204 research outputs found

    Design of the Annular Suspension and Pointing System (ASPS) (including design addendum)

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    The Annular Suspension and Pointing System is an experiment pointing mount designed for extremely precise 3 axis orientation of shuttle experiments. It utilizes actively controlled magnetic bearing to provide noncontacting vernier pointing and translational isolation of the experiment. The design of the system is presented and analyzed

    Direct, on-the-fly calculation of unresolved resonance region cross sections in Monte Carlo simulations

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    The theory, implementation, and testing of a method for on-the-fly unresolved resonance region cross section calculations in continuous-energy Monte Carlo neutron transport codes are presented. With this method, each time that a cross section value is needed within the simulation, a realization of unresolved resonance parameters is generated about the desired energy and temperature-dependent single-level Breit-Wigner resonance cross sections are computed directly via use of the analytical ψ − χ Doppler integrals. Results indicate that, in room-temperature simulations of a system that is known to be highly sensitive to the effects of resonance structure in unresolved region cross sections, the on-the-fly treatment produces results that are in excellent agreement with those produced with the well-established probability table method. Additionally, similar agreement is observed between results obtained from the on-the-fly and probability table methods for another intermediate spectrum system at temperatures of 293.6 K and 2500 K. With relatively tight statistical uncertainties at the ∼ 10 pcm level, all on-the-fly and probability table keff eigenvalues agree to within 2σ. Also, we use the on-the-fly approach to show that accounting for the resonance structure of competitive reaction cross sections can have non-negligible effects for intermediate/fast spectrum systems. Biases of up to 90 pcm are observed. Finally, the consequences of the on-the-fly method with respect to simulation runtime and memory requirements are briefly discussed.United States. Department of Energy (Consortium for Advanced Simulation of Light Water Reactors. Contract DE-AC05-00OR22725

    Secukinumab demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate-to-severe plaque psoriasis: long-term results from an interim analysis of the SERENA study.

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    Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m <sup>2</sup> were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA

    Net neutrality discourses: comparing advocacy and regulatory arguments in the United States and the United Kingdom

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    Telecommunications policy issues rarely make news, much less mobilize thousands of people. Yet this has been occurring in the United States around efforts to introduce "Net neutrality" regulation. A similar grassroots mobilization has not developed in the United Kingdom or elsewhere in Europe. We develop a comparative analysis of U.S. and UK Net neutrality debates with an eye toward identifying the arguments for and against regulation, how those arguments differ between the countries, and what the implications of those differences are for the Internet. Drawing on mass media, advocacy, and regulatory discourses, we find that local regulatory precedents as well as cultural factors contribute to both agenda setting and framing of Net neutrality. The differences between national discourses provide a way to understand both the structural differences between regulatory cultures and the substantive differences between policy interpretations, both of which must be reconciled for the Internet to continue to thrive as a global medium

    Net neutrality discourses: comparing advocacy and regulatory arguments in the United States and the United Kingdom

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    Telecommunications policy issues rarely make news, much less mobilize thousands of people. Yet this has been occurring in the United States around efforts to introduce "Net neutrality" regulation. A similar grassroots mobilization has not developed in the United Kingdom or elsewhere in Europe. We develop a comparative analysis of U.S. and UK Net neutrality debates with an eye toward identifying the arguments for and against regulation, how those arguments differ between the countries, and what the implications of those differences are for the Internet. Drawing on mass media, advocacy, and regulatory discourses, we find that local regulatory precedents as well as cultural factors contribute to both agenda setting and framing of Net neutrality. The differences between national discourses provide a way to understand both the structural differences between regulatory cultures and the substantive differences between policy interpretations, both of which must be reconciled for the Internet to continue to thrive as a global medium

    Templated Synthesis of Peptide Nucleic Acids via Sequence-Selective Base-Filling Reactions

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    The templated synthesis of nucleic acids has previously been achieved through the backbone ligation of preformed nucleotide monomers or oligomers. In contrast, here we demonstrate templated nucleic acid synthesis using a base-filling approach in which individual bases are added to abasic sites of a peptide nucleic acid (PNA). Because nucleobase substrates in this approach are not self-reactive, a base-filling approach may reduce the formation of nontemplated reaction products. Using either reductive amination or amine acylation chemistries, we observed efficient and selective addition of each of the four nucleobases to an abasic site in the middle of the PNA strand. We also describe the addition of single nucleobases to the end of a PNA strand through base filling, as well as the tandem addition of two bases to the middle of the PNA strand. These findings represent an experimental foundation for nonenzymatic information transfer through base filling.Chemistry and Chemical Biolog

    Perception and Impact of COVID-19 Pandemic in Psoriasis Patients: Data from the German PsoBest and the CoronaBest Registries

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    María José Valencia López,1,* Brigitte Stephan,1,* Anna Meineke,1 Sandra Wolf,1 Diamant Thaci,2 Ulrich Mrowietz,3 Valerie Andrees,1 Stephan Jeff Rustenbach,1 Kristian Reich,1 Linus Thalmann,1 Henriette Bogena,1 Petra Staubach,4 Ralph Michael von Kiedrowski,5 Matthias Augustin1 1Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; 2Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 3Psoriasis-Center, Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany; 4Department of Dermatology and Allergy, University Medical Center Mainz, Mainz, Germany; 5Dermatological Practice Selters, Selters, Germany*These authors contributed equally to this workCorrespondence: Matthias Augustin, Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, Hamburg, 20246, Germany, Tel +49 040 7410 55428, Fax +49 040 7410 55348, Email [email protected]: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany.Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies.Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others.Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (> 92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients.Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic.Keywords: psoriasis, COVID-19, SARS-CoV-2, pandemic, patient perception, risk factor

    Transient and sustained bacterial adaptation following repeated sublethal exposure to microbicides and a novel human antimicrobial peptide

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    Microbicides (biocides) play an important role in the prevention and treatment of infections. While there is currently little evidence for in-use treatment failures attributable to acquired reductions in microbicide susceptibility, the susceptibility of some bacteria can be reduced by sublethal laboratory exposure to certain agents. In this investigation, a range of environmental bacterial isolates (11 genera, 18 species) were repeatedly exposed to four microbicides (cetrimide, chlorhexidine, polyhexamethylene biguanide [PHMB], and triclosan) and a cationic apolipoprotein E-derived antimicrobial peptide (apoEdpL-W) using a previously validated exposure system. Susceptibilities (MICs and minimum bactericidal concentrations [MBCs]) were determined before and after 10 passages (P10) in the presence of an antimicrobial and then after a further 10 passages without an antimicrobial to determine the stability of any adaptations. Bacteria exhibiting >4-fold increases in MBCs were further examined for alterations in biofilm-forming ability. Following microbicide exposure, ≥4-fold decreases in susceptibility (MIC or MBC) occurred for cetrimide (5/18 bacteria), apoEdpL-W (7/18), chlorhexidine (8/18), PHMB (8/18), and triclosan (11/18). Of the 34 ≥4-fold increases in the MICs, 15 were fully reversible, 13 were partially reversible, and 6 were nonreversible. Of the 26 ≥4-fold increases in the MBCs, 7 were fully reversible, 14 were partially reversible, and 5 were nonreversible. Significant decreases in biofilm formation in P10 strains occurred for apoEdpL-W (1/18 bacteria), chlorhexidine (1/18), and triclosan (2/18), while significant increases occurred for apoEdpL-W (1/18), triclosan (1/18), and chlorhexidine (2/18). These data indicate that the stability of induced changes in microbicide susceptibility varies but may be sustained for some combinations of a bacterium and a microbicide

    Transcriptional regulation of the cinnamyl alcohol dehydrogenase gene from sweetpotato in response to plant developmental stage and environmental stress

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    Cinnamyl alcohol dehydrogenase (CAD) is a key enzyme in the biosynthesis of lignin. We have isolated full length of a cDNA encoding CAD (IbCAD1) that was previously identified as the most abundant gene in an EST library of sweetpotato suspension cells. Phylogenetic analysis revealed that IbCAD1 belongs to the family of defense-related CADs. High levels of IbCAD1 mRNA were found in the roots of sweetpotato, but not in the leaves and petioles. The IbCAD1 gene transcripts were highly induced by cold, wounding, and reactive oxygen species. Analyses of transcriptional regulation of the IbCAD1 gene in transgenic tobacco plants carrying the IbCAD1 promoter–GUS revealed that IbCAD1 promoter expression was strong in the roots, but barely detectable in the cotyledons. IbCAD1 promoter activity increased with increasing root age, and strong promoter expression was observed in the lateral root emergence sites and in root tips. Weak GUS expression was observed in lignified tissues of vascular system of mature leaves and stems. IbCAD1 promoter activity was strongly induced in response to the biotic and abiotic stresses, with the strongest inducer being wounding, and was also induced by salicylic acid (SA) and jasmonic acid (JA) as well as by abscisic acid (ABA) and 6-benzylaminopurine. Taken together, our data suggest that IbCAD1 can be involved in JA- and SA-mediated wounding response and ABA-mediated cold response, respectively. The IbCAD1 gene may play a role in the resistance mechanism to biotic and abiotic stresses as well as in tissue-specific developmental lignification

    STUDI ALTERNATIF PERENCANAAAN SISTEM RANGKA PEMIKUL MOMEN KHUSUS (SRPMK) DENGAN KOLOM BULAT PADA KANTOR PUSAT ESTIKES KEPANJEN MALANG

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    Kolom merupakam elemen vertikal suatu struktur yang berfungsi menahan beban aksial dan momen sebagai akibat beban gravitasi dan beban lateral yang bekerja pada struktur. Oleh karena itu, kolom memegan penampang penting pada keutuhan struktur, apabila kolom mengalami kegagalan akan berakibat pada keruntuhan struktur bangunan atas gedung. perbedaan kolom bulat dan kolom persegi sangkat mendasar. Jika ditinjau dari tulangan sengkang, kolom bulat perpenampang spiral memiliki jarak sengkang yang berdekatan diabnding dengan kolom dengan kolom persegi yang mempunya bentuk sengkang tunggal dan jarak antara yang relatif besaar. Kolom bulat yang menghasilkan kapsitas penampang, gaya – gaya dalam seperti gaya aksial; gaya geser; gaya momen, dan simpangan (maximum displacement) sehingga dalam skripsi ini untuk mengetahui desain kolom bulat yang efisien dan efikas didalam perencanaan. Hasil yang diperoleh dari perenanaan struktur gedung dengan kolom bulat pada gedung kantor pusat stikes kepanjen malang dengan program bantu STAAD PRO V 8, yang ditinjau dari kapasitas penampang dengan luas mutu beton kolom bulat menghasilkan ØPn (aksial nominal) = 3988,690 kN, ØMn ( Momen nominal ) = 478,812 kNm, Vn (Geser nominal) = 681629,848 N. Sehingga kolom bulat memiliki kapasitas penampang yang lebih besar dan efektif. Ditinjau dari rasio dan gaya-gaya dalam struktur, kolom bulat memiliki gaya aksial = 0,021, kekakuan struktur pada kolom bulat memiliki simpangan (maximum displacements) yang lebih besar dari kolom persegi. Sehingga kekakuan pada kolom bulat lebih tinggi dengan kolom persegi
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