Calibration of Computational Models with Categorical Parameters and Correlated Outputs via Bayesian Smoothing Spline ANOVA

It has become commonplace to use complex computer models to predict outcomes in regions where data does not exist. Typically these models need to be calibrated and validated using some experimental data, which often consists of multiple correlated outcomes. In addition, some of the model parameters may be categorical in nature, such as a pointer variable to alternate models (or submodels) for some of the physics of the system. Here we present a general approach for calibration in such situations where an emulator of the computationally demanding models and a discrepancy term from the model to reality are represented within a Bayesian Smoothing Spline (BSS) ANOVA framework. The BSS-ANOVA framework has several advantages over the traditional Gaussian Process, including ease of handling categorical inputs and correlated outputs, and improved computational efficiency. Finally this framework is then applied to the problem that motivated its design; a calibration of a computational fluid dynamics model of a bubbling fluidized which is used as an absorber in a CO2 capture system

Can Instagram be used to deliver an evidence-based exercise program for young women A process evaluation

Background Instagram provides an opportunity to deliver low cost, accessible and appealing physical activity content. This study evaluated the feasibility of delivering an exercise program for young women using Instagram. Methods A single-group pre- and post-intervention trial examined the feasibility and preliminary efficacy of a 12-week Instagram-delivered program with young inactive women (n = 16; M = 23 years), which prescribed running and body weight exercises to complete three times per week. Daily Instagram posts delivered the exercises, video demonstrations and motivational content. Feasibility was evaluated by examining exposure (Instagram posts viewed per week), engagement (likes, comments and tags on Instagram posts; number of exercise sessions completed per week; retention, defined as completion of the online survey at weeks 6 and 12), and acceptability [whether the program increased participants’ motivation to exercise (1 = strongly disagree-5 = strongly agree); satisfaction with the program (1 = not satisfied-5 = very satisfied)]. Preliminary efficacy was evaluated by comparing baseline and 12-week self-reported physical activity (IPAQ short-form) and fitness (cardiorespiratory and muscle strength; 1 = very poor-5 = very good, International Fitness Scale) using the Exact sign test. Results On average, participants reported seeing six posts in their Instagram feed per week. Posts received an average of five likes (IQR = 3–6). A total of four comments and one tag were observed across all posts. On average, participants reported completing two exercise sessions per week. Retention was 88% at 6 weeks but dropped to 56% at 12 weeks. Participants reported increased motivation to exercise (Mdn = 4, IQR = 3–4) and were satisfied with the program (Mdn = 4, IQR = 3–4). Only self-reported cardiorespiratory fitness showed a meaningful, though nonsignificant, improvement (MdnΔ = 1, IQR = 0–1, p = .06). Conclusions Although Instagram has the potential to deliver a low cost, convenient exercise program for young women, additional research is needed to identify methods of improving engagement (interaction with the Instagram content, exercise sessions completed, and retention in the program). Future research could examine the use of behaviour change theory and provide information that enables participants to tailor the exercises to their interests and needs. Additionally, the use of objective assessments of physical activity and fitness among a larger participants sample is needed

KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II

SummaryThe transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited to promoter-proximal regions in a catalytically inactive state bound to the 7SK small nuclear ribonucleoprotein (snRNP) complex. However, it remains unclear how and why the 7SK snRNP is assembled at these sites. Here we report that the transcriptional regulator KAP1 continuously tethers the 7SK snRNP to PRG promoters to facilitate P-TEFb recruitment and productive elongation in response to stimulation. Remarkably, besides PRGs, genome-wide studies revealed that KAP1 and 7SK snRNP co-occupy most promoter-proximal regions containing paused Pol II. Collectively, we provide evidence of an unprecedented mechanism controlling 7SK snRNP delivery to promoter-proximal regions to facilitate "on-site" P-TEFb activation and Pol II elongation

Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types

Using Natural Language Processing and Sentiment Analysis to Augment Traditional User-Centered Design: Development and Usability Study

Background: Sarcopenia, defined as the age-associated loss of muscle mass and strength, can be effectively mitigated through resistance-based physical activity. With compliance at approximately 40% for home-based exercise prescriptions, implementing a remote sensing system would help patients and clinicians to better understand treatment progress and increase compliance. The inclusion of end users in the development of mobile apps for remote-sensing systems can ensure that they are both user friendly and facilitate compliance. With advancements in natural language processing (NLP), there is potential for these methods to be used with data collected through the user-centered design process. Objective: This study aims to develop a mobile app for a novel device through a user-centered design process with both older adults and clinicians while exploring whether data collected through this process can be used in NLP and sentiment analysis. Methods: Through a user-centered design process, we conducted semistructured interviews during the development of a geriatric-friendly Bluetooth-connected resistance exercise band app. We interviewed patients and clinicians at weeks 0, 5, and 10 of the app development. Each semistructured interview consisted of heuristic evaluations, cognitive walkthroughs, and observations. We used the Bing sentiment library for a sentiment analysis of interview transcripts and then applied NLP-based latent Dirichlet allocation (LDA) topic modeling to identify differences and similarities in patient and clinician participant interviews. Sentiment was defined as the sum of positive and negative words (each word with a +1 or −1 value). To assess utility, we used quantitative assessment questionnaires—System Usability Scale (SUS) and Usefulness, Satisfaction, and Ease of use (USE). Finally, we used multivariate linear models—adjusting for age, sex, subject group (clinician vs patient), and development—to explore the association between sentiment analysis and SUS and USE outcomes. Results: The mean age of the 22 participants was 68 (SD 14) years, and 17 (77%) were female. The overall mean SUS and USE scores were 66.4 (SD 13.6) and 41.3 (SD 15.2), respectively. Both patients and clinicians provided valuable insights into the needs of older adults when designing and building an app. The mean positive-negative sentiment per sentence was 0.19 (SD 0.21) and 0.47 (SD 0.21) for patient and clinician interviews, respectively. We found a positive association with positive sentiment in an interview and SUS score (ß=1.38; 95% CI 0.37 to 2.39; P=.01). There was no significant association between sentiment and the USE score. The LDA analysis found no overlap between patients and clinicians in the 8 identified topics. Conclusions: Involving patients and clinicians allowed us to design and build an app that is user friendly for older adults while supporting compliance. This is the first analysis using NLP and usability questionnaires in the quantification of user-centered design of technology for older adults

Engineering Proteinase Inihibitor Genes For Plant Defense Against Predators

Small proteinaceous inhibitors (Mr\u3c20,000) of the digestive serine proteinases of animals and microorganisms are found as moderately abundant proteins in storage organs and leaves of many plant genera. The proteins are powerful inhibitors of the digestive enzymes of plant predators and therefore are considered to be part of the array of defensive chemicals of plants. Proteinase inhibitor genes show excellent promise, using DNA technology, to manipulate plant genomes to express these biologically active proteins in order to improve natural defense systems. Members of two unrelated families of serine proteinase inhibitors found in tomato and potato plants, called Inhibitor I (monomer Mr 8000) and Inhibitor II (monomer Mr 12,300), are under both environmental and developmental regulation in different tissues of the plants. Genes coding for wound-inducible Inhibitors I and II have been isolated from both tomato and potato genomes and characterized. Tobacco plants have been transformed with the chimeric genes containing wound-inducible promoters fused with the reporter gene, chloramphenicol acetyl transferase, to assess promoter function and signal transmission. Transacting factors that regulate their expression in response to wounding are also being identified and purified. Intact genes are being employed to transform agriculturally important crop plants to determine their potential usefulness to enhance defensive capabilities of plants against herbivores and pathogens

Type IIb Supernova SN 2011dh: Spectra and Photometry from the Ultraviolet to the Near-Infrared

We report spectroscopic and photometric observations of the Type IIb SN 2011dh obtained between 4 and 34 days after the estimated date of explosion (May 31.5 UT). The data cover a wide wavelength range from 2,000 Angstroms in the UV to 2.4 microns in the NIR. Optical spectra provide line profiles and velocity measurements of HI, HeI, CaII and FeII that trace the composition and kinematics of the SN. NIR spectra show that helium is present in the atmosphere as early as 11 days after the explosion. A UV spectrum obtained with the STIS reveals that the UV flux for SN 2011dh is low compared to other SN IIb. The HI and HeI velocities in SN 2011dh are separated by about 4,000 km/s at all phases. We estimate that the H-shell of SN 2011dh is about 8 times less massive than the shell of SN 1993J and about 3 times more massive than the shell of SN 2008ax. Light curves (LC) for twelve passbands are presented. The maximum bolometric luminosity of $1.8 \pm 0.2 \times 10^{42}$ erg s$^{-1}$ occurred about 22 days after the explosion. NIR emission provides more than 30% of the total bolometric flux at the beginning of our observations and increases to nearly 50% of the total by day 34. The UV produces 16% of the total flux on day 4, 5% on day 9 and 1% on day 34. We compare the bolometric light curves of SN 2011dh, SN 2008ax and SN 1993J. The LC are very different for the first twelve days after the explosions but all three SN IIb display similar peak luminosities, times of peak, decline rates and colors after maximum. This suggests that the progenitors of these SN IIb may have had similar compositions and masses but they exploded inside hydrogen shells that that have a wide range of masses. The detailed observations presented here will help evaluate theoretical models for this supernova and lead to a better understanding of SN IIb.Comment: 23 pages, 14 figures, 9 tables, accepted by Ap

Hubble Space Telescope and Ground-Based Observations of the Type Iax Supernovae SN 2005hk and SN 2008A

We present Hubble Space Telescope (HST) and ground-based optical and near-infrared observations of SN 2005hk and SN 2008A, typical members of the Type Iax class of supernovae (SNe). Here we focus on late-time observations, where these objects deviate most dramatically from all other SN types. Instead of the dominant nebular emission lines that are observed in other SNe at late phases, spectra of SNe 2005hk and 2008A show lines of Fe II, Ca II, and Fe I more than a year past maximum light, along with narrow [Fe II] and [Ca II] emission. We use spectral features to constrain the temperature and density of the ejecta, and find high densities at late times, with n_e >~ 10^9 cm^-3. Such high densities should yield enhanced cooling of the ejecta, making these objects good candidates to observe the expected "infrared catastrophe," a generic feature of SN Ia models. However, our HST photometry of SN 2008A does not match the predictions of an infrared catastrophe. Moreover, our HST observations rule out a "complete deflagration" that fully disrupts the white dwarf for these peculiar SNe, showing no evidence for unburned material at late times. Deflagration explosion models that leave behind a bound remnant can match some of the observed properties of SNe Iax, but no published model is consistent with all of our observations of SNe 2005hk and 2008A.Comment: 20 pages, 15 figure

Functions of maize genes encoding pyruvate phosphate dikinase in developing endosperm

Maize opaque2 (o2) mutations are beneficial for endosperm nutritional quality but cause negative pleiotropic effects for reasons that are not fully understood. Direct targets of the bZIP transcriptional regulator encoded by o2 include pdk1 and pdk2 that specify pyruvate phosphate dikinase (PPDK). This enzyme reversibly converts AMP, pyrophosphate, and phosphoenolpyruvate to ATP, orthophosphate, and pyruvate and provides diverse functions in plants. This study addressed PPDK function in maize starchy endosperm where it is highly abundant during grain fill. pdk1 and pdk2 were inactivated individually by transposon insertions, and both genes were simultaneously targeted by endosperm-specific RNAi. pdk2 accounts for the large majority of endosperm PPDK, whereas pdk1 specifies the abundant mesophyll form. The pdk1- mutation is seedling-lethal, indicating that C4 photosynthesis is essential in maize. RNAi expression in transgenic endosperm eliminated detectable PPDK protein and enzyme activity. Transgenic kernels weighed the same on average as nontransgenic siblings, with normal endosperm starch and total N contents, indicating that PPDK is not required for net storage compound synthesis. An opaque phenotype resulted from complete PPDK knockout, including loss of vitreous endosperm character similar to the phenotype conditioned by o2-. Concentrations of multiple glycolytic intermediates were elevated in transgenic endosperm, energy charge was altered, and starch granules were more numerous but smaller on average than normal. The data indicate that PPDK modulates endosperm metabolism, potentially through reversible adjustments to energy charge, and reveal that o2- mutations can affect the opaque phenotype through regulation of PPDK in addition to their previously demonstrated effects on storage protein gene expression