A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2017; you can also visit the original URL.
The file type is
Lecture Notes in Computer Science
Interactive learning environments have been built to support various audiences from preschool to university students. However, it is not yet known how to bring the great promise of tutorial dialogue systems, which engage students in rich natural language, to bear for young learners such as those in grades K-5. This doctoral consortium paper presents our goal of developing a dialogue system in the form of an interactive spoken dialogue agent with embedded assessment to support K-5 students indoi:10.1007/978-3-319-19773-9_136 fatcat:qegp3fgm6zaw3gmfamehgfwcpa
more »... rning computer science. It discusses the challenges faced so far and how we plan to solve those challenges to bring individualized dialogue systems technology to young learners.
This paper presents a solution to count all moving vehicles in a target region. This is a large-scale counting that cannot be easily solved without a global view. However, there is no single force that can provide such a global view. To achieve an accurate result without either double-or miscounting, the local counting at each checkpoint is synchronized in our wireless communication by using the information carried by vehicles along the traffic flow. Our analytical and experimental resultsdoi:10.1109/icpp.2014.61 dblp:conf/icpp/0001STJ14 fatcat:3doscpxzqnaeperhwommz5cgrm
more »... trate the correctness of the proposed scheme in both closed and open road systems -even when the wireless signal is affected by many factors. In this way, we provide an essential support for the resource management in VANETs. In this paper, we synchronize the counting in the entire target area under the "everyone" model, in which each site will apply the same generic process in a fully-distributed manner. The impact of the inconsistence among local views can be mitigated. The counting converges with the ultimate result at the global view level in a cost-effective way -without any infrastructure support at the global view. The contribution of our infrastructure-less counting is fourfold. 1) We first implement the counting scheme in an "everyone" model at each checkpoint in a fully-distributed manner, where only short range surveillance and communication are available. 2) We prove that, by precisely controlling each checkpoint, active or not, in our synchronization, neither mis-nor double-counting will occur. 3) Some extension work is provided so that our approach will still be effective when the overtake, lossy communication, and odd traffic patterns are considered. We also extend our work from the closed system to the open road system. Moreover, we provide an efficient method to gather those local views from the entire system and then to constitute the global result. 4) We develop a simulation. Its results verify the correctness of our approach and show its scalability as a practical solution for the large-scale problem. The remainder of this paper is organized as follows: Section 2 introduces the target problem and related work. Section 3 provides some preliminary information. Section 4 presents our approach, extended from the closed system under a simple road model to the open system under the realistic road model. Its correctness will be analyzed and then be verified in Section 5 with our experimental results. Lastly, Section 6 concludes this paper and provides ideas for future research.
Ferroportin (FPN) is the only known cellular iron exporter in mammalian cells and plays a critical role in the maintenance of both cellular and systemic iron balance. During iron deprivation, the translation of FPN is repressed by iron regulatory proteins (IRPs), which bind to the 59 untranslated region (UTR), to reduce iron export and preserve cellular iron. Here, we report a novel iron-responsive mechanism for the post-transcriptional regulation of FPN, mediated by miR-485-3p, which isdoi:10.1371/journal.pgen.1003408 pmid:23593016 pmcid:PMC3616902 fatcat:y63cx4equ5eh7psvom6wq2rhyy
more »... during iron deficiency and represses FPN expression by directly targeting the FPN 39UTR. The overexpression of miR-485-3p represses FPN expression and leads to increased cellular ferritin levels, consistent with increased cellular iron. Conversely, both inhibition of miR-485-3p activity and mutation of the miR-485-3p target sites on the FPN 39UTR are able to relieve FPN repression and lead to decreased cellular iron levels. Together, these findings support a model that includes both IRPs and microRNAs as iron-responsive post-transcriptional regulators of FPN. The involvement of microRNA in the iron-responsive regulation of FPN offers additional stability and fine-tuning of iron homeostasis within different cellular contexts. MiR-485-3p-mediated repression of FPN may also offer a novel potential therapeutic mechanism for circumventing hepcidin-resistant mechanisms responsible for some iron overload diseases.
Elementary computer science has gained increasing attention within the computer science education research community. We have only recently begun to explore the many unanswered questions about how young students learn computer science, how they interact with each other, and how their skill levels and backgrounds vary. One set of unanswered questions focuses on gender equality for young computer science learners. This paper examines how the gender composition of collaborative groups indoi:10.1145/2839509.2844605 dblp:conf/sigcse/TsanBL16 fatcat:z2jvtwyihrehxfwmfdxfn76n44
more »... computer science relates to student achievement. We report on data collected from an in-school 5th grade computer science elective offered over four quarters in 2014-2015. We found a significant difference in the quality of artifacts produced by learner groups depending upon their gender composition, with groups of all female students performing significantly lower than other groups. Our analyses suggest important factors that are influential as these learners begin to solve computer science problems. This new evidence of gender disparities in computer science achievement as young as ten years of age highlights the importance of future study of these factors in order to provide effective, equitable computer science education to learners of all ages.
Human erythrocytes are terminally differentiated, anucleate cells long thought to lack RNAs. However, previous studies have shown the persistence of many small-sized RNAs in erythrocytes. To comprehensively define the erythrocyte transcriptome, we used high-throughput sequencing to identify both short (18-24 nt) and long (>200 nt) RNAs in mature erythrocytes. Results: Analysis of the short RNA transcriptome with miRDeep identified 287 known and 72 putative novel microRNAs. Unexpectedly, we alsodoi:10.1186/s12864-015-2156-2 pmid:26573221 pmcid:PMC4647483 fatcat:7uxatmihijcppkd26t3nyw5nje
more »... uncover an extensive repertoire of long erythrocyte RNAs that encode many proteins critical for erythrocyte differentiation and function. Additionally, the erythrocyte long RNA transcriptome is significantly enriched in the erythroid progenitor transcriptome. Joint analysis of both short and long RNAs identified several loci with co-expression of both microRNAs and long RNAs spanning microRNA precursor regions. Within the miR-144/451 locus previously implicated in erythroid development, we observed unique co-expression of several primate-specific noncoding RNAs, including a lncRNA, and miR-4732-5p/-3p. We show that miR-4732-3p targets both SMAD2 and SMAD4, two critical components of the TGF-β pathway implicated in erythropoiesis. Furthermore, miR-4732-3p represses SMAD2/4-dependent TGF-β signaling, thereby promoting cell proliferation during erythroid differentiation. Conclusions: Our study presents the most extensive profiling of erythrocyte RNAs to date, and describes primate-specific interactions between the key modulator miR-4732-3p and TGF-β signaling during human erythropoiesis.
Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-derived 2)-like 2), an oxidative stress regulator. We found that activation of NRF2 with sulforaphane (SFN) in erythroid progenitors significantly increased the expression of NRF2 targets HMOX1, NQO1, and HBG1 (subunit of fetal hemoglobin) in adoi:10.1371/journal.pone.0152895 pmid:27071063 pmcid:PMC4829228 fatcat:rzkjzr5mjrfxbf7ub25iikefq4
more »... e-dependent manner. Therefore, we hypothesized that NRF2 activation with SFN may offer therapeutic benefits for SCD patients by restoring oxidative capacity and increasing fetal hemoglobin concentration. To test this hypothesis, we performed a Phase 1, open-label, dose-escalation study of SFN, contained in a broccoli sprout homogenate (BSH) that naturally contains SFN, in adults with SCD. The primary and secondary study endpoints were safety and physiological response to NRF2 activation, respectively. We found that BSH was well tolerated, and the few adverse events that occurred during the trial were not likely related to BSH consumption. We observed an increase in the mean relative whole blood mRNA levels for the NRF2 target HMOX1 (p = 0.02) on the last day of BSH treatment, compared to pre-treatment. We also observed a trend toward increased mean relative mRNA levels of the NRF2 target HBG1 (p = 0.10) from baseline to end of treatment, but without significant changes in HbF protein. We conclude that BSH, in the provided doses, is safe in stable SCD patients and may induce changes in gene expression levels. We therefore propose investigation of more potent NRF2 inducers, which may elicit more robust physiological changes and offer clinical benefits to SCD patients.
Erythropoietin (EPO) and its cell surface receptor (EPOR) are essential for erythropoiesis; can modulate non-erythroid target tissues; and have been reported to affect the progression of certain cancers. Basic studies of EPOR expression and trafficking, however, have been hindered by low-level EPOR occurrence, and the limited specificity of anti-EPOR antibodies. Consequently, these aspects of EPOR biology are not well defined, nor are actions of polycythemia-associated mutated EPOR alleles.doi:10.1371/journal.pone.0029064 pmid:22253704 pmcid:PMC3257245 fatcat:32un3oa4czd4fc4mx6yajvxa3u
more »... g novel rabbit monoclonal antibodies to intracellular, PY-activated and extracellular EPOR domains, the following properties of the endogenous hEPOR in erythroid progenitors first are unambiguously defined. 1) High-Mr EPOR forms become obviously expressed only when EPO is limited. 2) EPOR-68K plus -70K species sequentially accumulate, and EPOR-70K comprises an apparent cell surface EPOR population. 3) Brefeldin A, N-glycanase and associated analyses point to EPOR-68K as a core-glycosylated intracellular EPOR pool (of modest size). 4) In contrast to recent reports, EPOR inward trafficking is shown (in UT7epo cells, and primary proerythroblasts) to be sharply ligand-dependent. Beyond this, when Cterminal truncated hEPOR-T mutant alleles as harbored by polycythemia patients are co-expressed with the wild-type EPOR in EPO-dependent erythroid progenitors, several specific events become altered. First, EPOR-T alleles are persistently activated upon EPO-challenge, yet are also subject to apparent turn-over (to low-Mr EPOR products). Furthermore, during exponential cell growth EPOR-T species become both over-represented, and hyper-activated. Interestingly, EPOR-T expression also results in an EPO dose-dependent loss of endogenous wild-type EPOR's (and, therefore, a squelching of EPOR C-terminal-mediated negative feedback effects). New knowledge concerning regulated EPOR expression and trafficking therefore is provided, together with new insight into mechanisms via which mutated EPOR-T polycythemia alleles dysregulate the erythron. Notably, specific new tools also are characterized for studies of EPOR expression, activation, action and metabolism. Citation: Singh S, Verma R, Pradeep A, Leu K, Mortensen RB, et al. (2012) Dynamic Ligand Modulation of EPO Receptor Pools, and Dysregulation by Polycythemia-Associated EPOR Alleles. PLoS ONE 7(1): e29064.
We investigate how to improve new physics detection strategies exploiting variational autoencoders and normalizing flows for anomaly detection at the Large Hadron Collider. As a working example, we consider the DarkMachines challenge dataset. We show how different design choices (e.g., event representations, anomaly score definitions, network architectures) affect the result on specific benchmark new physics models. Once a baseline is established, we discuss how to improve the anomaly detectionarXiv:2110.08508v3 fatcat:4wynpqwt6jbu5mt2upff55xm24
more »... accuracy by exploiting normalizing flow layers in the latent space of the variational autoencoder.
The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin. Background Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biological pathways that may underlie these events. Methods Aspirin was administered, followed by whole-blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1) (n ¼ 50) and 2 validation cohorts of healthy volunteers (HV2) (n ¼ 53) anddoi:10.1016/j.jacc.2013.05.073 pmid:23831034 pmcid:PMC3786046 fatcat:vwwjum4hfnaqbeh27m35v7i4gq
more »... outpatient cardiology patients (OPC) (n ¼ 25). Platelet function was assessed using the platelet function score (PFS) in HV1 and HV2 and the VerifyNow Aspirin Test (Accumetrics, Inc., San Diego, California) in OPC. Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for associations with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death or MI in 2 patient cohorts (n ¼ 587 total) from RNA samples collected at cardiac catheterization. Results A set of 60 coexpressed genes named the "aspirin response signature" (ARS) was associated with PFS in HV1 (r ¼ À0.31, p ¼ 0.03), HV2 (r ¼ À0.34, Bonferroni p ¼ 0.03), and OPC (p ¼ 0.046). Corresponding proteins for the 17 ARS genes were identified in the platelet proteome, of which 6 were associated with PFS. The ARS was associated with death or MI in both patient cohorts (odds ratio: 1.2 [p ¼ 0.01]; hazard ratio: 1.5 [p ¼ 0.001]), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index ¼ 31% to 37%, p 0.0002) was improved by including the ARS or 1 of its genes, ITGA2B. Conclusions RNA profiles of platelet-specific genes are novel biomarkers for identifying patients who do not respond adequately to aspirin and who are at risk for death or MI. (J Am Coll Cardiol 2013;62:1267-76) ª
Journal of Virology
ABSTRACTIn August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipelinedoi:10.1128/jvi.02418-15 pmid:26656685 pmcid:PMC4733988 fatcat:origbadzhzar3kpgurjlb27p3a
more »... or EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 outbreak. With these data in hand, we performed phylogenetic analyses of complete genome and VP1 capsid protein sequences. Notably, we observed considerable genetic diversity among EV-D68 isolates in Kansas City, manifest as phylogenetically distinct lineages, indicative of multiple introductions of this virus into the city. In addition, we identified an intersubclade recombination event within EV-D68, the first recombinant in this virus reported to date. Finally, we found no significant association between EV-D68 genetic variation, either lineages or individual mutations, and a variety of demographic and clinical variables, suggesting that host factors likely play a major role in determining disease severity. Overall, our study revealed the complex pattern of viral evolution within a single geographic locality during a single outbreak, which has implications for the design of effective intervention and prevention strategies.IMPORTANCEUntil recently, EV-D68 was considered to be an uncommon human pathogen, associated with mild respiratory illness. However, in 2014 EV-D68 was responsible for more than 1,000 disease cases in North America, including severe respiratory illness in children and acute flaccid myelitis, raising concerns about its potential impact on public health. Despite the emergence of EV-D68, a lack of full-length genome sequences means that little is known about the molecular evolution of this virus within a single geographic locality during a single outbreak. Here, we doubled the number of publicly available complete genome sequences of EV-D68 by performing high-throughput next-generation sequencing, characterized the evolutionary history of this outbreak in detail, identified a recombination event, and investigated whether there was any correlation between the demographic and clinical characteristics of the patients and the viral variant that infected them. Overall, these results will help inform the design of intervention strategies for EV-D68.
Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell-cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation ofdoi:10.1091/mbc.e07-04-0309 pmid:17699589 pmcid:PMC2043540 fatcat:g5aknbx4ifb6fiewzud2vgmwzi
more »... ell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. This article was published online ahead of print in MBC in Press
When the J-domain of the heat shock protein DnaJB1 is fused to the catalytic (C) subunit of cAMP-dependent protein kinase (PKA), replacing exon 1, this fusion protein, J-C subunit (J-C), becomes the driver of fibrolamellar hepatocellular carcinoma (FL-HCC). Here, we use cryo-electron microscopy (cryo-EM) to characterize J-C bound to RIIβ, the major PKA regulatory (R) subunit in liver, thus reporting the first cryo-EM structure of any PKA holoenzyme. We report several differences in bothdoi:10.1371/journal.pbio.3001018 pmid:33370777 fatcat:xjpokb3ssfcu3cb7bi5dtnbrrm
more »... e and dynamics that could not be captured by the conventional crystallography approaches used to obtain prior structures. Most striking is the asymmetry caused by the absence of the second cyclic nucleotide binding (CNB) domain and the J-domain in one of the RIIβ:J-C protomers. Using molecular dynamics (MD) simulations, we discovered that this asymmetry is already present in the wild-type (WT) RIIβ2C2 but had been masked in the previous crystal structure. This asymmetry may link to the intrinsic allosteric regulation of all PKA holoenzymes and could also explain why most disease mutations in PKA regulatory subunits are dominant negative. The cryo-EM structure, combined with small-angle X-ray scattering (SAXS), also allowed us to predict the general position of the Dimerization/Docking (D/D) domain, which is essential for localization and interacting with membrane-anchored A-Kinase-Anchoring Proteins (AKAPs). This position provides a multivalent mechanism for interaction of the RIIβ holoenzyme with membranes and would be perturbed in the oncogenic fusion protein. The J-domain also alters several biochemical properties of the RIIβ holoenzyme: It is easier to activate with cAMP, and the cooperativity is reduced. These results provide new insights into how the finely tuned allosteric PKA signaling network is disrupted by the oncogenic J-C subunit, ultimately leading to the development of FL-HCC.
Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating Correspondence should be addressed to MRS (email@example.com) and PAF (firstname.lastname@example.org).doi:10.1038/ng.349 pmid:19330029 pmcid:PMC2873835 fatcat:cbkojhrw2jdt5oh4yz5q6rlqym
Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNAdoi:10.1038/nature05610 pmid:17344846 pmcid:PMC2712719 fatcat:ni2kccg52jgvle3njqeihc7cm4
Versus Medium-Chain Triglycerides/Long-Chain Triglycerides in Adult Patients Undergoing Gastrointestinal Surgery Ming-Hsun Wu, MD; Ming-Yang Wang, MD; Chin-Yao Yang, MD; Min-Liang Kuo, PhD; and Ming-Tsan ... Lutgart De Pourcqg, PharmD; Martin Hiele, MD; and Ludo Willems, PhD, PharmD Maximum Tolerated Osmolarity for Peripheral Administration of Parenteral Nutrition in Pediatric Patients Shannon Dugan, PharmD; Jennifer ...
« Previous Showing results 1 — 15 out of 98 results