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Background: Calcium (Ca 2+ ) plays a pivotal role in regulating physiological processes in the heart including excitation-contraction coupling, Ca 2+ signaling, and mitochondrial function. It is well established that both Ca 2+ dysregulation and altered cardiac energy metabolism are universal features of heart failure (HF). Dwarf open reading frame (DWORF), a newly discovered microprotein, increases SERCA2a activity in part by relieving SERCA2a inhibition by phospholamban (PLN). DWORF overexpression via cardiac specific transgene or gene therapy is cardioprotective in genetic and experimental HF mouse models. In addition to activation of SERCA2a by PLN displacement, preliminary data indicates that enhanced mitochondrial function contributes to the cardioprotective effects of DWORF. Here we tested the effects of DWORF overexpression on cardiac mitochondrial function and Ca 2+ dynamics. Methods and Results: We isolated mitochondria from wildtype (WT) and DWORF transgenic (Tg) mouse hearts and measured O 2 consumption rates using a Seahorse mito stress test. We found that DWORF Tg mice have increased respiratory capacity compared to WT (DWORF Tg 1150.0 pmol/min, WT 799.4 pmol/min +/-146.2) and enhanced spare respiratory capacity (DWORF Tg 489.1 pmol/min, WT 229.4 pmol/min +/- 102.1). To measure mitochondrial Ca 2+ dynamics, we performed Ca 2+ retention capacity assays and found that DWORF Tg mice have increased Ca 2+ uptake rates compared to WT (DWORF Tg 32.32 s, WT 46.46 s +/- 4.39). Western blot analysis of the mitochondrial Ca 2+ uniporter (MCU) in mito extracts from WT and DWORF Tg hearts indicated elevated levels of MCU. However, electron transport chain (ETC) protein expression indicated no significant differences, indicating the enhanced mitochondrial activity observed in DWORF Tg mice was not due to increased ETC levels. Conclusions: DWORF Tg mouse heart mitochondria exhibit increased maximal respiration rates and enhanced spare respiratory capacity. However, ETC protein levels are unchanged, indicating altered enzyme activity rather than expression. Additionally, mitochondria from DWORF Tg hearts uptake Ca 2+ faster into the mitochondria through the increased levels of MCU, suggesting enhanced mitochondrial Ca 2+ dynamics.

The purpose of this study was to discover relationships between metrics and usability standards to assess the success of the University of North Carolina System Office website. Though no relationship was arguably found, the study results will be used to improve the UNC System Office website and other non-transactional websites that convey policy based information to the general public. Remote usability testing with nine users on desktop computers revealed that the site succeeds in terms of aesthetic design and top-level navigation but suffers from critical errors, poor organization, and an overuse of industry-specific terminology. The testing results demonstrate the importance of presenting the wide breadth of information to the general public in a way that is visually appealing and topical for some while direct and deeply specialized for others. Above all, the study provides a case study in conducting usability testing.

Novel technology can be a powerful tool for enhancing students' interest in many learning domains. However, the sustainability and overall impact of such interest is unclear. This study tests the longer-term effects of technology on students' task and course interest. The experimental study was conducted with students in foreign language classes (n = 122): a 12-week experimental trial that included pre- and post-course interest, and a sequence of task interest measures. Employing a counterbalanced design, at three week intervals students engaged in separate speaking tasks with each of a Human and “Chatbot” partner. Students' interest in successive tasks and in the course (pre-post), were used to assess differential partner effects and course interest development trajectories. Comparisons of task interest under different partner conditions over time indicated a significant drop in students' task interest with the Chatbot but not Human partner. After accounting for initial course interest, Structural Equation Modelling indicated that only task interest with the Human partner contributed to developing course interest. While Human partner task interest predicted future course interest, task interest under Chatbot partner conditions did not. Under Chatbot partner conditions there was a drop in task interest after the first task: a novelty effect. Implications for theory and practice are discussed.

This paper presents the use of Terrestrial laser scanners (TLS) to model the surface of satellite dish. In this case, the dish was an inexpensive 9m parabolic satellite dish with a mesh surface, and was to be utilised in radio astronomy. The aim of the modelling process was to determine the deviation of the surface away from its true parabolic shape, in order to estimate the surface efficiency with respect to its principal receiving frequency. The main mathematical problems were the optimal and unbiased estimation the orientation of the dish and the fitting of a parabola to the local orientation or coordinate system, which were done by both orthogonal and algebraic minimization using the least-squares method. Due to the mesh structure of the dish, a classification method was also applied to filter out erroneous points being influenced by the supporting structure behind the dish. Finally, a comparison is performed between the ideal parabolic shape, and the data collected from three different temporal intervals.

We design a provenance system for documents on clouds. The system allows writing documents by several collaborating individuals. Provenance allows recovery of information about the sequence of significant events relevant to the documents. Existing provenance systems focus on editing events, such as creation or removal of document parts. In this work, we introduce provenance of exposure events, allowing identification of one, or more, individuals which are possible sources of the exposure to external source of a particular version of documents. Our design provides a practical solution for provenance of documents via not-fully-trusted cloud systems, with support for provenance of both exposure and editing events.

Every year, an unacceptably large number of infant deaths occur in developing nations, with premature birth and asphyxia being two of the leading causes. A well-regulated thermal environment is critical for neonatal survival. Advanced incubators currently exist, but they are far too expensive to meet the needs of developing nations. We are developing a thermodynamically advanced low-cost incubator suitable for operation in a low-resource environment. Our design features three innovations: (1) a disposable baby chamber to reduce infant mortality due to nosocomial infections, (2) a passive cooling mechanism using low-cost heat pipes and evaporative cooling from locally found clay pots, and (3) insulated panels and a thermal bank consisting of water that effectively preserve and store heat. We developed a prototype incubator and visited and presented our design to our partnership hospital site in Mysore, India. After obtaining feedback, we have determined realistic, nontrivial design requirements and constraints in order to develop a new prototype incubator for clinical trials in hospitals in India.

The serine protease inhibitors SERPINB3 and SERPINB4 have been implicated in allergic disorders. We have recently demonstrated a role for the serine protease inhibitor Serpinb3a (the mouse homolog of SERPINB3 and SERPINB4) in a mouse model of asthma. Elevated levels of SERPINB3 and SERPINB4 are detected in the serum of patients with atopic dermatitis (AD) and they have been proposed as possible biomarkers for AD. Serine proteases are critical for epidermal barrier homeostasis and aberrant expression and/or activity of serine proteases have been associated with AD in human studies. We also observe a significant induction in the expression of Serpinb3a in a mouse model of cutaneous inflammation that has many similarities to AD. However the role of Serpinb3a in the skin is unknown. Using our mouse model of skin inflammation, we observed attenuation in trans-epidermal water loss, skin inflammation scores, decreased levels of total IgE, and pro-inflammatory markers like S100A8 in mice lacking Serpinb3a following exposure to Aspergillus fumigatus extract. In humans, we have identified a single nucleotide polymorphism (SNP) in the locus that encodes SERPINB3 and SERPINB4 that is associated with trans-epidermal water loss (p-val=0.031). In conclusion, we demonstrate that SERPINB3 and SERPINB4 contribute to cutaneous inflammation and work is ongoing to elucidate the role of this protein in regulating the skin barrier.

The factors that promote IL17A production during the pathogenesis of severe asthma remain undefined. Diesel exhaust particles (DEP) are a major component of traffic related air pollution and are implicated in asthma exacerbation. We assessed the impact of DEP exposure on asthma severity in asthmatic children from the Greater Cincinnati Pediatric Clinic Repository. Among high DEP-exposed children with allergic asthma, 32.2% of the children had severe asthma, compared to only 14.2% in the low DEP-exposed group. Similarly, Balb/c mice co-exposed to DEP and house dust mite extract (HDM) markedly demonstrated enhanced airway inflammation and hyperresponsiveness (AHR) compared to HDM alone. Exposure to DEP alone did not induce classic features of asthma but generated a Th17 response. DEP and HDM co-exposures enhanced pulmonary Th2 and Th17 cell numbers compared to HDM alone. High DEP-exposed children with allergic asthma had elevated serum IL17A levels compared with low DEP-exposed children. Finally, IL17A neutralization alleviated DEP-induced exacerbation of AHR. In conclusion, Th17 cells contribute to DEP-mediated exacerbation of allergen-induced asthma. Neutralization of IL17A may be a useful therapeutic strategy to counteract the asthma promoting effects of traffic related air pollution especially in severe asthmatics.

Asthma is a major public health burden worldwide. Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production remain largely unknown and therapies to effectively target mucus hypersecretion are lacking. Using a murine asthma model, we showed that SerpinB3a, the mouse ortholog of the serine protease inhibitors, SERPINB4 and B3, contribute to house dust mite induced airway hyperresponsiveness (AHR), mucus production and goblet cell hyperplasia and expression of SPDEF, a transcription factor that mediates goblet cell differentiation. Microarray analysis revealed attenuated expression of multiple IL-13 regulated genes that contribute to mucus production in the Serpinb3a null mice and IL-13 treated mice showed attenuated AHR and mucus production. Our data have revealed a novel non-redundant role for SERPINB4 and B3 in mediating mucus production through regulation of SPDEF expression.

The mechanisms underlying the adjuvant effect of diesel exhaust particles (DEP) on allergen-induced airways responses are not well understood. We aim to define how T-cells are affected by exposures to DEP and house dust mite (HDM). Balb/c mice were exposed intra-tracheally to DEP, HDM, or both, three times a week for three weeks. Airway inflammation and FACS analysis of lung and draining lymph node T-cells were assessed 24h or 1 week after the last exposure. Exposure to DEP alone generated airway neutrophilia whereas exposure to HDM was characterized by eosinophilia. Coexposure to HDM and DEP resulted in a significant increase in BALF cells over HDM alone. The percentage of CD4+ T-cells expressing the activation marker CD69 were increased in all three groups over saline exposed mice. However, significantly more activated CD4+ T-cells were observed in the lungs and mediastinal lymph nodes of mice coexposed to HDM+DEP. Alterations in Foxp3+ regulatory T-cells were limited following coexposure to HDM and DEP resulting in a favorable ratio of activated T-cells over Tregs. One week after the last exposure, pulmonary inflammation and DEP containing macrophages could still be observed. Interestingly, levels of activated T-cells remain elevated in all three groups compared to saline exposed control mice, but the further increase observed after coexposure was no longer significant. Taken together, these results suggest that DEP exacerbates the early acute allergic responses.