High Quality, Transferable Graphene Grown on Single Crystal Cu(111) Thin Films on Basal-Plane Sapphire

The current method of growing large-area graphene on Cu surfaces (polycrystalline foils and thin films) and its transfer to arbitrary substrates is technologically attractive. However, the quality of graphene can be improved significantly by growing it on single-crystal Cu surfaces. Here we show that high quality, large-area graphene can be grown on epitaxial single-crystal Cu(111) thin films on reusable basal-plane sapphire (alpha-Al2O3(0001)) substrates and then transferred to another substrate. While enabling graphene growth on Cu single-crystal surfaces, this method has the potential to avoid the high cost and extensive damage to graphene associated with sacrificing bulk single-crystal Cu during graphene transfer.Comment: 10 pages, 3 figure

Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans

We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of D. yakuba, and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans, indicating greater variation in D. yakuba. Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting deleterious impacts are common. D. simulans shows larger numbers of whole gene duplications in comparison to larger proportions of gene fragments in D. yakuba. D. simulans displays an excess of high frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X or demographic forces driving duplicates to high frequency. We identify 78 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans, as well as 143 cases of recruited non-coding sequence in D. yakuba and 96 in D. simulans, in agreement with rates of chimeric gene origination in D. melanogaster. Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.Comment: Revised Version- Accepted at Molecular Biology and Evolutio

Regulation of Membrane Targeting of the G Protein-coupled Receptor Kinase 2 by Protein Kinase A and Its Anchoring Protein AKAP79

The beta 2 adrenergic receptor (beta 2AR) undergoes desensitization by a process involving its phosphorylation by both protein kinase A (PKA) and G protein-coupled receptor kinases (GRKs). The protein kinase A-anchoring protein AKAP79 influences beta 2AR phosphorylation by complexing PKA with the receptor at the membrane. Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors. In human embryonic kidney 293 cells, overexpression of AKAP79 enhances agonist-induced phosphorylation of both the beta 2AR and a mutant of the receptor that cannot be phosphorylated by PKA (beta 2AR/PKA-). Mutants of AKAP79 that do not bind PKA or target to the beta 2AR markedly inhibit phosphorylation of beta 2AR/PKA-. We show that PKA directly phosphorylates GRK2 on serine 685. This modification increases Gbeta gamma subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. Abrogation of the phosphorylation of serine 685 on GRK2 by mutagenesis (S685A) or by expression of a dominant negative AKAP79 mutant reduces GRK2-mediated translocation to beta 2AR and phosphorylation of agonist-occupied beta 2AR, thus reducing subsequent receptor internalization. Agonist-stimulated PKA-mediated phosphorylation of GRK2 may represent a mechanism for enhancing receptor phosphorylation and desensitization

Is laryngeal hypersensitivity the basis of unexplained or refractory chronic cough?

Refractory chronic cough (RCC) and unexplained chronic cough (UCC) are common problems seen in primary care and subspecialty clinics. The role of cough hypersensitivity and laryngeal dysfunction in contributing to the persistence of cough in RCC/UCC is not well recognised. Data of patients with RCC and UCC evaluated in 2019 by an interdisciplinary cough clinic led by a pulmonologist and speech–language pathology team was reviewed. Patients completed validated questionnaires including the Leicester cough questionnaire (LCQ), voice handicap index (VHI) and dyspnoea index (DI) questionnaire at initial encounter. Presence of cough hypersensitivity was based upon a history of allotussia and hypertussia. Laryngeal dysfunction was diagnosed in those with a history of laryngeal paresthesias, throat clearing, voice abnormalities, upper airway dyspnoea and documentation of functional or anatomic laryngeal abnormalities on nasoendoscopy. Of the 60 UCC/RCC patients analysed, 75% of patients were female and 85% were over 40 years of age. Cough hypersensitivity was documented in all patients and multiple cough triggers occurred in 75% of patients. 95%, 50% and 25% of patients reported laryngeal paresthesias, voice abnormalities and upper airway dyspnoea, respectively. Significant associations between LCQ and VHI and DI scores occurred when adjusting for age, sex, ethnicity and body mass index. Laryngeal functional abnormalities were documented on 44 out of 60 patients on nasoendoscopy. Hypertussia, allotussia and laryngeal dysfunction are common in patients with RCC and UCC. Evaluation of UCC and RCC can delineate laryngeal hypersensitivity and allows appropriate treatment to be directed at this phenotype

OneStopRNAseq: A Web Application for Comprehensive and Efficient Analyses of RNA-Seq Data

Over the past decade, a large amount of RNA sequencing (RNA-seq) data were deposited in public repositories, and more are being produced at an unprecedented rate. However, there are few open source tools with point-and-click interfaces that are versatile and offer streamlined comprehensive analysis of RNA-seq datasets. To maximize the capitalization of these vast public resources and facilitate the analysis of RNA-seq data by biologists, we developed a web application called OneStopRNAseq for the one-stop analysis of RNA-seq data. OneStopRNAseq has user-friendly interfaces and offers workflows for common types of RNA-seq data analyses, such as comprehensive data-quality control, differential analysis of gene expression, exon usage, alternative splicing, transposable element expression, allele-specific gene expression quantification, and gene set enrichment analysis. Users only need to select the desired analyses and genome build, and provide a Gene Expression Omnibus (GEO) accession number or Dropbox links to sequence files, alignment files, gene-expression-count tables, or rank files with the corresponding metadata. Our pipeline facilitates the comprehensive and efficient analysis of private and public RNA-seq data

Effects of Onshore and Offshore Environmental Parameters on the Leading Edge Erosion of Wind Turbine Blades : A Comparative Study

Author's accepted manuscript.Available from 13/01/2022.The presence of rain-induced leading edge erosion of wind turbine blades necessitates the development of erosion models. One of the essential parameters for erosion modelling is the relative impact velocity between rain droplets and the rotating blade. Based on this parameter, the erosion damage rate of a wind turbine blade is calculated to estimate the expected leading edge lifetime. The environmental conditions that govern this parameter have site-specific variations, and thus, rain and wind loading on a turbine differ for onshore and offshore locations. In addition, there are wave loads present in the offshore environment. The present paper tries to provide guidelines for erosion modelling and investigates whether there are differences in erosion of blades due to (1) varying rainfall conditions modelled using different droplet size distributions for onshore and offshore locations in combination with (2) winds of varying turbulence intensities and (3) wave-induced loads. Aero-hydro-servo-elastic simulations are carried out for an onshore wind turbine and a monopile-supported offshore wind turbine. Furthermore, erosion variables such as the relative impact velocities and the associated erosion damage rate of a blade are analysed for various blade azimuth angles. The study shows that the rainfall intensity and turbulence intensity minorly influence the impact velocity and pressure but have a substantial effect on the overall erosion damage rate. Additionally, a significantly higher erosion damage rate is found for blades exposed to offshore rainfall conditions than for blades under onshore rainfall conditions. Furthermore, no substantial influence on erosion is found because of wave-induced loads.acceptedVersio

Developments in Australian general practice 2000–2002: what did these contribute to a well functioning and comprehensive Primary Health Care System?

BACKGROUND: In recent years, national and state/territory governments have undertaken an increasing number of initiatives to strengthen general practice and improve its links with the rest of the primary health care sector. This paper reviews how far these initiatives were contributing to a well functioning and comprehensive primary health care system during the period 2000–2002, using a normative model of primary health care and data from a descriptive study to evaluate progress. RESULTS: There was a significant number of programs, at both state/territory and national level. Most focused on individual care, particularly for chronic disease, rather than population health approaches. There was little evidence of integration across programs: each tended to be based in and focus on a single jurisdiction, and build capacity chiefly within the services funded through that jurisdiction. As a result, the overall effect was patchy, with similar difficulties being noted across all jurisdictions and little gain in overall system capacity for effective primary health care. CONCLUSION: Efforts to develop more effective primary health care need a more balanced approach to reform, with a better balance across the different elements of primary health care and greater integration across programs and jurisdictions. One way ahead is to form a single funding agency, as in the UK and New Zealand, and so remove the need to work across jurisdictions and manage their competing interests. A second, perhaps less politically challenging starting point, is to create an agreed framework for primary health care within which a collective vision for primary health care can be developed, based on population health needs, and the responsibilities of different sectors services can be negotiated. Either of these approaches would be assisted by a more systematic and comprehensive program of research and evaluation for primary health care

Cellphone Laws and Teens\u27 Calling While Driving: Analysis of Repeated Cross-Sectional Surveys in 2013, 2015, 2017, and 2019

BACKGROUND: Distracted driving among teens is a public health and safety concern. Most states in the U.S. have sought to restrict cellphone use while driving by enacting laws. This study examines the difference in prevalence of self-reported calling while driving (CWD) between states with different cellphone bans. METHODS: Demographics and CWD data were extracted from state Youth Risk Behavior Surveys (YRBS) from 14 states in 2013, 2015, 2017, and 2019. The state YRBS is conducted every 2 years with a representative sample of 9th through 12th grade students attending public school. States were grouped by type of cellphone law(s): no ban (the absence of both handheld calling ban and young driver ban), young driver ban (a ban on all forms of cellphone use while driving, for young drivers only), or concurrent ban (a young driver ban plus a ban on handheld calling for all drivers irrespective of age). Poisson regression models with robust variance were used to estimate prevalence ratios comparing CWD prevalence across ban types. RESULTS: In total, 157,423 high school students participated in the surveys, and 65,044 (45%) participants reached the minimum age to obtain an intermediate license and drove during the 30 days prior the survey. Approximately 53% of participants reported CWD at least once during the previous 30 days, and the percentages varied widely by states (range: 51-55%). Compared to students from states with no ban, those from states with concurrent bans were 19%(95% CI: 14-24%) less likely to engage in CWD. Students in states with concurrent bans were 23% less likely to engage in CWD compared to students in states with young driver bans (95% CI:17-27%). CONCLUSIONS: Engaging in CWD is common among teen drivers. The concurrent implementation of a handheld calling ban and a young driver ban was associated with a lower prevalence of CWD