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Within the framework of the Transboundary Waters Assessment Programme (TWAP), initiated by the Global Environment Facility (GEF), we contributed to a comprehensive baseline assessment of transboundary aquifers (TBAs) by quantifying different groundwater indicators using the global water resources and water use model WaterGAP 2.2. All indicators were computed under current (2010) and projected conditions in 2030 and 2050 for 91 selected TBAs larger than 20,000 km2 and for each nation’s share of the TBAs (TBA-CU: country unit). TBA outlines were provided by the International Groundwater Resources Assessment Centre (IGRAC). The set of indicators comprises groundwater recharge, groundwater depletion, per-capita groundwater recharge, dependency on groundwater, population density, and groundwater development stress (groundwater withdrawals to groundwater recharge). Only the latter four indicators were projected to 2030 and 2050. Current-state indicators were quantified using the Watch Forcing Data climate dataset, while projections were based on five climate scenarios that were computed by five global climate models for the high-emissions scenario RCP 8.5. Water use projections were based on the Shared Socio-economic Pathway SSP2 developed within ISI-MIP. Furthermore, two scenarios of future irrigated areas were explored. For individual water use sectors, the fraction of groundwater abstraction was assumed to remain at the current level.
According to our assessment, aquifers with the highest current groundwater depletion rates worldwide are not transboundary. Exceptions are the Neogene Aquifer System (Syria) with 53 mm/yr between 2000 and 2009 and the Indus River Plain aquifer (India) with 28 mm/yr. For current conditions, we identified 20 out of 258 TBA-CUs suffering from medium to very high groundwater development stress, which are located in the Middle East and North Africa region, in South Asia, China, and the USA. Considering projections, ensemble means of per-cent changes or percent point changes to current conditions were determined. Per-capita groundwater recharge is projected to decrease in 80-90% of all TBA-CUs until 2030/2050. Due to the strongly varying projections of the global climate models, we applied a worst-case scenario approach to define future hotspots of groundwater development stress, taking into account the strongest computed increase until either 2030 or 2050 among all scenarios and individual GCMs. Based on this approach, the number of TBA-CUs under at least medium groundwater development stress increases from 20 to 58, comprising all hotspots under current conditions. New hotspots are projected to develop mainly in Sub-Saharan Africa, China, and Mexico.
Abstract: Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non-random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring.
Author Summary: The problem of how the brain wires itself up has important implications for the understanding of both brain development and cognition. The microscopic structure of the circuits of the adult neocortex, often considered the seat of our highest cognitive abilities, is still poorly understood. Recent experiments have provided a first set of findings on the structural features of these circuits, but it is unknown how these features come about and how they are maintained. Here we present a neural network model that shows how these features might come about. It gives rise to numerous connectivity features, which have been observed in experiments, but never before simultaneously produced by a single model. Our model explains the development of these structural features as the result of a process of self-organization. The results imply that only a few simple mechanisms and constraints are required to produce, at least to the first approximation, various characteristic features of a typical fragment of brain microcircuitry. In the absence of any of these mechanisms, simultaneous production of all desired features fails, suggesting a minimal set of necessary mechanisms for their production.
Islamic State (IS), previously known as the Islamic State in Iraq and Syria (ISIS), has shown nothing but destruction, chaos and sectarianism. Through terror strategies, they rapidly spread over great parts of eastern Syria and north and central Iraq. Their new recruits came from all over the world, but mainly from Islamic countries. Arab countries had the biggest share of recruits. While IS was assembling supporters and sympathisers, Sunni Clergymen constantly called for ‘material and moral’ support to the Syrian rebels, and accordingly, thousands of foreign fighters flooded into Syria for Jihad. According to a Soufan Group research in 2014 on the foreign fighters in Syria, it is estimated that the highest number of foreign fighters came from Tunisia (about 3,000), Saudi Arabia (about 2,500), Morocco (about 1,500), Russia (about 800), France (700), Turkey and the United Kingdom (about 400 each). These numbers exclude the Syrians and Iraqis who are already in IS...
This thesis contributes to the field of machine learning with a specific focus on the methods for learning relations between the inputs. Learning relationships between images is the most common primitive in vision. There are many vision tasks in which relationships across images play an important role. Some of them are motion estimation, activity recognition, stereo vision, multi-view geometry and visual odometry. Many of such tasks mainly depend on motion and disparity cues, which are inferred based on the relations across multiple image pairs. The approaches presented in this thesis mainly deal with, but are not limited to, learning of the representations for motion and depth. This thesis by articles consists of five articles which present relational feature learning models along with their applications in computer vision. In the first article, we present an approach for encoding motion in videos. To this end, we show that the detection of spatial transformations can be viewed as detection of coincidence or synchrony between the given sequence of frames and a sequence of features which are related by the transformation we wish to detect. Learning to detect synchrony is possible by introducing "multiplicative interactions'' into the hidden units of single layered sparse coding models.
We show that the learned motion representations employed for the task of activity recognition achieve competitive performance on multiple benchmarks. Stereo vision is an important challenge in computer vision and useful for many applications in that field. In the second article, we extend the energy based learning models, which were previously used for motion encoding, to the context of depth perception. Given the common architecture of the models for encoding motion and depth, we show that it is possible to define a single model for learning a unified representation for both the cues. Our experimental results show that learning a combined representation for depth and motion makes it possible to achieve state-of-the-art performance at the task of 3-D activity analysis, and to perform better than the existing hand-engineered 3-D motion features. Autoencoder is a popular unsupervised learning method for learning efficient encoding for a given set of data samples. Typically, regularized autoencoders which are used to learn over-complete and sparse representations for the input data, were shown to fail on intrinsically high dimensional data like videos. In the third article, we investigate the reason for such a behavior. It can be observed that the regularized autoencoders typically learn negative hidden unit biases. We show that the learning of negative biases is the result of hidden units being responsible for both the sparsity and the representation of the input data. It is shown that, as a result, the behavior of the model resembles clustering methods which would require exponentially large number of features to model intrinsically high dimensional data. Based on this understanding, we propose a new activation function which decouples the roles of hidden layer and uses linear encoding. This allows to learn representations on data with very high intrinsic dimensionality. We also show that gating connections in the bi-linear models and the single layer models from articles one and two of this thesis can be thought of as a way to attain a linear encoding scheme which allows them to learn good representations on videos. Visual odometry is the task of inferring egomotion of a moving object from visual information such as images and videos. It can primarily be used for the task of localization and has many applications in the fields of robotics and navigation. The work in article four was motivated by the idea of using deep learning techniques, which are successful methods for many vision tasks, for visual odometry. The visual odometry task mainly requires inference of motion and depth information from visual input which can then be mapped to velocity and change in direction. We use relational feature models presented in the articles one and two for inferring a combined motion and depth representation from stereo video sequences. The combined representation is then mapped to discrete velocity and change in direction labels using convolutional neural networks. Our approach is an end-to-end deep learning-based architecture which uses a single type of computational model and learning rule. Preliminary results show that the architecture is capable of learning the mapping from input video to egomotion. Activity recognition is a challenging computer vision task with many real world applications. It is well know that it is a hard task to use computer vision research for real-time applications. In the fifth article of this thesis, we present a real-time activity recognition system based on deep learning based methods. Our approach uses energy based relational feature learning models for the computation of local motion features directly from videos. A bag-of-words over the local motion features is used for the analysis of activity in a given video sequence. We implement this system on a distributed computational platform and demonstrate its performance on the iCub robot. Using GPUs we demonstrate real time performance which makes the deployment of activity recognition systems in real world scenarios possible.
Background: Prions and amyloid-β (Aβ) oligomers trigger neurodegeneration by hijacking a poorly understood cellular signal mediated by the prion protein (PrP) at the plasma membrane. In early zebrafish embryos, PrP-1-dependent signals control cell-cell adhesion via a tyrosine phosphorylation-dependent mechanism.
Results: Here we report that the Src family kinases (SFKs) Fyn and Yes act downstream of PrP-1 to prevent the endocytosis and degradation of E-cadherin/β-catenin adhesion complexes in vivo. Accordingly, knockdown of PrP-1 or Fyn/Yes cause similar zebrafish gastrulation phenotypes, whereas Fyn/Yes expression rescues the PrP-1 knockdown phenotype. We also show that zebrafish and mouse PrPs positively regulate the activity of Src kinases and that these have an unexpected positive effect on E-cadherin-mediated cell adhesion. Interestingly, while PrP knockdown impairs β-catenin adhesive function, PrP overexpression enhances it, thereby antagonizing its nuclear, wnt-related signaling activity and disturbing embryonic dorsoventral specification. The ability of mouse PrP to influence these events in zebrafish embryos requires its neuroprotective, polybasic N-terminus but not its neurotoxicity-associated central region. Remarkably, human Aβ oligomers up-regulate the PrP-1/SFK/E-cadherin/β-catenin pathway in zebrafish embryonic cells, mimicking a PrP gain-of-function scenario.
Conclusions: Our gain- and loss-of-function experiments in zebrafish suggest that PrP and SFKs enhance the cell surface stability of embryonic adherens junctions via the same complex mechanism through which they over-activate neuroreceptors that trigger synaptic damage. The profound impact of this pathway on early zebrafish development makes these embryos an ideal model to study the cellular and molecular events affected by neurotoxic PrP mutations and ligands in vivo. In particular, our finding that human Aβ oligomers activate the zebrafish PrP/SFK/E-cadherin pathway opens the possibility of using fish embryos to rapidly screen for novel therapeutic targets and compounds against prion- and Alzheimer's-related neurodegeneration. Altogether, our data illustrate PrP-dependent signals relevant to embryonic development, neuronal physiology and neurological disease.
Five books I liked in 2015
(2016)
Here are five books I read in 2015 that I particularly liked. Expect an eclectic mix of fiction and non-fiction, and not necessarily social-sciency. Although I tend to pick those books that end up having some social science-stuff / politics in them without explicitly looking for it. That, and books about spaceships...
Constitutionalization beyond the nation state can be observed as an evolutionary process that leads in two quite different directions: (1) constitutions evolve in transnational political processes outside the nation state; (2) simulta-neously, constitutions evolve outside international politics in global society’s ‘private’ sectors. What, however, is the specifically societal element in societal constitutionalism? This is currently the object of a controversy regarding the subjects of non-state constitutions, their origin, their legitimization, their scope, and their internal structures. This article interprets the controversy as a theme with a number of variations. What is the distinctive ‘compositional principle’ in each particular variation? Which problems become evident in its ‘development’? What are its most valuable ‘motifs’? The article starts with David Sciulli’s theme of societal constitutionalism. Then it presents six variations on Sciulli. In a first group, constitutionalization is perceived as the expansion of a single rationality into all spheres of society. In a second group, the motif of the unity of the consti-tution can still be heard, despite the essential pluralism of societal constitution-alism. In the final movement, three further variations will then reprise and devel-op further the most important motifs, in a resumption of the original theme.
„Wir sind im Krieg mit Russland.“ Diese gleichermaßen lakonische wie wuchtige Bewertung des Journalisten Jan-Philipp Hein lässt den Leser unwillkürlich zusammenzucken, klingt sie doch wie ein aus der Zeit gefallenes Zitat einer längst überwundenen Ost-West-Konfrontation. Zudem erscheint sie verstörend irreal, da die sich in den Vordergrund drängenden aktuellen sicherheitspolitischen Herausforderungen wie islamistischer Terrorismus, anhaltend große (und vielfach unkontrollierte) Flüchtlingsströme und eng damit verknüpft ein Erstarken rechtsextremistischer Kräfte in den vergangenen Monaten die gesamte Aufmerksamkeit zu absorbieren schienen...
Schätzwerte mittelfristiger Gleichgewichtszinsen mit der Methode nach Laubach und Williams (2003) werden inzwischen vielfach in der Diskussion um die Geld- und Fiskalpolitik zitiert. Unter anderem wurden sie von Summers (2014a) als Evidenz für eine säkulare Stagnation angeführt und von Yellen (2015) zur Rechtfertigung der Nullzinspolitik verwendet. In diesem Papier nehmen wir eine umfangreiche Untersuchung und Sensitivitätsanalyse dieser Schätzwerte für die Vereinigten Staaten, Deutschland und den Euro-Raum vor. Aufgrund der hohen Unsicherheit und Sensitivität, die mit den Schätzwerten mittelfristiger Gleichgewichtszinsen mit der Laubach-Williams-Methode und ähnlichen Ansätzen verbunden ist, sollten diese Schätzungen nicht den Ausschlag für entscheidende Weichenstellungen in der Geld- und Fiskalpolitik geben.
Epigenetic marks critically control gene expression and thus the cellular activity state. The functions of many epigenetic modifiers in the vascular system have not yet been studied. We screened for histone modifiers in endothelial cells and observed a fairly high expression of the histone plant homeodomain finger protein 8 (PHF8). Given its high expression, we hypothesize that this histone demethylase is important for endothelial cell function. Overexpression of PHF8 catalyzed the removal of methyl-groups from histone 3 lysine 9 (H3K9) and H4K20, whereas knockdown of the enzyme increased H3K9 methylation. Knockdown of PHF8 by RNAi also attenuated endothelial proliferation and survival. As a functional readout endothelial migration and tube formation was studied. PHF8 siRNA attenuated the capacity for migration and developing of capillary-like structures. Given the impact of PHF8 on cell cycle genes, endothelial E2F transcription factors were screened, which led to the identification of the gene repressor E2F4 to be controlled by PHF8. Importantly, PHF8 maintains E2F4 but not E2F1 expression in endothelial cells. Consistently, chromatin immunoprecipitation revealed that PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation. Conclusion: PHF8 by controlling E2F4 expression maintains endothelial function.
Introduction: Interferon alpha (IFNα) is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1) is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling.
Results: We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs) of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment.
Conclusion: We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in ‘silent’ metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and monitor therapeutic response of IFNα treatment in the future.
The swine plasma metabolome chronicles "many days" biological timing and functions linked to growth
(2016)
The paradigm of chronobiology is based almost wholly upon the daily biological clock, or circadian rhythm, which has been the focus of intense molecular, cellular, pharmacological, and behavioral, research. However, the circadian rhythm does not explain biological timings related to fundamental aspects of life history such as rates of tissue/organ/body size development and control of the timing of life stages such as gestation length, age at maturity, and lifespan. This suggests that another biological timing mechanism is at work. Here we focus on a "many days" (multidien) chronobiological period first observed as enigmatic recurring growth lines in developing mammalian tooth enamel that is strongly associate with all adult tissue, organ, and body masses as well as life history attributes such as gestation length, age at maturity, weaning, and lifespan, particularly among the well studied primates. Yet, knowledge of the biological factors regulating the patterning of mammalian life, such as the development of body size and life history structure, does not exist. To identify underlying molecular mechanisms we performed metabolome and genome analyses from blood plasma in domestic pigs. We show that blood plasma metabolites and small non-coding RNA (sncRNA) drawn from 33 domestic pigs over a two-week period strongly oscillate on a 5-day multidien rhythm, as does the pig enamel rhythm. Metabolomics and genomics pathway analyses actually reveal two 5-day rhythms, one related to growth in which biological functions include cell proliferation, apoptosis, and transcription regulation/protein synthesis, and another 5-day rhythm related to degradative pathways that follows three days later. Our results provide experimental confirmation of a 5-day multidien rhythm in the domestic pig linking the periodic growth of enamel with oscillations of the metabolome and genome. This association reveals a new class of chronobiological rhythm and a snapshot of the biological bases that regulate mammalian growth, body size, and life history.
In the last decades, natural products from lichens have gained more interest for pharmaceutical application due to the broad range of their biological activity. However, isolation of the compounds of interest directly from the lichen is neither feasible nor sustainable due to slow growth of many lichens. In order to develop a pipeline for heterologous expression of lichen biosynthesis gene clusters and thus the sustainable production of their bioactive compounds we have identified and characterized the phosphopantheteinyl transferase (PPTase) EppA from the lichen Evernia prunastri. The Sfp-type PPTase EppA was functionally characterized through heterologous expression in E. coli using the production of the blue pigment indigoidine as readout and by complementation of a lys5 deletion in S. cerevisiae.
Background: In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice.
Aim: Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary) from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice.
Procedures: Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J), and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes) and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections.
Results: In the mouse genome there are eight intact solitary genes: Olfr19 (M12), Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings favor Olfr266 as a model gene to investigate odorant receptor gene choice.
Introduction: The Helicopter Emergency Medical Service (HEMS) was established for the prehospital trauma care of patients. Improved rescue times and increased coverage areas are discussed as specific advantages of HEMS. We recently found evidence that HEMS exerts beneficial effects on outcomes for severely injured patients. However, it still remains unknown which group of trauma patients might benefit most from HEMS rescue. Consequently, the unique aim of this study was to reveal which patients might benefit most from HEMS rescue.
Methods: Trauma patients (ISS ≥9) primarily treated by HEMS or ground emergency medical services (GEMS) between 2002 and 2012 were analysed using the TraumaRegister DGU. A multivariate regression analysis was used to reveal the survival benefit between different trauma populations.
Results: The study included 52 281 trauma patients. Of these, 68.8% (35 974) were rescued by GEMS and 31.2% (16 307) by HEMS. HEMS patients were more severely injured compared to GEMS patients (ISS: HEMS 24.8±13.5 vs. GEMS 21.7±18.0) and more frequently suffered traumatic shock (SBP sys <90mmHg: HEMS 18.3% vs. GEMS 14.8%). However, logistic regression analysis revealed that HEMS rescues resulted in an overall survival benefit compared to GEMS (OR 0.81, 95% CI [0.75–0.87], p<0.001, Nagelkerke's R squared 0.526, area under the ROC curve 0.922, 95% CI [0.919–0.925]). Analysis of specific subgroups demonstrated that patients aged older than 55 years (OR 0.62, 95% CI [0.50–0.77]) had the highest survival benefit after HEMS treatment. Furthermore, HEMS rescue had the most significant impact after ‘low falls’ (OR 0.68, 95% CI [0.55–0.84]) and in the case of minor severity injuries (ISS 9–15) (OR 0.66, 95% CI [0.49–0.88]).
Conclusions: In general, trauma patients benefit from HEMS rescue with in-hospital survival as the main outcome parameter. Focusing on special subgroups, middle aged and older patients, low-energy trauma, and minor severity injuries had the highest survival benefit when rescued by HEMS. Further studies are required to determine the potential reasons of this benefit.
This paper investigates the potential implications of say on pay on management remuneration in Germany. We try to shed light on some key aspects by presenting quantitative data that allows us to gauge the pertinent effects of the German natural experiment that originates with the 2009 amendments to the Stock Corporation Act of 1965. In order to do this, we deploy a hand-collected data set for Germany's major firms (i.e. DAX 30), for the years 2006-2012. Rather than focusing exclusively on CEO remuneration we collected data for all members of the management board for the whole period under investigation. We observe that the compensation packages of management board members of Germany's DAX30-firms are quite closely linked to key performance measures. In addition, we find that salaries increase with the size of the company and that ownership concentration has no significant effect on compensation. Also, our findings suggest that the two-tier system seems to matter a lot when it comes to compensation. However, it would be misleading to state that we see no significant impact of the introduction of the German say on pay-regime. Our findings suggest that supervisory boards anticipate shareholder-behavior.
In a production economy with trade in financial markets motivated by the desire to share labor-income risk and to speculate, we show that speculation increases volatility of asset returns and investment growth, increases the equity risk premium, and reduces welfare. Regulatory measures, such as constraints on stock positions, borrowing constraints, and the Tobin tax have similar effects on financial and macroeconomic variables. Borrowing limits and a financial transaction tax improve welfare because they substantially reduce speculative trading without impairing excessively risk-sharing trades.
The old boy network: the impact of professional networks on remuneration in top executive jobs
(2016)
We investigate the impact of social networks on earnings using a dataset of over 20,000 senior executives of European and US firms. The size of an individual's network of influential former colleagues has a large positive association with current remuneration. An individual at the 75th percentile in the distribution of connections could expect to have a salary nearly 20 per cent higher than an otherwise identical individual at the median. We use a placebo technique to show that our estimates reflect the causal impact of connections and not merely unobserved individual characteristics. Networks are more weakly associated with women's remuneration than with men's. This mainly reflects an interaction between unobserved individual characteristics and firm recruitment policies. The kinds of firm that best identify and advance talented women are less likely to give them access to influential networks than are firms that do the same for the most talented men.