263 research outputs found

    Brood size, sibling competition, and the cost of begging in great tits (Parus major)

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    Evolutionary theory of parent-offspring conflict explains begging displays of nestling birds as selfish attempts to influence parental food allocation. Models predict that this conflict may be resolved by honest signaling of offspring need to parents, or by competition among nestmates, leading to escalated begging scrambles. Although the former type of models has been qualitatively supported by experimental studies, the potential for a begging component driven by scramble competition cannot be excluded by the evidence. In a brood-size manipulation experiment with great tits, Parus major, we explored the scramble component in the begging activity of great tit nestlings by investigating the mechanisms of sibling competition in relation to brood size. While under full parental compensation, the feeding rate per nestling will remain constant over all brood sizes for both types of models; the scramble begging models alone predict an increase in begging intensity with brood size, if begging costs do not arise exclusively through predation. Great tit parents adjusted feeding rates to brood size and fed nestlings at similar rates and with similar prey sizes in all three brood-size categories. Despite full parental compensation, the begging and food solicitation activities increased with experimental brood size, whereas nestling body condition deteriorated. These findings support a scramble component in begging and suggest that the competition-induced costs of food solicitation behavior play an important role in the evolution of parent-offspring communicatio

    Influence of the Pulse Duration in the ps-Regime on the Ablation Efficiency of Metals

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    AbstractAblation characteristics of copper and stainless steel with laser pulses from 10 to 100 ps at 1064nm wavelength were studied. The influence of the pulse duration and the number of pulses on the threshold fluence and the penetration depth has been investigated. The results show a strong decrease of the ablation efficiency and quality with increasing pulse duration

    Revealing cytotoxic substructures in molecules using deep learning

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    In drug development, late stage toxicity issues of a compound are the main cause of failure in clinical trials. In silico meth ods are therefore of high importance to guide the early design process to reduce time, costs and animal testing. Technical advances and the ever growing amount of available toxicity data enabled machine learning, especially neural networks, to impact the feld of predictive toxicology. In this study, cytotoxicity prediction, one of the earliest handles in drug discovery, is investigated using a deep learning approach trained on a highly consistent in-house data set of over 34,000 compounds with a share of less than 5% of cytotoxic molecules. The model reached a balanced accuracy of over 70%, similar to previ ously reported studies using Random Forest. Albeit yielding good results, neural networks are often described as a black box lacking deeper mechanistic understanding of the underlying model. To overcome this absence of interpretability, a Deep Taylor Decomposition method is investigated to identify substructures that may be responsible for the cytotoxic efects, the so-called toxicophores. Furthermore, this study introduces cytotoxicity maps which provide a visual structural interpretation of the relevance of these substructures. Using this approach could be helpful in drug development to predict the potential toxicity of a compound as well as to generate new insights into the toxic mechanism. Moreover, it could also help to de-risk and optimize compounds

    Picosecond-laser-induced structural modifications in the bulk of single-crystal diamond

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    Arrays of through laser-graphitized microstructureshavebeenfabricatedintypeIIasingle-crystal1.2-mmthick diamond plates by multipulse laser irradiation with 10-ps pulses at λ=532 nm wavelength. Raman and photoluminescence (PL) spectroscopy studies of the bulk microstructures have evidenced the diamond transformation to amorphous carbon and graphitic phases and the formation of radiation defects pronounced in the PL spectra as the self-interstitial related center, the 3H center, at 504 nm. It is found that the ultrafast-laser-induced structural modifications in the bulk of single-crystal diamond plates occur along{111}planes, known as the planes of the lowest cleavage energy and strength in diamond

    Prevalence of mental disorders in the Zurich Cohort Study: a twenty year prospective study

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    Background — In order to minimise retrospective recall in developing estimates of the prevalence of mental dis-orders in the general population, we conducted a prospective study of a cohort of youth from Zurich, Switzerland. Method — A 20 year prospective study of a community-based cohort aged 19-20 from Zurich Switzerland. The sample was enriched by subjects scoring high on the Symptom Checklist 90 R (Derogatis, 1977). A semi-structured diagnostic interview was administered by clinically experienced psychologists and psychiatrists. The six interviews from 1979 to 1999 assessed diagnoses and sub-threshold manifestations of major diagnostic categories (with the exception of schizophrenia) for the past twelve months, depending on the current DSM versions (DSM-IH, DSM-HI R, DSM-IV). Additional information on symptoms and treatment were collected for the years between the interviews. The reported prevalence rates are weighted for stratified sampling and cumulate the one-year rates of the six interviews. Results — The cumulative weighted prevalence rates for any psychiatric disorder were 48.6% excluding, and 57.7% including tobacco dependence. In addition 29.2% and 21.8%, respectively manifested sub-diagnostic syndromes. Overall there were no significant gender differences. The corresponding treatment prevalence rates were 22.4% and 31.1%, respectively for the diagnostic subjects and 6.9% and 6.1 %, respectively for the sub-diagnostic groups. The total treatment prevalence rate was 37.2% of the population (males 30.0%, females 44.1%). Conclusions — Our findings reveal that psychiatric disorders are quite common in the general population. When the spectra of mental disorders are considered, nearly three quarters of the general population will have manifested at least one of the mental disorders across their lifetime. Limitations — The data are based on a relatively small sample; a single age cohort, and the study was conducted in Zurich, Switzerland. These study features may diminish the generalisability of the findings. Declaration of Interest: this work was supported by Grant 3200-050881.97/1 of the Swiss National Science Foundation, and Research Scientist Development Awards (MH 46376 and DA00293) from the US National Institutes of Health (Dr. Merikangas

    Small Molecules Targeting Human UDP-GlcNAc 2-Epimerase

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    Uridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay. We validated nine of the primary actives with an orthogonal real-time NMR assay and verified their IC50 values in the low micromolar to nanomolar range manually. Stability and solubility studies revealed three compounds for further evaluation. Thermal shift assays, analytical size exclusion, and interferometric scattering microscopy demonstrated that the GNE inhibitors acted on the oligomeric state of the protein. Finally, hydrogen-deuterium exchange mass spectrometry (HDX-MS) revealed which sections of GNE were shifted upon the addition of the inhibitors. In summary, we have identified three small molecules as GNE inhibitors with high potency in vitro, which serve as promising candidates to modulate sialic acid biosynthesis in more complex systems

    The decline of water hyacinth on Lake Victoria was due to biological control by Neochetina spp

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    There has been some debate recently about the cause of the decline of water hyacinth on Lake Victoria. While much of this evidence points to classical biological control as the major factor, the El Niño associated weather pattern of the last quarter of 1997 and the first half of 1998 has confused the issue. We argue first that the reductions in water hyacinth on Lake Victoria were ultimately caused by the widespread and significant damage to plants by Neochetina spp., although this process was increased by the stormy weather associated with the El Niño event; second that increased waves and current on Lake Victoria caused by El Niño redistributed water hyacinth plants around the lake; and third that a major lake-wide resurgence of water hyacinth plants on Lake Victoria has not occurred and will not occur unless the weevil populations are disrupted. We conclude that the population crash of water hyacinth on Lake Victoria would not have occurred in the absence of the weevils, but that it may have been hastened by stormy weather associated with the El Niño event
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