The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D ...synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subångström length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
Hybridization and speciation Abbott, R.; Albach, D.; Ansell, S. ...
Journal of evolutionary biology,
February 2013, Volume:
26, Issue:
2
Journal Article
Peer reviewed
Open access
Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via ...adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.
Human cytomegalovirus (HCMV) is a major cause of disease in immunocompromised individuals and the most common cause of congenital infection and neurosensorial disease. The expanding target ...populations for HCMV antiviral treatment along with the limitations of the currently available HCMV DNA polymerase inhibitors underscore the need for new antiviral agents with alternative modes of action. The antimalarial artemisinin derivative artesunate was shown to inhibit HCMV
yet has demonstrated limited antiviral efficacy
, prompting our search for more potent anti-HCMV artemisinin derivatives. Here we show that the innovative artemisinin derivative artemisone, which has been screened for its activity against malaria parasites in human clinical studies, is a potent and noncytotoxic inhibitor of HCMV. Artemisone exhibited an antiviral efficacy comparable to that of ganciclovir (50% effective concentration, 1.20 ± 0.46 μM) in human foreskin fibroblasts, with enhanced relative potency in lung fibroblasts and epithelial cells. Significantly, the antiviral efficacy of artemisone was consistently ≥10-fold superior to that of artesunate in all cells. Artemisone effectively inhibited both laboratory-adapted and low-passage-number clinical strains, as well as drug-resistant HCMV strains. By using quantitative viral kinetics and gene expression studies, we show that artemisone is a reversible inhibitor targeting an earlier phase of the viral replication cycle than ganciclovir. Importantly, artemisone most effectively inhibited HCMV infection
in a clinically relevant multicellular model of integral human placental tissues maintained in organ culture. Our promising findings encourage preclinical and clinical studies of artemisone as a new inhibitor against HCMV.
The development of ultrafast gas electron diffraction with nonrelativistic electrons has enabled the determination of molecular structures with atomic spatial resolution. It has, however, been ...challenging to break the picosecond temporal resolution barrier and achieve the goal that has long been envisioned—making space- and-time resolved molecular movies of chemical reaction in the gas-phase. Recently, an ultrafast electron diffraction (UED) apparatus using mega-electron-volt (MeV) electrons was developed at the SLAC National Accelerator Laboratory for imaging ultrafast structural dynamics of molecules in the gas phase. The SLAC gas-phase MeV UED has achieved 65 fs root mean square temporal resolution, 0.63 Å spatial resolution, and 0.22 Å−1 reciprocal-space resolution. Such high spatial-temporal resolution has enabled the capturing of real-time molecular movies of fundamental photochemical mechanisms, such as chemical bond breaking, ring opening, and a nuclear wave packet crossing a conical intersection. In this paper, the design that enables the high spatial-temporal resolution of the SLAC gas phase MeV UED is presented. The compact design of the differential pump section of the SLAC gas phase MeV UED realized five orders-of-magnitude vacuum isolation between the electron source and gas sample chamber. The spatial resolution, temporal resolution, and long-term stability of the apparatus are systematically characterized.
BACKGROUND:Reported infection rates following anterior cruciate ligament (ACL) reconstruction are low, but infections are associated with high morbidity including reoperations and inferior clinical ...outcomes. The purpose of the current study was to investigate the rate of infection after ACL reconstruction with and without graft preparation with a vancomycin irrigant.
METHODS:All ACL reconstructions performed between May 2009 and August 2018 at a single academic institution were reviewed and categorized based on vancomycin use. Patients with <90-day follow-up, intraoperative graft preparation with an antibiotic other than vancomycin, or previous ipsilateral knee infection were excluded. Infection was defined as a return to the operating room for irrigation and debridement within 90 days after ACL reconstruction. Descriptive and inferential statistical analysis using t tests and Poisson regression were performed, with significance defined as p < 0.05.
RESULTS:In total, 1,640 patients (952 males; 58.0%) with a mean age (and standard deviation) of 27.7 ± 11.4 years underwent ACL reconstruction (1,379 primary procedures; 84.1%) and were included for analysis. Intraoperative vancomycin was used in 798 cases (48.7%), whereas 842 ACL reconstructions (51.3%) were performed without intraoperative vancomycin. In total, 11 reconstructions (0.7%) were followed by infection, which occurred in 10 (1.2%) of the patients in whom the graft was not soaked in vancomycin and in 1 (0.1%) of the patients in whom the graft was soaked in vancomycin (p = 0.032). Age (p = 0.571), sex (p = 0.707), smoking (p = 0.407), surgeon (p = 0.124), and insurance type (p = 0.616) were not associated with postoperative infection risk. Autograft use was associated with decreased infections (p = 0.045). There was an 89.4% relative risk reduction with the use of intraoperative vancomycin. An increased body mass index (BMI) (p = 0.029), increased operative time (p = 0.001), and the absence of ACL graft preparation with vancomycin (p = 0.032) independently predicted postoperative infection.
CONCLUSIONS:The use of vancomycin-soaked grafts was associated with a 10-fold reduction in infection after ACL reconstruction (0.1% versus 1.2%; p = 0.032). Other risk factors for infection after ACL reconstruction included increased BMI and increased operative time.
LEVEL OF EVIDENCE:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Orbital phase-dependent variations in thermal emission and reflected stellar energy spectra can provide meaningful constraints on the climate states of terrestrial extrasolar planets orbiting M dwarf ...stars. Spatial distributions of water vapor, clouds, and surface ice are controlled by climate. In turn, water, in each of its thermodynamic phases, imposes significant modulations to thermal and reflected planetary spectra. Here we explore these characteristic spectral signals, based on 3D climate simulations of Earth-sized aquaplanets orbiting M dwarf stars near the habitable zone. By using 3D models, we can self-consistently predict surface temperatures and the location of water vapor, clouds, and surface ice in the climate system. Habitable zone planets in M dwarf systems are expected to be in synchronous rotation with their host star and thus present distinct differences in emitted and reflected energy fluxes depending on the observed hemisphere. Here we illustrate that icy, temperate, and incipient runaway greenhouse climate states exhibit phase-dependent spectral signals that enable their characterization.
A diversity of dusty AGN tori Burtscher, L; Meisenheimer, K; Tristram, K R W ...
Astronomy and astrophysics (Berlin),
10/2013, Volume:
558
Journal Article
Peer reviewed
Open access
The AGN-heated dust distribution is increasingly recognized not only as the absorber required in unifying models, but as a tracer for the reservoir that feeds the nuclear super-massive black hole. ...Yet, even its most basic structural properties are unknown for all but a few archetypical objects. In order to understand how the properties of AGN tori are related to feeding and obscuration, we need to resolve the matter distribution on parsec scales. Since most AGNs are unresolved in the mid-IR, even with the largest telescopes, we utilize the MID-infrared interferometric Instrument (MIDI) at the Very Large Telescope Interferometer (VLTI) that is sensitive to structures as small as a few milli-arcseconds. Variations in the relative contribution of extended dust in the narrow line region or heated by star formation vs. compact AGN-heated dust and non-thermal emission also have to be taken into account.
Lupus nephritis (LN) is a serious complication for many patients who develop systemic lupus erythematosus, which primarily afflicts women. Our studies to identify biomarkers and the pathogenic ...mechanisms underlying LN will provide a better understanding of disease progression and sex bias, and lead to identification of additional potential therapeutic targets. The glycosphingolipid lactosylceramide (LacCer) and N-linked glycosylated proteins (N-glycans) were measured in urine and serum collected from LN and healthy control (HC) subjects (10 females and 10 males in each group). The sera from the LN and HC subjects were used to stimulate cytokine secretion and intracellular Ca
flux in female- and male-derived primary human renal mesangial cells (hRMCs). Significant differences were observed in the urine of LN patients compared to HCs. All major LacCers species were significantly elevated and differences between LN and HC were more pronounced in males. 72 individual N-glycans were altered in LN compared to HC and three N-glycans were significantly different between the sexes. In hRMCs, Ca
flux, but not cytokine secretion, was higher in response to LN sera compared to HC sera. Ca
flux, cytokine secretion, and glycosphingolipid levels were significantly higher in female-derived compared to male-derived hRMCs. Relative abundance of some LacCers and hexosylceramides were higher in female-derived compared to male-derived hRMCs. Urine LacCers and N-glycome could serve as definitive LN biomarkers and likely reflect renal disease activity. Despite higher sensitivity of female hRMCs, males may experience greater increases in LacCers, which may underscore worse disease in males. Elevated glycosphingolipid metabolism may poise renal cells to be more sensitive to external stimuli.
Context. Tori of Active Galactic Nuclei (AGN) are made up of a mixture of hot and cold gas, as well as dust. In order to protect the dust grains from destruction by the surrounding hot gas as well as ...by the energetic (UV/optical) radiation from the accretion disk, the dust is often assumed to be distributed in clouds. Aims. A new three-dimensional model of AGN dust tori is extensively investigated. The torus is modelled as a wedge-shaped disk within which dusty clouds are randomly distributed throughout the volume, by taking the dust density distribution of the corresponding continuous model into account. We especially concentrate on the differences between clumpy and continuous models in terms of the temperature distributions, the surface brightness distributions and interferometric visibilities, as well as spectral energy distributions. Methods. Radiative transfer calculations with the help of the three-dimensional Monte Carlo radiative transfer code MC3D are used in order to simulate spectral energy distributions as well as surface brightness distributions at various wavelengths. In a second step, interferometric visibilities for various inclination as well as position angles and baselines are calculated, which can be used to directly compare our models to interferometric observations with the MIDI instrument. Results. We find that the radial temperature distributions of clumpy models possess significantly enhanced scatter compared to the continuous cases. Even at large distances, clouds can be heated directly by the central accretion disk. The existence of the silicate 10 μm-feature in absorption or in emission depends sensitively on the distribution, the size and optical depth of clouds in the innermost part of the dust distribution. With this explanation, failure and success of previous modelling efforts of clumpy tori can be understood. The main reason for this outcome are shadowing effects of clouds within the central region. We underline this result with the help of several parameter variations. After adapting the parameters of our clumpy standard model to the circumstances of the Seyfert 2 Circinus galaxy, it can qualitatively explain recent mid-infrared interferometric observations performed with MIDI, as well as high resolution spectral data.
We report on the properties of pre-main-sequence objects in the Taurus molecular clouds as observed in seven mid- and far-infrared bands with the Spitzer Space Telescope. There are 215 previously ...identified members of the Taurus star-forming region in our ~44 deg2 map these members exhibit a range of Spitzer colors that we take to define young stars still surrounded by circumstellar dust (noting that ~20% of the bona fide Taurus members exhibit no detectable dust excesses). We looked for new objects in the survey field with similar Spitzer properties, aided by extensive optical, X-ray, and ultraviolet imaging, and found 148 new candidate members of Taurus. We have obtained follow-up spectroscopy for about half the candidate sample, thus far confirming 34 new members, three probable new members, and 10 possible new members, an increase of 15%-20% in Taurus members. Of the objects for which we have spectroscopy, seven are now confirmed extragalactic objects, and one is a background Be star. The remaining 93 candidate objects await additional analysis and/or data to be confirmed or rejected as Taurus members. Most of the new members are Class II M stars and are located along the same cloud filaments as the previously identified Taurus members. Among non-members with Spitzer colors similar to young, dusty stars are evolved Be stars, planetary nebulae, carbon stars, galaxies, and active galactic nuclei.
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