Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotoxic and Biological Evaluation of a Nano Silica Cross Linked Composite Specifically Used for Intra-Vas Device

The Context: Aims: To evaluate the biocompatibility and in vitro genotoxicity of a non-copper nano silica polymer modified composite for filtering-type intra-vas devices. Settings and Design: Academic research laboratory, Huazhong University of Science and Technology. Prospective experimental study. Methods and Material: Non-copper nano silica polymer modified composite rods were implanted into the back muscle of rabbits for biocompatibility evaluation. Comet assay was applied to the determination of DNA damage, while, Mutagenic activity was tested by means of Ames test using Salmonella typhimurium TA98 and TA 100 tester strains with and without metabolic activation. Statistical analysis used: qualitative and quantitative data were tested using the Chi-square test and Student’s test. Results: Only mild inflammatory reaction was observed in the surrounding tissues of the implanted nano-silica modified polymer composite in the early implantation stage, which was similar to that of the sham-operated group. The inflammatory reaction was completely disappeared after 12 weeks. No significant DNA damage (P > 0.05) were tested on the nano-silica modified polymer composite in Comet assay. In Ames test, the extracts from non-copper composite did not exert mutagenic effect on the bacterial. Conclusions: The non-copper nano silica modified composite did not exhibit in vitro genotoxicity and obvious inflammation in tissue, it would be a safe biomaterial for further clinical trial.
NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive effects of TGF-β receptor signalling

Objectives The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1β/IL-18, but its potential role in autoimmunity is speculative. Methods We generated and phenotyped Nlrp3-deficient, Asc-deficient, Il-1r-deficient and Il-18-deficient C57BL/6-lpr/lpr mice, the latter being a mild model of spontaneous lupus-like autoimmunity. Results While lack of IL-1R or IL-18 did not affect the C57BL/6-lpr/lpr phenotype, lack of NLRP3 or ASC triggered massive lymphoproliferation, lung T cell infiltrates and severe proliferative lupus nephritis within 6 months, which were all absent in age-matched C57BL/6-lpr/lpr controls. Lack of NLRP3 or ASC increased dendritic cell and macrophage activation, the expression of numerous proinflammatory mediators, lymphocyte necrosis and the expansion of most T cell and B cell subsets. In contrast, plasma cells and autoantibody production were hardly affected. This unexpected immunosuppressive effect of NLRP3 and ASC may relate to their known role in SMAD2/3 phosphorylation during tumour growth factor (TGF)-β receptor signalling, for example, Nlrp3-deficiency and Asc-deficiency significantly suppressed the expression of numerous TGF-β target genes in C57BL/6-lpr/lpr mice and partially recapitulated the known autoimmune phenotype of Tgf-β1-deficient mice. Conclusions These data identify a novel non-canonical immunoregulatory function of NLRP3 and ASC in autoimmunity.
A new method for analyzing data from continuous depth-sensing microindentation tests

A new parameter, hardness/modulus^2 ( H/E ^2), has been derived from the equations used to calculate the hardness and elastic modulus from data taken during continuous depth-sensing microindentation tests. This paper discusses the use of this parameter to treat the data obtained from a sample whose surface roughness was of the same scale as the size of the indents. The resulting data were widely scattered. This scatter was reduced when the data were plotted in terms of H/E ^2 versus stiffness. The effect of surface roughness on the hardness and elastic modulus results is removed via stiffness measurements, provided single contacts are made between the indenter and the specimen. The function relating the cross-sectional area of the indenter versus the distance from its point is not required for calculation of H/E ^2, but the hardness and modulus cannot be determined separately. The parameter H/E ^2 indicates resistance to plastic penetration in this case.
Prospective validation of the Bleeding Academic Research Consortium classification in the all-comer PRODIGY trial.

AIMS The Bleeding Academic Research Consortium (BARC) classification has been proposed by consensus to standardize bleeding endpoint definition and reporting in cardiovascular clinical trials. There are no prospective studies on its prognostic impact. METHODS AND RESULTS We explored the association of BARC-defined bleeding with mortality and compared its prognostic value against two validated bleeding scales: the Thrombolysis in Myocardial Infarction (TIMI) and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) scales. Non-coronary artery bypass graft (CABG)-related bleedings within the PRODIGY trial were prospectively adjudicated by a blinded Clinical Event Committee and analysed according to multiple statistical modelling. At 2 years, bleeding occurred in 143 patients (7.1%) according to BARC Type 2, 3, or 5; in 50 patients (2.5%) according to TIMI minor or major; and in 61 patients (3.1%) according to GUSTO moderate or severe. One hundred sixty-three patients died (8.1%). After multivariable modelling, BARC Type 2, 3, or 5 bleeding was associated with increased 2-year mortality [hazard ratio (HR): 3.77; 95% confidence interval (CI): 2.37-5.98]. Bleeding Academic Research Consortium Type 3 or 5 was associated with an increased mortality rate at 2 years (adjusted HR: 7.72; 95% CI: 4.75-12.54) similar to that provided by TIMI (HR: 7.64, 95% CI: 4.53-12.87) or GUSTO (HR: 7.36, 95% CI: 4.38-12.34) criteria. CONCLUSIONS In a contemporary, all-comer percutaneous coronary intervention trial actionable BARC bleedings were associated with increased risk of mortality with BARC Type 3 or 5 bleedings providing a similar mortality risk to that posed by TIMI or GUSTO scales.
Measuring fiber and its effectiveness in ruminant diets

It appears that ruminants such as cattle and sheep evolved as forage consumers. Plant cell walls, which we measure as fiber, cannot be digested by animals, but must be fermented by microorganisms. Fermentative digestion of fiber is slow and incomplete, and ruminants have developed many attributes that result in efficient digestion. They swallow large particles of forage and selectively retain them in the rumen to allow adequate time for fermentation. They regurgitate and rechew the large particles (rumination) to enhance digestion and allow passage through the digestive tract. During chewing, they produce salivary buffers that help maintain the pH in the rumen. Ideally, roughages should be an integral part of the diet of ruminants to take advantage of their unique digestive capability. However, there are nutritional, operational, and economic reasons for limiting the forage or roughage content in some ruminant rations.
Two Agents Acting as One

We consider two agents, each equipped with a controller. When they achieve a joint goal configuration, their coordination can be measured informationally. We show that the amount of coordination that two agents need to configure in a certain way depends on the amount of information they obtain from their environment. Furthermore the environment imposes a coordination pressure on the agents that depends on the size of the environment. In a second scenario we introduce a shared centralized controller which leads to a synchronisation of the agents’ actions for suboptimal policies. However, in the optimal case this intrinsic coordination vanishes and the shared centralized controller can be split into two individual controllers.
Effective Question Recommendation Based on Multiple Features for Question Answering Communities

We propose a new method of recommending questions to answerers so as to suit the answerers’ knowledge and interests in User-Interactive Question Answering (QA) communities. A question recommender can help answerers select the questions that interest them. This increases the number of answers, which will activate QA communities. An effective question recommender should satisfy the following three requirements: First, its accuracy should be higher than the existing category-based approach; more than 50% of answerers select the questions to answer according a fixed system of categories. Second, it should be able to recommend unanswered questions because more than 2,000 questions are posted every day. Third, it should be able to support even those people who have never answered a question previously, because more than 50% of users in current QA communities have never given any answer. To achieve an effective question recommender, we use question histories as well as the answer histories of each user by combining collaborative filtering schemes and content-base filtering schemes. Experiments on real log data sets of a famous Japanese QA community, Oshiete goo, show that our recommender satisfies the three requirements.
Competition between Sec‐ and TAT‐dependent protein translocation in Escherichia coli

Recently, a new protein translocation pathway, the twin‐arginine translocation (TAT) pathway, has been identified in both bacteria and chloroplasts. To study the possible competition between the TAT‐ and the well‐characterized Sec translocon‐dependent pathways in Escherichia coli, we have fused the TorA TAT‐targeting signal peptide to the Sec‐dependent inner membrane protein leader peptidase (Lep). We find that the soluble, periplasmic P2 domain from Lep is re‐routed by the TorA signal peptide into the TAT pathway. In contrast, the full‐length TorA–Lep fusion protein is not re‐routed into the TAT pathway, suggesting that Sec‐targeting signals in Lep can override TAT‐targeting information in the TorA signal peptide. We also show that the TorA signal peptide can be converted into a Sec‐targeting signal peptide by increasing the hydrophobicity of its h‐region. Thus, beyond the twin‐arginine motif, the overall hydrophobicity of the signal peptide plays an important role in TAT versus Sec targeting. This is consistent with statistical data showing that TAT‐targeting signal peptides in general have less hydrophobic h‐regions than Sec‐targeting signal peptides.
On Policy Interactions Among Nations: When Do Cooperation and Commitment Matter?

This paper offers a framework to study commitment and cooperation issues in games with multiple policymakers. To reconcile some puzzles in the recent literature on the nature of policy interactions among nations, we prove that games characterized by different commitment and cooperation schemes can admit the same equilibrium outcome if certain spillover effects vanish at the common solution of these games. We provide a detailed discussion of these spillovers, showing that, in general, commitment and cooperation are non-trivial issues. Yet, in linear-quadratic models with multiple policymakers commitment and cooperation schemes are shown to become irrelevant under certain assumptions. The framework is sufficiently general to cover a broad range of results from the recent literature on policy interactions as special cases, both within monetary unions and among fully sovereign nations.
The effects of mobile banking application user satisfaction and system usage on bank-customer relationships

This study examines mobile banking (m-banking) application usage in Finland by linking it with customer-bank relationship development. Specifically, we examine how usage is related to relationship commitment, overall satisfaction, intention to recommend the bank and future intentions to remain with the bank. A survey was used to collect data from experienced m-banking application users. In total, 273 valid responses were received. The results support the hypotheses and reveal that user satisfaction with m-banking application usage has a strong positive association with usage of m-banking applications. Usage, in turn, was positively related to all examined bank-customer relationship related variables. The results have both theoretical and practical implications for m-banking usage and its effects on bank-customer relationships.
Intracellular Astrocyte Calcium Waves In Situ Increase the Frequency of Spontaneous AMPA Receptor Currents in CA1 Pyramidal Neurons

Spontaneous neurotransmitter release and activation of group I metabotropic glutamate receptors (mGluRs) each play a role in the plasticity of neuronal synapses. Astrocytes may contribute to short- and long-term synaptic changes by signaling to neurons via these processes. Spontaneous whole-cell AMPA receptor (AMPAR) currents were recorded in CA1 pyramidal cells in situ while evoking Ca2+ increases in the adjacent stratum radiatum astrocytes by uncaging IP3. Whole-cell patch clamp was used to deliver caged IP3 and the Ca2+ indicator dye Oregon green BAPTA-1 to astrocytes. Neurons were patch-clamped and filled with Alexa 568 hydrazide dye to visualize their morphological relationship to the astrocyte. On uncaging of IP3, astrocyte Ca2+ responses reliably propagated as a wave into the very fine distal processes, synchronizing Ca2+ activity within astrocyte microdomains. The intracellular astrocyte Ca2+ wave coincided with a significant increase in the frequency of AMPA spontaneous EPSCs, but with no change in their kinetics. AMPAR current amplitudes were increased as well, but not significantly (p = 0.06). The increased frequency of AMPAR currents was sensitive to the group I mGluR antagonists LY367385 and 2-methyl-6-(phenylethynyl)-pyridine, suggesting that (1) astrocytes released glutamate in response to IP3 uncaging, and (2) glutamate released by astrocytes activated group I mGluRs to facilitate the release of glutamate from excitatory neuronal presynaptic boutons. These results extend previous studies, which have shown astrocyte modulation of neuronal activity in vitro and suggest that astrocyte-to-neuron signaling in intact tissue may contribute to synaptic plasticity.
A novel function for Hedgehog signalling in retinal pigment epithelium differentiation

Sonic hedgehog is involved in eye field separation along the proximodistal axis. We show that Hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. We show that two other Hedgehog proteins, Banded hedgehog and Cephalic hedgehog, related to the mouse Indian hedgehog and Desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surrounding the ciliary marginal zone. By contrast, downstream components of the Hedgehog signalling pathway, Gli2, Gli3 and X-Smoothened, are expressed in this narrow peripheral epithelium. We show that this zone contains cells that are in the proliferative state. This equivalent region in the adult mammalian eye, the pigmented ciliary epithelium, has been identified as a zone in which retinal stem cells reside. These data, combined with double labelling and the use of other retinal pigment epithelium markers, show that the retinal pigment epithelium of tadpole embryos has a molecularly distinct peripheral to central axis. In addition, Gli2, Gli3 and X-Smoothened are also expressed in the neural retina, in the most peripheral region of the ciliary marginal zone, where retinal stem cells are found in Xenopus, suggesting that they are good markers for retinal stem cells. To test the role of the Hedgehog pathway at different stages of retinogenesis, we activated the pathway by injecting a dominant-negative form of PKA or blocking it by treating embryos with cyclopamine. Embryos injected or treated at early stages display clear proximodistal defects in the retina. Interestingly, the main phenotype of embryos treated with cyclopamine at late stages is a severe defect in RPE differentiation. This study thus provides new insights into the role of Hedgehog signalling in the formation of the proximodistal axis of the eye and the differentiation of retinal pigment epithelium.
Regulation of Gene Expression by Cyclic GMP

Abstract— Cyclic GMP, produced in response to nitric oxide and natriuretic peptides, is a key regulator of vascular smooth muscle cell contractility, growth, and differentiation, and is implicated in opposing the pathophysiology of hypertension, cardiac hypertrophy, atherosclerosis, and vascular injury/restenosis. cGMP regulates gene expression both positively and negatively at transcriptional as well as at posttranscriptional levels. cGMP-regulated transcription factors include the cAMP-response element binding protein CREB, the serum response factor SRF, and the nuclear factor of activated T cells NF/AT. cGMP can regulate CREB directly, through phosphorylation by cGMP-dependent protein kinase, or indirectly, through activation of mitogen-activated protein kinase pathways; regulation of SRF and NF/AT by cGMP is indirect, through modulation of RhoA and calcineurin signaling, respectively. Downregulation of the RNA-binding protein HuR by cGMP leads to destabilization of guanylate cyclase mRNA, but this posttranscriptional mechanism may affect many more cGMP-regulated genes. In this review, we discuss the role of cGMP-regulated gene expression in (patho)physiological processes most relevant to the cardiovascular system, such as regulation of vascular tone, cardiac hypertrophy, phenotypic modulation of vascular smooth muscle cells, and regulation of cell proliferation and apoptosis.
Chymase and angiotensin converting enzyme activities in a hamster model of glaucoma filtering surgery

Purpose. Two pathways for the formation of angiotensin II (Ang II) in local tissues are known to exist, one involving angiotensin-converting enzyme (ACE), and the other in which chymase plays a role. It has been shown that chymase activity is present in monkey, dog, and hamster eyes. Because chymase activates various cytokines by increasing Ang II formation, thereby promoting the production of extracellular matrix, the role of Ang II in wound healing has attracted much interest. In this work, we created sclerocorneal wounds in hamster eyes and measured the levels of ACE and chymase activities in the eye during the wound healing process. Methods. Sclerocorneal wounds were made at 6 locations on the corneal limbus of one eye in each of 36 hamsters. Using the contralateral eyes as controls, we measured levels of chymase and ACE activities in the overall eye at 3, 7, and 21 days postoperatively. Histopathological evaluations of the sclerocorneal wounds in the treated eyes were also carried out for samples stained with toluidine blue. Results. Chymase activity in the treated eyes tended to be higher than that in the control at 21 days. ACE activity in the treated eyes was significantly higher than that in the control at 3, 7, and 21 days postoperatively. Histopathological examination revealed increased mast cells in the subconjunctival tissue and around the tunnel opening in the sclerocornea. Conclusions. These findings show that not only ACE but also chymase contributes to the formation of Ang II in the healing of sclerocorneal wounds in hamster eyes. This leads to the suggestion that ACE inhibitors or chymase inhibitors could potentially inhibit scarring in glaucoma filtering surgery.
Capturing the Interaction between Aggregation and Text Planning in Two Generation Systems

In natural language generation, different generation tasks often interact with each other in a complex way. We think that how to resolve the complex interactions inside and between tasks is more important to the generation of a coherent text than how to model each individual factor. This paper focuses on the interaction between aggregation and text planning, and tries to explore what preferences exist among the features considered by the two tasks. The preferences are implemented in two generation systems, namely ILEX-TS and a text planner using a Genetic Algorithm. The evaluation emphasises the second implementation and shows that capturing these preferences properly can lead to coherent text.
Inclusion of aggregate angularity, texture, and form in estimating dynamic modulus of asphalt mixes

The present study was undertaken to develop a model that utilizes aggregate shape parameters (i.e. angularity, texture and form) in estimating the dynamic modulus of asphalt mixes. Dynamic modulus tests were conducted on 20 different mixes comprised of different aggregate sources, sizes, asphalt binder, and air void levels. The coarse and fine aggregates were recovered from each mix, and their shape parameters were measured using an automated aggregate image measurement system (AIMS). A nonlinear regression model was developed to estimate the dynamic modulus of the mix in terms of its aggregate gradation, aggregate shape parameters, viscosity of asphalt binder, and volumetric properties. The correlation coefficient (R 2) for the developed model was found to be 0.95 and 0.92 on logarithmic and arithmetic scales, respectively, with a mean average relative error (MARE) of 21.9%. The performance of this model was compared with the widely accepted Witczak model that does not use the shape parameters of the aggregates. The MARE for the Witczak model was estimated significantly higher than the developed model. Results show that the dynamic modulus of the mix increases with an increase in the angularity and texture of aggregates and that the inclusion of shape parameters can enhance the prediction capability of a model.
Angiotensin analogs: the influence of sarcosine substituted in position 1.

Sarcosine (N-methylglycine), substituted for aspartic acid in position one, enhanced the antagonistic activity of [8-isoleucine]angiotensin II in vivo . To test whether this enhancement was the result of increased binding or decreased degradation, [1-sarcosine] angiotensin II was synthesized and its activity was compared with angiotensin II. [1-Sarcosine]angiotensin II had 10 times the contractile activity of angiotensin II when tested on isolated rabbit aorta. The analog [1-sarcosine, 8-isoleucine]angiotensin II blocked the contractile response of both angiotensin II and [1-sarcosine]angiotensin II. The pA 2 values obtained were 9.3 and 8.9, respectively, which are not significantly different. When kidney leucine aminopeptidase was incubated with angiotensin II and [1-sarcosine]angiotensin II, both substrates were hydrolyzed to the same degree. However, a crude preparation of angiotensinase A, prepared from human plasma, degraded angiotensin II but not [1-sarcosine]angiotensin II. Experiments with Dowex-50 indicate that [1-sarcosine] is more tightly bound than angiotensin II. With [1-sarcosine, 8-isoleucine] as an antagonist, similar pA 2 values were obtained for angiotensin II and [1-sarcosine] angiotensin II. From this it was concluded that both agonists act on the same receptor site. In cross-tachyphylaxis experiments, tissues made tachyphylactic to [1-sarcosine] angiotensin II did not respond to angiotensin. Thus the increased agonistic activity of [1-sarcosine]angiotensin II on isolated rabbit aorta may be due to a decreased rate of enzymatic breakdown as well as to an increased binding affinity. Therefore, the increased in vivo potency of the [1-sarcosine]angiotensin analogs may be due to their increased in vivo half-life.