Icing: Large-scale inference of immunoglobulin clonotypes

Immunoglobulin (IG) clonotype identification is a fundamental open question in modern immunology. An accurate description of the IG repertoire is crucial to understand the variety within the immune system of an individual, potentially shedding light on the pathogenetic process. Intrinsic IG heterogeneity makes clonotype inference an extremely challenging task, both from a computational and a biological point of view. Here we present icing, a framework that allows to reconstruct clonal families also in case of highly mutated sequences. icing has a modular structure, and it is designed to be used with large next generation sequencing (NGS) datasets, a technology which allows the characterisation of large-scale IG repertoires. We extensively validated the framework with clustering performance metrics on the results in a simulated case. icing is implemented in Python, and it is publicly available under FreeBSD licence at https://github.com/slipguru/icing

Electro-Magnetic Nucleon Form Factors and their Spectral Functions in Soliton Models

It is demonstrated that in simple soliton models essential features of the electro-magnetic nucleon form factors observed over three orders of magnitude in momentum transfer $t$ are naturally reproduced. The analysis shows that three basic ingredients are required: an extended object, partial coupling to vector mesons, and relativistic recoil corrections. We use for the extended object the standard skyrmion, one vector meson propagator for both isospin channels, and the relativistic boost to the Breit frame. Continuation to timelike $t$ leads to quite stable results for the spectral functions in the regime from the 2- or 3-pion threshold to about two rho masses. Especially the onset of the continuous part of the spectral functions at threshold can be reliably determined and there are strong analogies to the results imposed on dispersion theoretic approaches by the unitarity constraint.Comment: 24 pages, (RevTeX), 5 PS-figures; Data points in fig.2 and corresponding references added. Final version, to be published in Z.Physik

Physical activity, additional breast cancer events, and mortality among early-stage breast cancer survivors: findings from the WHEL Study

ObjectiveResearch suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.MethodsA total of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate-vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.ResultsThose who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.ConclusionsHigher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis

Venture capital-backed firms, unavoidable value-destroying trade sales, and fair value protections

This paper investigates the implications of the fair value protections contemplated by the standard corporate contract (i.e., the standard contract form for which corporate law provides) for the entrepreneur–venture capitalist relationship, focusing, in particular, on unavoidable value-destroying trade sales. First, it demonstrates that the typical entrepreneur–venture capitalist contract does institutionalize the venture capitalist’s liquidity needs, allowing, under some circumstances, for counterintuitive instances of contractually-compliant value destruction. Unavoidable value-destroying trade sales are the most tangible example. Next, it argues that fair value protections can prevent the entrepreneur and venture capitalist from allocating the value that these transactions generate as they would want. Then, it shows that the reality of venture capital-backed firms calls for a process of adaptation of the standard corporate contract that has one major step in the deactivation or re-shaping of fair value protections. Finally, it argues that a standard corporate contract aiming to promote social welfare through venture capital should feature flexible fair value protections.info:eu-repo/semantics/publishedVersio

Malaria pigment crystals as magnetic micro-rotors: Key for high-sensitivity diagnosis

The need to develop new methods for the high-sensitivity diagnosis of malaria has initiated a global activity in medical and interdisciplinary sciences. Most of the diverse variety of emerging techniques are based on research-grade instruments, sophisticated reagent-based assays or rely on expertise. Here, we suggest an alternative optical methodology with an easy-to- use and cost-effective instrumentation based on unique properties of malaria pigment reported previously and determined quantitatively in the present study. Malaria pigment, also called hemozoin, is an insoluble microcrystalline form of heme. These crystallites show remarkable magnetic and optical anisotropy distinctly from any other components of blood. As a consequence, they can simultaneously act as magnetically driven micro-rotors and spinning polarizers in suspensions. These properties can gain importance not only in malaria diagnosis and therapies, where hemozoin is considered as drug target or immune modulator, but also in the magnetic manipulation of cells and tissues on the microscopic scale

Language, Truth, and Logic and the Anglophone reception of the Vienna Circle

A. J. Ayer’s Language, Truth, and Logic had been responsible for introducing the Vienna Circle’s ideas, developed within a Germanophone framework, to an Anglophone readership. Inevitably, this migration from one context to another resulted in the alteration of some of the concepts being transmitted. Such alterations have served to facilitate a number of false impressions of Logical Empiricism from which recent scholarship still tries to recover. In this paper, I will attempt to point to the ways in which LTL has helped to foster the various mistaken stereotypes about Logical Empiricism which were combined into the received view. I will begin by examining Ayer’s all too brief presentation of an Anglocentric lineage for his ideas. This lineage, as we shall see, simply omits the major 19th century Germanophone influences on the rise of analytic philosophy. The Germanophone ideas he presents are selectively introduced into an Anglophone context, and directed towards various concerns that arose within that context. I will focus on the differences between Carnap’s version of the overcoming of metaphysics, and Ayer’s reconfiguration into what he calls the elimination of metaphysics. Having discussed the above, I will very briefly outline the consequences that Ayer’s radicalisation of the Vienna Circle’s doctrines had on the subsequent Anglophone reception of Logical Empiricism

Altered Composition of Liver Proteasome Assemblies Contributes to Enhanced Proteasome Activity in the Exceptionally Long-Lived Naked Mole-Rat

The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life