Showing papers by "University of Graz published in 2014"
ETH Zurich1, Brandenburg University of Technology2, Danish Meteorological Institute3, Centre national de la recherche scientifique4, University of Graz5, University of Bonn6, Max Planck Society7, Royal Netherlands Meteorological Institute8, Swedish Meteorological and Hydrological Institute9, University of Hohenheim10
TL;DR: In this article, an evaluation of the ERA-Interim-driven EURO-CORDEX regional climate model (RCM) ensemble is presented, focusing on near-surface air temperature and precipitation, and using the E-OBS data set as observational reference.
Abstract: . EURO-CORDEX is an international climate downscaling initiative that aims to provide high-resolution climate scenarios for Europe. Here an evaluation of the ERA-Interim-driven EURO-CORDEX regional climate model (RCM) ensemble is presented. The study documents the performance of the individual models in representing the basic spatiotemporal patterns of the European climate for the period 1989–2008. Model evaluation focuses on near-surface air temperature and precipitation, and uses the E-OBS data set as observational reference. The ensemble consists of 17 simulations carried out by seven different models at grid resolutions of 12 km (nine experiments) and 50 km (eight experiments). Several performance metrics computed from monthly and seasonal mean values are used to assess model performance over eight subdomains of the European continent. Results are compared to those for the ERA40-driven ENSEMBLES simulations. The analysis confirms the ability of RCMs to capture the basic features of the European climate, including its variability in space and time. But it also identifies nonnegligible deficiencies of the simulations for selected metrics, regions and seasons. Seasonally and regionally averaged temperature biases are mostly smaller than 1.5 °C, while precipitation biases are typically located in the ±40% range. Some bias characteristics, such as a predominant cold and wet bias in most seasons and over most parts of Europe and a warm and dry summer bias over southern and southeastern Europe reflect common model biases. For seasonal mean quantities averaged over large European subdomains, no clear benefit of an increased spatial resolution (12 vs. 50 km) can be identified. The bias ranges of the EURO-CORDEX ensemble mostly correspond to those of the ENSEMBLES simulations, but some improvements in model performance can be identified (e.g., a less pronounced southern European warm summer bias). The temperature bias spread across different configurations of one individual model can be of a similar magnitude as the spread across different models, demonstrating a strong influence of the specific choices in physical parameterizations and experimental setup on model performance. Based on a number of simply reproducible metrics, the present study quantifies the currently achievable accuracy of RCMs used for regional climate simulations over Europe and provides a quality standard for future model developments.
778 citations
TL;DR: In this article, the state-of-the-art literature about 21st century climate change in the Alps based on existing literature and additional analyses is reviewed, which explicitly considers the reliability and uncertainty of climate projections.
693 citations
Institut Gustave Roussy1, University of São Paulo2, Katholieke Universiteit Leuven3, University of Burgundy4, Sapienza University of Rome5, Istituto Superiore di Sanità6, Vrije Universiteit Brussel7, University of Manchester8, University of Michigan9, National University of Cuyo10, Pierre-and-Marie-Curie University11, New York University12, University of Salento13, University of Crete14, Charles University in Prague15, University of Erlangen-Nuremberg16, University Hospital Heidelberg17, University of Pittsburgh18, University of Helsinki19, National Institutes of Health20, University of Bonn21, Providence Portland Medical Center22, National University of Singapore23, Ghent University24, University of Milan25, University of Graz26, University of Paris-Sud27, University College London28, Tuscia University29, McMaster University30, Technische Universität München31, Medical University of Vienna32, Karolinska Institutet33, University of Nice Sophia Antipolis34, University of Turin35, QIMR Berghofer Medical Research Institute36, Université de Montréal37, Dow University of Health Sciences38, French Institute of Health and Medical Research39, University of Colorado Denver40, University of Hawaii41, Stony Brook University42, Paris Descartes University43
TL;DR: Strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative I CD inducers are outlined, based on a high-content, high-throughput platform that was recently developed.
Abstract: Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.
665 citations
Royal Free Hospital1, Carlos III Health Institute2, University of California, San Diego3, Paris Diderot University4, University of Padua5, University of Graz6, Université libre de Bruxelles7, University of Bologna8, Saarland University9, Katholieke Universiteit Leuven10, University of Barcelona11, King's College London12, Virginia Commonwealth University13, Yale University14, University College London15
TL;DR: An in-depth review and a position statement on bacterial infections in cirrhosis are reported, which suggest that research on biomarkers of early infection may be useful in early diagnosis and treatment of infections.
664 citations
TL;DR: Inhibition of WAT browning represents a promising approach to ameliorate cachexia in cancer patients and is shown to reduce the severity of cachexia.
512 citations
TL;DR: A significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources.
497 citations
TL;DR: Assessment of three specific executive abilities for creative thought provided direct support for the executive involvement in creative thought and shed further light on the functional relationship between intelligence and creativity.
481 citations
TL;DR: Technology platforms following the principles of bio-refineries shall be established to enable the design of sustainable and economically feasible production of marketable microalgal products.
Abstract: As major part of the phytoplankton, microalgae are pivotal for the global food chain. Their exceptional capacity for CO2-fixation illustrates their indispensable significance to sustain earth's ecosystems. Further, they play a still underestimated role in eliminating contaminants from various environments. In addition to ecological benefit, many microalgal species exhibit high nutritional value and, at the same time, generate valued bio-products: Pigments, lipids, bioactive compounds, certain polysaccharides, bio-hydrogen and even biopolyesters with plastic-like properties have the potential for successful market penetration. Three substantial pigment groups, namely chlorophylls, carotenoids, and phycobilins, are essential for light harvesting and CO2 fixation. Those pigments will most likely undergo quick commercial success in “functional food”, cosmetics, aquaculture, pharmaceuticals, or food technology. Due to often high contents of polyunsaturated fatty acids essential for human metabolism, microalgal oils can be commercialized as health food and in the pharmaceutical and therapeutic field, creating much higher value than by converting them to biofuel. Finally, algal biomass remaining as residue after product recovery can be used as forage, biogas feedstock or biofertilizer. This utilization is needed for balancing the material- and energy cycles of the entire process. Thus, technology platforms following the principles of bio-refineries shall be established to enable the design of sustainable and economically feasible production of marketable microalgal products.
467 citations
TL;DR: In this paper, a conceptual framework for corporate sustainability management is developed which offers an integrated view on the relevance of sustainability aspects for an individual company and enables the integration of these sustainability aspects on different management levels.
Abstract: Sustainable development can be a source of success, innovation, and profitability for companies. To use this source and to deal with the challenge of sustainability, corporations need a framework they can rely on in order to identify opportunities and threats and to develop, implement, control, and improve corporate sustainability strategies to be both more sustainable (for themselves and the society) and more successful in economic terms. Based on an extensive literature review of strategic management, CSR, and corporate sustainability, a conceptual framework is developed which offers an integrated view on the relevance of sustainability aspects for an individual company and enables the integration of these sustainability aspects on different management levels. Contextual factors are used to identify the relevance of sustainable development and the significant sustainability aspects. Based on this initial step, the relevance of sustainability issues for the different management levels, as well as opportunities and threats related to sustainable development, can be identified. The framework distinguishes three different management levels: normative management, strategic management, and operational management. Questions of vision and mission of a company and of the fit between sustainability engagement and organizational culture are in focus of the normative management level. Developing an effective corporate sustainability strategy is part of the strategic level. The implementation of the sustainability strategy in the different corporate functions is part of the operational level. This framework for corporate sustainability management is supported by instruments which are clustered in different areas like performance measurement, assessment and evaluation, operational management or strategic management. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
463 citations
TL;DR: This mini-review acting as editorial presents retrospectives and future perspectives for plant microbiome studies as well as information gaps in this emerging research field and the contribution of this research topic to the solution of various issues is discussed.
Abstract: Most eukaryotes develop close interactions with microorganisms that are essential for their performance and survival. Thus, eukaryotes and prokaryotes in nature can be considered as meta-organisms or holobionts. Consequently, microorganisms that colonize different plant compartments contain the plant’s second genome. In this respect, many studies in the last decades have shown that plant-microbe interactions are not only crucial in understanding plant growth and health, but also for sustainable crop production in a changing world. This mini-review acting as editorial presents retrospectives and future perspectives for plant microbiome studies as well as information gaps in this emerging research field. In addition, the contribution of this research topic to the solution of various issues is discussed.
455 citations
Technische Universität München1, Novosibirsk State University2, GSI Helmholtz Centre for Heavy Ion Research3, University of Kentucky4, Fermilab5, Washington University in St. Louis6, University of Graz7, University of Vienna8, University of Maryland, College Park9, Max Planck Society10, Vienna University of Technology11, Thomas Jefferson National Accelerator Facility12, Hampton University13, University of Bonn14, University of Washington15, Complutense University of Madrid16, University of Mainz17, Moscow Institute of Physics and Technology18, University of Groningen19, University of Paris-Sud20, Indiana University21, Lawrence Livermore National Laboratory22, University of California, Davis23, University of Helsinki24, University of Virginia25, Istituto Nazionale di Fisica Nucleare26, Forschungszentrum Jülich27, University of Bern28, Warsaw University of Technology29, CERN30, Kent State University31, Utrecht University32, National Research Nuclear University MEPhI33, Lawrence Berkeley National Laboratory34, University of Valencia35, University of Granada36, Brookhaven National Laboratory37, Stony Brook University38, University of Naples Federico II39, University of Santiago de Compostela40, Ruhr University Bochum41, Far Eastern Federal University42
TL;DR: In this paper, the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment, are highlighted, highlighting how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as searches for physics beyond the Standard Model.
Abstract: We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.
TL;DR: An overview of the existing literature about lipid nanoparticles for pulmonary application is given to provide the reader with some background information for pulmonary drug delivery, i.e., anatomy and physiology of the respiratory system, formulation requirements, application forms, clearance from the lung, pharmacological benefits and nanotoxicity.
TL;DR: It is shown that nutrient starvation causes rapid depletion of AcCoA, and multiple distinct manipulations designed to increase or reduce cytosolic Ac CoA led to the suppression or induction of autophagy, respectively, both in cultured human cells and in mice, delineating Ac coenzyme A-centered pharmacological strategies that allow for the therapeutic manipulation ofautophagy.
TL;DR: Highlights ► EEG Alpha activity is sensitive to different creativity-related demands and alpha increases during creative cognition reflect internal processing demands.
TL;DR: Tissue-specific inactivation of Atg5, essential for the formation of autophagosomes, markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage of tumour-bearing mice, suggesting a link between deregulated autophagy and regulatory T cell controlled anticancer immunity.
Abstract: Autophagy prolongs the survival of cells in stressful conditions but its role in cancer is unclear. Here, Rao et al. show that loss of the autophagic protein Atg5 enhanced cancer incidence but impaired tumour progression in a mouse model of lung cancer.
TL;DR: To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs, a randomized double-blind, placebo-controlled, single-center trial is conducted.
Abstract: different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study.
National Institutes of Health1, Centraalbureau voor Schimmelcultures2, University of Perugia3, University of Sydney4, University of Gothenburg5, University of Tennessee6, University of Illinois at Urbana–Champaign7, Royal Botanic Gardens8, University of Tartu9, Purdue University10, Mae Fah Luang University11, Kunming Institute of Botany12, Complutense University of Madrid13, American Museum of Natural History14, University of Pretoria15, Spanish National Research Council16, University of British Columbia17, Academy of Sciences of the Czech Republic18, University of Toronto19, Aberystwyth University20, University of Graz21, University of the Free State22, Commonwealth Scientific and Industrial Research Organisation23, Swedish Museum of Natural History24, Rural Development Administration25, University of California, Davis26, Landcare Research27, Hungarian Academy of Sciences28, Eötvös Loránd University29, Field Museum of Natural History30, University of Szeged31, United States Department of Agriculture32, University of Alabama33, University of Helsinki34, Thailand National Science and Technology Development Agency35, University of Wisconsin-Madison36, National Research Council37, University of North Carolina at Greensboro38, Sungkyunkwan University39, Hirosaki University40, Brandon University41, University of Jena42, University of Findlay43, University of Tübingen44, McMaster University45, Rutgers University46
TL;DR: A set of standards and protocols are proposed to improve the data quality of new sequences, and it is suggested how type and other reference sequences can be used to improve identification of Fungi.
Abstract: DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.
TL;DR: The results suggest that the ability to generate creative ideas is characterized by increased functional connectivity between the inferior prefrontal cortex and the default network, pointing to a greater cooperation between brain regions associated with cognitive control and low-level imaginative processes.
TL;DR: In patients with CLI, IA-DEB had comparable efficacy to PTA and met the noninferiority hypothesis, but there was a trend towards an increased major amputation rate through 12 months compared to Pta.
TL;DR: The process of idea generation can be generally understood as a state of focused internally-directed attention involving controlled semantic retrieval and left inferior parietal cortex and left prefrontal regions may subserve the flexible integration of previous knowledge for the construction of new and creative ideas.
École Normale Supérieure1, Ludwig Maximilian University of Munich2, University of Jyväskylä3, Hungarian Academy of Sciences4, University of Paris5, French Institute of Health and Medical Research6, University Hospital of Lausanne7, Pierre Mendès-France University8, Cardiff University9, Technische Universität München10, University of Zurich11, Max Planck Society12, University of Graz13, University of Salzburg14
TL;DR: This article analyzed concurrent predictions of phonological processing (awareness and memory) and rapid automatized naming (RAN) for literacy development in a rural area of the United States and found that the cognitive underpinnings of reading and spelling are universal or language/orthography-specific.
TL;DR: The present research extends recent applications of LSA in creativity research and provides support for the notion that both associative and executive processes underlie the production of novel ideas.
Abstract: How does the mind produce creative ideas? Past research has pointed to important roles of both executive and associative processes in creative cognition. But such work has largely focused on the influence of one ability or the other—executive or associative—so the extent to which both abilities may jointly affect creative thought remains unclear. Using multivariate structural equation modeling, we conducted two studies to determine the relative influences of executive and associative processes in domain-general creative cognition (i.e., divergent thinking). Participants completed a series of verbal fluency tasks, and their responses were analyzed by means of latent semantic analysis (LSA) and scored for semantic distance as a measure of associative ability. Participants also completed several measures of executive function—including broad retrieval ability (Gr) and fluid intelligence (Gf). Across both studies, we found substantial effects of both associative and executive abilities: As the average semantic distance between verbal fluency responses and cues increased, so did the creative quality of divergent-thinking responses (Study 1 and Study 2). Moreover, the creative quality of divergent-thinking responses was predicted by the executive variables—Gr (Study 1) and Gf (Study 2). Importantly, the effects of semantic distance and the executive function variables remained robust in the same structural equation model predicting divergent thinking, suggesting unique contributions of both constructs. The present research extends recent applications of LSA in creativity research and provides support for the notion that both associative and executive processes underlie the production of novel ideas.
TL;DR: It is suggested that the in-transit interaction between two closely launched coronal mass ejections resulted in the extreme enhancement of the ejecta magnetic field observed near 1 AU at STEREO A and the formation of the extreme storm showed striking novel features.
Abstract: Space weather refers to dynamic conditions on the Sun and in the space environment of the Earth, which are often driven by solar eruptions and their subsequent interplanetary disturbances. It has been unclear how an extreme space weather storm forms and how severe it can be. Here we report and investigate an extreme event with multi-point remote-sensing and in situ observations. The formation of the extreme storm showed striking novel features. We suggest that the in-transit interaction between two closely launched coronal mass ejections resulted in the extreme enhancement of the ejecta magnetic field observed near 1 AU at STEREO A. The fast transit to STEREO A (in only 18.6 h), or the unusually weak deceleration of the event, was caused by the preconditioning of the upstream solar wind by an earlier solar eruption. These results provide a new view crucial to solar physics and space weather as to how an extreme space weather event can arise from a combination of solar eruptions.
TL;DR: In this article, an ensemble of 15 regional climate simulations downscaling six transient global climate simulations was used to identify the respective time periods corresponding to 2C global warming, describe the range of projected changes for the European climate for this level of global warming and investigate the uncertainty across the multi-model ensemble.
Abstract: A global warming of 2 C relative to pre-industrial climate has been considered as a threshold which society should endeavor to remain below, in order to limit the dangerous effects of anthropogenic climate change. The possible changes in regional climate under this target level of global warming have so far not been investigated in detail. Using an ensemble of 15 regional climate simulations downscaling six transient global climate simulations, we identify the respective time periods corresponding to 2 C global warming, describe the range of projected changes for the European climate for this level of global warming, and investigate the uncertainty across the multi-model ensemble. Robust changes in mean and extreme temperature, precipitation, winds and surface energy budgets are found based on the ensemble of simulations. The results indicate that most of Europe will experience higher warming than the global average. They also reveal strong distributional patterns across Europe, which will be important in subsequent impact assessments and adaptation responses in different countries and regions. For instance, a North‐South (West‐East) warming gradient is found for summer (winter) along with a general increase in heavy precipitation and summer extreme temperatures. Tying the ensemble analysis to time periods with a prescribed global temperature change rather than fixed time periods allows for the identification of more robust regional patterns of temperature changes due to removal of some of the uncertainty related to the global models’ climate sensitivity.
TL;DR: This work critically examines drugs and behaviors to which life- or healthspan-extending properties have been ascribed and discusses the underlying molecular mechanisms.
TL;DR: This paper introduced positive psychology to the study of language by describing its key tenets and contextualized the potential contributions of positive psychology with reference to prior work, including the humanistic movement in language teaching, models of motivation, the concept of an affective filter, studies of the good language learner, and the concepts related to the self.
Abstract: Positive psychology is a rapidly expanding subfield in psychology that has important implications for the field of second language acquisition (SLA). This paper introduces positive psychology to the study of language by describing its key tenets. The potential contributions of positive psychology are contextualized with reference to prior work, including the humanistic movement in language teaching, models of motivation, the concept of an affective filter, studies of the good language learner, and the concepts related to the self. There are reasons for both encouragement and caution as studies inspired by positive psychology are undertaken. Papers in this special issue of SSLLT cover a range of quantitative and qualitative methods with implications for theory, research, and teaching practice. The special issue serves as a springboard for future research in SLA under the umbrella of positive psychology.
TL;DR: It is shown that peptide integration into the membrane causes delocalization of essential peripheral membrane proteins essential for respiration and cell-wall biosynthesis, limiting cellular energy and undermining cell- wall integrity.
Abstract: Short antimicrobial peptides rich in arginine (R) and tryptophan (W) interact with membranes. To learn how this interaction leads to bacterial death, we characterized the effects of the minimal pharmacophore RWRWRW-NH2. A ruthenium-substituted derivative of this peptide localized to the membrane in vivo, and the peptide also integrated readily into mixed phospholipid bilayers that resemble Gram-positive membranes. Proteome and Western blot analyses showed that integration of the peptide caused delocalization of peripheral membrane proteins essential for respiration and cell-wall biosynthesis, limiting cellular energy and undermining cell-wall integrity. This delocalization phenomenon also was observed with the cyclic peptide gramicidin S, indicating the generality of the mechanism. Exogenous glutamate increases tolerance to the peptide, indicating that osmotic destabilization also contributes to antibacterial efficacy. Bacillus subtilis responds to peptide stress by releasing osmoprotective amino acids, in part via mechanosensitive channels. This response is triggered by membrane-targeting bacteriolytic peptides of different structural classes as well as by hypoosmotic conditions.
TL;DR: Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-I secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age) later in life, values decrease continuously.
Abstract: Context: Measurement of IGF-I is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-I assays and for establishment of normative data. Objectives: Our objectives were development and validation of a novel automated IGF-I immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness. Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15 014 subjects (6697 males and 8317 females, 0–94 years of age). Main Outcome Measures: We measured concentrations of IGF-I as determined by the IDS iSYS IGF-I assay. Results: A new IGF-I assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was de...
TL;DR: Because the human data fit this general primate pattern, the adoption of cooperative breeding by the authors' hominin ancestors also provides the most parsimonious explanation for the origin of human hyper-cooperation.
Abstract: Proactive, that is, unsolicited, prosociality is a key component of our hyper-cooperation, which in turn has enabled the emergence of various uniquely human traits, including complex cognition, morality and cumulative culture and technology. However, the evolutionary foundation of the human prosocial sentiment remains poorly understood, largely because primate data from numerous, often incommensurable testing paradigms do not provide an adequate basis for formal tests of the various functional hypotheses. We therefore present the results of standardized prosociality experiments in 24 groups of 15 primate species, including humans. Extensive allomaternal care is by far the best predictor of interspecific variation in proactive prosociality. Proactive prosocial motivations therefore systematically arise whenever selection favours the evolution of cooperative breeding. Because the human data fit this general primate pattern, the adoption of cooperative breeding by our hominin ancestors also provides the most parsimonious explanation for the origin of human hyper-cooperation.
TL;DR: Protein design expands the repertoire of coiled-coil structures to α-helical barrels and hyperstable helical bundles, and describes a procedure for designing proteins with backbones produced by varying the parameters in the Crick coiled coil–generating equations.
Abstract: We describe a procedure for designing proteins with backbones produced by varying the parameters in the Crick coiled coil-generating equations. Combinatorial design calculations identify low-energy sequences for alternative helix supercoil arrangements, and the helices in the lowest-energy arrangements are connected by loop building. We design an antiparallel monomeric untwisted three-helix bundle with 80-residue helices, an antiparallel monomeric right-handed four-helix bundle, and a pentameric parallel left-handed five-helix bundle. The designed proteins are extremely stable (extrapolated ΔGfold > 60 kilocalories per mole), and their crystal structures are close to those of the design models with nearly identical core packing between the helices. The approach enables the custom design of hyperstable proteins with fine-tuned geometries for a wide range of applications.