From Local Covalent Bonding to Extended Electric Field Interactions in Proton Hydration.

Seemingly simple yet surprisingly difficult to probe, excess protons in water constitute complex quantum objects with strong interactions with the extended and dynamically changing hydrogen-bonding network of the liquid. Proton hydration plays pivotal roles in energy transport in hydrogen fuel cells and signal transduction in transmembrane proteins. While geometries and stoichiometry have been widely addressed in both experiment and theory, the electronic structure of these specific hydrated proton complexes has remained elusive. Here we show, layer by layer, how utilizing novel flatjet technology for accurate x-ray spectroscopic measurements and combining infrared spectral analysis and calculations, we find orbital-specific markers that distinguish two main electronic-structure effects: Local orbital interactions determine covalent bonding between the proton and neigbouring water molecules, while orbital-energy shifts measure the strength of the extended electric field of the proton.

Modulating chitin synthesis in marine algae with iminosugars obtained by SmI2 and FeCl3-mediated diastereoselective carbonyl ene reaction.

Strategies for synthesizing polyhydroxylated piperidines such as iminosugars have received broad attention. These substances are known to interact with carbohydrate related enzymes, glycosidases and glycosyltransferases, to which also the large enzyme families of chitin synthases and cellulose synthases belong. Many chemical and biological aspects of chitin synthases remain unexplored due to the fact that modulating substances are hardly available or expensive. Starting from enantiopure D- and L-amino acids, a series of iminosugars was prepared by a Lewis acid-catalyzed cyclization of amino acid-derived unsaturated aldehydes as key step. Therefore, different Lewis acids were tested. For samarium diiodide we observed a superior stereoselectivity in comparison to iron(III) chloride and methylaluminium dichloride. To increase water solubility for testing and measurement of enzyme activity, the cyclization products were further functionalized. We established a novel biological chitin synthesis test system which allows quantitative investigation of chitin synthesis in the chitin fiber producing diatom algae Thalassiosira in vivo under the light microscope. None of the compounds displayed cytotoxicity, but two of the four iminosugars increased the length of the chitin fibers produced. This is a strong indicator that these compounds mimic carbohydrates responsible for restarting chitin polymerization.

Health and economic benefits of secondary education in the context of poverty: Evidence from Burkina Faso.

Even though formal education is considered a key determinant of individual well-being globally, enrollment in secondary schooling remains low in many low- and middle-income countries, suggesting that the perceived returns to such schooling may be low. We jointly estimate survival and monetary benefits of secondary schooling using detailed demographic and surveillance data from the Boucle du Mouhoun region, Burkina Faso, where national upper secondary schooling completion rates are among the lowest globally (<10%). We first explore surveillance data from the Nouna Health and Demographic Surveillance System from 1992 to 2016 to determine long-term differences in survival outcomes between secondary and higher and primary schooling using Cox proportional hazards models. To estimate average increases in asset holdings associated with secondary schooling, we use regionally representative data from the Burkina Faso Demographic Health Surveys (2003, 2010, 2014, 2017-18; N = 3,924). Survival was tracked for 14,892 individuals. Each year of schooling was associated with a mortality reduction of up to 16% (95% CI 0.75-0.94), implying an additional 1.9 years of life expectancy for men and 5.1 years for women for secondary schooling compared to individuals completing only primary school. Relative to individuals with primary education, individuals with secondary or higher education held 26% more assets (SE 0.02; CI 0.22-0.30). Economic returns for women were 3% points higher than male returns with 10% (SE 0.03; CI 0.04-0.16) vs. 7% (SE 0.02; CI 0.02-0.012) and in rural areas 20% points higher than in urban areas with 30% (SE 0.06; CI 0.19-0.41) vs. 4% (SE 0.01; CI 0.02-0.07). Our results suggest that secondary education is associated with substantial health and economic benefits in the study area and should therefore be considered by researchers, governments, and other major stakeholders to create for example school promotion programs.

Electronic Structure Changes of an Aromatic Amine Photoacid along the Förster Cycle.

Photoacids show a strong increase in acidity in the first electronic excited state, enabling real-time studies of proton transfer in acid-base reactions, proton transport in energy storage devices and biomolecular sensor protein systems. Several explanations have been proposed for what determines photoacidity, ranging from variations in solvation free energy to changes in electronic structure occurring along the four stages of the Förster cycle. Here we use picosecond nitrogen K-edge spectroscopy to monitor the electronic structure changes of the proton donating group in a protonated aromatic amine photoacid in solution upon photoexcitation and subsequent proton transfer dynamics. Probing core-to-valence transitions locally at the amine functional group and with orbital specificity, we clearly reveal pronounced electronic structure, dipole moment and energetic changes on the conjugate photobase side. This result paves the way for a detailed electronic structural characterization of the photoacidity phenomenon.

Shot noise limited soft x-ray absorption spectroscopy in solution at a SASE-FEL using a transmission grating beam splitter.

X-ray absorption near-edge structure (XANES) spectroscopy provides element specificity and is a powerful experimental method to probe local unoccupied electronic structures. In the soft x-ray regime, it is especially well suited for the study of 3d-metals and light elements such as nitrogen. Recent developments in vacuum-compatible liquid flat jets have facilitated soft x-ray transmission spectroscopy on molecules in solution, providing information on valence charge distributions of heteroatoms and metal centers. Here, we demonstrate XANES spectroscopy of molecules in solution at the nitrogen K-edge, performed at FLASH, the Free-Electron Laser (FEL) in Hamburg. A split-beam referencing scheme optimally characterizes the strong shot-to-shot fluctuations intrinsic to the process of self-amplified spontaneous emission on which most FELs are based. Due to this normalization, a sensitivity of 1% relative transmission change is achieved, limited by fundamental photon shot noise. The effective FEL bandwidth is increased by streaking the electron energy over the FEL pulse train to measure a wider spectral window without changing FEL parameters. We propose modifications to the experimental setup with the potential of improving the instrument sensitivity by two orders of magnitude, thereby exploiting the high peak fluence of FELs to enable unprecedented sensitivity for femtosecond XANES spectroscopy on liquids in the soft x-ray spectral region.

Causal effect of children's secondary education on parental health outcomes: findings from a natural experiment in Botswana.

OBJECTIVES: A growing literature highlights the intergenerational transmission of human capital from parents to children. However, far less is known about 'upward transmission' from children to parents. In this study, we use a 1996 Botswana education policy reform as a natural experiment to identify the causal effect of children's secondary schooling on their parents' health. SETTING: Botswana's decennial census (2001 and 2011). Data were obtained through the Integrated Public Use Microdata Series and are 10% random samples of the complete population in each of these census years. PARTICIPANTS: Survey respondents who were citizens born in Botswana, at least 18 years old at the time of the census and born in or after 1975 (n=89 721). PRIMARY AND SECONDARY OUTCOME MEASURES: Parental survival and disability at the time of the census, separately for mothers and fathers. RESULTS: The 1996 reform caused a large increase in grade 10 enrolment, inducing an additional 0.4 years of schooling for the first cohorts affected (95% CI 0.3 to 0.5, p<0.001). The reform, however, had no effect on parental survival and disability by the time exposed child cohorts reach age 30. Results were robust to a wide array of sensitivity analyses. CONCLUSIONS: This study found little evidence that parents' survival and disability were affected by their offspring's educational attainment in Botswana. Parents' health may not be necessarily affected by increasing their offspring's educational attainment.

Author Correction: Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate.

SETD2 catalyzes methylation at lysine 36 of histone H3 and it has many disease connections. We investigated the substrate sequence specificity of SETD2 and identified nine additional peptide and one protein (FBN1) substrates. Our data showed that SETD2 strongly prefers amino acids different from those in the H3K36 sequence at several positions of its specificity profile. Based on this, we designed an optimized super-substrate containing four amino acid exchanges and show by quantitative methylation assays with SETD2 that the super-substrate peptide is methylated about 290-fold more efficiently than the H3K36 peptide. Protein methylation studies confirmed very strong SETD2 methylation of the super-substrate in vitro and in cells. We solved the structure of SETD2 with bound super-substrate peptide containing a target lysine to methionine mutation, which revealed better interactions involving three of the substituted residues. Our data illustrate that substrate sequence design can strongly increase the activity of protein lysine methyltransferases.

Soft X-ray Absorption Spectroscopy of Aqueous Solutions Using a Table-Top Femtosecond Soft X-ray Source.

We demonstrate the feasibility of soft X-ray absorption spectroscopy in the water window using a table-top laser-based approach with organic molecules and inorganic salts in aqueous solution. A high-order harmonic source delivers femtosecond pulses of short wavelength radiation in the photon energy range from 220 to 450 eV. We report static soft X-ray absorption measurements in transmission on the solvated compounds O=C(NH2)2, CaCl2, and NaNO3 using flatjet technology. We monitor the absorption of the molecular samples between the carbon (∼280 eV) and nitrogen (∼400 eV) K-edges and compare our results with previous measurements performed at the BESSYII facility. We discuss the roles of pulse stability and photon flux in the outcome of our experiments. Our work paves the way toward table-top femtosecond, solution-phase soft X-ray absorption spectroscopy in the water window.

Soft X-ray Spectroscopy of the Amine Group: Hydrogen Bond Motifs in Alkylamine/Alkylammonium Acid-Base Pairs.

We use N K-edge absorption spectroscopy to explore the electronic structure of the amine group, one of the most prototypical chemical functionalities playing a key role in acid-base chemistry, electron donor-acceptor interactions, and nucleophilic substitution reactions. In this study, we focus on aliphatic amines and make use of the nitrogen 1s core electron excitations to elucidate the roles of N-H σ* and N-C σ* contributions in the unoccupied orbitals. We have measured N K-edge absorption spectra of the ethylamine bases Et xNH3- x ( x = 0...3; Et- = C2H5-) and the conjugate positively charged ethylammonium cation acids Et yNH4- y+ ( y = 0...4; Et- = C2H5-) dissolved in the protic solvents ethanol and water. Upon consecutive exchange of N-H for ethyl-groups, we observe a spectral shift, a systematic decrease of the N K-edge pre-edge peak, and a major contribution in the post-edge region for the ethylamine series. Instead, for the ethylammonium ions, the consecutive exchange of N-H for ethyl groups leads to an apparent reduction of pre-edge and post-edge intensities relative to the main-edge band, without significant frequency shifts. Building on findings from our previously reported study on aqueous ammonia and ammonium ions, we can rationalize these observations by comparing calculated N K-edge absorption spectra of free and hydrogen-bonded clusters. Hydrogen bonding interactions lead only to minor spectral effects in the ethylamine series, but have a large impact in the ethylammonium ion series. Visualization of the unoccupied molecular orbitals shows the consecutive change in molecular orbital character from N-H σ* to N-C σ* in these alkylamine/alkylammonium ion series. This can act as a benchmark for future studies on chemically more involved amine compounds.

Differences in procedural knowledge after a "spaced" and a "massed" version of an intensive course in emergency medicine, investigating a very short spacing interval.

BACKGROUND: Distributing a fixed amount of teaching hours over a longer time period (spaced approach) may result in better learning than delivering the same amount of teaching within a shorter time (massed approach). While a spaced approach may provide more opportunities to elaborate the learning content, a massed approach allows for more economical utilisation of teaching facilities and to optimise time resources of faculty. Favourable effects of spacing have been demonstrated for postgraduate surgery training and for spacing intervals of weeks to months. It is however unknown, whether a spacing effect can also be observed for shorter intervals and in undergraduate medical education. Therefore, we aimed to evaluate the effect of a short spacing intervention within an undergraduate intensive course in emergency medicine (EM) on students' procedural knowledge. METHODS: An EM intensive course of 26 teaching hours was delivered over either 4.5 days, or 3.0 days. After the course students' procedural knowledge was assessed by a specifically developed video-case based key-feature test (KF-test). RESULTS: Data sets of 156 students (81.7 %, 191 students eligible) were analysed, 54 from the spaced, and 102 from the massed version. In the KF-test students from the spaced version reached a mean of 14.8 (SD 2.0) out of 22 points, compared to 13.7 (SD 2.0) in the massed version (p = .002). Effect size was moderate (Cohen's d: 0.558). CONCLUSION: A significant spacing effect was observable even for a short spacing interval in undergraduate medical education. This effect was only moderate and may be weighed against planning needs of faculty and teaching resources.