Singly-resonant sum frequency generation of visible light in a semiconductor disk laser

In this paper a generic approach for visible light generation is presented. It is based on sum frequency generation between a semiconductor disk laser and a solid-state laser, where the frequency mixing is achieved within the cavity of the semiconductor disk laser using a singlepass of the solid-state laser light. This exploits the good beam quality and high intra-cavity power present in the semiconductor disk laser to achieve high conversion efficiency. Combining sum frequency mixing and semiconductor disk lasers in this manner allows in principle for generation of any wavelength within the visible spectrum, by appropriate choice of semiconductor material and single-pass laser wavelength

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

Rosetta FunFolDes - A general framework for the computational design of functional proteins

The robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function and stability. The low success rates of computational design protocols and the extensive in vitro optimization often required, highlight the challenge of designing proteins that perform essential biochemical functions, such as binding or catalysis. One of the most simplistic approaches for the design of function is to adopt functional motifs in naturally occurring proteins and transplant them to computationally designed proteins. The structural complexity of the functional motif largely determines how readily one can find host protein structures that are "designable", meaning that are likely to present the functional motif in the desired conformation. One promising route to enhance the "designability" of protein structures is to allow backbone flexibility. Here, we present a computational approach that couples conformational folding with sequence design to embed functional motifs into heterologous proteins-Rosetta Functional Folding and Design (FunFolDes). We performed extensive computational benchmarks, where we observed that the enforcement of functional requirements resulted in designs distant from the global energetic minimum of the protein. An observation consistent with several experimental studies that have revealed function-stability tradeoffs. To test the design capabilities of FunFolDes we transplanted two viral epitopes into distant structural templates including one de novo "functionless" fold, which represent two typical challenges where the designability problem arises. The designed proteins were experimentally characterized showing high binding affinities to monoclonal antibodies, making them valuable candidates for vaccine design endeavors. Overall, we present an accessible strategy to repurpose old protein folds for new functions. This may lead to important improvements on the computational design of proteins, with structurally complex functional sites, that can perform elaborate biochemical functions related to binding and catalysis

UV radiation enhanced oxygen vacancy formation caused by the PLD plasma plume

Pulsed Laser Deposition is a commonly used non-equilibrium physical deposition technique for the growth of complex oxide thin films. A wide range of parameters is known to influence the properties of the used samples and thin films, especially the oxygen-vacancy concentration. One parameter has up to this point been neglected due to the challenges of separating its influence from the influence of the impinging species during growth: the UV-radiation of the plasma plume. We here present experiments enabled by a specially designed holder to allow a separation of these two influences. The influence of the UV-irradiation during pulsed laser deposition on the formation of oxygen-vacancies is investigated for the perovskite model material SrTiO3. The carrier concentration of UV-irradiated samples is nearly constant with depth and time. By contrast samples not exposed to the radiation of the plume show a depth dependence and a decrease in concentration over time. We reveal an increase in Ti-vacancy–oxygen-vacancy-complexes for UV irradiated samples, consistent with the different carrier concentrations. We find a UV enhanced oxygen-vacancy incorporation rate as responsible mechanism. We provide a complete picture of another influence parameter to be considered during pulsed laser depositions and unravel the mechanism behind persistent-photo-conductivity in SrTiO3

The integration of occlusion and disparity information for judging depth in autism spectrum disorder

In autism spectrum disorder (ASD), atypical integration of visual depth cues may be due to flattened perceptual priors or selective fusion. The current study attempts to disentangle these explanations by psychophysically assessing within-modality integration of ordinal (occlusion) and metric (disparity) depth cues while accounting for sensitivity to stereoscopic information. Participants included 22 individuals with ASD and 23 typically developing matched controls. Although adults with ASD were found to have significantly poorer stereoacuity, they were still able to automatically integrate conflicting depth cues, lending support to the idea that priors are intact in ASD. However, dissimilarities in response speed variability between the ASD and TD groups suggests that there may be differences in the perceptual decision-making aspect of the task

Local and regional drivers influence how aquatic community diversity, resistance and resilience vary in response to drying

Disturbance events govern how the biodiversity of ecological communities varies in both space and time. In freshwater ecosystems, there is evidence that local and regional‐scale drivers interact to influence ecological responses to drying disturbances. However, most research provides temporal snapshots at the local scale, whereas few studies encompass a gradient of drying severity spanning multiple years. Using a dataset of rare spatiotemporal extent and detail, we demonstrate how independent and interacting local and regional‐scale factors drive shifts in the α and β diversities of communities in dynamic river ecosystems. We examined aquatic invertebrate assemblage responses to hydrological variability (as characterized by monthly observations of instream conditions) at 30 sites over a 12‐year period encompassing typical years and two severe drought disturbances. Sites varied in their disturbance regimes and hydrological connectivity at both local (i.e. site‐specific) and regional (i.e. river catchment) scales. Whereas α diversity was mainly influenced by local factors including flow permanence and the temporal extent of ponded and dry conditions, both temporal and spatial β diversities also responded to regional‐scale metrics such as the spatial extent of flow and hydrological connectivity. We observed stronger local negative responses for taxa with lower capacities to tolerate drying (i.e. resistance) and/or to recover after flow resumes (i.e. resilience), whereas taxa with functional traits promoting resilience made an increasing contribution to spatial β diversity as hydrological connectivity declined. As droughts increase in extent and severity across global regions, our findings highlight the functional basis of taxonomic responses to disturbance and connectivity, and thus advance understanding of how drying disturbances shape biodiversity in river networks. Our identification of the role of regional hydrological factors could inform catchment‐scale management strategies that support ecosystem resilience in a context of global change

Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus aureus foreign body infection

BACKGROUND: Daptomycin is a novel cyclic lipopeptide whose bactericidal activity is not affected by current antibiotic resistance mechanisms displayed by S. aureus clinical isolates. This study reports the therapeutic activity of high-dose daptomycin compared to standard regimens of oxacillin and vancomycin in a difficult-to-treat, rat tissue cage model of experimental therapy of chronic S. aureus foreign body infection. METHODS: The methicillin-susceptible S. aureus (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs, and time-kill curves of each antibiotic were evaluated as recommended by NCCLS, including supplementation with physiological levels (50 mg/L) of Ca(2+ )for daptomycin. Two weeks after local infection of subcutaneously implanted tissue cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin, oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple comparisons procedures. RESULTS: The MICs and MBCs of daptomycin, oxacillin, or vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L, respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of daptomycin compared to oxacillin or vancomycin. Twice-daily administered daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin) yielded bactericidal antibiotic levels in infected cage fluids throughout therapy. Before therapy, mean (± SEM) viable counts of strain I20 were 6.68 ± 0.10 log(10 )CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (± SEM) reduction in viable counts of MSSA I20 was 2.62 (± 0.30) log(10 )CFU/mL in cages (n = 18) of daptomycin-treated rats, exceeding by >2-fold (P < 0.01) the viable count reductions of 0.92 (± 0.23; n = 19) and 0.96 (± 0.24; n = 18) log(10 )CFU/mL in cages of oxacillin-treated and vancomycin-treated rats, respectively. Viable counts in cage fluids of untreated animals increased by 0.48 (± 0.24; n = 19) log(10 )CFU/mL. CONCLUSION: The improved efficacy of the twice-daily regimen of daptomycin (30 mg/kg) compared to oxacillin (200 mg/kg) or vancomycin (50 mg/kg) may result from optimisation of its pharmacokinetic and bactericidal properties in infected cage fluids