Miracle-dz/UniFAR-FTUs huggingface dataset:
The MicroRNA let-7a Modulates Interleukin-6-dependent STAT-3 Survival Signaling in Malignant Human Cholangiocytes*

The inflammation-associated cytokine interleukin-6 (IL-6) can contribute to tumor growth and resistance to therapy by the activation of survival mechanisms. In several human cancers, IL-6-activated survival signaling involves the signal transducers and activators of transcription (Stat) factors or protein kinase cascades. microRNAs (miRNAs) are endogenous regulators of gene expression that are altered in expression in many cancers. However, the effect of inflammatory cytokines on miRNA expression and the role of miRNA in modulating IL-6-mediated cell survival are unknown. We investigated the involvement of miRNA in malignant cholangiocytes stably transfected to overexpress IL-6, which enhances tumor growth in vivo by inhibition of apoptosis. We provide evidence that (i) miRNA expression both in vitro and in vivo is altered by overexpression of IL-6; (ii) selective miRNAs including let-7a are up-regulated and contribute to the survival effects of enforced IL-6 activity; and (iii) let-7a contributes to the constitutively increased phosphorylation of Stat-3 by a mechanism involving the neurofibromatosis 2 (NF2) gene. These findings reveal a novel mechanism by which IL-6 mediates tumor cell survival that may be therapeutically targeted and emphasize the presence of complex interrelationships between deregulated expression of miRNA and transcription factors in human cancers.
Interferon beta‐1b inhibits gelatinase secretion and in vitro migration of human T cells: A possible mechanism for treatment efficacy in multiple sclerosis

Treatment with interferon beta‐1b has substantial clinical benefit in the demyelinating disease multiple sclerosis, yet the mechanism of action in the disease remains largely unknown. Gelatinase A (matrix metalloproteinase‐2, 72‐kd gelatinase) and B (matrix metalloproteinase‐9, 92‐kd gelatinase) are matrix metalloproteinases capable of enzymatic digestion of subendothelial basement membrane constituents. In human T cells, interleukin‐2 induces gelatinase secretion and enhances gelatinase‐dependent migration across an artificial basement membrane‐like layer in vitro. Pretreatment of T cells with interferon beta‐lb for 48 hours decreased interleukin‐2‐induced gelatinase production and secretion as determined by zymography. In parallel to the downregulation of gelatinase secretion, pretreatment with interferon beta‐lb inhibited T‐cell migration across the basement membrane in vitro by up to 90%, but had only a minor impact on cell locomotion per se. For both gelatinase secretion and T‐cell migration, the inhibitory effect mediated by exposure to interferon beta‐1b was dose dependent. Fluorescence‐activated cell sorter analysis also showed that interferon beta‐1b downregulates the interleukin‐2 receptor α‐chain and lowered the affinity of interleukin‐2 to the cell surface by 30%, which may represent an additional mechanism for the observed effects of interferon beta‐1b. The dramatic effects of interferon beta‐1b on gelatinase expression and migration raise the possibility that its beneficial effects in multiple sclerosis may result from interference with the capacity of activated T cells to traverse the basement membrane and migrate to the central nervous system.
Global Impact of Salmonella Pathogenicity Island 2-secreted Effectors on the Host Phosphoproteome*

During the late stages of infection, Salmonella secretes numerous effectors through a type III secretion system that is encoded within Salmonella pathogenicity island 2 (SPI2). Despite the importance of SPI2 as a major virulence factor leading to the systemic spread of the bacteria and diseases, a global view of its effects on host responses is still lacking. Here, we measured global impacts of SPI2 effectors on the host phosphorylation and protein expression levels in RAW264.7 and in HeLa cells, as macrophage and nonphagocytic models of infection. We observe that SPI2 effectors differentially modulate the host phosphoproteome and cellular processes (e.g. protein trafficking, cytoskeletal regulation, and immune signaling) in a host cell-dependent manner. Our unbiased approach reveals the involvement of many previously unrecognized proteins, including E3 ligases (HERC4, RanBP2, and RAD18), kinases (CDK, SIK3, and WNK1), and histones (H2B1F, H4, and H15), in late stages of Salmonella infection. Furthermore, from this phosphoproteome analysis and other quantitative screens, we identified HSP27 as a direct in vitro and in vivo molecular target of the only type III secreted kinase, SteC. Using biochemical and cell biological assays, we demonstrate that SteC phosphorylates multiple sites in HSP27 and induces actin rearrangement through this protein. Together, these results provide a broader landscape of host players contributing to specific processes/pathways mediated by SPI2 effectors than was previously appreciated.
Tomorrow's skeleton staff: mesenchymal stem cells and the repair of bone and cartilage

Abstract. Stem cells are regenerating medicine. Advances in stem cell biology, and bone marrow‐derived mesenchymal stem cells in particular, are demonstrating that many clinical options once thought to be science fiction may be attainable as fact. The extra‐ and intra‐cellular signalling used by stem cells as they differentiate into lineages appropriate to their destination are becoming understood. Thus, the growth stimuli afforded by LIF, FGF‐2 and HGF, as well as the complementary roles of Wnt and Dickkopf‐1 in stem cell proliferation are evident. The ability to direct multi‐lineage mesenchymal stem sell (MSC) potential towards an osteogenic phenotype by stimulation with Menin and Shh are important, as are the modulatory roles of Notch‐1 and PPARγ. Control of chondrocytic differentiation is effected by interplay of Brachyury, BMP‐4 and TGFβ3. Smads 1, 4 and 5 also play a role in these phenotypic expressions. The ability to culture MSC has led to their use in tissue repair, both as precursor and differentiated cell substitutes, and with successful animal models of bone and cartilage repair using MSC, their clinical use is accelerating. However, MSC also suppress some T‐cell functions in transplanted hosts, and could facilitate tumour growth, so a cautious approach is needed.
Quantitative study of nasal tip support and the effect of reconstructive rhinoplasty.

OBJECTIVES To develop a method to quantify nasal tissue resilience, to establish the normal range for persons without nasal obstruction, and to measure the changes in tissue resilience resulting from standard open rhinoplastic techniques. METHODS A new device is described that determines nasal tissue resilience. Measurements on the nasal tip were obtained in triplicate at 5 distinct anatomical sites. Normal values (N = 60) were stratified for both sexes into 3 different age groups. Preoperative and postoperative measurements were also obtained in 6 patients who underwent open rhinoplasty for airway obstruction. One patient who underwent intranasal valve repair was included for comparison. All operative patients underwent preoperative and postoperative rhinomanometric measurements. RESULTS Across all age and sex groups the anterior septal angle is the firmest area of the nasal tip. The mean tissue resilience over the interdomal area and the midcolumella is significantly greater in men than in women. The resilience of the interdomal area exhibits an age effect, with decreasing stiffness over time. The postoperative changes seen correlate well with the placement of structural grafts during rhinoplasty. CONCLUSIONS Nasal tip support can be quantified. Normative values have been established, which allow one to identify areas of inadequate tip support in persons with nasal obstruction. Alterations in tip support resulting from surgical intervention can be quantified. Open rhinoplasty techniques are an excellent tool to restore deficiencies in nasal tip support.
Endophytic Colonization of Rice by a Diazotrophic Strain of Serratia marcescens

ABSTRACT Six closely related N2-fixing bacterial strains were isolated from surface-sterilized roots and stems of four different rice varieties. The strains were identified as Serratia marcescens by 16S rRNA gene analysis. One strain, IRBG500, chosen for further analysis showed acetylene reduction activity (ARA) only when inoculated into media containing low levels of fixed nitrogen (yeast extract). Diazotrophy of IRBG500 was confirmed by measurement of15N2 incorporation and by sequence analysis of the PCR-amplified fragment of nifH. To examine its interaction with rice, strain IRBG500 was marked with gusAfused to a constitutive promoter, and the marked strain was inoculated onto rice seedlings under axenic conditions. At 3 days after inoculation, the roots showed blue staining, which was most intense at the points of lateral root emergence and at the root tip. At 6 days, the blue precipitate also appeared in the leaves and stems. More detailed studies using light and transmission electron microscopy combined with immunogold labeling confirmed that IRBG500 was endophytically established within roots, stems, and leaves. Large numbers of bacteria were observed within intercellular spaces, senescing root cortical cells, aerenchyma, and xylem vessels. They were not observed within intact host cells. Inoculation of IRBG500 resulted in a significant increase in root length and root dry weight but not in total N content of rice variety IR72. The inoculated plants showed ARA, but only when external carbon (e.g., malate, succinate, or sucrose) was added to the rooting medium.
In Vitro Activities of a Wide Panel of Antifungal Drugs against Various Scopulariopsis and Microascus Species

ABSTRACT The in vitro activities of 11 antifungal drugs against 68 Scopulariopsis and Microascus strains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 μg/ml and 0.125 to 16 μg/ml, respectively. The MIC and MEC modes were both 1 µg/ml for terbinafine and caspofungin; the MIC50 and MEC50 were 1 µg/ml for both drugs, whereas the MIC90 and MEC90 were 4 µg/ml and 16 µg/ml, respectively.
Big data analysis for an electric vehicle charging infrastructure using open data and software

This paper describes a big data analysis strategy for electric vehicle charging infrastructure, mainly built upon open data sets and open software components. The data acquisition module periodically retrieves the real-time status information of each charger from the public data portal, while the downloaded XML files are parsed to extract fields of interest. At this stage, we present the distribution of charging facilities in Jeju City based on our own map viewer implementation, the city-wide dynamics of the number of chargers in operation based on MySQL queries, and the visualization of regional occupancy rates based on the R GISTools library. After combining a variety of statistical and machine learning techniques to understand the demand pattern of electric vehicle charging, we will integrate renewable energy to charging-intensive power grids as much as possible.
Use of hydroxyl-modified carbon nanotubes for detecting SF6 decomposition products under partial discharge in gas insulated switchgear

Gas-insulated switchgear (GIS) has inherent internal defects that may result in partial discharge (PD) and the eventual development of equipment faults. PD in GIS can lead to the generation of multiple decomposition products of SF6, and the detection and analysis of these decomposition products is important for fault diagnosis. In this paper, a molecular dynamics simulation software package, Materials Studio (MS), is used to model accurately the processes by which single-walled carbon nanotubes modified by hydroxyl (SWNT-OH) adsorb the main decomposition products of SF6 (SOF2, SO2F2, SO2 and CF4) generated by PD. In addition, experimental studies are performed to validate the predicted gas-sensing characteristics. The theoretical calculations and experimental results both indicate that, of the four gases, SWNT-OH showed the fastest response time and highest sensitivity to SO2. The sensitivities of SWNT-OH to the other gases were low, and response times long. We conclude that SWNT-OH shows good sensitivity and selectivity to SO2.
Expression of HLA-B27 causes loss of migratory dendritic cells in a rat model of spondylarthritis.

OBJECTIVE In rats transgenic for human HLA-B27 and β(2) -microglobulin (B27-transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27-transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4+ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4+ T cell differentiation would be aberrant in B27-transgenic rats. METHODS Migrating intestinal lymph DCs were collected via thoracic duct cannulation from B27-transgenic and control (HLA-B7-transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed. RESULTS Lymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self-antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27-transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27-transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin-17 (IL-17) production from naive CD4+ T cells. CONCLUSION We describe 2 different mechanisms by which HLA-B27 may contribute to inflammatory disease: increased apoptotic death of B27-transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL-17 production from CD4+ T cells stimulated by the surviving B27-transgenic DCs.
Pressure-overload-induced angiotensin-mediated early remodeling in mouse heart

Our previous work on angiotensin II-mediated electrical-remodeling in canine left ventricle, in connection with a long history of other studies, suggested the hypothesis: increases in mechanical load induce autocrine secretion of angiotensin II (A2), which coherently regulates a coterie of membrane ion transporters in a manner that increases contractility. However, the relation between load and A2 secretion was correlative. We subsequently showed a similar or identical system was present in murine heart. To investigate whether the relation between mechanical load and A2-mediated electrical remodeling was causal, we employed transverse aortic constriction in mice to subject the left ventricle to pressure overload for short-term (1 to 2 days) or long-term (1 to 2 weeks) periods. Heart-to-body weight ratios and cell capacitance measurements were used to determine hypertrophy. Whole-cell patch clamp recordings of the predominant repolarization currents Ito,fast and IK,slow were used to assess electrical remodeling. Hearts or myocytes subjected to long-term load displayed significant hypertrophy, which was not evident in short-term load. However, short-term load induced significant reductions in Ito,fast and IK,slow. Incubation of these myocytes with the angiotensin II type 1 receptor inhibitor saralasin for 2 hours restored Ito,fast and IK,slow to control levels. The number of Ito.fast or IK,slow channels did not change with A2 or long-term load, however the hypertrophic increase in membrane area reduced the current densities for both channels. For Ito,fast but not IK,slow there was an additional reduction that was reversed by inhibition of angiotensin receptors. These results suggest increased load activates an endogenous renin angiotensin system that initially reduces Ito,fast and IK,slow prior to the onset of hypertrophic growth. However, there are functional interactions between electrical and anatomical remodeling. First, hypertrophy tends to reduce all current densities. Second, the hypertrophic program can modify signaling between the angiotensin receptor and target current.
Population pharmacokinetic and pharmacodynamic models of remifentanil in healthy volunteers using artificial neural network analysis.

AIMS An ordinary sigmoid E(max) model could not predict overshoot of electroencephalographic approximate entropy (ApEn) during recovery from remifentanil effect in our previous study. The aim of this study was to evaluate the ability of an artificial neural network (ANN) to predict ApEn overshoot and to evaluate the predictive performance of the pharmacokinetic model, and pharmacodynamic models of ANN with respect to data used. METHODS Using a reduced number of ApEn instances (n = 1581) to make NONMEM modelling feasible and complete ApEn data (n = 24 509), the presence of overshoot was assessed. A total of 1077 measured remifentanil concentrations and ApEn data, and a total of 24 509 predicted concentrations and ApEn data were used in the pharmacodynamic model A and B of ANN, respectively. The testing subset of model B (n = 7352) was used to evaluate the ability of ANN to predict overshoot of ApEn. Mean squared error (MSE) was calculated to evaluate the predictive performance of the ANN models. RESULTS With complete ApEn data, ApEn overshoot was observed in 66.7% of subjects, but only in 37% with a reduced number of ApEn instances. The ANN model B predicted 77.8% of ApEn overshoot. MSE (95% confidence interval) was 57.1 (3.22, 71.03) for the pharmacokinetic model, 0.148 (0.004, 0.007) for model A and 0.0018 (0.0017, 0.0019) for model B. CONCLUSIONS The reduced ApEn instances interfered with the approximation of true electroencephalographic response. ANN predicted 77.8% of ApEn overshoot. The predictive performance of model B was significantly better than that of model A.
Managing Innovation Resources in Accordance with Sustainable Development Ethics: Typological Analysis

The regional development path depends on managing innovation resources. However, increasing the quantity of innovation activity and managing innovation resources only by financial indicators does not guarantee progress in sustainable development. This paper argues that basic conditions for effective sustainability-oriented innovation activities are: (1) the accordance of relevant activities with sustainable development ethics and (2) their marked focus on systemic and long-term sustainable development targets. These parameters can be considered fundamental principles for designing and developing effective sustainability-oriented innovation systems and innovation policies. Analysis of the two basic principles precedes estimation of the effectiveness of innovation activities, innovation systems, or innovation policies. In this paper, a special typological analysis technique was applied to assess basic conditions for the effectiveness of sustainability-oriented innovation activities observed in the case of the Tyumen region, Russia. It was found that since 2009 the Tyumen regional innovation support system has not been conceptually designed in accordance with sustainable development ethics or considering a long-term vision. Therefore, the projects themselves afford only temporary solutions to regional problems by implementing innovations that mainly have short-term and mid-term social–economic effects. As a result of the analysis of fundamental conditions for sustainability-oriented innovation activities in Tyumen region, this paper proposes recommendations on necessary measures for redesigning decision-making principles of regional innovation support systems in order to significantly increase the potential impact on the development of a truly sustainable regional economy.
Edge Snapping-Based Depth Enhancement for Dynamic Occlusion Handling in Augmented Reality

Dynamic occlusion handling is critical for correct depth perception in Augmented Reality (AR) applications. Consequently it is a key component to ensure realistic and immersive AR experiences. Existing solutions to tackle this challenge typically suffer from various limitations, e.g. assumption of a static scene or high computational complexity. In this work, we propose an algorithm for depth map enhancement for dynamic occlusion handling in AR applications. The key of our algorithm is an edge snapping approach, formulated as discrete optimization, that improves the consistency of object boundaries between RGB and depth data. The optimization problem is solved efficiently via dynamic programming and our system runs in near real-time on the tablet platform. Experimental evaluations demonstrate that our approach largely improves the raw sensor data and is particularly suitable compared to several related approaches in terms of both speed and quality. Furthermore, we demonstrate visually pleasing dynamic occlusion effects for multiple AR use cases based on our edge snapping results.
Pathways through the intercellular clefts of frog mesenteric capillaries.

1. The three‐dimensional ultrastructure of endothelial intercellular clefts of frog mesenteric capillaries of known hydraulic permeability (Lp) has been investigated in the absence and presence of lanthanum ions as tracers of extracellular solute. 2. Experiments were carried out on the exposed mesenteries of pithed frogs and Lp of a chosen microvessel perfused with a Ringer solution containing serum albumin (10‐40 mg ml‐1) was determined. In some experiments the mesentery was fixed in situ with 2.5% glutaraldehyde immediately after Lp had been measured. In other experiments, measurement of Lp was followed by brief microperfusion (10‐20 s) with a second Ringer solution containing 1% lanthanum nitrate as a tracer before in situ fixation of the tissue. The tissue was prepared for electron microscopy using standard techniques. The perfused capillary was identified in the block and serial transverse sections were cut along its length over regions where Lp had been measured. 3. In six capillaries where the tissues were fixed immediately after measurement of Lp, Lp had a mean value (+/‐ S.E.M.) of 4 (+/‐ 0.5) x 10(‐7) cm s‐1 (cmH2O)‐1. Serial (30‐40 nm) sections of these vessels revealed that a single short narrow region of the intercellular clefts ran almost continuously from section to section. Additional tight regions were regularly seen, but they usually extended for relatively few sections. In 13.36 microns of reconstructed cleft, there were three interruptions of the tight region of 0.14, 0.14 and 0.17 microns respectively. In the region of these discontinuities, the wide region was uninterrupted from luminal to abluminal surface. 4. Examination of the tight junction on a tilting stage revealed that the outer leaflets of the adjacent cells were not fused, but separated by a gap of mean width (+/‐ S.E.M.) 2.3 (+/‐ 0.1) nm. 5. In four capillaries perfused with lanthanum nitrate before fixation, mean Lp (+/‐ S.E.M.) was 6.5 (+/‐ 0.02) x 10(‐7) cm s‐1 (cmH2O)‐1. Segments of intercellular clefts, totalling 23.56 microns in length, were reconstructed from serial sections and throughout these, electron‐dense deposits of lanthanum were observed to fill the luminal parts of the intercellular clefts up to the tight region. Lanthanum deposits filled the entire cleft to the abluminal surface at eleven sites, which accounted for a length of 2.52 microns out of the 23.56 microns. Only five of these regions were delimited within a continuous series of sections and their mean length (+/‐ S.E.M.) was 0.16 (+/‐ 0.063) microns. (ABSTRACT TRUNCATED AT 400 WORDS)