Miracle-dz/UniFAR-FTUs huggingface dataset:
Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2

Significance Our understanding of the molecular basis of our sense of hearing and balance has improved significantly, although some of the key players in sensory hair cells have yet to be identified. Sensory hair cells depend on extracellular filaments known as tip links to transduce mechanical stimuli into electrical signals. We demonstrate that the tip link protein PCDH15 interacts with two integral member proteins, TMC1 and TMC2, which have recently been put forth as candidates for the mechanotransduction channel. The tip link protein protocadherin 15 (PCDH15) is a central component of the mechanotransduction complex in auditory and vestibular hair cells. PCDH15 is hypothesized to relay external forces to the mechanically gated channel located near its cytoplasmic C terminus. How PCDH15 is coupled to the transduction machinery is not clear. Using a membrane-based two-hybrid screen to identify proteins that bind to PCDH15, we detected an interaction between zebrafish Pcdh15a and an N-terminal fragment of transmembrane channel-like 2a (Tmc2a). Tmc2a is an ortholog of mammalian TMC2, which along with TMC1 has been implicated in mechanotransduction in mammalian hair cells. Using the above-mentioned two-hybrid assay, we found that zebrafish Tmc1 and Tmc2a can interact with the CD1 or CD3 cytoplasmic domain isoforms of Pcdh15a, and this interaction depends on the common region shared between the two Pcdh15 isoforms. Moreover, an interaction between mouse PCDH15-CD3 and TMC1 or TMC2 was observed in both yeast two-hybrid assays and coimmunoprecipitation experiments. To determine whether the Pcdh15–Tmc interaction is relevant to mechanotransduction in vivo, we overexpressed N-terminal fragments of Tmc2a in zebrafish hair cells. Overexpression of the Tmc2a N terminus results in mislocalization of Pcdh15a within hair bundles, together with a significant decrease in mechanosensitive responses, suggesting that a Pcdh15a–Tmc complex is critical for mechanotransduction. Together, these results identify an evolutionarily conserved association between the fish and mouse orthologs of PCDH15 and TMC1 and TMC2, supporting the notion that TMCs are key components of the transduction complex in hair cells.
A three-step data transmission scheme for machine type devices in 3GPP LTE systems

This paper proposes a three-step data transmission scheme for massive machine type devices (MTDs) in 3GPP LTE systems. To reduce the signaling overhead for MTDs in idle mode, the proposed scheme adopts a modified random access procedure which enables a MTD to transmit a small-sized data packet once it receives the random access response message. Numerical results have shown that the proposed scheme can increase the maximum number of supportable MTDs by about 30 % compared to the conventional schemes.
On-line Evolutionary Sentiment Topic Analysis Modeling

As the rapid booming of reviews, a valid sentiment analysis model will significantly boost the review recommendation system’s capability, and present more constructive information for consumers. Topic probabilistic models have already shown many advantages for detecting potential structure of topics and sentiments in reviews corpus. However, most reviews are presented through time-dependent data streams and some respects of the potential structure are unfixed and time-varying, such as topic number and word probability distribution. In this paper, a novel probabilistic topic modelling framework is proposed, called on-line evolutionary sentiment/topic modeling (OESTM), which has the capacity for achieving the optimization of the aforementioned aspects. Firstly, OESTM depends on an improved non-parametric Bayesian model for estimating the best number of topics that can perfectly explain the current time-slice, and analyzes these latent topics and sentiment polarities simultaneously. Secondly, OESTM implements the birth, death and inheritance for detected topics through the transfer of parameters from previous time slices to the updated time slice. The experiments show that significant improvements have been achieved by the proposed model with respect to other state-of-the-art models.
Curative effect of transcatheter arterial chemoembolization combined with radiofrequency ablation in treating hepatic cell carcinoma and its effect on serum markers.

BACKGROUND Hepatic cell carcinoma (HCC) is more common in clinical practice, and has high malignant degree. OBJECTIVE This study aims to analyze the curative effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating hepatic cell carcinoma (HCC) and its effect on serum markers. METHODS A total of 106 cases of patients with hepatic cell carcinoma treated in our hospital were randomly divided into two groups: observation group and control group. Patients in the observation group (53 cases) received transcatheter arterial chemoembolization combined with radiofrequency ablation therapy, while subjects in the control group (53 cases) received transcatheter arterial chemoembolization therapy. Differences in the overall effect, indicators of inflammation and oxidative stress, tumor activity-related indicators and tumor recurrence-related indicators between these two groups were compared. RESULTS At one and two weeks after treatment, the number of cases of CR and PR in the observation group was higher than that in the control group, the number of cases of SD was not different from that in the control group, and the number of cases of PD was lower than that in the control group. At two weeks after treatment, differences in serum MDA, SOD, GSH, CRP, TNF-α and ESR between the two groups were significant. However, serum EC, VEGF, MMP, AFP, CA199 and GGT content was significantly lower in the observation group than that in the control group. CONCLUTIONS Transcatheter arterial chemoembolization combined with radiofrequency ablation therapy can effectively control the growth of liver cancer lesions, reduce the levels of tumor-related serum markers, and inhibit the activity of tumor cells.
Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis: A Systematic Review

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB.
Understanding the Features of IEEE 802. 11g in High Data Rate Wireless LANs

In a practical application scenario, high data rates are required with increasing demand of wireless LANs. To upgrade the data rate of WLANs, the IEEE presented the IEEE 802.11g standard for providing higher data rates up to 54 Mbps at the 2.4 GHz frequency band. In this paper, performance of IEEE 802.11g standard is described with respect to WLANs. The review study of this paper provides the features of IEEE 802.11g by comparing it with previous IEEE standards to evaluate the efficiency of WLANs.
An Expressed Fgf4 Retrogene Is Associated with Breed-Defining Chondrodysplasia in Domestic Dogs

Going Retro In a year celebrating Darwin, the question of how new functional genes arise during evolution is of particular interest. Through a multibreed genetic analysis of the domestic dog, Parker et al. (p. 995, published online 16 July; see the Perspective by Kaessmann) find that the short-legged phenotype that characterizes at least 19 common dog breeds, including the corgi, dachshund, and basset hound, is specifically associated with the expression in developing bone of a gene encoding fibroblast growth factor 4 (fgf4), a member of a gene family previously implicated in dwarfism in humans. Interestingly, the culprit fgf4 gene in dogs has the hallmarks of a “retrogene,” a gene that arises when a parental gene is duplicated through an RNA-based copying mechanism. The short legs that characterize certain dog breeds are associated with a gene that arose recently by RNA-based gene duplication. Retrotransposition of processed mRNAs is a common source of novel sequence acquired during the evolution of genomes. Although the vast majority of retroposed gene copies, or retrogenes, rapidly accumulate debilitating mutations that disrupt the reading frame, a small percentage become new genes that encode functional proteins. By using a multibreed association analysis in the domestic dog, we demonstrate that expression of a recently acquired retrogene encoding fibroblast growth factor 4 (fgf4) is strongly associated with chondrodysplasia, a short-legged phenotype that defines at least 19 dog breeds including dachshund, corgi, and basset hound. These results illustrate the important role of a single evolutionary event in constraining and directing phenotypic diversity in the domestic dog.
Carbon membranes for gas separation processes: recent progress and future perspective

Carbon membrane can be produced using a wide variety of polymer precursor materials via heat treatment process. A general concept route of precursor selection-preparation-modification-performance analysis platform for the carbon membrane has been proposed to promote the development of carbon membrane material for a wide range of application. The current review considers the recent progress of carbon membrane preparation and the potential applications in gas separation and membrane reactor system. In particular, the current carbon membranes for CO2, N2, and H2 separation are reviewed, along with special emphasis to their membrane precursor materials and the technique used to improve the membrane’s performance. Issues affecting membrane performance such as the preparation method to produce supported carbon membrane are explored aligned with the future research to achieve commercially viable processes. For future perspective, carbon membranes hold significant potential and great promise for further investigation, development, and application.
Upregulation of p18Ink4c expression by oncogenic HPV E6 via p53‐miR‐34a pathway

Binding of p53 to miR‐34a promoter activates the expression of tumor‐suppressive miR‐34a. Oncogenic human papillomavirus (HPV) infection downregulates miR‐34a expression through viral E6 degradation of p53. In our report, we found that miR‐34a specifically targets p18Ink4c, a CDK4 and CDK6 inhibitor induced by E2F transactivation. HPV18+ HeLa cells with ectopic miR‐34a expression or by E6 siRNA knockdown‐induced expression of endogenous miR‐34a exhibited a substantial reduction of p18Ink4c in a dose‐dependent manner, but had no effect on p16Ink4a, another member of CDK4/6 inhibitor family. In contrast, de novo infection by oncogenic HPVs of human keratinocyte‐derived raft tissues increased p18Ink4c expression. Suppression of endogenous miR‐34a in cell lines with a miR‐34a inhibitor also increased p18Ink4c. We found that miR‐34a suppresses the expression of p18Ink4c by binding to a specific seed match in the 5′ UTR of p18Ink4c. Further investigation found remarkable increase of p18Ink4c in cervical precancer lesions and cervical cancer. Immunohistochemical staining of cervical tissue arrays showed increased expression of p18Ink4c in 68% of cervical cancer, 8.3% of chronic cervical inflammation and 4.8% of normal cervix. Although p18Ink4c inhibits cell proliferation in general and regulates E2F1 expression in HCT116 cells, it appears not to function as a tumor suppressor in cervical cancer cells lacking an intact G1 checkpoint because of viral E7 degradation of pRB. In summary, our study demonstrates an intimate connection among oncogenic HPV E6, p53, miR‐34a and p18Ink4c and identifies p18Ink4c as a possible biomarker for cervical cancer.
Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

AIM To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODS Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTS For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSION The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.
The Measurement and Performance Analysis of Inter-firm RelationshipQuality:Based on Close Relationship Theory

With the increase of inter-firm cooperation,it is becoming more important for enhancing cooperative performance that improves inter-firm relationship quality.Based on the description of close relationship theory,we sent questionnaire surveys to some domestic firms to learn their opinions concerning inter-firm relationship.Using the data,we have analyzed how to measure the relationship quality.The result shows that the relationship quality of Chinese firms can be measured through the relationship strength,the relationship symmetry and the relationship duration.Moreover we tests the relationship between the relationship quality and the cooperative performance.
Discovery of Urinary Biomarkers*

A myriad of proteins and peptides can be identified in normal human urine. These are derived from a variety of sources including glomerular filtration of blood plasma, cell sloughing, apoptosis, proteolytic cleavage of cell surface glycosylphosphatidylinositol-linked proteins, and secretion of exosomes by epithelial cells. Mass spectrometry-based approaches to urinary protein and peptide profiling can, in principle, reveal changes in excretion rates of specific proteins/peptides that can have predictive value in the clinical arena, e.g. in the early diagnosis of disease, in classification of disease with regard to likely therapeutic responses, in assessment of prognosis, and in monitoring response to therapy. These approaches have potential value, not only in diseases of the kidney and urinary tract but also in systemic diseases that are associated with circulating small protein and peptide markers that can pass the glomerular filter. Most large scale biomarker discovery studies reported thus far have used one of two approaches to identify proteins and peptides whose excretion in urine changes in specific disease states: 1) two-dimensional electrophoresis with mass spectrometric and/or immunochemical identification of proteins and 2) top-down mass spectrometric methods (SELDI-TOF-MS and capillary electrophoresis-MS). These studies have been chiefly in the areas of nephrology, urology, and oncology. We review these applications, focusing on two areas of progress, viz. in bladder cancer and in acute rejection of renal transplants. Progress has been limited so far. However, with the advent of powerful LC-MS/MS methods along with methods for quantifying LC-MS/MS output, there is hope for an accelerated discovery and validation of disease biomarkers in urine.
Magnetic Resonance Characterization of Ischemic Tissue Metabolism

Magnetic resonance imaging (MRI) and spectroscopy (MRS) are versatile diagnostic techniques capable of characterizing the complex stroke pathophysiology, and hold great promise for guiding stroke treatment. Particularly, tissue viability and salvageability are closely associated with its metabolic status. Upon ischemia, ischemic tissue metabolism is disrupted including altered metabolism of glucose and oxygen, elevated lactate production/accumulation, tissue acidification and eventually, adenosine triphosphate (ATP) depletion and energy failure. Whereas metabolism impairment during ischemic stroke is complex, it may be monitored non-invasively with magnetic resonance (MR)-based techniques. Our current article provides a concise overview of stroke pathology, conventional and emerging imaging and spectroscopy techniques, and data analysis tools for characterizing ischemic tissue damage.
The cholinergic system in the basal forebrain of the Atlantic white‐sided dolphin (Lagenorhynchus acutus)

The basal forebrain (BFB) cholinergic neurotransmitter system is important in a number of brain functions including attention, memory, and the sleep‐wake cycle. The size of this region has been linked to the increase in encephalization of the brain in a number of species. Cetaceans, particularly those belonging to the family Delphinidae, have a relatively large brain compared to its body size and it is expected that the cholinergic BFB in the dolphin would be a prominent feature. However, this has not yet been explored in detail. This study examines and maps the neuroanatomy and cholinergic chemoarchitecture of the BFB in the Atlantic white‐sided dolphin (Lagenorhynchus acutus). As in some other mammals, the BFB in this species is a prominent structure along the medioventral surface of the brain. The parcellation and distribution of cholinergic neural elements of the dolphin BFB was comparable to that observed in other mammals in that it has a medial septal nucleus, a nucleus of the vertical limb of the diagonal band of Broca, a nucleus of the horizontal limb of the diagonal band of Broca, and a nucleus basalis of Meynert. The observed BFB cholinergic system of this dolphin is consistent with evolutionarily conserved and important functions for survival.
Dynamic BRG1 Recruitment during T Helper Differentiation and Activation Reveals Distal Regulatory Elements

ABSTRACT T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes.
Dissecting the Etiology of Type 2 Diabetes in the Pima Indian Population

The Pima Indian population of Arizona has one of the highest prevalence of diabetes of any population in the world, and the Pima Indians of the Gila River Indian Community have probably been the most studied group for the causes and consequences of diabetes. They develop what would be considered to be classic type 2 diabetes, characterized by obesity and insulin resistance with progression to diabetes characterized by progressive β-cell dysfunction (1). Given the low degree of admixture and high heritability of type 2 diabetes in the Pima Indians (2), the population should also represent a honeypot for genetic discovery. While in recent years there has been progress in identifying type 2 diabetes risk variants in this population (3,4), the understanding of the genetic contribution to diabetes risk remains far from complete. Like many initiatives in genetics, whole-genome/exome sequencing is now being applied in the hope that rare/low-frequency variants with large effects on diabetes risk will be found. In this issue of Diabetes , Baier et al. (5) report on the results of a targeted sequencing project focusing on the genes encoding the two subunits of the β-cell KATP channel. Variants identified by whole-genome sequencing in ABCC8 and KCNJ11 in 335 Pima Indians are genotyped in 7,710 individuals of full Pima Indian heritage or mixed American Indian heritage (∼4/8th Pima Indian). They identify an R1420H variant present in 3.3% of the population that is associated with …
Trajectory Sampling : White Paper Draft

TS implements consistent packet sampling. Conceptually, e ch packet traversing a measurement domain is sampled either on every link traversed, or on no link at all . Some highly compressed information on sampled packets are collected centrally in a collection s ystem, which is then able to reconstruct the trajectory (path) of each sampled packet [5]. This set of sam pled packet trajectories provides a complete and statistically representative view of the flow of traffic t hrough the domain. A wide range of applicationspecific metrics and derived views (such as traffic matrices f or traffic engineering or sink trees for a DDoS attack) can be inferred from this raw trajectory informatio n.