Exploring the Effects of Geocaching on Understanding Natural Resources and History

Abstract Since 2000, geocaching has been enjoyed by enthusiasts who wish to combine technology with a love for the outdoors. The purpose of this exploratory study was to examine if geocaching can contribute to a participant’s understanding of natural resources and history. To comprehend these effects, a study was conducted at Minnesota’s Wild River State Park in the summer of 2010. Four volunteer participants were recruited for in-depth interviews and qualitative inquiry was employed to learn about their geocaching experience and collect their responses. Inductive content analysis was used to analyze the interview data and identify possible geocaching effects based on participants’ perceptions. Six main categories were identified including learning, enjoyment, new attractions, constraints, economic benefits, and damage to the environment. Findings suggest that participants believed that their knowledge of park history and natural resources increased through geocaching. Recommendations, based on the findings, were given to park managers and the Minnesota DNR

Design of co-solute formulations for stable, highly concentrated monoclonal antibody solutions with low viscosity

Highly concentrated (> 200 mg/mL) monoclonal antibody (mAb) formulations with low viscosities are strongly desired for subcutaneous drug delivery for the treatment of diseases such as cancer, as well as for improved process performance and yield in the manufacture of biologic drug products using techniques such as tangential flow ultrafiltration (TFF). High solution viscosities and protein aggregation at high concentration lead to significant challenges in delivery and manufacture due to large injection forces, product loss to aggregation, and significant filter membrane fouling and flux decay. Small-molecule co-solutes such as arginine and various electrolytes have in some cases been shown to greatly reduce the viscosity of concentrated mAbs. However, the mechanism by which co-solutes modify mAb viscosity is not well understood. Herein, we investigate the effects of several amino acids and inorganic ionic co-solutes on the viscosity of mAbs up to 250 mg/mL. We relate the viscosities to measurable changes in the protein-protein interactions (PPI), mAb structure and self-association behavior as assessed through small-volume techniques such as dynamic light scattering (DLS), static light scattering (SLS) and fluorescence correlation spectroscopy (FCS) in order to develop a hierarchical understanding of the co-solute effects on the mAb behavior. We demonstrate that the viscosity reduction is correlated with the disruption of mAb self-association and attractive PPI, as directly probed by SLS, DLS, FCS and rheology. We also relate these changes in the PPI and viscosity to the physical properties of the co-solute, including the co-solute charge, size and shape. Finally, we demonstrate that the ability to mitigate aggregation and membrane fouling by the combined addition of viscosity-reducing co-solutes and selection of hollow fiber filter geometries resulted in a high-concentration transmembrane flux three-fold higher than that of conventional low co-solute buffer formulations. The reduced viscosities also led to more uniform axial transmembrane pressure and shear stress profiles, which led to reduce irreversible aggregation and solution turbidity during ultrafiltration.Chemical Engineerin

Cytosolic DNA Promotes Signal Transducer and Activator of Transcription 3 (STAT3) Phosphorylation by TANK-binding Kinase 1 (TBK1) to Restrain STAT3 Activity

Cytosolic DNA can elicit beneficial as well as undesirable immune responses. For example, viral or microbial DNA triggers cell-intrinsic immune responses to defend against infections, whereas aberrant cytosolic accumulation of self-DNA results in pathological conditions, such as autoimmunity. Given the importance of these DNA-provoked responses, a better understanding of their molecular mechanisms is needed. Cytosolic DNA engages stimulator of interferon genes (STING) to activate TANK-binding kinase 1 (TBK1), which subsequently phosphorylates the transcription factor interferon regulatory factor 3 (IRF3) to promote interferon expression. Recent studies have reported that additional transcription factors, including nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6), are also activated by cytosolic DNA, suggesting that cytosolic DNA-induced gene expression is orchestrated by multiple factors. Here we show that cytosolic DNA activates STAT3, another member of the STAT family, via an autocrine mechanism involving interferon β (IFNβ) and IL-6. Additionally, we observed a novel cytosolic DNA-induced phosphorylation at serine 754 in the transactivation domain of STAT3. Upon cytosolic DNA stimulation, Ser 754 is directly phosphorylated by TBK1 in a STING-dependent manner. Moreover, Ser 754 phosphorylation inhibits cytosolic DNA-induced STAT3 transcriptional activity and selectively reduces STAT3 target genes that are up-regulated in response to cytosolic DNA. Taken together, our results suggest that cytosolic DNA-induced STAT3 activation via IFNβ and IL-6 is restrained by Ser 754 phosphorylation of STAT3. Our findings reveal a new signaling axis downstream of the cytosolic DNA pathway and suggest potential interactions between innate immune responses and STAT3-driven oncogenic pathways

An Overview of 2014 SBIR Phase I and Phase II Materials Structures for Extreme Environments

NASA's Small Business Innovation Research (SBIR) program focuses on technological innovation by investing in development of innovative concepts and technologies to help NASA mission directorates address critical research needs for Agency programs. This report highlights nine of the innovative SBIR 2014 Phase I and Phase II projects that emphasize one of NASA Glenn Research Center's six core competencies-Materials and Structures for Extreme Environments. The technologies cover a wide spectrum of applications such as high temperature environmental barrier coating systems, deployable space structures, solid oxide fuel cells, and self-lubricating hard coatings for extreme temperatures. Each featured technology describes an innovation, technical objective, and highlights NASA commercial and industrial applications. This report provides an opportunity for NASA engineers, researchers, and program managers to learn how NASA SBIR technologies could help their programs and projects, and lead to collaborations and partnerships between the small SBIR companies and NASA that would benefit both

An Overview of 2014 SBIR Phase 1 and Phase 2 Communications Technology and Development

NASA's Small Business Innovation Research (SBIR) program focuses on technological innovation by investing in development of innovative concepts and technologies to help NASA mission directorates address critical research needs for Agency programs. This report highlights eight of the innovative SBIR 2014 Phase I and Phase II projects that emphasize one of NASA Glenn Research Center's six core competencies-Communication Technology and Development. The technologies cover a wide spectrum of applications such as X-ray navigation, microsensor instrument for unmanned aerial vehicle airborne atmospheric measurements, 16-element graphene-based phased array antenna system, interferometric star tracker, ultralow power fast-response sensor, and integrated spacecraft navigation and communication. Each featured technology describes an innovation, technical objective, and highlights NASA commercial and industrial applications. This report provides an opportunity for NASA engineers, researchers, and program managers to learn how NASA SBIR technologies could help their programs and projects, and lead to collaborations and partnerships between the small SBIR companies and NASA that would benefit both

Funding and Strategic Alignment Guidance for Infusing Small Business Innovation Research Technology Into Aeronautics Research Mission Directorate Projects at NASA Glenn Research Center for 2015

This document is intended to enable the more effective transition of NASA Glenn Research Center (GRC) SBIR technologies funded by the Small Business Innovation Research (SBIR) program as well as its companion, the Small Business Technology Transfer (STTR) program into NASA Aeronautics Research Mission Directorate (ARMD) projects. Primarily, it is intended to help NASA program and project managers find useful technologies that have undergone extensive research and development (RRD), through Phase II of the SBIR program; however, it can also assist non-NASA agencies and commercial companies in this process. aviation safety, unmanned aircraft, ground and flight test technique, low emissions, quiet performance, rotorcraf

Minority stress, resilience, and health in Italian and Taiwanese LGB+ people : a cross-cultural comparison

The present study, using a moderated mediational model, explored levels of distal/proximal stressors, rumination, resilience, and health in a group of Italian and Taiwanese LGB+ people. The study also examined the role of internalized sexual stigma (ISS) and rumination as mediators between discrimination and health, and resilience as a moderator of the relationship between discrimination and ISS, rumination, and health, respectively. An online survey was administered to 508 LGB+ participants (270 Italian and 238 Taiwanese) whose age ranged from 18 to 70 years (M = 37.93, SD = 13.53). The moderated mediation model was tested through a series of path analyses stratified by group nationality. Italian participants reported higher discrimination and resilience, but lower ISS, rumination, and health problems compared to their Taiwanese counterparts. The only common path between groups was the direct effect of discrimination on health problems. The mediating role of ISS and rumination in the relationship between discrimination and health, as well as the moderating role of resilience, were partly significant only for the Italian group. Conclusions: The findings suggest that mediators and moderators used to evaluate the effects of minority stress on health may differ between groups; further culturally sensitive research in the field of LGB+ health is needed

Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy

Background: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. Methods: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from the transcriptomic data using the CIBERSORTx algorithm. A co-expression network was constructed employing weighted gene co-expression network analysis (WGCNA) on the top 5000 most variable transcripts. The modules were interrogated with pathway analysis tools (InnateDB) and correlated with clinical phenotypes and cellular immune responses. Results: Proportions of neutrophils were positively correlated and CD4+ T-cells and regulatory T-cells (Tregs) were negatively correlated with modules of nut allergy. We also identified 2 upregulated genes, namely Interferon Induced With Helicase C Domain 1 (IFIH1), DNA damage-regulated autophagy modulator 1 (DRAM1) and a downregulated gene Zinc Finger Protein 512B (ZNF512B) as hub genes for nut allergy. Further pathway analysis showed enrichment of type 1 interferon signalling in nut allergy. Conclusions: Our findings suggest that upregulation of type 1 interferon signalling and neutrophil responses and downregulation of CD4+ T-cells and Tregs are features of the pathogenesis of nut allergy

Antipsychotic Prescribing Pathways, Polypharmacy, and Clozapine Use in Treatment of Schizophrenia

Objective To ensure optimal care for patients with schizophrenia, antipsychotic medications must be appropriately prescribed and used. Therefore, the primary objectives of this study were to identify and describe pathways for antipsychotic prescribing, assess the consistency of observed pathways with treatment guidelines, and describe variability across facilities. Methods Data from Veterans Affairs administrative data sets from fiscal year (FY) 2003 to FY 2007 were gathered for analysis in this retrospective cohort study of antipsychotic prescribing pathways among 13 facilities across two regional networks. Patients with a new episode of care for schizophrenia or schizoaffective disorder in FY 2005 were identified, and antipsychotic prescribing history was obtained for two years before and after the index diagnosis. Demographic characteristics and distribution of comorbidities were assessed. Median medical center rates of polypharmacy were calculated and compared with Fisher’s exact test. Results Of 1,923 patients with a new episode of schizophrenia care, 1,003 (52%) had complete data on prescribing pathways. A majority (74%) of patients were prescribed antipsychotic monotherapy, and 19% received antipsychotic polypharmacy. Of patients receiving antipsychotic polypharmacy, 65% began polypharmacy within 90 days of starting any antipsychotic treatment. There was a fourfold difference in polypharmacy across facilities. Antipsychotic polypharmacy was not associated with geographic location or medical center patient volume. Clozapine utilization was low (0%–2%). Conclusions Retrospective examination of longitudinal prescribing patterns identified multiple antipsychotic prescribing pathways. Although most patients received guideline-concordant care, antipsychotic polypharmacy was commonly used as initial treatment, and there was substantial variability among facilities. Study findings suggest the utility of secondary data to assess treatment adaptation or switching for practical clinical trials

Gene Expression Profiling of Muscle Stem Cells Identifies Novel Regulators of Postnatal Myogenesis

International audienceSkeletal muscle growth and regeneration require a population of muscle stem cells, the satellite cells, located in close contact to the myofiber. These cells are specified during fetal and early postnatal development in mice from a Pax3/7 population of embryonic progenitor cells. As little is known about the genetic control of their formation and maintenance, we performed a genome-wide chronological expression profile identifying the dynamic transcriptomic changes involved in establishment of muscle stem cells through life, and acquisition of muscle stem cell properties. We have identified multiple genes and pathways associated with satellite cell formation, including set of genes specifically induced (EphA1, EphA2, EfnA1, EphB1, Zbtb4, Zbtb20) or inhibited (EphA3, EphA4, EphA7, EfnA2, EfnA3, EfnA4, EfnA5, EphB2, EphB3, EphB4, EfnBs, Zfp354c, Zcchc5, Hmga2) in adult stem cells. Ephrin receptors and ephrins ligands have been implicated in cell migration and guidance in many tissues including skeletal muscle. Here we show that Ephrin receptors and ephrins ligands are also involved in regulating the adult myogenic program. Strikingly, impairment of EPHB1 function in satellite cells leads to increased differentiation at the expense of self-renewal in isolated myofiber cultures. In addition, we identified new transcription factors, including several zinc finger proteins. ZFP354C and ZCCHC5 decreased self-renewal capacity when overexpressed, whereas ZBTB4 increased it, and ZBTB20 induced myogenic progression. The architectural and transcriptional regulator HMGA2 was involved in satellite cell activation. Together, our study shows that transcriptome profiling coupled with myofiber culture analysis, provides an efficient system to identify and validate candidate genes implicated in establishment/maintenance of muscle stem cells. Furthermore, tour de force transcriptomic profiling provides a wealth of data to inform for future stem cell-based muscle therapies