111 research outputs found

    A functional analysis of haptic feedback in digital musical instrument interactions

    Get PDF
    An experiment is presented that measured aspects of functionality, usability and user experience for four distinct types of device feedback. The goal was to analyse the role of haptic feedback in functional digital musical instrument (DMI) interactions. Quantitative and qualitative human–computer interaction analysis techniques were applied in the assessment of prototype DMIs that displayed unique elements of haptic feedback; specifically, full haptic (constant-force and vibrotactile) feedback, constant-force only, vibrotactile only and no feedback. From the analysis, data are presented that comprehensively quantify the effects of feedback in haptic interactions with DMI devices. The investigation revealed that the various types of haptic feedback applied had no significant functional effect upon device performance in pitch selection tasks; however, a number of significant effects were found upon the users’ perception of usability and their experiences with each of the different feedback types

    PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

    Get PDF
    Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13--blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test

    Examining the effects of social media in co-located classrooms: A case study based on SpeakUp

    Get PDF
    The broad availability of mobile computing devices has prompted the apparition of social media applications that support teaching and learning. However, so far, there is conflicting evidence as to whether the benefits such applications provide in terms of engagement and interaction, outweigh their potential cost as a source of distraction. To help in clarifying these issues, the present paper presents a case study on the impact of using SpeakUp (an app aimed at promoting student participation through anonymous chatrooms) in an authentic face-to-face learning scenario. Concretely, we focus on the connection between SpeakUp and the student engagement, distraction, social interaction, and the influence of the teachers' style. Our findings highlight that SpeakUp favored students' engagement and social interaction, but they also point towards its limitations in keeping students communicating about content relevant to the course

    Coordinating the impact of structural genomics on the human α-helical transmembrane proteome

    Get PDF
    Given the recent successes in determining membrane-protein structures, we explore the tractability of determining representatives for the entire human membrane proteome. This proteome contains 2,925 unique integral α-helical transmembrane-domain sequences that cluster into 1,201 families sharing more than 25% sequence identity. Structures of 100 optimally selected targets would increase the fraction of modelable human α-helical transmembrane domains from 26% to 58%, providing structure and function information not otherwise available

    A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests

    Get PDF
    Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing improved treatments for mood disorders and other brain disorders with altered chromatin-mediated neuroplasticity.Stanley Medical Research InstituteNational Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01DA030321

    Ectopic synaptic ribbons in dendrites of mouse retinal ON- and OFF-bipolar cells

    Get PDF
    The ectopic distribution of synaptic ribbons in dendrites of mouse retinal bipolar cells was examined by using genetic ablation of metabotropic glutamate receptor subtype 6 (mGluR6), electron microscopy, and immunocytochemistry. Ectopic ribbons were observed in dendrites of rod and ON-cone bipolar cells in the mGluR6-deficient mouse but not in those of wild-type mice. The number of rod spherules facing the ectopic ribbons in mGluR6-deficient rod bipolar dendrites increased gradually during early growth and reached a plateau level of about 20% at 12 weeks. These ectopic ribbons were immunopositive for RIBEYE, a ribbon-specific protein, but the associated vesicles were immunonegative for synaptophysin, a synaptic-vesicle-specific protein. The presence of ectopic ribbons was correlated with an increase in the roundness of the invaginating dendrites of the rod bipolar cells. We further confirmed ectopic ribbons in dendrites of OFF-cone bipolar cells in wild-type retinas. Of the four types of OFF-cone bipolar cells (T1–T4), only the T2-type, which had a greater number of synaptic ribbons at the axon terminal and a thicker axon cylinder than the other types, had ectopic ribbons. Light-adapted experiments revealed that, in wild-type mice under enhanced-light adaptation (considered similar to the mGluR6-deficient state), the roundness in the invaginating dendrites and axon terminals of rod bipolar cells increased, but no ectopic ribbons were detected. Based on these findings and known mechanisms for neurotransmitter release and protein trafficking, the possible mechanisms underlying the ectopic ribbons are discussed on the basis of intracellular transport for the replenishment of synaptic proteins

    Histone Deacetylases Control Neurogenesis in Embryonic Brain by Inhibition of BMP2/4 Signaling

    Get PDF
    Background Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs) lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. Principal Findings As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. Conclusions Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical neurogenesis. The results also suggest that HDACs may regulate the developmental switch from neurogenesis to astrogliogenesis that occurs in late gestation

    First Measurement of the Muon Neutrino Charged Current Single Pion Production Cross Section on Water with the T2K Near Detector

    Get PDF
    The T2K off-axis near detector, ND280, is used to make the first differential cross section measurements of muon neutrino charged current single positive pion production on a water target at energies 0.8{\sim}0.8 GeV. The differential measurements are presented as a function of muon and pion kinematics, in the restricted phase-space defined by pπ+>200p_{\pi^+}>200MeV/c, pμ>200p_{\mu^-}>200MeV/c, cosθπ+>0.3\cos \theta_{\pi^+}>0.3 and cosθμ>0.3\cos \theta_{\mu^-}>0.3. The total flux integrated νμ\nu_\mu charged current single positive pion production cross section on water in the restricted phase-space is measured to be σϕ=4.25±0.48(stat)±1.56(syst)×1040cm2/nucleon\langle\sigma\rangle_\phi=4.25\pm0.48 (\mathrm{stat})\pm1.56 (\mathrm{syst})\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}. The total cross section is consistent with the NEUT prediction (5.03×1040cm2/nucleon5.03\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}) and 2σ\sigma lower than the GENIE prediction (7.68×1040cm2/nucleon7.68\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}). The differential cross sections are in good agreement with the NEUT generator. The GENIE simulation reproduces well the shapes of the distributions, but over-estimates the overall cross section normalization
    corecore