐skin), the limitations of human skin have not previously been overcome. For the first time, the development of a stimulus‐discriminating and linearly sensitive bimodal E‐skin that can simultaneously detect and discriminate pressure and temperature stimuli in real time is reported. By introducing a novel device design and using a temperature‐independent material, near‐perfect stimulus discriminability is realized. In addition, the hierarchical contact behavior of the surface‐wrinkled microstructure and the optimally reduced graphene oxide in the E‐skin contribute to linear sensitivity to applied pressure/temperature stimuli over wide intensity range. The E‐skin exhibits a linear and high pressure sensitivity of 0.7 kPa−1 up to 25 kPa. Its operation is also robust and exhibits fast response to pressure stimulus within 50 ms. In the case of temperature stimulus, the E‐skin shows a linear and reproducible temperature coefficient of resistance of 0.83% K−1 in the temperature range 22–70 °C and fast response to temperature change within 100 ms. In addition, two types of stimuli are simultaneously detected and discriminated in real time by only impedance measurements.
Transfer of Enteric Viruses Adenovirus and Coxsackievirus and Bacteriophage MS2 from Liquid to Human Skin

Enteric viruses (viruses that infect the gastrointestinal tract) are responsible for most water-transmitted diseases. They are shed in high concentrations in the feces of infected individuals, persist for an extended period of time in water, and are highly infective. Exposure to contaminated water directly (through ingestion) or indirectly (for example, through hand-water contacts followed by hand-to-mouth contacts) increases the risk of virus transmission. The work described herein provides a quantitative model for estimating human-pathogenic virus retention on skin following contact with contaminated water. The work will be important in refining the contribution of indirect transmission of virus to risks associated with water-related activities. ABSTRACT Indirect exposure to waterborne viruses increases the risk of infection, especially among children with frequent hand-to-mouth contacts. Here, we quantified the transfer of one bacteriophage (MS2) and two enteric viruses (adenovirus and coxsackievirus) from liquid to skin. MS2, a commonly used enteric virus surrogate, was used to compare virus transfer rates in a volunteer trial to those obtained using human cadaver skin and synthetic skin. MS2 transfer to volunteer skin was similar to transfer to cadaver skin but significantly different from transfer to synthetic skin. The transfer of MS2, adenovirus, and coxsackievirus to cadaver skin was modeled using measurements for viruses attaching to the skin (adsorbed) and viruses in liquid residual on skin (unadsorbed). We find virus transfer per surface area is a function of the concentration of virus in the liquid and the film thickness of liquid retained on the skin and is estimable using a linear model. Notably, the amount of MS2 adsorbed on the skin was on average 5 times higher than the amount of adenovirus and 4 times higher than the amount of coxsackievirus. Quantification of pathogenic virus retention to skin would thus be overestimated using MS2 adsorption data. This study provides models of virus transfer useful for risk assessments of water-related activities, demonstrates significant differences in the transfer of pathogenic virus and MS2, and suggests cadaver skin as an alternative testing system for studying interactions between viruses and skin. IMPORTANCE Enteric viruses (viruses that infect the gastrointestinal tract) are responsible for most water-transmitted diseases. They are shed in high concentrations in the feces of infected individuals, persist for an extended period of time in water, and are highly infective. Exposure to contaminated water directly (through ingestion) or indirectly (for example, through hand-water contacts followed by hand-to-mouth contacts) increases the risk of virus transmission. The work described herein provides a quantitative model for estimating human-pathogenic virus retention on skin following contact with contaminated water. The work will be important in refining the contribution of indirect transmission of virus to risks associated with water-related activities.
Query grouping–based multi‐query optimization framework for interactive SQL query engines on Hadoop

In the past few years, executing high‐concurrency queries with interactive SQL query engines on Hadoop has become an important activity for many organizations. However, these systems do not adopt Multi‐Query Optimization (MQO) to accelerate the process. There are two major concerns. Firstly, traditional MQO researches assume that multiple queries have high similarity. However, these systems usually serve a variety of applications. Although queries from the same application have high similarity, queries from different applications may have low similarity, so using traditional MQO will be inefficient and time consuming. Secondly, integrating MQO may lead to lots of system modifications. To integrate MQO into interactive SQL query engines on Hadoop efficiently, a query grouping–based MQO framework is proposed. A lightweight mechanism is used to represent SQL queries, on which a grouping method is exploited to speed up the optimization process. A cost model is integrated to estimate the execution cost of interactive SQL query engines on Hadoop. By using the proposed framework, we modify Impala system to support MQO, and the experimental results on TPC‐DS show significant performance improvements.
Individual Incentive Based Reward Policy for an Ad Exchange to Mitigate the Threat of Ad Blocking

This article investigates the fairness of the existing business model of advertisement blocking and ad exchange companies by using exchange frameworks and equity theory. It then provides an individual-centric approach for an ad exchange, which aims to provide a fair compensation to individuals in exchange for their information and effort in the targeting and viewing/filtering of online advertisements. In this article, it is shown that by providing a higher value proposition to individuals in an online advertisement ecosystem, the ad exchange can not only increase individuals' equity in the system, but it can also mitigate the threat of ad blocking for publisher websites and advertisers. An efficient algorithm that estimates the monetary impact of the proposed approach and determines a fair monetary incentive—compensation—for individuals' personal information and actions—engagement—is presented in this article.
Real-Time Bidding in Online Display Advertising

Display advertising is a major source of revenue for many of the online publishers and content providers. Historically, display advertising impressions have been sold through pre-negotiated contracts, known as reservation contracts, between publishers and advertisers. In recent years, a growing number of impressions are being sold in real-time bidding (RTB), where advertisers bid for impressions in real-time, as consumers visit publishers’ websites. RTB allows advertisers to target consumers at an individual level using browser cookie information, and enables them to customize their ads for each individual. The rapid growth of RTB has created new challenges for advertisers and publishers on how much budget and ad inventory to allocate to RTB. In this paper, we use a game theory model with two advertisers and a publisher to study the effects of RTB on advertisers’ and publishers’ strategies and their profits. We show that symmetric advertisers use asymmetric strategies where one advertiser buys all of his impressions in RTB whereas the other advertiser focuses on reservation contracts. Interestingly, we find that while both advertisers benefit from existence of RTB, the advertiser that focuses on reservation contracts benefits more than the advertiser that focuses on RTB. We show that while RTB lowers the equilibrium price of impressions in reservation contracts, it increases the publisher’s total revenue. Despite many analysts’ belief that, because of being more efficient, RTB will replace reservation contracts in the future, we show that publishers have to sell a sufficiently large fraction of their impressions in reservation contracts in order to maximize their revenue. We extend our model to consider premium consumers, publisher’s uncertainty about the number of future visitors, and effectiveness of ad customization.
High-Performance, Low-Complexity Deadlock Avoidance for Arbitrary Topologies/Routings

Recently, the use of graph-based network topologies has been proposed as an alternative to traditional networks such as tori or fat-trees due to their very good topological characteristics. However they pose practical implementation challenges such as the lack of deadlock avoidance strategies. Previous proposals either lack flexibility, underutilise network resources or are exceedingly complex. We propose--and prove formally--three generic, low-complexity deadlock avoidance mechanisms that only require local information. Our methods are topology- and routing-independent and their virtual channel count is bounded by the length of the longest path. We evaluate our algorithms through an extensive simulation study to measure the impact on the performance using both synthetic and realistic traffic. First we compare against a well-known HPC mechanism for dragonfly and achieve similar performance level. Then we moved to Graph-based networks and show that our mechanisms can greatly outperform traditional, spanning-tree based mechanisms, even if these use a much larger number of virtual channels. Overall, our proposal provides a simple, flexible and high performance deadlock-avoidance solution.
Online Subjective Assessment of the Speech of Deaf and Hard of Hearing Children

The aim of this paper is to present the results of a two-year speech production training of hearing impaired children with the help of a Speech Assistant system. It was developed as part of a research project that was carried out jointly by the University of Debrecen and the University of Miskolc within the framework of the project called 'Basic and Applied Research for Internet-based Speech Development of Deaf and Hard of Hearing People and for Objective Measurement of Their Progress'. The project is aimed at solving basic and applied research tasks to develop an application for supporting the improvement of speech production of deaf and hard of hearing people more effectively than the methods that are already known. The idea of the Speech Assistant came from an audio-visual transcoder for sound visualization developed at the University of Debrecen, and a three-dimensional head model for articulation presentation, called 'talking head', developed at the University of Miskolc. The most important aim of the research was to create a complex system to assist the speech production improvement of hearing impaired children by the visualization of speech sound and articulation. In addition, the system has many other features (such as prosody display, automatic assessment and knowledge-based systems implementation), which subsequently allow individual practice not only on computers but also on mobile devices. However, it is important to note that the personal contribution of specialized teachers cannot be replaced. The module performing the audio-visual transcoding required is language-independent, the talking head and the automatic assessment of utterance can be adapted to other languages. The online evaluation system developed for measuring the progress of children in speech production is also shown in this paper.