Classificatory Theory in Data-Intensive Science: The Case of Open Biomedical Ontologies

publication-status: Publishedtypes: ArticleThis is the author's version of a paper that was subsequently published in International Studies in the Philosophy of Science. Please cite the published version by following the DOI link.Knowledge-making practices in biology are being strongly affected by the availability of data on an unprecedented scale, the insistence on systemic approaches and growing reliance on bioinformatics and digital infrastructures. What role does theory play within data-intensive science, and what does that tell us about scientific theories in general? To answer these questions, I focus on Open Biomedical Ontologies, digital classification tools that have become crucial to sharing results across research contexts in the biological and biomedical sciences, and argue that they constitute an example of classificatory theory. This form of theorizing emerges from classification practices in conjunction with experimental know-how and expresses the knowledge underpinning the analysis and interpretation of data disseminated online.Economic and Social Research Council (ESRC)The British AcademyLeverhulme Trus

The emergence of modern statistics in agricultural science : Analysis of variance, experimental design and the reshaping of research at Rothamsted Experimental Station, 1919–1933

During the twentieth century statistical methods have transformed research in the experimental and social sciences. Qualitative evidence has largely been replaced by quantitative results and the tools of statistical inference have helped foster a new ideal of objectivity in scientific knowledge. The paper will investigate this transformation by considering the genesis of analysis of variance and experimental design, statistical methods nowadays taught in every elementary course of statistics for the experimental and social sciences. These methods were developed by the mathematician and geneticist R. A. Fisher during the 1920s, while he was working at Rothamsted Experimental Station, where agricultural research was in turn reshaped by Fisher’s methods. Analysis of variance and experimental design required new practices and instruments in field and laboratory research, and imposed a redistribution of expertise among statisticians, experimental scientists and the farm staff. On the other hand the use of statistical methods in agricultural science called for a systematization of information management and made computing an activity integral to the experimental research done at Rothamsted, permanently integrating the statisticians’ tools and expertise into the station research programme. Fisher’s statistical methods did not remain confined within agricultural research and by the end of the 1950s they had come to stay in psychology, sociology, education, chemistry, medicine, engineering, economics, quality control, just to mention a few of the disciplines which adopted them

Support for maternal manipulation of developmental nutrition in a facultatively eusocial bee, Megalopta genalis (Halictidae)

Developmental maternal effects are a potentially important source of phenotypic variation, but they can be difficult to distinguish from other environmental factors. This is an important distinction within the context of social evolution, because if variation in offspring helping behavior is due to maternal manipulation, social selection may act on maternal phenotypes, as well as those of offspring. Factors correlated with social castes have been linked to variation in developmental nutrition, which might provide opportunity for females to manipulate the social behavior of their offspring. Megalopta genalis is a mass-provisioning facultatively eusocial sweat bee for which production of males and females in social and solitary nests is concurrent and asynchronous. Female offspring may become either gynes (reproductive dispersers) or workers (non-reproductive helpers). We predicted that if maternal manipulation plays a role in M. genalis caste determination, investment in daughters should vary more than for sons. The mass and protein content of pollen stores provided to female offspring varied significantly more than those of males, but volume and sugar content did not. Sugar content varied more among female eggs in social nests than in solitary nests. Provisions were larger, with higher nutrient content, for female eggs and in social nests. Adult females and males show different patterns of allometry, and their investment ratio ranged from 1.23 to 1.69. Adult body weight varied more for females than males, possibly reflecting increased variation in maternal investment in female offspring. These differences are consistent with a role for maternal manipulation in the social plasticity observed in M. genalis

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c.) with keyhole limpet hemocyanin (KLH) or human papillomavirus (HPV)16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002) or 6 mg/animal poly I:C12U (p = 0.001) when compared with immunization with KLH alone. Notably, poly ICLC—but not CpG-C given at the same dose—also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell–activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01). This was paralleled by the reduced production of the homeostatic T cell–attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants for virus-specific Th1 and humoral immune responses in nonhuman primates

Secondary Endoleak Management Following TEVAR and EVAR.

Endovascular abdominal and thoracic aortic aneurysm repair and are widely used to treat increasingly complex aneurysms. Secondary endoleaks, defined as those detected more than 30 days after the procedure and after previous negative imaging, remain a challenge for aortic specialists, conferring a need for long-term surveillance and reintervention. Endoleaks are classified on the basis of their anatomic site and aetiology. Type 1 and type 2 endoleaks (EL1 and EL2) are the most common endoleaks necessitating intervention. The management of these requires an understanding of their mechanics, and the risk of sac enlargement and rupture due to increased sac pressure. Endovascular techniques are the main treatment approach to manage secondary endoleaks. However, surgery should be considered where endovascular treatments fail to arrest aneurysm growth. This chapter reviews the aetiology, significance, management strategy and techniques for different endoleak types

Learning from Data Journeys

This is the final version. Available on open access from Springer via the DOI in this recordThis chapter discusses the idea of data journeys as an investigative tool and a theoretical framework for this volume and broader scholarship on data. Building on a relational and historicized understanding of data as lineages, I reflect on the methodological, conceptual and social challenges involved in mapping, analysing and comparing the production, movement and use of data within and across research fields - and some of the strategies developed to cope with such difficulties. I then provide an overview of the significant variation among the data practices garnered in this volume. Specific nodes of difference and similarity across data journeys are identified, while also emphasising the extent to which such commonalities are dependent on specific situations of inquiry. In closing, I highlight the significance of this approach towards addressing concerns raised by data-centric science and the emergence of big and open data.European CommissionAlan Turing Institut

Matter in Strong Magnetic Fields

The properties of matter are significantly modified by strong magnetic fields, $B>>2.35\times 10^9$ Gauss ($1 G =10^{-4} Tesla$), as are typically found on the surfaces of neutron stars. In such strong magnetic fields, the Coulomb force on an electron acts as a small perturbation compared to the magnetic force. The strong field condition can also be mimicked in laboratory semiconductors. Because of the strong magnetic confinement of electrons perpendicular to the field, atoms attain a much greater binding energy compared to the zero-field case, and various other bound states become possible, including molecular chains and three-dimensional condensed matter. This article reviews the electronic structure of atoms, molecules and bulk matter, as well as the thermodynamic properties of dense plasma, in strong magnetic fields, $10^9G << B < 10^{16}G$. The focus is on the basic physical pictures and approximate scaling relations, although various theoretical approaches and numerical results are also discussed. For the neutron star surface composed of light elements such as hydrogen or helium, the outermost layer constitutes a nondegenerate, partially ionized Coulomb plasma if $B<<10^{14}G$, and may be in the form of a condensed liquid if the magnetic field is stronger (and temperature $<10^6$ K). For the iron surface, the outermost layer of the neutron star can be in a gaseous or a condensed phase depending on the cohesive property of the iron condensate.Comment: 45 pages with 9 figures. Many small additions/changes. Accepted for publication in Rev. Mod. Phy

The IceCube Neutrino Observatory, the Pierre Auger Observatory and the Telescope Array: Joint Contribution to the 34th International Cosmic Ray Conference (ICRC 2015)

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube `high-energy starting events' sample and the other with 16 high-energy `track events'. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values $3^\circ$, $6^\circ$ and $9^\circ$ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches.Comment: one proceeding, the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The Netherlands; will appear in PoS(ICRC2015