Hierarchies and levels of reality

We examine some assumptions about the nature of \u27levels of reality\u27 in the light of examples drawn from physics. Three central assumptions of the standard view of such levels (for instance, Oppenheim and Putnam 1958) are (i) that levels are populated by entities of varying complexity, (ii) that there is a unique hierarchy of levels, ranging from the very small to the very large, and (iii) that the inhabitants of adjacent levels are related bu the parthood relation. Using examples from physics, we argue that it is more natural to view the inhabitants of levels as the behaviors of entities, rather than entities themselves. This suggests an account of reduction between levels, according to which one behavior reduces to another if the two are related by an appropriate limit relation. By considering cases where such inter-level reduction fails, we show the hierarchy of behaviors differs in several respects from the standard hierarchy of entities. In particular, while on the standard view, lower-level entities are \u27micro\u27 parts of higher-level entities, on our view, a system\u27s macro-level behavior can be seen as a (\u27non-spatial\u27) part of its micro-level behavior. We argue that this second hierarchy is not really in conflict with the standard view and that it better suits examples of explanation in science

Reduction, Autonomy and Causal Exclusion Among Physical Properties

Is there a problem of causal exclusion between micro- and macro-level physical properties? I argue that the properties that in fact are in competition are both macro, viz., the property of a (macro-) system of having such-and-such macro properties` (call this a macro property`) and the property of the same system of being constituted by such-and-such a micro-structure` (call this a micro-structural property`). I show that there are cases where, for lack of reducibility, there is a prima facie intra-level causal competition between the two kinds of properties. The problem can be resolved without giving up on the causal efficacy of the macro properties if we understand instances of macro properties to be parts of micro-structural property instances. The parthood relation of between both kinds of property instances can be mapped onto the way physical theory deals with the relation of their descriptions in the framework of perturbation theory

Stability in Cosmology, from Einstein to Inflation

I investigate the role of stability in cosmology through two episodes from the recent history of cosmology: (1) Einstein’s static universe and Eddington’s demonstration of its instability, and (2) the flatness problem of the hot big bang model and its claimed solution by inflationary theory. These episodes illustrate differing reactions to instability in cosmological models, both positive ones and negative ones. To provide some context to these reactions, I also situate them in relation to perspectives on stability from dynamical systems theory and its epistemology. This reveals, for example, an insistence on stability as an extreme position in relation to the spectrum of physical systems which exhibit degrees of stability and fragility, one which has a pragmatic rationale, but not any deeper one

Stability in Cosmology, from Einstein to Inflation

I investigate the role of stability in cosmology through two episodes from the recent history of cosmology: (1) Einstein’s static universe and Eddington’s demonstration of its instability, and (2) the flatness problem of the hot big bang model and its claimed solution by inflationary theory. These episodes illustrate differing reactions to instability in cosmological models, both positive ones and negative ones. To provide some context to these reactions, I also situate them in relation to perspectives on stability from dynamical systems theory and its epistemology. This reveals, for example, an insistence on stability as an extreme position in relation to the spectrum of physical systems which exhibit degrees of stability and fragility, one which has a pragmatic rationale, but not any deeper one

Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape:A Large-Scale Genome-Wide Interaction Study (vol 11, e1005378, 2015)

The arcOGEN Consortium should be listed as an author of this article. They contributed to the genome-wide association study results presented in this work. They should be listed in the author byline at position 292 and affiliated with The Arthritis Research UK Osteoarthritis Genetics Consortium. They should also be included in the footnote designating consortia which is underneath the author affiliation list in the PDF version of the article, and in the S2 Text. Please view the correct S2 Text below, containing correct consortia members

Emergence in physics

Discussions of emergence in physics usually adopt one of two general approaches. Starting from intuitive desiderata a concept of emergence should satisfy, one can (i) develop a philosophical account of emergence that incorporates and makes precise the initial intuitions and then try to find illustrations for this model in scientific practice\u27 alternatively, one can (ii) study cases in science where the intuitive desiderata seem to be satisfies and then develop a philosophical model of emergence that subsumes those cases. Given these different approaches, disagreements over which phenomena count as emergent are likely, even if everybody were to agree on the pre-theoretical desiderata. Differing views about the latter, of course, compound the conflicts. Whether emergent phenomena, for instance, supervene on \u27base level\u27 phenomena or whether the \u27completeness\u27 of physics at he base level should be satisfied are questions which different philosophical views will answer in different ways

Multi-Angle Effector Function Analysis of Human Monoclonal IgG Glycovariants.

Therapeutic performance of recombinant antibodies relies on two independent mechanisms: antigen recognition and Fc-mediated antibody effector functions. Interaction of Fc-fragment with different FcR triggers antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and determines longevity of the antibody in serum. In context of therapeutic antibodies FcγRs play the most important role. It has been demonstrated that the Fc-attached sugar moiety is essential for IgG effector functionality, dictates its affinity to individual FcγRs and determines binding to different receptor classes: activating or inhibitory. In this study, we systematically analyze effector functions of monoclonal IgG1 and its eight enzymatically engineered glycosylation variants. The analysis of interaction of glycovariants with FcRs was performed for single, as well as for antigen-bound antibodies and IgGs in a form of immune complex. In addition to functional properties we addressed impact of glycosylation on the structural properties of the tested glycovariants. We demonstrate a clear impact of glycosylation pattern on antibody stability and interaction with different FcγRs. Consistent with previous reports, deglycosylated antibodies failed to bind all Fcγ-receptors, with the exception of high affinity FcγRI. The FcγRII and FcγRIIIa binding activity of IgG1 was observed to depend on the galactosylation level, and hypergalactosylated antibodies demonstrated increased receptor interaction. Sialylation did not decrease the FcγR binding of the tested IgGs; in contrast, sialylation of antibodies improved binding to FcγRIIa and IIb. We demonstrate that glycosylation influences to some extent IgG1 interaction with FcRn. However, independent of glycosylation pattern the interaction of IgG1 with a soluble monomeric target surprisingly resulted in an impaired receptor binding. Here, we demonstrate, that immune complexes (IC), induced by multimeric ligand, compensated for the decreased affinity of target bound antibody towards FcRs, showing the importance of the IC-formation for the FcR- mediated effector functions

Motor-Independent Cognitive Testing in Motor Degenerative Diseases

Cognitive function is tested through speech- or writing-based neuropsychological instruments. The application and validity of those tests is impeded for patients with diseases that affect speech and hand motor skills. We therefore developed a “motor-free” gaze-controlled version of the Trail Making Test (TMT), including a calibration task to assess gaze accuracy, for completion by means of an eye-tracking computer system (ETCS). This electronic TMT version (eTMT) was evaluated for two paradigmatic “motor-neurodegenerative” diseases, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). We screened 146 subjects, of whom 44 were excluded, e.g., because of vision deficits. Patients were dichotomized into subgroups with less (ALS−, PD−) or severe motor affection (ALS+, PD+). All 66 patients and all 36 healthy controls (HC) completed the eTMT. Patients with sufficient hand motor control (ALS−, PD−, PD+) and all HC additionally completed the original paper–pencil-based version of the TMT. Sufficient and comparable gaze fixation accuracy across all groups and the correlations of the eTMT results with the TMT results supported the reliability and validity of the eTMT. PD+ patients made significantly more errors than HC in the eTMT-B. We hereby proved the good applicability of a motor-free cognitive test. Error rates could be a particularly sensitive marker of executive dysfunction

In the Eye of the Storm: Immune-mediated Toxicities Associated With CAR-T Cell Therapy

The success of chimeric antigen receptor (CAR)-T cell therapy with impressive response rates in hematologic malignancies but also promising data in solid tumors came along with the cognition of unexpected, potentially life-threatening immune-mediated toxicities, namely the cytokine release syndrome (CRS) and neurotoxicity recently referred to as immune effector cell-associated neurotoxicity syndrome (ICANS). These toxicities require urgent diagnostic and therapeutic interventions and targeted modulation of key cytokine pathways represents the mainstay of CRS treatment. However, as the underlying mechanisms of ICANS are not well understood, treatment options remain limited and further investigation is warranted. Importantly, after the recent market approval of 2 CAR-T cell constructs, the application of CAR-T cells will expand to nonacademic centers with limited experience in the management of CAR-T cell-associated toxicities. Here, we review the current evidence of CRS and ICANS pathophysiology, diagnostics, and treatment