Late Cretaceous ammonoids show that drivers of diversification are regionally heterogeneous

Palaeontologists have long sought to explain the diversification of individual clades to whole biotas at global scales. Advances in our understanding of the spatial distribution of the fossil record through geological time, however, has demonstrated that global trends in biodiversity were a mosaic of regionally heterogeneous diversification processes. Drivers of diversification must presumably have also displayed regional variation to produce the spatial disparities observed in past taxonomic richness. Here, we analyse the fossil record of ammonoids, pelagic shelled cephalopods, through the Late Cretaceous, characterised by some palaeontologists as an interval of biotic decline prior to their total extinction at the Cretaceous-Paleogene boundary. We regionally subdivide this record to eliminate the impacts of spatial sampling biases and infer regional origination and extinction rates corrected for temporal sampling biases using Bayesian methods. We then model these rates using biotic and abiotic drivers commonly inferred to influence diversification. Ammonoid diversification dynamics and responses to this common set of diversity drivers were regionally heterogeneous, do not support ecological decline, and demonstrate that their global diversification signal is influenced by spatial disparities in sampling effort. These results call into question the feasibility of seeking drivers of diversity at global scales in the fossil record

Improved protein structure prediction using potentials from deep learning

Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence1. This problem is of fundamental importance as the structure of a protein largely determines its function2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction5 (CASP13)—a blind assessment of the state of the field—AlphaFold created high-accuracy structures (with template modelling (TM) scores6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined7

Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13)

We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13 Submissions were made by three free-modelling methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on-par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 free-modelling assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group. (An average GDT_TS of 61.4.) The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 free-modelling domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods

Can majority support save an endangered language? A case study of language attitudes in Guernsey

Many studies of minority language revitalisation focus on the attitudes and perceptions of minorities, but not on those of majority group members. This paper discusses the implications of these issues, and presents research into majority andf minority attitudes towards the endangered indigenous vernacular of Guernsey, Channel Islands. The research used a multi-method approach (questionnaire and interview) to obtain attitudinal data from a representative sample of the population that included politicians and civil servants (209 participants). The findings suggested a shift in language ideology away from the post-second world war ‘culture of modernisation’ and monolingual ideal, towards recognition of the value of a bi/trilingual linguistic heritage. Public opinion in Guernsey now seems to support the maintenance of the indigenous language variety, which has led to a degree of official support. The paper then discusses to what extent this ‘attitude shift’ is reflected in linguistic behaviour and in concrete language planning measures

Improvisation and Transformation: Yes to the Mess

The field of organizational change has chiefly been studied from a teleological perspective. Most models of change emphasize action that is rational and goal oriented. What often gets overlooked and under theorized is the continuous, iterative nature of organizational life, the unplanned and serendipitous actions by and between people that lead to new discoveries and innovation. Recent research on organizational improvisation seeks to explore this area. In this chapter we will address two questions – what is the experience of improvisation and what are the conditions that support improvisation to flourish in organizations? In the first part of this paper, we look at the phenomenology of improvisation, the actual lived experience of those who improvise in the face of the unknown or in the midst of chaotic conditions. We will explore the strategies that some professional improvisers employ to deliberately create the improvisatory moment. We will then look at the dynamics of organizational life and explore the cultural beliefs, organizational structures, and leadership practices that support improvisation. We will draw primarily upon the model from Barrett (2012) that focuses on the how the nature of jazz improvisation and the factors that support improvisation can be transferred to leadership activities. This falls in the tradition of others who draw upon arts-based metaphors, including jazz music and theatrical improvisation, to suggest insights for leadership and ways of organizing. Since this is a book devoted to individual transformation as well as organizational transformation, we will also touch on the topic of how improvisation is a developmental project and explore the potential for improvisation to lead to personal transformation. We will attempt to move back and forth between both themes – organizational and personal transformation. Ultimately the two topics are not separate. Any significant organizational transformation begins with an improvisation. And any meaningful improvisatory move by a person is potentially a moment of self-discovery and an identity-shaping event

Perspectivas clásicas y modernas de las virtudes en la empresa (II)".

Este cuaderno contiene: "En busca de la virtud: el papel de las virtudes, los valores y las fortalezas de carácter en la toma de decisiones éticas" "Participar en el bien común de la empresa" "Antes de la virtud: biología, cerebro, comportamiento y ‘sentido moral’" "La posibilidad de la virtud

Mouse SLX4 Is a Tumor Suppressor that Stimulates the Activity of the Nuclease XPF-ERCC1 in DNA Crosslink Repair

SLX4 binds to three nucleases (XPF-ERCC1, MUS81-EME1, and SLX1), and its deficiency leads to genomic instability, sensitivity to DNA crosslinking agents, and Fanconi anemia. However, it is not understood how SLX4 and its associated nucleases act in DNA crosslink repair. Here, we uncover consequences of mouse Slx4 deficiency and reveal its function in DNA crosslink repair. Slx4-deficient mice develop epithelial cancers and have a contracted hematopoietic stem cell pool. The N-terminal domain of SLX4 (mini-SLX4) that only binds to XPF-ERCC1 is sufficient to confer resistance to DNA crosslinking agents. Recombinant mini-SLX4 enhances XPF-ERCC1 nuclease activity up to 100-fold, directing specificity toward DNA forks. Mini-SLX4-XPF-ERCC1 also vigorously stimulates dual incisions around a DNA crosslink embedded in a synthetic replication fork, an essential step in the repair of this lesion. These observations define vertebrate SLX4 as a tumor suppressor, which activates XPF-ERCC1 nuclease specificity in DNA crosslink repairope

Effect of exploitation and exploration on the innovative as outcomes in entrepreneurial firms

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Intuition: Myth or a Decision-making Tool?

Faced with today’s ill-structured business environment of fast-paced change and rising uncertainty, organizations have been searching for management tools that will perform satisfactorily under such ambiguous conditions. In the arena of managerial decision making, one of the approaches being assessed is the use of intuition. Based on our definition of intuition as a non-sequential information-processing mode, which comprises both cognitive and affective elements and results in direct knowing without any use of conscious reasoning, we develop a testable model of integrated analytical and intuitive decision making and propose ways to measure the use of intuition