Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Functional MicroRNA-126s Repress a Novel Target Gene p21-Activated Kinase 1 to Regulate Vascular Integrity in Zebrafish

Rationale: MicroRNAs (miRNAs) are key regulators of vascular development and diseases. The function and underlying mechanism of endothelial miRNAs have not been fully defined. Objective: To investigate the role of endothelial miR-126 in zebrafish vascular development. Methods and Results: Two homologs of miR-126, miR-126a (namely miR-126 in previous literature) and miR-126b, with only 1 nucleotide difference in their mature sequences, were identified in zebrafish genome. In vitro analysis showed that both precursors could sufficiently produce mature functional miRNAs. Expression analyses by Northern blot and quantitative RT-PCR showed that both miR-126s accumulated significantly 12 hours after fertilization and were specifically expressed in endothelial cells of zebrafish. Inhibition of miR-126a or miR-126b with specific morpholinos caused cranial hemorrhage, and simultaneous inhibition of both miR-126s resulted in a pronounced hemorrhage in higher percentage of embryos. Bioinformatics prediction showed that the targets of miR-126a/b partially overlapped but essentially differed. p21-activated kinase1 (pak1) was identified as a novel target of miR-126a/b, and pak1 3′ untranslated region was differently regulated by these 2 miRNAs. Quantitative RT-PCR, in situ hybridization, and Western blot analyses showed that the level of pak1 was reduced when miR-126a/b were overexpressed. Notably, pak1 expression in endothelial cells was increased when miR-126a/b were knocked down. Furthermore, overexpression of the active form of human pak1 caused cranial hemorrhage, and knockdown pak1 effectively rescued the hemorrhage caused by inhibiting miR-126a/b. Conclusions: Two functional endothelial cell–specific miRNAs, miR-126a and miR-126b, synergistically regulate zebrafish vascular integrity, and pak1 is a critical target of miR-126a/b in vascular development.
Determination of cytocompatibility and osteogenesis properties of in situ forming collagen-based scaffolds loaded with bone synthesizing drug for bone tissue engineering

ABSTRACT Bone tissue engineering using in situ forming 3D scaffolds can be an alternative to surgically treated scaffolds. This work aimed to develop in situ forming scaffolds using poly (lactic-co-glycolic acid) and a bone synthesizing drug (risedronate) with or without the porogenic agent (collagen). Hybrid scaffolds were formed through solvent-induced phase inversion technique and were morphologically evaluated using scanning electron microscopy (SEM). The effect of scaffolds on Saos-2 cell line viability using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test besides their effect on cell growth using fluorescence microscope was assessed. Furthermore, alkaline phosphatase (ALP) activity as well as Ca2+ deposition on the scaffolds was evaluated. SEM images revealed the porous structure for collagen-based scaffolds. Saos-2 cell proliferation was significantly enhanced with risedronate-loaded scaffolds compared to those lacking the drug. Porous collagen-based scaffolds were more favorable for both the cell growth and the promotion of ALP activity. Furthermore, collagen-based scaffolds promoted the Ca2+ deposition compared to their counterparts without collagen. Such results suggest that collagen-based scaffolds offer excellent biocompatibility for bone regeneration, where this biocompatible nature of scaffold leads to the proliferation of cells that lead to the deposition of mineral on the scaffold. Such in situ forming 3D scaffolds provide a promising noninvasive approach for bone tissue engineering. GRAPHICAL ABSTRACT
A design method for “whole-hand” human-computer interaction

A disciplined investigation of “whole-hand interfaces (often glove based, currently) and their appropriate use for the control of complex task domains is embodied by the design method for whole-hand input. This is a series of procedures—including a common basis for the description, design, and evaluation of whole-hand input, together with an accompanying taxonomy—that enumerates key issues and points for consideration in the development of whole-hand input. The method helps designers focus on task requirements, isolate problem areas, and choose appropriate whole-hand input strategies for their specified tasks. Several experiments were conducted to validate and demonstrate the use of the design method. The results of the experiments are summarized and discussed.
Nonvolatile Switching in Graphene Field-Effect Devices

The absence of a band gap in graphene restricts its straightforward application as a channel material in field-effect transistors. In this letter, we report on a new approach to engineer a band gap in graphene field-effect devices (FEDs) by controlled structural modification of the graphene channel itself. The conductance in the FEDs is switched between a conductive ldquoon-staterdquo and an insulating ldquooff-staterdquo with more than six orders of magnitude difference in conductance. Above a critical value of an electric field applied to the FED gate under certain environmental conditions, a chemical modification takes place to form insulating graphene derivatives. The effect can be reversed by electrical fields of opposite polarity or short current pulses to recover the initial state. These reversible switches could potentially be applied to nonvolatile memories and novel neuromorphic processing concepts.
Decolourization of Distillery Waste Water - Role of Microbes and their Potential Oxidative Enzymes (Review)

Detoxification and decolourization of industrial wastewater and distillery effluent is acquiring its importance in terms of environmental and aesthetic point of view. The characteristic of dark brown appearance of distillery wastewater is mainly due to the high molecular weight organic compounds called melanoidin. Studies dealing with pure culture of bacteria, fungi, and yeast and their oxidative enzymes (peroxidase, laccase) in decolourization of industrial wastewater to develop a better understanding of the phenomenon of microbial decolourization. This review paper presents an overview of the characteristics of the distillery wastewater in terms of its toxicity and as a pollutant and biological treatment using microbial enzymes.
Multi-Platform Compatible Software for Analysis of Polymer Bending Mechanics

Cytoskeletal polymers play a fundamental role in the responses of cells to both external and internal stresses. Quantitative knowledge of the mechanical properties of those polymers is essential for developing predictive models of cell mechanics and mechano-sensing. Linear cytoskeletal polymers, such as actin filaments and microtubules, can grow to cellular length scales at which they behave as semiflexible polymers that undergo thermally-driven shape deformations. Bending deformations are often modeled using the wormlike chain model. A quantitative metric of a polymer's resistance to bending is the persistence length, the fundamental parameter of that model. A polymer's bending persistence length is extracted from its shape as visualized using various imaging techniques. However, the analysis methodologies required for determining the persistence length are often not readily within reach of most biological researchers or educators. Motivated by that limitation, we developed user-friendly, multi-platform compatible software to determine the bending persistence length from images of surface-adsorbed or freely fluctuating polymers. Three different types of analysis are available (cosine correlation, end-to-end and bending-mode analyses), allowing for rigorous cross-checking of analysis results. The software is freely available and we provide sample data of adsorbed and fluctuating filaments and expected analysis results for educational and tutorial purposes.
High prevalence of osteoarthritis 14 years after an anterior cruciate ligament tear in male soccer players: a study of radiographic and patient relevant outcomes

Objective: To identify the consequences of an anterior cruciate ligament (ACL) tear in a cohort of male soccer players 14 years after the initial injury with respect to radiographic knee osteoarthritis and patient relevant outcomes. Methods: Of 219 male soccer players with an ACL injury in 1986, 205 (94%) were available for follow up after 14 years; 75% of the cohort (154/205) answered mailed questionnaires (KOOS, SF-36, and Lysholm knee scoring scale) and 122 of these consented to weight bearing radiographs. Results: Radiographic changes were found in 95 (78%) of the injured knees, while more advanced changes, comparable with Kellgren-Lawrence grade 2 or higher, were seen in 50 (41%). In the uninjured knees more advanced changes, comparable with Kellgren-Lawrence grade 2 or higher, were seen in five knees (4%). No differences were seen between surgically and conservatively treated players. The patient relevant outcome was affected and did not differ between subjects with and without radiographic changes. Eighty per cent reported reduced activity level. Conclusions: A high prevalence of radiographic knee osteoarthritis was seen in male soccer players 14 years after an ACL disruption. The injury and the osteoarthritis, irrespective of the treatment provided to these patients, often result in knee related symptoms that severely affect the knee related quality of life by middle age.
Free-energy-based reinforcement learning in a partially observable environment

Free-energy-based reinforcement learning (FERL) can han- dle Markov decision processes (MDPs) with high-dimensional state spaces by approximating the state-action value function with the negative equi- librium free energy of a restricted Boltzmann machine (RBM). In this study, we extend the FERL framework to handle partially observable MDPs (POMDPs) by incorporating a recurrent neural network that learns a memory representation sufficient for predicting future observations and rewards. We demonstrate that the proposed method successfully solves POMDPs with high-dimensional observations without any prior knowl- edge of the environmental hidden states and dynamics. After learning, task structures are implicitly represented in the distributed activation patterns of hidden nodes of the RBM.
Prolegomena for a Logic of Trust and Reputation

Reputation and trust are useful instruments in multi-agent systems to evaluate agent behaviour. Most of the works on trust and reputation adopt a quantitative representation of these concepts. Trust and reputation are commonly simplified to a numerical representation loosing important properties of these concepts. The aim of this paper is therefore to provide a qualitative formal analysis of trust and reputation on the basis of cognitive primitives. The proposed formalization is strongly inspired by Castelfranchi and Falcone’s model of social trust. The concepts of trust and reputation are built from the same bricks (goal, capability, power, and willingness) but in a different scope (individual belief vs. collective belief).
Standardized volume rendering for magnetic resonance angiography measurements in the abdominal aorta

Purpose: To compare three methods for standardizing volume rendering technique (VRT) protocols by studying aortic diameter measurements in magnetic resonance angiography (MRA) datasets. Material and Methods: Datasets from 20 patients previously examined with gadolinium-enhanced MRA and with digital subtraction angiography (DSA) for abdominal aortic aneurysm were retrospectively evaluated by three independent readers. The MRA datasets were viewed using VRT with three different standardized transfer functions: the percentile method (Pc-VRT), the maximum-likelihood method (ML-VRT), and the partial range histogram method (PRH-VRT). The aortic diameters obtained with these three methods were compared with freely chosen VRT parameters (F-VRT) and with maximum intensity projection (MIP) concerning inter-reader variability and agreement with the reference method DSA. Results: F-VRT parameters and PRH-VRT gave significantly higher diameter values than DSA, whereas Pc-VRT gave significantly lower values than DSA. The highest interobserver variability was found for F-VRT parameters and MIP, and the lowest for Pc-VRT and PRH-VRT. All standardized VRT methods were significantly superior to both MIP and F-VRT in this respect. The agreement with DSA was best for PRH-VRT, which was the only method with a mean error below 1 mm and which also had the narrowest limits of agreement (95% of cases between 2.1 mm below and 3.1 mm above DSA). Conclusion: All the standardized VRT methods compare favorably with MIP and VRT with freely selected parameters as regards interobserver variability. The partial range histogram method, although systematically overestimating vessel diameters, gives results closest to those of DSA.
Generating Domain-Specific Visual Language Tools from Abstract Visual Specifications

Domain-specific visual languages support high-level modeling for a wide range of application domains. However, building tools to support such languages is very challenging. We describe a set of key conceptual requirements for such tools and our approach to addressing these requirements, a set of visual language-based metatools. These support definition of metamodels, visual notations, views, modeling behaviors, design critics, and model transformations and provide a platform to realize target visual modeling tools. Extensions support collaborative work, human-centric tool interaction, and multiplatform deployment. We illustrate application of the metatoolset on tools developed with our approach. We describe tool developer and cognitive evaluations of our platform and our exemplar tools, and summarize key future research directions.
Terminal complement complex C5b‐9‐treated human monocyte‐derived dendritic cells undergo maturation and induce Th1 polarization

Sublytic C5b‐9 has been described as a pro‐inflammatory mediator that triggers cell activation rather than inducing cell death. Dendritic cells (DC) play a critical role in controlling antigen‐specific immune responses. Although DC maturation induced by various stimuli has been well characterized, the role of C5b‐9 in DC function has not been described. In this report, we use in vitro assembled functional C5b‐9 based on purified distal complement protein to show that DC maturation is promoted by sublytic C5b‐9. This was demonstrated by up‐regulation of CD83, HLA‐antigens and costimulatory molecules, including CD80, D86, B7‐H1, B7‐H3, B7‐H4 and BTLA. In addition, secretion of cytokines such as interleukin (IL)‐12 and tumor necrosis factor‐α was increased while the capacity for antigen uptake (FITC‐Dextran and Lucifer Yellow) was reduced in C5b‐9‐treated DC. Mixed lymphocyte reactions indicated that C5b‐9‐activated DC acted as stimulators that significantly promoted CD4+ T cell activation and elicited production of cytokines, including interferon‐γ and IL‐2. Interestingly, C5b‐9‐treated DC also orient CD4+CD45RA+ naïve T cells toward Th1 polarization. Our results are the first to report that DC are potential immunoregulatory targets of C5b‐9, suggesting that C5b‐9 bridges innate and acquired immunity by inducing DC maturation.
Bead-Based Multiplex Genotyping of 58 Cutaneous Human Papillomavirus Types

ABSTRACT Cutaneous human papillomaviruses (HPVs) are a heterogeneous, nonmonophyletic assembly, comprising about 50 characterized types and at least 133 isolates putatively representing new types. Their natural history of infection and potential association with nonmelanoma skin cancer are not well understood. Several PCR systems have been developed that amplify a broad spectrum of cutaneous HPVs. However, amplicon genotyping by sequencing or reverse line blot assays are complex and not well suited for high-throughput analyses. We developed a novel multiplex cutaneous papillomavirus genotyping (McPG) assay for 38 defined and 20 putative cutaneous HPVs of the beta, gamma, mu, and nu genera. Viral DNA was amplified by the use of a modified single-tube nested “hanging-droplet” FAP PCR. The amplifiable papillomavirus (PV) spectrum was enlarged by the use of 9 outer and 13 inner primers. Biotinylated PCR products were hybridized to type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads and analyzed using Luminex technology. Analytical sensitivity was analyzed for 38 defined HPVs and was ≤100 genome copies for all types. Integrated β-globin primers allow for simultaneous DNA quality control. McPG is characterized by high reproducibility (κ= 0.84, 95% confidence interval = 0.79 to 0.88), good concordance with the original nested FAP PCR, followed by sequencing (70.2% complete or partial agreement) when 322 skin biopsy DNA samples were analyzed, and improved ability to detect multiple infections (on average 2.5 HPV types per HPV-positive sample compared to 1.7 HPV types with nested FAP-PCR). In conclusion, McPG is a powerful tool for genotyping multiple cutaneous HPVs in a high-throughput format and is thus suitable for large-scale epidemiological studies.
Cost-effectiveness of zinc as adjunct therapy for acute childhood diarrhoea in developing countries.

OBJECTIVE To analyse the incremental costs, effects and cost-effectiveness of zinc used as adjunct therapy to standard treatment of acute childhood diarrhoea, including dysentery, and to reassess the cost-effectiveness of standard case management with oral rehydration salt (ORS). METHODS A decision tree was used to model expected clinical outcomes and expected costs under four alternative treatment strategies. The best available epidemiological, clinical and economic evidence was used in the calculations, and the United Republic of Tanzania was the reference setting. Probabilistic cost-effectiveness analysis was performed using a Monte-Carlo simulation technique and the potential impacts of uncertainty in single parameters were explored in one-way sensitivity analyses. FINDINGS ORS was found to be less cost-effective than previously thought. The use of zinc as adjunct therapy significantly improved the cost-effectiveness of standard management of diarrhoea for dysenteric as well as non-dysenteric illness. The results were particularly sensitive to mortality rates in non-dysenteric diarrhoea, but the alternative interventions can be defined as highly cost-effective even in pessimistic scenarios. CONCLUSION There is sufficient evidence to recommend the inclusion of zinc into standard case management of both dysenteric and non-dysenteric acute diarrhoea.A direct transfer of our findings from the United Republic of Tanzania to other settings is not justified, but there are no indications of large geographical differences in the efficacy of zinc. It is therefore plausible that our findings are also applicable to other developing countries.
CdtA, CdtB, and CdtC Form a Tripartite Complex That Is Required for Cytolethal Distending Toxin Activity

ABSTRACT Campylobacter jejuni encodes a cytolethal distending toxin (CDT) that causes cells to arrest in the G2/M transition phase of the cell cycle. Highly related toxins are also produced by other important bacterial pathogens. CDT activity requires the function of three genes: cdtA, cdtB, andcdtC. Recent studies have established that CdtB is the active subunit of CDT, exerting its effect as a nuclease that damages the DNA and triggers cell cycle arrest. Microinjection of CdtB into target cells led to G2/M arrest and cytoplasmic distention, in a manner indistinguishable from that caused by CDT treatment. Despite this progress, nothing is known about the composition of the CDT holotoxin or the function of CdtA and CdtC. We show here that, when applied individually, purified CdtA, CdtB, or CdtC does not exhibit toxic activity. In contrast, CdtA, CdtB, and CdtC when combined, interact with one another to form an active tripartite holotoxin that exhibits full cellular toxicity. CdtA has a domain that shares similarity with the B chain of ricin-related toxins. We therefore proposed that CDT is a tripartite toxin composed of CdtB as the enzymatically active subunit and of CdtA and CdtC as the heterodimeric B subunit required for the delivery of CdtB.
Development and Validation of a Rapid and Simple LC-MS/MS Method for Quantification of Vemurafenib in Human Plasma: Application to a Human Pharmacokinetic Study

Background: Vemurafenib (Zelboraf) is a new tyrosine kinase inhibitor that selectively targets activated BRAF V600E gene and is indicated for the treatment of advanced BRAF mutation-positive melanoma. We developed a simple method for vemurafenib quantification using liquid chromatography–tandem mass spectrometry. A stability study of vemurafenib in human plasma was also performed. Methods: 13C6-vemurafenib was used as the internal standard. A single-step protein precipitation was used for plasma sample preparation. Chromatography was performed on an Acquity UPLC system (Waters) with chromatographic separation by the use of an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7-mm particle size; Waters). Quantification was performed using the monitoring of multiple reactions of following transitions: m/z 488.2 → 381.0 for vemurafenib and m/z 494.2 → 387.0 for internal standard. Results: This method was linear over the range from 1.0 to 100.0 mcg/mL. The lower limit of quantification was 0.1 mcg/mL for vemurafenib in plasma. Vemurafenib remained stable for 1 month at all levels tested, when stored indifferently at room temperature (20°C), at +4°C, or at −20°C. This method was used successfully to perform a plasma pharmacokinetic study of vemurafenib in a patient after oral administration at a steady state. Conclusions: This liquid chromatography–tandem mass spectrometry method for vemurafenib quantification in human plasma is simple, rapid, specific, sensitive, accurate, precise, and reliable.
Locomotion of inchworm-inspired robot made of smart soft composite (SSC)

A soft-bodied robot made of smart soft composite with inchworm-inspired locomotion capable of both two-way linear and turning movement has been proposed, developed, and tested. The robot was divided into three functional parts based on the different functions of the inchworm: the body, the back foot, and the front foot. Shape memory alloy wires were embedded longitudinally in a soft polymer to imitate the longitudinal muscle fibers that control the abdominal contractions of the inchworm during locomotion. Each foot of the robot has three segments with different friction coefficients to implement the anchor and sliding movement. Then, utilizing actuation patterns between the body and feet based on the looping gait, the robot achieves a biomimetic inchworm gait. Experiments were conducted to evaluate the robot’s locomotive performance for both linear locomotion and turning movement. Results show that the proposed robot’s stride length was nearly one third of its body length, with a maximum linear speed of 3.6 mm s−1, a linear locomotion efficiency of 96.4%, a maximum turning capability of 4.3 degrees per stride, and a turning locomotion efficiency of 39.7%.