Miracle-dz/UniFAR-FTUs huggingface dataset:
To Be or Not to Be …Human? Theorizing the Role of Human-Like Competencies in Conversational Artificial Intelligence Agents

ABSTRACT Driven by the need to provide continuous, timely, and efficient customer service, firms are constantly experimenting with emerging technological solutions. In recent times firms have shown an increased interest in designing and implementing artificial intelligence (AI)-based interactional technologies, such as conversational AI agents and chatbots, that obviate the need for having human service agents for the provision of customer service. However, the business impact of conversational AI is contingent on customers using and adequately engaging with these tools. This engagement depends, in turn, on conversational AI’s similarity, or likeness to the human beings it is intended to replace. Businesses therefore need to understand what human-like characteristics and competencies should be embedded in customer-facing conversational AI agents to facilitate smooth user interaction. This focus on “human-likeness” for facilitating user engagement in the case of conversational AI agents is in sharp contrast to most prior information systems (IS) user engagement research, which is predicated on the “instrumental value” of information technology (IT). Grounding our work in the individual human competency and media naturalness literatures, we theorize the key role of human-like interactional competencies in conversational AI agents—specifically, cognitive, relational, and emotional competencies—in facilitating user engagement. We also hypothesize the mediating role of user trust in these relationships. Following a sequential mixed methods approach, we use a quantitative two-wave, survey-based study to test our model. We then examine the results in light of findings from qualitative follow-up interviews with a sampled set of conversational AI users. Together, the results offer a nuanced understanding of desirable human-like competencies in conversational AI agents and the salient role of user trust in fostering user engagement with them. We also discuss the implications of our study for research and practice.
A modification of TERRA RNA is required for telomere maintenance and is a 1 therapeutic target for ALT positive Neuroblastoma 2

34 Telomerase-negative tumors can maintain telomere length by alternative lengthening of 35 telomeres (ALT) but the mechanism behind ALT is poorly understood. Aggressive 36 Neuroblastoma (NB), in particular, relapsed tumors are positive for ALT (ALT+) which 37 suggests that better dissection of the ALT mechanism could provide novel therapeutic 38 opportunities. TERRA long non-coding RNA (lncRNA) which is derived from the telomere 39 ends is localized to telomeres in R-loop dependent manner and is essential for telomere 40 maintenance. In the present study, we provide evidence that RNA modification at the N6 41 position of internal adenosine (m6A) in TERRA RNA by methyltransferase METTL3 is 42 essential for telomere maintenance in ALT+ cells and that loss of TERRA m6A/METTL3 leads 43 to telomere damage. We observed that R-loop enriched TERRA is abundantly m6A modified 44 and m6A mediated recruitment of hnRNPA2B1 to TERRA RNA is essential for R-loop 45 formation. Our data suggest that m6A drives telomere targeting of TERRA via R-loop and this 46 m6A mediated R-loop formation could be a widespread mechanism utilized by other 47 chromatin-interacting lncRNAs. Furthermore, treating ALT+ NB cells with METTL3 inhibitor 48 leads to compromised telomere targeting of TERRA and accumulation of DNA damage over 49 telomere, suggesting METTL3 inhibition could be a therapeutic opportunity for ALT+ NB. 50 5
Ribosomal s6 kinase (RSK) is a mediator of aquaporin 2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib

Vasopressin (VP) activates PKA, resulting in phosphorylation and membrane accumulation of aquaporin-2 (AQP2). Epidermal growth factor receptor (EGFR) inhibition with erlotinib also induces AQP2 membrane trafficking with a phosphorylation pattern similar to VP, but without increasing PKA activity. Here, we identify the ribosomal s6 kinase (RSK) as the final mediator phosphorylating AQP2 in this novel, erlotinib-induced pathway. We found that RSK was expressed in medullary principal cells in rat kidneys. RSK inhibition with BI-D1870 or siRNA blocked erlotinib-induced AQP2 S256 phosphorylation and membrane trafficking. CRISPR-generated RSK knockout cells failed to show increased S256 phosphorylation in response to erlotinib. Like PKA, RSK was able to phosphorylate AQP2 S256 in vitro. Stimulation of PDK1, a known activator of RSK, caused AQP2 S256 phosphorylation and membrane accumulation similar to erlotinib and VP. We conclude that RSK is the terminal kinase phosphorylating AQP2 at S256 upon EGFR inhibition by erlotinib.
B vitamin quantification in lentil seed tissues using ultra-performance liquid chromatography-selected reaction monitoring mass spectrometry

Lentils are an important source of macronutrients, including protein and fiber, as well as micronutrients such as vitamins and minerals, especially in a plant-based diet. Quantifying variation among genotypes, including wild germplasm, is desirable to better understand the genetics of differential B vitamins content for breeding of this trait and to understand their potential contributions to the lentil crop. We analyzed thirty-four cultivated and three wild genotypes for vitamins B1, B2, B3, B5, B6, B7, and B9. Seeds were assayed whole, and separated into cotyledons only, or seed coats only. Variation for all B vitamins was observed across the cultivars. Overall, cotyledons had higher concentrations of B1 and B3, while seed coats had higher concentrations of B2, B5, B6, and B9. Wild accessions had the highest concentrations of vitamin B9 and were also among the highest for vitamin B2. These results demonstrate the differential distribution of B vitamins across seed tissues and lentil genotypes, and that dehulling prior to consumption results in the loss of B vitamins otherwise available in whole seeds. They also indicate there is genetic variability which could be used to increase B-vitamin levels in lentil via breeding.
Regulation of nuclear transcription by mitochondrial RNA in endothelial cells

Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome. The caRNAs reported to date are transcribed from the nuclear genome. Here, leveraging a recently developed assay for detection of caRNAs and their genomic association, we report that mitochondrial RNAs (mtRNAs) are attached to the nuclear genome and constitute a subset of caRNA, thus termed mt-caRNA. In four human cell types analyzed, mt-caRNAs preferentially attach to promoter regions. In human endothelial cells (ECs), the level of mt-caRNA–promoter attachment changes in response to environmental stress that mimics diabetes. Suppression of a non-coding mt-caRNA in ECs attenuates stress-induced nascent RNA transcription from the nuclear genome, including that of critical genes regulating cell adhesion, and abolishes stress-induced monocyte adhesion, a hallmark of dysfunctional ECs. Finally, we report increased nuclear localization of multiple mtRNAs in the ECs of human diabetic donors, suggesting many mtRNA translocate to the nucleus in a cell stress and disease-dependent manner. These data nominate mt-caRNAs as messenger molecules responsible for mitochondrial–nuclear communication and connect the immediate product of mitochondrial transcription with the transcriptional regulation of the nuclear genome.
May the force be with you: The role of hyper-mechanostability of the bone sialoprotein binding protein during early stages of Staphylococci infections

The bone sialoprotein-binding protein (Bbp) is a mechanoactive MSCRAMM protein expressed on the surface of Staphylococcus aureus that mediates adherence of the bacterium to fibrinogen-α (Fgα), a component of the bone and dentine extracellular matrix of the host cell. Mechanoactive proteins like Bbp have key roles in several physiological and pathological processes. Particularly, the Bbp:Fgα interaction is important in the formation of biofilms, an important virulence factor of pathogenic bacteria. Here, we investigated the mechanostability of the Bbp:Fgα complex using in silico single-molecule force spectroscopy (SMFS), in an approach that combines results from all-atom and coarse-grained steered molecular dynamics (SMD) simulations. Our results show that Bbp is the most mechanostable MSCRAMM investigated thus far, reaching rupture forces beyond the 2 nN range in typical experimental SMFS pulling rates. Our results show that high force-loads, which are common during initial stages of bacterial infection, stabilize the interconnection between the protein’s amino acids, making the protein more “rigid”. Our results offer new insights that are crucial on the development of novel anti-adhesion strategies.
Ocean currents drive the worldwide colonization of the most widespread marine plant, eelgrass (Zostera marina)

Currents are unique drivers of oceanic phylogeography and so determine the distribution of marine coastal species, along with past glaciations and sea level changes. Here, we reconstruct the worldwide colonization history of eelgrass (Zostera marina L.), the most widely distributed marine flowering plant or seagrass from its origin in the Northwest Pacific, based on nuclear and chloroplast genomes. We identified two divergent Pacific clades with evidence for admixture along the East Pacific coast. Multiple west to east (trans-Pacific) colonization events support the key role of the North Pacific Current. Time-calibrated nuclear and chloroplast phylogenies yielded concordant estimates of the arrival of Z. marina in the Atlantic through the Canadian Arctic, suggesting that eelgrass-based ecosystems, hotspots of biodiversity and carbon sequestration, have only been present since ∼208 Kya (thousand years ago). Mediterranean populations were founded ∼53 Kya while extant distributions along western and eastern Atlantic shores coincide with the end of the Last Glacial Maximum (∼20 Kya). The recent colonization and 5-to 7-fold lower genomic diversity of Atlantic compared to the Pacific populations raises concern and opportunity about how Atlantic eelgrass might respond to rapidly warming coastal oceans.
Amplitude and phase control of a coherent superposition of degenerate states. I. Theory

We present the theory for a technique, based on multistate variants of the stimulated Raman adiabatic passage STIRAP process, that allows efficient and robust preparation of a preselected superposition of two or three degenerate states magnetic sublevels of an atom and the measurement of their relative amplitudes and phases. Because the preparation utilizes adiabatic passage it is robust against small fluctuations of the Rabi frequencies and temporal shapes of the coupling fields. We here describe and, in the following companion paper we demonstrate, an approach to the experimental characterization of the superposition state, i.e., the measurement of the relative phases and the ratios of amplitudes of the components. That technique, termed phase-to-population mapping, is applicable to the characterization of a stream of identically prepared atoms and is based on laser-induced fluorescence after the atoms have undergone optical pumping cycles induced by an additional laser. The optical pumping process maps the phase into populations of a subset of levels by means of a filtering laser field, and is robust against variations in the intensity and detuning of that field. We describe four linkage patterns appropriate to the creation of superpositions of two or three degenerate states of angular momentum J=2, starting from J=0. We offer an interpretation, from three different perspectives, of the subsequent characterization procedure.
Leptospermum extract (QV0) suppresses pleural mesothelioma tumor growth in vitro and in vivo by mitochondrial dysfunction associated apoptosis

Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender® (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender® daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender®. Significantly enhanced tumor apoptosis was observed in the Defender®-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender® were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.
Comprehensive Evaluation of Rapamycin’s Specificity as an mTOR Inhibitor

Rapamycin is a macrolide antibiotic that functions as an immunosuppressive and anti-cancer agent, and displays robust anti-ageing effects in multiple organisms including humans. Importantly, rapamycin analogs (rapalogs) are of clinical importance against certain cancer types and neurodevelopmental diseases. Although rapamycin is widely perceived as an allosteric inhibitor of mTOR (mechanistic target of rapamycin), the master regulator of cellular and organismal physiology, its specificity has not been thoroughly evaluated so far. In fact, previous studies in cells and in mice suggested that rapamycin may be also acting independently from mTOR to influence various cellular functions. Here, we generated a gene-edited cell line, that expresses a rapamycin-resistant mTOR mutant (mTORRR), and assessed the effects of rapamycin treatment on the transcriptome and proteome of control or mTORRR-expressing cells. Our data reveal a striking specificity of rapamycin towards mTOR, demonstrated by virtually no changes in mRNA or protein levels in rapamycin-treated mTORRR cells, even following prolonged drug treatment. Overall, this study provides the first comprehensive and conclusive assessment of rapamycin’s specificity, with important potential implications for ageing research and human therapeutics.
Evaluation of the safety, immunogenicity and efficacy of a new live-attenuated lumpy skin disease vaccine in India

ABSTRACT Lumpy skin disease (LSD) was reported for the first time in India in 2019 and since then, it has become endemic. Since a homologous (LSD-virus based) vaccine was not available in the country, goatpox virus (GPV)-based heterologous vaccine was authorized for mass immunization to induce protection against LSD in cattle. This study describes the evaluation of safety, immunogenicity and efficacy of a new live-attenuated LSD vaccine developed by using an Indian field strain, isolated in 2019 from cattle. The virus was attenuated by continuous passage (P = 50) in Vero cells. The vaccine (50th LSDV passage in Vero cells, named as Lumpi-ProVacInd) did not induce any local or systemic reaction upon its experimental inoculation in calves (n = 10). At day 30 post-vaccination (pv), the vaccinated animals were shown to develop antibody- and cell-mediated immune responses and exhibited complete protection upon virulent LSDV challenge. A minimum Neethling response (0.018% animals; 5 out of 26,940 animals) of the vaccine was observed in the field trials conducted in 26,940 animals. There was no significant reduction in the milk yield in lactating animals (n = 10108), besides there was no abortion or any other reproductive disorder in the pregnant animals (n = 2889). Sero-conversion was observed in 85.18% animals in the field by day 30 pv.
Multiplex profiling of developmental enhancers with quantitative, single-cell expression reporters

The inability to scalably and precisely measure the activity of developmental enhancers in multicellular systems is a bottleneck in genomics. Here, we develop a dual RNA cassette that decouples the detection and quantification tasks inherent to multiplex single-cell reporter assays, resulting in accurate measurement of reporter expression over a >10,000-fold range of activity with a precision approaching the limit set by Poisson counting noise. Together with RNA barcode circularization, these single-cell quantitative expression reporters (scQers) provide high-contrast readouts analogous to classic in situ assays, but entirely from sequencing. Screening >200 enhancers in a multicellular in vitro model of early mammalian development, we identified numerous autonomous and cell-type-specific elements, including constituents of the Sox2 control region exclusively active in pluripotent cells, endoderm-specific enhancers, including near Foxa2 and Gata4, and a compact pleiotropic enhancer at the Lamc1 locus. scQers can be mobilized in developmental systems to quantitatively characterize native, perturbed, and synthetic enhancers at scale, with high sensitivity and at single-cell resolution.
Monomer and dimer structures of cytochrome bo3 ubiquinol oxidase from Escherichia coli

The E. coli cytochrome bo3 ubiquinol oxidase is a four-subunit heme-copper oxidase that serves as a proton pump in the E. coli aerobic respiratory chain. Despite many mechanistic studies on this protein, it is unclear whether this ubiquinol oxidase functions as a monomer, or as a dimer in a manner similar to its eukaryotic counterparts – the mitochondrial electron transport complexes. In this study, we determined the monomeric and dimeric structures of the E. coli cytochrome bo3 ubiquinol oxidase reconstituted in amphipol by cryogenic electron microscopy single particle reconstruction (cryo-EM SPR) to a resolution of 3.15 Å and 3.46 Å, respectively. We have discovered that the protein can form a dimer in C2 symmetry, with the dimerization interface maintained by interactions between the subunit II of one monomer and the subunit IV of the other monomer. Moreover, the dimerization does not induce significant structural changes in each monomer, except the movement of a loop in subunit IV (residues 67–74).
A Multi-Step Approach in Translating Natural Language into Logical Formula

Translating often has the meaning of converting from one human language to another. However, in a broader sense, it means transforming a message from one form of communication to another form. Logic is an important form of communication and the ability to translate natural language into logic is important in many different ﬁelds, in which logical reasoning and logical arguments are used. In the legal ﬁeld, for example, judges must often reason from facts and arguments presented in natural language to logical conclusions. In this paper, toward the goal of support for this kind of reasoning with machines, we propose a method for translating natural language into logical representations using a combination of deep learning methods. Our approach contributes methodologies and insights to the development of computational methods for converting natural language into logical representations.
Sequential and Two-Stage Fixed-Width Confidence Interval Estimation in Response-Adaptive Designs

Abstract Let be a sequence of consistent estimators of a parameter Δ in some response-adaptive design, where the data are not independent and identically distributed. A fixed-width confidence interval estimation involves determining a positive integer ν such that, for a given d (> 0) and α ∈ (0, 1), the coverage probability of the random interval for Δ is at least (1 − α). In this article, we first investigate such confidence intervals for a general structure of response-adaptive allocation design, for two-treatment allocation in clinical trials, in a complete sequential setup. We consider some examples in this context. We then carry out this exercise for a Stein-type two-stage procedure, where the parameters are estimated based on the first-stage data, which are then used for the allocation in the second stage. Fixed-width confidence intervals are obtained in this context. The procedures are evaluated by simulations. We then illustrate the proposed methodology using some real data set.
Reasoning with Legal Cases: A Hybrid ADF-ML Approach

Reasoning with legal cases has long been modelled using symbolic meth-ods. In recent years, the increased availability of legal data together with improved machine learning techniques has led to an explosion of interest in data-driven meth-ods being applied to the problem of predicting outcomes of legal cases. Although encouraging results have been reported, they are unable to justify the outcomes produced in satisfactory legal terms and do not exploit the structure inherent within legal domains; in particular, with respect to the issues and factors relevant to the decision. In this paper we present the technical foundations of a novel hybrid approach to reasoning with legal cases, using Abstract Dialectical Frameworks (ADFs) in conjunction with hierarchical BERT. ADFs are used to represent the legal knowledge of a domain in a structured way to enable justifications and improve performance. The machine learning is targeted at the task of factor ascription; once factors present in a case are ascribed, the outcome follows from reasoning over the ADF. To realise this hybrid approach, we present a new hybrid system to enable factor ascription, envisioned for use in legal domains, such as the European Convention on Human Rights that is used frequently in modelling experiments.
Nano-antivirals: A comprehensive review

Nanoparticles can be used as inhibitory agents against various microorganisms, including bacteria, algae, archaea, fungi, and a huge class of viruses. The mechanism of action includes inhibiting the function of the cell membrane/stopping the synthesis of the cell membrane, disturbing the transduction of energy, producing toxic reactive oxygen species (ROS), and inhibiting or reducing RNA and DNA production. Various nanomaterials, including different metallic, silicon, and carbon-based nanomaterials and nanoarchitectures, have been successfully used against different viruses. Recent research strongly agrees that these nanoarchitecture-based virucidal materials (nano-antivirals) have shown activity in the solid state. Therefore, they are very useful in the development of several products, such as fabric and high-touch surfaces. This review thoroughly and critically identifies recently developed nano-antivirals and their products, nano-antiviral deposition methods on various substrates, and possible mechanisms of action. By considering the commercial viability of nano-antivirals, recommendations are made to develop scalable and sustainable nano-antiviral products with contact-killing properties. Graphical Abstract