Photo-induced structural dynamics of o-nitrophenol by ultrafast electron diffraction.

The photo-induced dynamics of o-nitrophenol, particularly its photolysis, has garnered significant scientific interest as a potential source of nitrous acid in the atmosphere. Although the photolysis products and preceding photo-induced electronic structure dynamics have been investigated extensively, the nuclear dynamics accompanying the non-radiative relaxation of o-nitrophenol on the ultrafast timescale, which include an intramolecular proton transfer step, have not been experimentally resolved. Herein, we present a direct observation of the ultrafast nuclear motions mediating photo-relaxation using ultrafast electron diffraction. This work spatiotemporally resolves the loss of planarity which enables access to a conical intersection between the first excited state and the ground state after the proton transfer step, on the femtosecond timescale and with sub-Angstrom resolution. Our observations, supported by ab initio multiple spawning simulations, provide new insights into the proton transfer mediated relaxation mechanism in o-nitrophenol.

Predicting ecological outcomes using fuzzy interaction webs.

The past 100 years of empirical research in ecology have generated tremendous knowledge about the component interactions that structure ecological communities. Yet, we still lack the ability to reassemble these puzzle pieces to predict community responses to perturbations, a challenge that grows increasingly urgent given rapid global change. We summarize key advances in community ecology that have set the stage for modeling ecological systems and briefly review the evolution of ecological modeling efforts to identify critical hurdles to progress. We find that while Robert May demonstrated that quantitative models could theoretically predict community interactions nearly 50 years ago, in practice, we still lack the ability to predict ecological outcomes with reasonable accuracy for three reasons: (1) quantitative models require precise data for parameterization (often unavailable) and have restrictive assumptions that are rarely met; (2) estimating interaction strengths for all network components is extremely challenging; and (3) determining which species are essential to include in models is difficult (model structure uncertainty). We propose that fuzzy interaction webs (FIW), borrowed from the social sciences, hold the potential to overcome these modeling shortfalls by integrating quantitative and qualitative data (e.g., categorical data, natural history information, expert opinion) for generating reasonably accurate qualitative predictions sufficient for addressing many ecological questions. We outline recent advances developed for addressing model structure uncertainty, and we present a case study to illustrate how FIWs can be applied for estimating community interaction strengths and predicting complex ecological outcomes in a multitrophic (plants, herbivores, predators), multi-interaction-type (competition, predation, facilitation, omnivory) grassland ecosystem. We argue that incorporating FIWs into ecological modeling could significantly advance empirical and theoretical ecology.

Rehybridization dynamics into the pericyclic minimum of an electrocyclic reaction imaged in real-time.

Electrocyclic reactions are characterized by the concerted formation and cleavage of both σ and π bonds through a cyclic structure. This structure is known as a pericyclic transition state for thermal reactions and a pericyclic minimum in the excited state for photochemical reactions. However, the structure of the pericyclic geometry has yet to be observed experimentally. We use a combination of ultrafast electron diffraction and excited state wavepacket simulations to image structural dynamics through the pericyclic minimum of a photochemical electrocyclic ring-opening reaction in the molecule α-terpinene. The structural motion into the pericyclic minimum is dominated by rehybridization of two carbon atoms, which is required for the transformation from two to three conjugated π bonds. The σ bond dissociation largely happens after internal conversion from the pericyclic minimum to the electronic ground state. These findings may be transferrable to electrocyclic reactions in general.

Climate presses and pulses mediate the decline of a migratory predator.

Long-term climate changes and extreme climate events differentially impact animal populations, yet whether and why these processes may act synergistically or antagonistically remains unknown. Disentangling these potentially interactive effects is critical for predicting population outcomes as the climate changes. Here, we leverage the "press-pulse" framework, which is used to describe ecological disturbances, to disentangle population responses in migratory Magellanic penguins to long-term changes in climate means and variability (presses) and extreme events (pulses) across multiple climate variables and life history stages. Using an unprecedented 38-y dataset monitoring 53,959 penguins, we show for the first time that the presses and pulses of climate change mediate the rate of population decline by differentially impacting different life stages. Moreover, we find that climate presses and pulses can work both synergistically and antagonistically to affect animal population persistence, necessitating the need to examine both processes in concert. Negative effects of terrestrial heat waves (pulses) on adult survival, for example, were countered by positive effects of long-term changes in oceanographic conditions in migratory grounds (presses) on juvenile and adult survival. Taken together, these effects led to predicted population extirpation under all future climate scenarios. This work underscores the importance of a holistic approach integrating multiple climate variables, life stages, and presses and pulses for predicting the persistence of animals under accelerating climate change.

Observation of the non-linear Meissner effect.

A long-standing theoretical prediction is that in clean, nodal unconventional superconductors the magnetic penetration depth λ, at zero temperature, varies linearly with magnetic field. This non-linear Meissner effect is an equally important manifestation of the nodal state as the well studied linear-in-T dependence of λ, but has never been convincingly experimentally observed. Here we present measurements of the nodal superconductors CeCoIn5 and LaFePO which clearly show this non-linear Meissner effect. We further show how the effect of a small dc magnetic field on λ(T) can be used to distinguish gap nodes from non-nodal deep gap minima. Our measurements of KFe2As2 suggest that this material has such a non-nodal state.

Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy.

The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220-250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.

Conformer-specific photochemistry imaged in real space and time.

Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not conformer-sensitive. We report on a gas-phase megaelectronvolt ultrafast electron diffraction investigation of α-phellandrene undergoing an electrocyclic ring-opening reaction. We directly imaged the evolution of a specific set of α-phellandrene conformers into the product isomer predicted by the Woodward-Hoffmann rules in real space and time. Our experimental results are in quantitative agreement with nonadiabatic quantum molecular dynamics simulations, which provide considerable detail of how conformation influences the time scale and quantum efficiency of photoinduced ring-opening reactions.

Imaging the short-lived hydroxyl-hydronium pair in ionized liquid water.

The radiolysis of water is ubiquitous in nature and plays a critical role in numerous biochemical and technological applications. Although the elementary reaction pathways for ionized water have been studied, the short-lived intermediate complex and structural dynamic response after the proton transfer reaction remain poorly understood. Using a liquid-phase ultrafast electron diffraction technique to measure the intermolecular oxygen···oxygen and oxygen···hydrogen bonds, we captured the short-lived radical-cation complex OH(H3O+) that was formed within 140 femtoseconds through a direct oxygen···oxygen bond contraction and proton transfer, followed by the radical-cation pair dissociation and the subsequent structural relaxation of water within 250 femtoseconds. These measurements provide direct evidence of capturing this metastable radical-cation complex before separation, thereby improving our fundamental understanding of elementary reaction dynamics in ionized liquid water.

Emerging symmetric strain response and weakening nematic fluctuations in strongly hole-doped iron-based superconductors.

Electronic nematicity is often found in unconventional superconductors, suggesting its relevance for electronic pairing. In the strongly hole-doped iron-based superconductors, the symmetry channel and strength of the nematic fluctuations, as well as the possible presence of long-range nematic order, remain controversial. Here, we address these questions using transport measurements under elastic strain. By decomposing the strain response into the appropriate symmetry channels, we demonstrate the emergence of a giant in-plane symmetric contribution, associated with the growth of both strong electronic correlations and the sensitivity of these correlations to strain. We find weakened remnants of the nematic fluctuations that are present at optimal doping, but no change in the symmetry channel of nematic fluctuations with hole doping. Furthermore, we find no indication of a nematic-ordered state in the AFe2As2 (A = K, Rb, Cs) superconductors. These results revise the current understanding of nematicity in hole-doped iron-based superconductors.

A prospective, multi-center, practice-based cohort study on all-ceramic crowns.

OBJECTIVES: The aim of this prospective, multi-center, practice-based cohort study was to analyze factors associated with the success of all-ceramic crowns. METHODS: All-ceramic crowns placed in a practice-based research network ([Ceramic Success Analysis, AG Keramik) were analyzed. Data from 1254 patients with (mostly in-office CAD/CAM) all-ceramic crowns placed by 101 dentists being followed up for more than 5 years were evaluated. At the last follow-up visit crowns were considered as successful (not failed) if they were sufficient, whereas crowns were considered as survived (not lost) if they were still in function. Multi-level Cox proportional hazards models were used to evaluate the association between a range of predictors and time of success or survival. RESULTS: Within a mean follow-up period (SD) of 7.2(2)years [maximum:15years] 776 crowns were considered successful (annual failure rate[AFR]:8.4%) and 1041 crowns survived (AFR:4.9%). The presence of a post in endodontically treated teeth resulted in a risk for failure 2.7 times lower than that of restorations without a post (95%CI:1.4-5.0;p = 0.002). Regarding the restorative material and adhesive technique, hybrid composite ceramics and single-step adhesives showed a 3.4 and 2.2 times higher failure rate than feldspathic porcelain and multi-step adhesives, respectively (p < 0.001). Use of an oxygen-blocking gel as well as an EVA instrument resulted in a 1.5-1.8 times higher failure rate than their non-use (p ≤ 0.001). SIGNIFICANCE: After up to 15years AFR were rather high for all-ceramic crowns. Operative factors, but no patient- or tooth-level factors were significantly associated with failure. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00020271).

Efficacy of a self-assembling peptide to remineralize initial caries lesions - A systematic review and meta-analysis.

INTRODUCTION/OBJECTIVES: The present review systematically analyzed clinical studies investigating the efficacy of self-assembling peptides (SAP) to reduce initiation of or to remineralize initial caries lesions. DATA: Prospective controlled (non-)randomized clinical trials investigating the efficacy of a self-assembling peptide compared to any other (placebo) treatment or untreated/standard control. Outcomes were visual analog scale (VAS), laser fluorescence, ICDAS score or morphometric measurements. SOURCES: Three electronic databases (Central, PubMed, Ovid EMBASE) were screened. No language or time restrictions were applied.. Risk of Bias and level of evidence was graded using Risk of Bias 2.0 tool and Grade Profiler 3.6. STUDY SELECTION/RESULTS: Seven studies with 508 teeth being affected in 294 patients were included. All studies were randomized controlled trials (RCT), five with a split-mouth and two with a parallel-arm design. Meta-analysis could be performed for SAP (plus fluoride varnish (FV)) vs. no treatment (plus FV) (control treatment). Depending on the outcome after up to 12 months SAP showed a significantly higher optical improvement than the control treatment (laser fluorescence: Standardized Mean Difference (SMD)[95 %CI] = -0.87[-1.39,-0.34; VAS: Mean Difference (MD)[95 %CI] = -35.38[-43.13,-27.64]) or no significant difference could be observed (ICDAS/activity score; Relative Risk (RR)[95 %CI] = 0.6[0.21,1.74]; morphometric measurements: SMD[95 %CI] = -1.95[-4.54,0.65]). Level of evidence was very low for all 4 outcomes. Furthermore, six studies showed a high risk of bias and six studies were (partially) funded by the manufactures of the tested products. CONCLUSION: Based on a low number of clinical trials with relatively short follow up-periods and high risks of bias, self-assembling peptides may be a viable option to remineralize enamel caries. CLINICAL SIGNIFICANCE: Self-assembling peptides may be a viable option to remineralize enamel caries. However, results should be interpretated with caution due the low number of clinical trials, the short follow-up periods and the limiting grade of evidence.

Antiretroviral treatment outcomes among late HIV presenters initiating treatment with integrase inhibitors or protease inhibitors.

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.

Correlation of objective image quality and working length measurements in different CBCT machines: An ex vivo study.

To investigate potential correlations between objective CBCT image parameters and accuracy in endodontic working length determination ex vivo. Contrast-to-noise ratio (CNR) and spatial resolution (SR) as fundamental objective image parameters were examined using specific phantoms in seven different CBCT machines. Seven experienced observers were instructed and calibrated. The order of the CBCTs was randomized for each observer and observation. To assess intra-operator reproducibility, the procedure was repeated within six weeks with a randomized order of CBCT images. Multivariate analysis (MANOVA) did not reveal any influence of the combined image quality factors CNR and SR on measurement accuracy. Inter-operator reproducibility as assessed between the two observations was poor, with a mean intra-class correlation (ICC) of 0.48 (95%-CI  0.38, 0.59) for observation No. 1. and 0.40 (95%-CI 0.30, 0.51) for observation No. 2. Intra-operator reproducibility pooled over all observers between both observations was only moderate, with a mean ICC of 0.58 (95%-CI 0.52 to 0.64). Within the limitations of the study, objective image quality measures and exposure parameters seem not to have a significant influence on accuracy in determining endodontic root canal lengths in CBCT scans. The main factor of variance is the observer.

16S rRNA Gene Diversity in Ancient Gray and Pink Salt from San Simón Salt Mines in Tarija, Bolivia.

DNA from 250 million-year-old pink and gray salts from mines in Tarija, Bolivia, subjected to 16S rRNA gene amplicon sequencing and analysis provided evidence for similar but distinct prokaryotic communities. The results constitute a snapshot of archaeal and bacterial microorganisms in these remote and ancient salt deposits.

16S rRNA Gene Diversity in the Salt Crust of Salar de Uyuni, Bolivia, the World's Largest Salt Flat.

Salar de Uyuni is a vast, high-altitude salt flat in Bolivia with extreme physico-geochemical properties approaching multiple limits of life. Evidence for diverse halophilic bacteria and archaea was found in its surface and near-surface salt crust using 16S amplicon analysis, providing a snapshot of prokaryotic life.

Survey of Toxoplasma gondii Exposure in Muskrats in a Relatively Pristine Ecosystem.

Waterborne transmission of Toxoplasma gondii is assumed to be enhanced in areas with human-altered landscapes (e.g., urbanization, agriculture) and increased populations of non-native domestic and feral cats (Felis catus). However, little is known concerning T. gondii exposure risks in more natural watersheds (e.g., reduced human footprint, no domestic or feral cats) to establish a baseline for comparisons. In this study, muskrats (Ondatra zibethicus) were used as sentinels to assess baseline T. gondii exposure in a relatively pristine watershed in the Greater Voyageurs Ecosystem, northern Minnesota, during the summers of 2018-2019. Toxoplasma gondii antibodies were assayed in sera of live-trapped muskrats (n = 70) using a modified agglutination test. None of our samples were positive for T. gondii antibodies (P = 0.00, 95% Wald Score Confidence Interval = 0.00-0.05). This study establishes a baseline to compare T. gondii waterborne transmission risks in other human-modified watersheds.

Liquid-phase mega-electron-volt ultrafast electron diffraction.

The conversion of light into usable chemical and mechanical energy is pivotal to several biological and chemical processes, many of which occur in solution. To understand the structure-function relationships mediating these processes, a technique with high spatial and temporal resolutions is required. Here, we report on the design and commissioning of a liquid-phase mega-electron-volt (MeV) ultrafast electron diffraction instrument for the study of structural dynamics in solution. Limitations posed by the shallow penetration depth of electrons and the resulting information loss due to multiple scattering and the technical challenge of delivering liquids to vacuum were overcome through the use of MeV electrons and a gas-accelerated thin liquid sheet jet. To demonstrate the capabilities of this instrument, the structure of water and its network were resolved up to the 3 rd hydration shell with a spatial resolution of 0.6 Å; preliminary time-resolved experiments demonstrated a temporal resolution of 200 fs.

Photodissociation of aqueous I 3 - observed with liquid-phase ultrafast mega-electron-volt electron diffraction.

Developing femtosecond resolution methods for directly observing structural dynamics is critical to understanding complex photochemical reaction mechanisms in solution. We have used two recent developments, ultrafast mega-electron-volt electron sources and vacuum compatible sub-micron thick liquid sheet jets, to enable liquid-phase ultrafast electron diffraction (LUED). We have demonstrated the viability of LUED by investigating the photodissociation of tri-iodide initiated with a 400 nm laser pulse. This has enabled the average speed of the bond expansion to be measured during the first 750 fs of dissociation and the geminate recombination to be directly captured on the picosecond time scale.

Sex and Gender Differences in Rilpivirine based ART - Data from the HIVCENTER Frankfurt.

OBJECTIVE: While Rilpivirine has shown high overall response rates in treatment-naïve patients without sex and gender specific differences in clinical trials, Sex and gender specific data in treatment experienced patients receiving rilpivirine are still limited. We conducted a 48 week efficacy and safety analysis in naïve and treatment experienced men and women using retrospective data from the HIVCENTER Frankfurt. MATERIALS AND METHODS: In this retrospective observational study data of all patients who received a rilpivirine based regimen at the HIVCENTER between March 2011 and December 2015 were analyzed. Primary endpoint was the proportion of patients with any discontinuation until week 48. Virologic response rates (FDA snapshot analysis; HIV-1 RNA <50 copies/mL) were assessed at week 48. RESULTS: 194 patients (34% female) were included in the analysis. 74% were treatment-experienced and 26% naïve, respectively. Discontinuations were observed in 31 (15.9%) patients. Regarding sex differences, the proportion of discontinuations was significantly higher in women than in men (24.2% vs. 11.7%; p=0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Virologic failure occurred in 8 PLWHIV (4.1%). CONCLUSION: While virologic overall response rates to rilpivirine based ART were high for both treatment-experienced and -naïve patients the proportion of discontinuations was significantly higher in women (24.2% vs. 11.7%; p = 0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Although the total number of patients with virologic failure was low (4.1%), the higher rate of ART discontinuations in female patients receiving RPV require close monitoring in the first months of treatment addressing special needs of women living with HIV.