Using experimental and computational energy equilibration to understand hierarchical self-assembly of Fmoc-dipeptide amphiphiles

Despite progress, a fundamental understanding of the relationships between the molecular structure and self-assembly configuration of Fmoc-dipeptides is still in its infancy. In this work, we provide a combined experimental and computational approach that makes use of free energy equilibration of a number of related Fmoc-dipeptides to arrive at an atomistic model of Fmoc-threonine-phenylalanine-amide (Fmoc-TF-NH2) which forms twisted fibres. By using dynamic peptide libraries where closely related dipeptide sequences are dynamically exchanged to eventually favour the formation of the thermodynamically most stable configuration, the relative importance of C-terminus modifications (amide versus methyl ester) and contributions of aliphatic versus aromatic amino acids (phenylalanine F vs. leucine L) is determined (F > L and NH2 > OMe). The approach enables a comparative interpretation of spectroscopic data, which can then be used to aid the construction of the atomistic model of the most stable structure (Fmoc-TF-NH2). The comparison of the relative stabilities of the models using molecular dynamic simulations and the correlation with experimental data using dynamic peptide libraries and a range of spectroscopy methods (FTIR, CD, fluorescence) allow for the determination of the nanostructure with atomistic resolution. The final model obtained through this process is able to reproduce the experimentally observed formation of intertwining fibres for Fmoc-TF-NH2, providing information of the interactions involved in the hierarchical supramolecular self-assembly. The developed methodology and approach should be of general use for the characterization of supramolecular structures

Mid-Infrared High-Contrast Imaging of HD 114174 B : An Apparent Age Discrepancy in a "Sirius-Like" Binary System

We present new observations of the faint "Sirius-like" companion discovered to orbit HD 114174. Previous attempts to image HD 114174 B at mid-infrared wavelengths using NIRC2 at Keck have resulted in a non-detection. Our new L'-band observations taken with the Large Binocular Telescope and LMIRCam recover the companion ($\Delta L$ = 10.15 $\pm$ 0.15 mag, $\rho$ = 0.675'' $\pm$ 0.016'') with a high signal-to-noise ratio (10 $\sigma$). This measurement represents the deepest L' high-contrast imaging detection at sub-arcsecond separations to date, including extrasolar planets. We confirm that HD 114174 B has near-infrared colors consistent with the interpretation of a cool white dwarf ($J-L'$ = 0.76 $\pm$ 0.19 mag, $K-L'$ = 0.64 $\pm$ 0.20). New model fits to the object's spectral energy distribution indicate a temperature $T_{\rm eff}$ = 4260 $\pm$ 360 K, surface gravity log g = 7.94 $\pm$ 0.03, a cooling age t$_{c} \approx$ 7.8 Gyr, and mass $M$ = 0.54 $\pm$ 0.01 $M_{\odot}$. We find that the cooling age given by theoretical atmospheric models do not agree with the age of HD 114174 A derived from both isochronological and gyrochronological analyses. We speculate on possible scenarios to explain the apparent age discrepancy between the primary and secondary. HD 114174 B is a nearby benchmark white dwarf that will ultimately enable a dynamical mass estimate through continued Doppler and astrometric monitoring. Efforts to characterize its physical properties in detail will test theoretical atmospheric models and improve our understanding of white dwarf evolution, cooling, and progenitor masses.Comment: 6 pages, 3 figures, to be published in the Astrophysical Journal Letter

A Map of the Inorganic Ternary Metal Nitrides

Exploratory synthesis in novel chemical spaces is the essence of solid-state chemistry. However, uncharted chemical spaces can be difficult to navigate, especially when materials synthesis is challenging. Nitrides represent one such space, where stringent synthesis constraints have limited the exploration of this important class of functional materials. Here, we employ a suite of computational materials discovery and informatics tools to construct a large stability map of the inorganic ternary metal nitrides. Our map clusters the ternary nitrides into chemical families with distinct stability and metastability, and highlights hundreds of promising new ternary nitride spaces for experimental investigation--from which we experimentally realized 7 new Zn- and Mg-based ternary nitrides. By extracting the mixed metallicity, ionicity, and covalency of solid-state bonding from the DFT-computed electron density, we reveal the complex interplay between chemistry, composition, and electronic structure in governing large-scale stability trends in ternary nitride materials

Barriers to and Facilitators of Help-Seeking Behavior Among Men Who Experience Sexual Violence

Research on sexual violence and related support services access has mainly focused on female victims; there is still a remarkable lack of research on men who experience sexual violence. Research demonstrates that people who both self-identify as men and are members of sexual-orientation minority populations are at higher risk of sexual violence. They are also less likely to either report or seek support services related to such experiences. The present study is an exploratory one aimed at filling the gap in the literature and better understanding how men, both straight and gay as well as cisgender and transgender, conceptualize, understand, and seek help related to sexual violence. A sample of 32 men was recruited on-line and participated in either a one-on-one in-depth interview (N = 19) or one of two focus group discussions (N = 13). All interviews and groups were audiotaped, professionally transcribed and coded using NVivo 9 qualitative software. The present analysis focused on barriers to and facilitators of support service access. Emergent and cross-cutting themes were identified and presented, with an emphasis on understanding what factors may prevent disclosure of a sexual violence experience and facilitate seeking support services and/or professional help. Through this analysis, the research team aims to add knowledge to inform the development of tools to increase service access and receipt, for use by both researchers and service professionals. Although this study contributes to the understanding of the issue of men’s experiences of sexual violence, more research with diverse populations is needed

Data-driven methods for diffusivity prediction in nuclear fuels

The growth rate of structural defects in nuclear fuels under irradiation is intrinsically related to the diffusion rates of the defects in the fuel lattice. The generation and growth of atomistic structural defects can significantly alter the performance characteristics of the fuel. This alteration of functionality must be accurately captured to qualify a nuclear fuel for use in reactors. Predicting the diffusion coefficients of defects and how they impact macroscale properties such as swelling, gas release, and creep is therefore of significant importance in both the design of new nuclear fuels and the assessment of current fuel types. In this article, we apply data-driven methods focusing on machine learning (ML) to determine various diffusion properties of two nuclear fuels, uranium oxide and uranium nitride. We show that using ML can increase, often significantly, the accuracy of predicting diffusivity in nuclear fuels in comparison to current analytical models. We also illustrate how ML can be used to quickly develop fuel models with parameter dependencies that are more complex and robust than what is currently available in the literature. These results suggest there is potential for ML to accelerate the design, qualification, and implementation of nuclear fuels

UV-Optical Pixel Maps of Face-On Spiral Galaxies -- Clues for Dynamics and Star Formation Histories

UV and optical images of the face-on spiral galaxies NGC 6753 and NGC 6782 reveal regions of strong on-going star formation that are associated with structures traced by the old stellar populations. We make NUV--(NUV-I) pixel color-magnitude diagrams (pCMDs) that reveal plumes of pixels with strongly varying NUV surface brightness and nearly constant I surface brightness. The plumes correspond to sharply bounded radial ranges, with (NUV-I) at a given NUV surface brightness being bluer at larger radii. The plumes are parallel to the reddening vector and simple model mixtures of young and old populations, thus neither reddening nor the fraction of the young population can produce the observed separation between the plumes. The images, radial surface-brightness, and color plots indicate that the separate plumes are caused by sharp declines in the surface densities of the old populations at radii corresponding to disk resonances. The maximum surface brightness of the NUV light remains nearly constant with radius, while the maximum I surface brightness declines sharply with radius. An MUV image of NGC 6782 shows emission from the nuclear ring. The distribution of points in an (MUV-NUV) vs. (NUV-I) pixel color-color diagram is broadly consistent with the simple mixture model, but shows a residual trend that the bluest pixels in (MUV-NUV) are the reddest pixels in (NUV-I). This may be due to a combination of red continuum from late-type supergiants and [SIII] emission lines associated with HII regions in active star-forming regions. We have shown that pixel mapping is a powerful tool for studying the distribution and strength of on-going star formation in galaxies. Deep, multi-color imaging can extend this to studies of extinction, and the ages and metallicities of composite stellar populations in nearby galaxies.Comment: LaTeX with AASTeX style file, 29 pages with 12 figures (some color, some multi-part). Accepted for publication in The Astrophysical Journa

Efficacy of nutritional interventions to lower circulating ceramides in young adults: FRUVEDomic pilot study

The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely composed of fruit and vegetables. Consuming a diet high in fruit and vegetables and low in refined carbohydrates and saturated fat may reduce an individual’s risk for type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic inflammation, and metabolic syndrome (MetS). Several recent studies have implicated the bioactive sphingolipid ceramide as an associative and causative biomarker for the development of these conditions. Considering that the intake of fruit and vegetables is frequently inadequate in young adults, we performed a pilot investigation to assess the efficacy of a free-living fruit and vegetable intervention on overall metabolic health, circulating ceramide supply, and inflammatory status in young adults. We discovered that adoption of the recommended DGA for fruit and vegetable intake for 8 weeks decreased waist circumference, systolic blood pressure, and circulating cholesterol. Lipidomics analysis revealed that nutritional intervention can lower circulating ceramides, including C24:0 ceramide, a known inhibitor of insulin signaling. Unexpectedly, we observed an increase in C16:0 ceramide, suggesting that this form of ceramide in circulation is not associated with metabolic disease in humans. We also observed an improved inflammatory status with enhanced fruit and vegetable intake that was correlated with ceramide concentrations. These data suggest that adopting the recommended DGA is associated with a reduction of many, but not all, ceramide species and may help to prevent or mitigate MetS. Future research needs to assess whether the ceramide-lowering ability of nutritional intervention is associated with reduced risk of developing metabolic disease

Enhanced Th17-Cell Responses Render CCR2-Deficient Mice More Susceptible for Autoimmune Arthritis

CCR2 is considered a proinflammatory mediator in many inflammatory diseases such as rheumatoid arthritis. However, mice lacking CCR2 develop exacerbated collagen-induced arthritis. To explore the underlying mechanism, we investigated whether autoimmune-associated Th17 cells were involved in the pathogenesis of the severe phenotype of autoimmune arthritis. We found that Th17 cells were expanded approximately 3-fold in the draining lymph nodes of immunized CCR2−/− mice compared to WT controls (p = 0.017), whereas the number of Th1 cells and regulatory T cells are similar between these two groups of mice. Consistently, levels of the Th17 cell cytokine IL-17A and Th17 cell-associated cytokines, IL-6 and IL-1β were approximately 2–6-fold elevated in the serum and 22–28-fold increased in the arthritic joints in CCR2−/− mice compared to WT mice (p = 0.04, 0.0004, and 0.01 for IL-17, IL-6, and IL-1β, respectively, in the serum and p = 0.009, 0.02, and 0.02 in the joints). Furthermore, type II collagen-specific antibodies were significantly increased, which was accompanied by B cell and neutrophil expansion in CCR2−/− mice. Finally, treatment with an anti-IL-17A antibody modestly reduced the disease severity in CCR2−/− mice. Therefore, we conclude that while we detect markedly enhanced Th17-cell responses in collagen-induced arthritis in CCR2-deficient mice and IL-17A blockade does have an ameliorating effect, factors additional to Th17 cells and IL-17A also contribute to the severe autoimmune arthritis seen in CCR2 deficiency. CCR2 may have a protective role in the pathogenesis of autoimmune arthritis. Our data that monocytes were missing from the spleen while remained abundant in the bone marrow and joints of immunized CCR2−/− mice suggest that there is a potential link between CCR2-expressing monocytes and Th17 cells during autoimmunity