The cost, size and availability of electron accelerators are dominated by the achievable accelerating gradient. Conventional high-brightness radio-frequency accelerating structures operate with 30-50 ...MeV m(-1) gradients. Electron accelerators driven with optical or infrared sources have demonstrated accelerating gradients orders of magnitude above that achievable with conventional radio-frequency structures. However, laser-driven wakefield accelerators require intense femtosecond sources and direct laser-driven accelerators suffer from low bunch charge, sub-micron tolerances and sub-femtosecond timing requirements due to the short wavelength of operation. Here we demonstrate linear acceleration of electrons with keV energy gain using optically generated terahertz pulses. Terahertz-driven accelerating structures enable high-gradient electron/proton accelerators with simple accelerating structures, high repetition rates and significant charge per bunch. These ultra-compact terahertz accelerators with extremely short electron bunches hold great potential to have a transformative impact for free electron lasers, linear colliders, ultrafast electron diffraction, X-ray science and medical therapy with X-rays and electron beams.
Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.
In this event-driven, double-blind ...study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.
The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval CI, 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 95% CI, 1.05 to 2.32; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.
Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).
Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from ...COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air-liquid interface, in a configuration compatible with high resolution in-situ imaging and real-time sensing. We apply this platform to influenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV-NL63 and SARS-CoV-2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confirm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efficacy of camostat mesylate, a known inhibitor of HCoV-NL63 infection. This new capability can be used to address a major gap in the rapid assessment of therapeutic efficacy of small molecules and antiviral agents against influenza and other respiratory viruses including coronaviruses.
Quantum biology revisited Cao, Jianshu; Cogdell, Richard J; Coker, David F ...
Science advances,
04/2020, Letnik:
6, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Photosynthesis is a highly optimized process from which valuable lessons can be learned about the operating principles in nature. Its primary steps involve energy transport operating near theoretical ...quantum limits in efficiency. Recently, extensive research was motivated by the hypothesis that nature used quantum coherences to direct energy transfer. This body of work, a cornerstone for the field of quantum biology, rests on the interpretation of small-amplitude oscillations in two-dimensional electronic spectra of photosynthetic complexes. This Review discusses recent work reexamining these claims and demonstrates that interexciton coherences are too short lived to have any functional significance in photosynthetic energy transfer. Instead, the observed long-lived coherences originate from impulsively excited vibrations, generally observed in femtosecond spectroscopy. These efforts, collectively, lead to a more detailed understanding of the quantum aspects of dissipation. Nature, rather than trying to avoid dissipation, exploits it via engineering of exciton-bath interaction to create efficient energy flow.
ABSTRACT We present 0 4 resolution extinction-independent distributions of star formation and dust in 11 star-forming galaxies (SFGs) at z = 1.3-3.0. These galaxies are selected from sensitive ...blank-field surveys of the 2′ × 2′ Hubble Ultra-Deep Field at λ = 5 cm and 1.3 mm using the Karl G. Jansky Very Large Array and Atacama Large Millimeter/submillimeter Array. They have star formation rates (SFRs), stellar masses, and dust properties representative of massive main-sequence SFGs at z ∼ 2. Morphological classification performed on spatially resolved stellar mass maps indicates a mixture of disk and morphologically disturbed systems; half of the sample harbor X-ray active galactic nuclei (AGNs), thereby representing a diversity of z ∼ 2 SFGs undergoing vigorous mass assembly. We find that their intense star formation most frequently occurs at the location of stellar-mass concentration and extends over an area comparable to their stellar-mass distribution, with a median diameter of 4.2 1.8 kpc. This provides direct evidence of galaxy-wide star formation in distant blank-field-selected main-sequence SFGs. The typical galactic-average SFR surface density is 2.5 M yr−1 kpc−2, sufficiently high to drive outflows. In X-ray-selected AGN where radio emission is enhanced over the level associated with star formation, the radio excess pinpoints the AGNs, which are found to be cospatial with star formation. The median extinction-independent size of main-sequence SFGs is two times larger than those of bright submillimeter galaxies, whose SFRs are 3-8 times larger, providing a constraint on the characteristic SFR (∼300 M yr−1) above which a significant population of more compact SFGs appears to emerge.
This review documents the development of high-bunch charge electron pulses with sufficient combined spatiotemporal resolution and intensity to literally light up atomic motions. This development ...holds promise in coming to a first-principles understanding of diverse problems, ranging from molecular reaction dynamics and structure-function correlations in biology to cooperativity in strongly correlated electron-lattice systems. It is now possible to directly observe the key modes involved in propagating structural changes and the enormous reduction in dimensionality that occurs in barrier crossing regions, which is central to chemistry and makes reaction mechanisms transferrable concepts. This information will help direct theoretical advances that will undoubtedly lead to generalized principles with respect to scaling relations in structural dynamics that will bridge chemistry to biology. In this quest, the limitations and future directions for further development are discussed to give an overview of the present status of the field.
With the recent advances in ultrabright electron and x-ray sources, it is now possible to extend crystallography to the femtosecond time domain to literally light up atomic motions involved in the ...primary processes governing structural transitions. This review chronicles the development of brighter and brighter electron and x-ray sources that have enabled atomic resolution to structural dynamics for increasingly complex systems. The primary focus is on achieving sufficient brightness using pump-probe protocols to resolve the far-from-equilibrium motions directing chemical processes that in general lead to irreversible changes in samples. Given the central importance of structural transitions to conceptualizing chemistry, this emerging field has the potential to significantly improve our understanding of chemistry and its connection to driving biological processes.
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