Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear Factor of Activated T Cells c1 Induces Osteoclast-associated Receptor Gene Expression during Tumor Necrosis Factor-related Activation-induced Cytokine-mediated Osteoclastogenesis*

Osteoclast differentiation from hematopoietic precursors is controlled by the tumor necrosis factor family member tumor necrosis factor-related activation-induced cytokine (TRANCE) via induction of various transcription factors, including nuclear factor of activated T cells (NFAT) c1. During osteoclast differentiation, NFATc1 is further activated via calcium signaling when costimulatory receptors expressed on osteoclast precursors, such as osteoclast-associated receptor (OSCAR), are stimulated. Here we show that NFATc1 expression precedes that of OSCAR during TRANCE-mediated osteoclastogenesis and that inhibition of NFATc1 by cyclosporin A abolishes TRANCE-induced OSCAR expression and subsequent osteoclast differentiation. Moreover, we show that the 1.0-kb promoter region of the OSCAR gene contains three potential NFATc1-binding sites. Induction of an OSCAR promoter-luciferase reporter is significantly increased when transiently transfected into 293T cells in combination with NFATc1 expression plasmid. Deletion and site-directed mutant constructs confirmed that NFATc1-binding sites are both functional and NFATc1-specific. Furthermore, NFATc1 synergistically activates an OSCAR reporter construct together with microphthalmia transcription factor and PU.1, transcription factors previously shown to be critical for osteoclast differentiation. In addition, a plasmid expressing constitutively active MAP kinase kinase 6 enhances the transactivation activity of NFATc1/microphthalmia transcription factor/PU.1 on the OSCAR promoter. Taken together, our results indicate that NFATc1 is an important transcription factor in the induction of OSCAR during osteoclastogenesis. Elucidation of NFATc1 as a transcription factor for OSCAR expression implies the presence of a positive feedback circuit of TRANCE-induced activation of NFATc1, involving NFATc1-mediated OSCAR expression and its subsequent activation of NFATc1, necessary for efficient differentiation of osteoclasts.
Role of Ubiquitin-Mediated Degradation System in Plant Biology

Ubiquitin-mediated proteasomal degradation is an important mechanism to control protein load in the cells. Ubiquitin binds to a protein on lysine residue and usually promotes its degradation through 26S proteasome system. Abnormal proteins and regulators of many processes, are targeted for degradation by the ubiquitin-proteasome system. It allows cells to maintain the response to cellular level signals and altered environmental conditions. The ubiquitin-mediated proteasomal degradation system plays a key role in the plant biology, including abiotic stress, immunity, and hormonal signaling by interfering with key components of these pathways. The involvement of the ubiquitin system in many vital processes led scientists to explore more about the ubiquitin machinery and most importantly its targets. In this review, we have summarized recent discoveries of the plant ubiquitin system and its involvement in critical processes of plant biology.
The use of virtual reality for creating unusual environmental stimulation to motivate students to explore creative ideas

This paper discusses the roles of simulation in creativity education and how to apply immersive virtual environments to enhance students’ learning experiences in university, through the provision of interactive simulations. An empirical study of a simulated virtual reality was carried out in order to investigate the effectiveness of providing virtual simulation to enrich students’ learning experiences. The researchers found that virtual reality can possibly enhance students’ learning experiences by providing them with a heuristic and highly interactive simulated virtual environment. Being explorative and fun are essential parts of students’ learning experiences in virtual reality. This paper suggests that educators create stimulated virtual learning environments, for example game-like environments, to help students develop positive learning behaviors in the learning process.
Negotiation of Antibiotic Treatment in Medical Consultations: A Corpus Based Study

Doctor-patient conversation is considered a contributing factor to antibiotic overprescription. Some language practices have been identified as parent pressuring doctors for prescribing; other practices are considered as likely to engender parent resistance to non-antibiotic treatment recommendations. In social science studies, approaches such as conversation analysis have been applied to identify those language practices. Current research for dialogue systems offer an alternative approach. Past research proved that corpusbased approaches have been effectively used for research involving modeling dialogue acts and sequential relations. In this proposal, we propose a corpus-based study of doctor-patient conversations of antibiotic treatment negotiation in pediatric consultations. Based on findings from conversation analysis studies, we use a computational linguistic approach to assist annotating and modeling of doctor-patient language practices, and analyzing their influence on antibiotic over-prescribing.
CARDIO : A Methodology for Troubleshooting Reachability Issues in a Campus Network

— The Internet today, aims to work as a single cohesive backbone, satisfying the connectivity requirements of all the individual entities while giving them sufficient room to implement their own control and policy regulations. This independence given to the individual entities at times leads to a set of conflicting regulations resulting in unreachability problems. While most of the existing research has rightly blamed BGP policy configurations and tried to offer solutions for the same, a significant part of unreachability issues, like those occurring within a domain (intra-AS), have not yet been fully addressed. Reachability problems such as these might occur due to several factors (like firewall and router misconfigurations) which are independent of Inter-AS routing policies. Such problems are especially applicable to campus networks given their size and dynamism. In this paper we present CARDIO – CAmpus-wide Reachability DIagnostic Operations – a work which leverages the Campus-wide network Performance monitoring and Recovery (CPR) project at Georgia Tech and provides a methodology to troubleshoot reachability issues within a network. We focus mainly on firewall misconfigurations and present a three phase analysis using our active probing techniques to locate the faulty firewall(s). Our work will assist Network Operators in unreachability scenarios by informing them about the exact nature and location of the misconfiguration(s) causing the unreachability.
Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries

Background:Viral load and CD4% are often not available in resource-limited settings for monitoring children's responses to antiretroviral therapy (ART). We aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months following initiation of ART in children, and to assess the association between poor weight gain and subsequent responses to ART. Design:Analysis of data from HIV-infected children younger than 10 years old from African and Asian clinics participating in the International epidemiologic Databases to Evaluate AIDS. Methods:The generalized additive model for location, scale, and shape was used to construct normative percentile curves for weight gain at 6, 12, 18, and 24 months following ART initiation. Cox proportional models were used to assess the association between lower percentiles (< 50th) of weight gain distribution at the different time points and subsequent death, virological suppression, and virological failure. Results:Among 7173 children from five regions of the world, 45% were underweight at baseline. Weight gain below the 50th percentile at 6, 12, 18, and 24 months of ART was associated with increased risk of death, independent of baseline characteristics. Poor weight gain was not associated with increased hazards of virological suppression or virological failure. Conclusion:Monitoring weight gain on ART using age-specific and sex-specific normative curves specifically developed for HIV-infected children on ART is a simple, rapid, sustainable tool that can aid in the identification of children who are at increased risk of death in the first year of ART.
NoVA: Non-Visual Access to the Digital Library: The use of Digital Library Interfaces by Blind and Visually Impaired People. Annotated Bibliography January 2001 Annotated bibliography of documents relevant to the NoVA

Abels, E. G. , M. D. White, et al. (1999). “A user-based design process for Web sites. ” OCLC Systems and Services, 15(1). Reports on the second of a two-part project to identify and implement user-based criteria in web sites. A user based design process has been adopted which gathers user input at three stages of the four stage process. The four stages comprise information gathering, development, test and evaluation, implementation.
Characterisation of the biological activity of xenin-25 degradation fragment peptides.

Xenin-25, a peptide co-secreted with the incretin hormone glucose-dependent insulinotropic polypeptide (GIP), possesses promising therapeutic actions for obesity-diabetes. However, native xenin-25 is rapidly degraded by serum enzymes to yield the truncated metabolites: xenin 9-25, xenin 11-25, xenin 14-25 and xenin 18-25. This study has examined the biological activities of these fragment peptides. In vitro studies using BRIN-BD11 cells demonstrated that native xenin-25 and xenin 18-25 possessed significant (P<0.05 to P<0.001) insulin-releasing actions at 5.6 and 16.7 mM glucose, respectively, but not at 1.1 mM glucose. In addition, xenin 18-25 significantly (P<0.05) potentiated the insulin-releasing action of the stable GIP mimetic (D-Ala²)GIP. In contrast, xenin 9-25, xenin 11-25 and xenin 14-25 displayed neither insulinotropic nor GIP-potentiating actions. Moreover, xenin 9-25, xenin 11-25 and xenin 14-25 significantly (P<0.05 to P<0.001) inhibited xenin-25 (10⁻⁶ M)-induced insulin release in vitro. I.p. administration of xenin-based peptides in combination with glucose to high fat-fed mice did not significantly affect the glycaemic excursion or glucose-induced insulin release compared with controls. However, when combined with (D-Ala²)GIP, all xenin peptides significantly (P<0.01 to P<0.001) reduced the overall glycaemic excursion, albeit to a similar extent as (D-Ala²)GIP alone. Xenin-25 and xenin 18-25 also imparted a potential synergistic effect on (D-Ala²)GIP-induced insulin release in high fat-fed mice. All xenin-based peptides lacked significant satiety effects in normal mice. These data demonstrate that the C-terminally derived fragment peptide of xenin-25, xenin 18-25, exhibits significant biological actions that could have therapeutic utility for obesity-diabetes.
Image Retrieval of Semantic Similarity Measure based on Probability-weighted

For multi-level semantic structure, the asymmetry of similarity between semantic concepts, as well as the different correlation of semantics between the children nodes and father node, this dissertation proposed a novel similarity calculation method of image semantic based on the probabilistic weighting. This method combines the image feature mapping the visual characteristics of the underlying semantic with the domain ontology description to build a tree-like hierarchical semantic model. According to what the posterior probability and conditional probability were gained by Bayesian network learning, and further for those semantic similarity who are based on semantic distance took the weighted processing so as to get the final similarity of image semantic. Moreover, taking the medical image semantics as the experiment object in weighted method can improve the retrieval performance compared with the non-weighted similarity calculation method.
Peer Grading in a Course on Algorithms and Data Structures: Machine Learning Algorithms do not Improve over Simple Baselines

Peer grading is the process of students reviewing each others' work, such as homework submissions, and has lately become a popular mechanism used in massive open online courses (MOOCs). Intrigued by this idea, we used it in a course on algorithms and data structures at the University of Hamburg. Throughout the whole semester, students repeatedly handed in submissions to exercises, which were then evaluated both by teaching assistants and by a peer grading mechanism, yielding a large dataset of teacher and peer grades. We applied different statistical and machine learning methods to aggregate the peer grades in order to come up with accurate final grades for the submissions (supervised and unsupervised, methods based on numeric scores and ordinal rankings). Surprisingly, none of them improves over the baseline of using the mean peer grade as the final grade. We discuss a number of possible explanations for these results and present a thorough analysis of the generated dataset.
Quaternary-vector-list for totally computational treating of switching algebraic tasks

In this paper an advanced form of vector-list called quaternary-vector-list QVL is introduced. QVL is the computational representation of Boolean function or switching function respectively and enables the total computational treatment of switching algebraic tasks. It has advantages in terms of memory usage, simplicity, clarity and also in computation time. Furthermore, important operations as complement, intersection and union are demonstrated for the advanced QVL-arithmetic. By the use of QVL the computational utilization of the extended basis function forms of switching function will be granted. By QVL the already available ternary-vector-list TVL is supplemented and substituted.
Wing-pitching mechanism of hovering Ruby-throated hummingbirds

In hovering flight, hummingbirds reverse the angle of attack of their wings through pitch reversal in order to generate aerodynamic lift during both downstroke and upstroke. In addition, the wings may pitch during translation to further enhance lift production. It is not yet clear whether these pitching motions are caused by the wing inertia or actuated through the musculoskeletal system. Here we perform a computational analysis of the pitching dynamics by incorporating the realistic wing kinematics to determine the inertial effects. The aerodynamic effect is also included using the pressure data from a previous three-dimensional computational fluid dynamics simulation of a hovering hummingbird. The results show that like many insects, pitch reversal of the hummingbird is, to a large degree, caused by the wing inertia. However, actuation power input at the root is needed in the beginning of pronation to initiate a fast pitch reversal and also in mid-downstroke to enable a nose-up pitching motion for lift enhancement. The muscles on the wing may not necessarily be activated for pitching of the distal section. Finally, power analysis of the flapping motion shows that there is no requirement for substantial elastic energy storage or energy absorption at the shoulder joint.
Invited commentary: lubricating the rusty wheel, new insights into iron oxidizing bacteria through comparative genomics

Iron is the fourth most abundant mineral in the Earth's lithosphere (Weber et al., 2006; Emerson et al., 2013), where it is present at a mean concentration of 5% (Hedrich et al., 2011). Iron can exist in two oxidation stages as ferrous (Fe(II)) and ferric (Fe(III)) iron and some bacteria and archaea have evolved to use iron as an obligate or facultative energy source, giving them the name “Iron Oxidizing Bacteria” (FeOB) and “Iron Oxidizing Archaea” (FeOA), respectively (Figure ​(Figure1). 1). The oxidation from Fe(II) to Fe(III) can occur under both oxic and anoxic conditions within a pH range between 0.5 to 8.4 (Edwards et al., 2000; Weber et al., 2006; Hedrich et al., 2011). Here, the microbially mediated oxidation of iron under (micro-)aerobic circum-neutral conditions will be discussed.
Depressive-Like Effects of the κ-Opioid Receptor Agonist Salvinorin A on Behavior and Neurochemistry in Rats

Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of κ-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A (SalvA), a potent and highly selective κ-opioid agonist, would produce depressive-like effects in the forced swim test (FST) and intracranial self-stimulation (ICSS) test, which are behavioral models often used to study depression in rats. We extracted, isolated, and purified SalvA from Salvia divinorum plant leaves and examined its effects on behavior in the FST and ICSS test across a range of doses (0.125–2.0 mg/kg) after systemic (intraperitoneal) administration. SalvA dose dependently increased immobility in the FST, an effect opposite to that of standard antidepressant drugs. Doses of SalvA that produced these effects in the FST did not affect locomotor activity in an open field. Furthermore, SalvA dose dependently elevated ICSS thresholds, an effect similar to that produced by treatments that cause depressive symptoms in humans. At a dose that caused the depressive-like effects in both the FST and ICSS assays, SalvA decreased extracellular concentrations of dopamine (DA) within the nucleus accumbens (NAc), a critical component of brain reward circuitry, without affecting extracellular concentrations of serotonin (5-HT). These data provide additional support for the hypothesis that stimulation of brain κ-opioid receptors triggers depressive-like signs in rats and raise the possibility that decreases in extracellular concentrations of DA within the NAc contribute to these effects.
Oscillatory Neurocomputers with Dynamic Connectivity

Our study of thalamo-cortical systems suggests a new architecture for a neurocomputer that c of oscillators having different frequencies and that are connected weakly via a common medium by an external input. Even though such oscillators are all interconnected homogeneously, the e input imposes a dynamic connectivity. We use Kuramoto’s model to illustrate the idea and to that such a neurocomputer has oscillatory associative properties. Then we discuss a general ca advantage of such a neurocomputer is that it can be built using voltage controlled oscillators, o oscillators, lasers, microelectromechanical systems, Josephson junctions, macromolecules, or os of other kinds. (Provisional patent 60 y108,353) [S0031-9007(99)08813-4]
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1

Methylation Mediation Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characterized in plants, involves the removal of the 5mC base, and its replacement by C, via a DNA repair mechanism. Kriaucionis and Heintz (p. 929, published online 16 April) now show that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin. Tahiliani et al. (p. 930, published online 16 April) find that the protein TET1 is capable of converting 5mC into 5hmC both in vitro and in vivo. 5-Hydroxymethylcytosine is also present in embryonic stem cells, and levels of 5hmC and TET1 show correlated variation during cell differentiation. Methylated C bases, an important epigenetic mark in genomic DNA, can be enzymically converted to 5-hydroxymethylcytosine. DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference–mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.
Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion

The homotypic fusion of endoplasmic reticulum (ER) membranes is mediated by atlastin (ATL), which consists of an N-terminal cytosolic domain containing a GTPase module and a three-helix bundle followed by two transmembrane (TM) segments and a C-terminal tail (CT). Fusion depends on a GTP hydrolysis-induced conformational change in the cytosolic domain. Here, we show that the CT and TM segments also are required for efficient fusion and provide insight into their mechanistic roles. The essential feature of the CT is a conserved amphipathic helix. A synthetic peptide corresponding to the helix, but not to unrelated amphipathic helices, can act in trans to restore the fusion activity of tailless ATL. The CT promotes vesicle fusion by interacting directly with and perturbing the lipid bilayer without causing significant lysis. The TM segments do not serve as mere membrane anchors for the cytosolic domain but rather mediate the formation of ATL oligomers. Point mutations in either the C-terminal helix or the TMs impair ATL’s ability to generate and maintain ER morphology in vivo. Our results suggest that protein–lipid and protein–protein interactions within the membrane cooperate with the conformational change of the cytosolic domain to achieve homotypic ER membrane fusion.
Synaptic Activation of Presynaptic Glutamate Transporter Currents in Nerve Terminals

Glutamate uptake by high-affinity transporters is responsible for limiting the activation of postsynaptic receptors and maintaining low levels of ambient glutamate. The reuptake process generates membrane currents, which can be activated by synaptically released glutamate in glial cells and some postsynaptic neurons. However, less is known about presynaptic transporter currents because the small size of synaptic boutons precludes direct recordings. Here, we have recorded from two giant nerve terminals: bipolar cell synaptic terminals in goldfish retina and the calyx of Held in rat auditory brainstem. Exocytosis was evoked by brief depolarizations and measured as an increase in membrane capacitance. In isolated bipolar cell terminals, exocytosis was associated with an anion (NO3- or Cl-) current. The current peaked 2.8 msec after the start of the depolarization and decayed with a mean time constant of 8.5 msec. It was inhibited by the nontransportable glutamate transporter antagonist sc-threo-β-benzyloxyaspartate (TBOA) but was insensitive to the GLT1/EAAT2 subtype-selective antagonist dihydrokainate and was affected by extracellular pH buffering. A TBOA-sensitive anion current was also evoked by application of exogenous glutamate to bipolar cell terminals. The large single-channel conductance, derived from noise analysis, and previous immunolocalization studies suggest that synaptically released glutamate activates EAAT5-type transporters in bipolar cell terminals. In contrast, neither exocytosis nor exogenous glutamate evoked a transporter current in the calyx of Held. Glutamate transporter currents with rapid kinetics are therefore identified and characterized in bipolar cell terminals, providing a valuable system for investigating the function and modulation of presynaptic glutamate transporters.