Esophageal candidiasis is a frequent cause of morbidity in immunocompromised patients. Isavuconazole is a novel, broad-spectrum antifungal developed for the treatment of opportunistic fungal ...infections. This phase 2 trial compared the efficacy and safety of three oral dosing regimens of isavuconazole with an oral fluconazole regimen in the primary treatment of uncomplicated esophageal candidiasis. The isavuconazole regimens were as follows: 200 mg on day 1 and then 50 mg once daily (arm A), 400 mg on day 1 and then 400 mg once-weekly (arm B), and 400 mg on day 1 and then 100 mg once daily (arm C). Patients in arm D received fluconazole at 200 mg on day 1 and then 100 mg once daily. The minimum treatment duration was 14 days. The primary endpoint was the rate of endoscopically confirmed clinical response at end of therapy. Safety and tolerability were also assessed. Efficacy was evaluated in 153 of 160 enrolled patients. Overall, 146 (95.4%) achieved endoscopically confirmed clinical success. Each of the isavuconazole regimens was shown to be not inferior to fluconazole, i.e., arm A versus D, -0.5% (95% confidence interval CI -10.0 to 9.4), arm B versus D, 3.5% (95% CI, -5.6 to 12.7), and arm C versus D, -0.2% (95% CI, -9.8 to 9.4). The frequency of adverse events was similar in arm A (n = 22; 55%), arm B (n = 18; 45%), and arm D (n = 22; 58%), but higher in arm C (n = 29; 71%). In summary, efficacy and safety of once-daily and once-weekly isavuconazole were comparable with once-daily fluconazole in the primary treatment of uncomplicated esophageal candidiasis.
This paper provides a detailed analysis of how the European Emission Trading System (EU ETS) as the core climate policy instrument of the European Union has impacted innovation. Towards this end, we ...investigate the impact of the EU ETS on research, development and demonstration (RD&D), adoption, and organizational change. In doing so, we pay particular attention to the relative influences of context factors (policy mix, market factors and public acceptance) and firm characteristics (value chain position, technology portfolio, size and vision). Empirically, our qualitative analysis is based on multiple case studies with 19 power generators, technology providers and project developers in the German power sector which were conducted in 2008/09. We find that the innovation impact of the EU ETS has remained limited so far because of the scheme's initial lack of stringency and predictability and the relatively greater importance of context factors. Additionally, the impact varies significantly across technologies, firms, and innovation dimensions and is most pronounced for RD&D on carbon capture technologies and organizational changes. Our analysis suggests that the EU ETS on its own may not provide sufficient incentives for fundamental changes in corporate innovation activities at a level which ensures political long-term targets can be achieved.
Abstract Direct laser acceleration (DLA) of electrons in plasmas of near-critical density (NCD) is a very advancing platform for high-energy PW-class lasers of moderate relativistic intensity ...supporting Inertial Confinement Fusion research. Experiments conducted at the PHELIX sub-PW Nd:glass laser demonstrated application-promising characteristics of DLA-based radiation and particle sources, such as ultra-high number, high directionality and high conversion efficiency. In this context, the bright synchrotron-like (betatron) radiation of DLA electrons, which arises from the interaction of a sub-ps PHELIX laser pulse with an intensity of 10 19 W/cm 2 with pre-ionized low-density polymer foam, was studied. The experimental results show that the betatron radiation produced by DLA electrons in NCD plasma is well directed with a half-angle of 100–200 mrad, yielding (3.4 ± 0.4)·10 10 photons/keV/sr at 10 keV photon energy. The experimental photon fluence and the brilliance agree well with the particle-in-cell simulations. These results pave the way for innovative applications of the DLA regime using low-density pre-ionized foams in high energy density research.
Dimethyl sulfide (DMS), produced by marine organisms, represents the most abundant, biogenic sulfur emission into the Earth’s atmosphere. The gas-phase degradation of DMS is mainly initiated by the ...reaction with the OH radical forming first CH3SCH2O2 radicals from the dominant H-abstraction channel. It is experimentally shown that these peroxy radicals undergo a two-step isomerization process finally forming a product consistent with the formula HOOCH2SCHO. The isomerization process is accompanied by OH recycling. The rate-limiting first isomerization step, CH3SCH2O2 → CH2SCH2OOH, followed by O2 addition, proceeds with k = (0.23 ± 0.12) s–1 at 295 ± 2 K. Competing bimolecular CH3SCH2O2 reactions with NO, HO2, or RO2 radicals are less important for trace-gas conditions over the oceans. Results of atmospheric chemistry simulations demonstrate the predominance (≥95%) of CH3SCH2O2 isomerization. The rapid peroxy radical isomerization, not yet considered in models, substantially changes the understanding of DMS’s degradation processes in the atmosphere.
The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. ...However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550-541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 μM) was a key requirement for the development of early animal-based ecosystems.
Objective
We have recently shown that priming of synovial fibroblasts (SFs) drives arthritis flares. Pathogenic priming of SFs is essentially mediated by epigenetic reprogramming. Bromodomain and ...extraterminal motif (BET) proteins translate epigenetic changes into transcription. Here, we used a BET inhibitor (I‐BET151) to target inflammatory tissue priming and to reduce flare severity in a murine experimental arthritis model.
Methods
BALB/c mice were treated by intraperitoneal injection or by local injection in the paw with I‐BET151, which blocks the interaction of BET proteins with acetylated histones. We assessed the effects of I‐BET151 on acute arthritis and/or inflammatory tissue priming in a model of repeated injections of monosodium urate crystals or zymosan into the mouse paw. I‐BET151 was given before arthritis induction, at peak inflammation, or after healing of the first arthritis bout. We performed transcriptomic (RNA‐Seq), epigenomic (ATAC‐Seq), and functional (invasion, cytokine production, migration, senescence, metabolic flux) analyses of murine and human SFs treated with I‐BET151 in vitro or in vivo.
Results
Systemic I‐BET151 administration did not affect acute inflammation but abolished inflammatory tissue priming and diminished flare severity in both preventive and therapeutic treatment settings. I‐BET151 was also effective when applied locally in the joint. BET inhibition also inhibited osteoclast differentiation, while macrophage activation in the joint was not affected. Flare reduction after BET inhibition was mediated, at least in part, by rolling back the primed transcriptional, metabolic, and pathogenic phenotype of SFs.
Conclusion
Inflammatory tissue priming is dependent on transcriptional regulation by BET proteins, making them promising therapeutic targets for prevention of arthritis flares in previously affected joints.
Diffusion of atoms or molecules (generally: particles) is driven by differences and gradients of the chemical potential of the particles in their accessible space. If the difference of the chemical ...potential is due to differences of concentrations alone, one arrives at the diffusion equations of Fick. The diffusion coefficients are described in known models by vibrations of atoms in condensed matter which cause the exchange of preferentially neutral particles with neighbouring particles, impurities, interstitial places and vacancies near or on surfaces, grain boundaries, dislocation lines and in the homogeneous bulk. The rates of electronic transitions, however, increase also in melts and solids of chemically bonded particles with increasing temperature. Such transitions cause large fluctuating deviations of the local energy, the charge distribution and the local chemical and electrical potentials. The fluctuating deviations interact with the core ions and drive particles to interchange. This mechanism that supplements the known mechanisms of diffusion has not yet found adequate attention in the literature until now. Foundations, experimental results, evidence and consequences for diffusion are discussed.
Translation
Die Diffusion von Atomen oder Molekülen (allgemein: Teilchen) hat ihre Triebkraft infolge von Unterschieden und Gradienten des chemischen Potenzials der Teilchen in ihrem zugänglichen Raum. Wenn der Potenzialunterschied allein von Konzentrationsunterschieden herrührt, gelangt man zu den bekannten Diffusionsgleichungen nach Fick. Um die Diffusionskoeffizienten auf atomare Bewegungen in kondensierter Materie zurückzuführen, wurden in bisher bekannten Modellen Platzwechselvorgänge zumeist neutraler Teilchen mit Nachbarteilchen, Verunreinigungen, Zwischengitterplätzen, Leerstellen an Oberflächen, Korngrenzen, Versetzungen und im homogenen Volumen betrachtet. Es ist bekannt, dass in Schmelzen und Festkörpern mit chemischen Bindungen mit zunehmender Temperatur elektronische Übergänge auftreten, wodurch fluktuierende Abweichungen in der Ladungsverteilung und den lokalen chemischen und elektrischen Potenzialen entstehen. Diese Abweichungen üben Kräfte auf die Position der Rumpf‐Ionen aus und machen daher ebenfalls Platzwechsel von Teilchen möglich. Dieser ergänzende Mechanismus für die Diffusion wurde bisher in der Literatur nicht hinreichend beachtet. Grundlagen, experimentelle Ergebnisse, Hinweise und Folgerungen für den Diffusionsvorgang werden aufgezeigt und diskutiert.
The fluctuating occupancy of bosonic (phonon or vibrational) states is often considered to drive self‐diffusion of atoms in solids and melts without additional external driving forces. Several experimental observations and their interpretation produce evidence, however, that the concomitant fluctuating occupancy of fermionic states (electrons and holes) and their transitions drive self‐diffusion as well.
From heat to entropy Hoffmann, H.‐J.
Materialwissenschaft und Werkstofftechnik,
September 2020, Letnik:
51, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Milestones in the development of thermodynamics are the discovery of the absolute temperature scale and the recognition that differential “heat” is a form of energy given as the product of absolute ...temperature and differential entropy. Following a new path, the last statement results from a careful analysis of the heat transfer applying the first theorem without reference to the usual cycles in thermodynamics. This confirms also characteristic properties of entropy. In particular, the total entropy can never decrease in a process. In thermal equilibrium, the differential thermal energy is proportional to the differential entropy with the constant of proportionality being the temperature of the heat and entropy. Hence, thermal energy and entropy are transferred simultaneously into the same storage facilities, some of which are mentioned. However, the issue which one is the superior quantity is obsolete. The entropy is maximum for a given amount of exchanged thermal energy and, vice versa, for a given amount of exchanged entropy the concomitant energy is minimum. We calculate the thermal energy and entropy of phonons (as bosons) in oscillators and of electrons (as fermions) in their states of solids and melts as examples from statistical thermodynamics. The thermal energy or heat is the sum of the energies of all bosons and fermions in their elementary states or quantum states according to Bose Einstein and Fermi Dirac statistics in thermal equilibrium minus the total energy in the limit T→0 K. The entropy can be written as mixing entropy of all of these quantum states weighted with their occupancies, in agreement with an earlier publication. Thus, entropy is a logarithmic metrics of the number of all possible variants to distribute the respective total energy over all elementary states in thermal equilibrium.
Translation
Zu den Meilensteinen in der Entwicklung der Thermodynamik gehören die Entdeckung der absoluten Temperaturskala und die Erkenntnis, dass „Wärme“ eine Form von Energie ist, wobei differentielle „Wärme“ das Produkt von absoluter Temperatur und differentieller Entropie ist. Auf neuem Weg wird gezeigt, dass letzteres durch Analyse des Wärmeübertrags bereits aus dem ersten Hauptsatz ohne die üblicherweise betrachteten Kreisprozesse folgt. Wichtige Eigenschaften der Entropie lassen sich hieraus begründen. Insbesondere folgt die Gesamt‐Entropie in einem Prozess einem einseitigen Erhaltungssatz, indem sie nicht vernichtet oder verzehrt werden kann, wohl aber erzeugt oder – im Grenzfall ‐ konstant bleiben kann. Differenzielle thermische Energie und Entropie sind im thermischen Gleichgewicht über die absolute Temperatur als Faktor eindeutig und untrennbar verbunden. Sie werden daher in gleiche Speicher übertragen. Speichermöglichkeiten werden aufgezählt. Es erübrigt sich daher die Frage nach der Priorität beider Größen. Bei vorgegebenem Austausch an thermischer Energie ist die gleichzeitig ausgetauschte Entropie maximal und, im Umkehrschluss, die ausgetauschte thermische Energie ist bei vorgegebenem Entropieaustausch minimal. Thermische Energie und Entropie werden für Phononen in Anregungszuständen elastischer Oszillatoren (als Bosonen) und für Elektronen (als Fermionen) in deren Anregungszuständen berechnet. Die thermische Energie bzw. Wärme ergibt sich dann als Summe der mittleren Energien aller Bosonen und Fermionen in ihren angeregten elementaren Zuständen, die nach der Bose‐Einstein oder Fermi‐Dirac Verteilung im thermischen Gleichgewicht besetzt werden minus der Gesamtenergie im Grenzfall T→0 K. Für die Entropie wird in Übereinstimmung mit einer früheren Arbeit abgeleitet, dass sie als Mischungsentropie aller besetzten Zustände dargestellt werden kann. Damit ist Entropie ein logarithmisches Maß der Anzahl aller möglichen Verteilungen der jeweiligen thermischen Gesamtenergie eines Systems auf die elementaren Zustände im thermischen Gleichgewicht.
Thermal entropy is introduced by a new approach and its meaning is clarified based on Bose Einstein statistics for bosons and Fermi Dirac statistics for fermions. It corresponds to mixing entropy representing Boltzmann's constant, k, times the natural logarithm of the number of all different variants to store the thermal energy in the elementary states at a given equilibrium temperature T.
Objective
This study utilized the Reflect! platform, an educational tool, as an instrument to structure deliberations among small groups of people with conflicting views. Can a technology designed to ...provide guidance for self‐directed learning in small teams of students also be used in projects with “real” stakeholders involved in actual conflicts?
Method
In an exploratory case study, the investigator invited three representatives of civic organizations in Atlanta, Georgia, to collaborate on the problem of dealing with the Confederate Memorial carved in Stone Mountain. The study included qualitative analysis of observational data, structured participant interviews, and participant‐generated materials.
Results
Participants succeeded in formulating a shared position on what to do with the Confederate Memorial on Stone Mountain. However, the study highlights limitations in the interpretation of findings, as well as certain advantages and disadvantages of the platform.
Conclusion
It seems that the Reflect! approach could do most good somewhere in the middle between large‐scale deliberations such as a town hall meeting and professional conflict management. With its step‐by‐step activities and its focus on stimulating reflection, the Reflect! platform can support mutual understanding on highly controversial issues.
IMesh, the tile processor architecture's on-chip interconnection network, connects the multicore processor's tiles with five 2D mesh networks, each specialized for a different use. taking advantage ...of the five networks, the C-based ILIB interconnection library efficiently maps program communication across the on-chip interconnect. the tile processor's first implementation, the tile64, contains 64 cores and can execute 192 billion 32-bit operations per second at 1 Ghz.
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