arXiv subjects

Andreas Mayer

Publications and source records attributed to Andreas Mayer.

15 recordsLinked to original sources

arXiv2025

Infrastructuring Contestability: A Framework for Community-Defined AI Value Pluralism

The proliferation of AI-driven systems presents a fundamental challenge to Human-Computer Interaction (HCI) and Computer-Supported Cooperative Work (CSCW), often diminishing user agency and failing to account for value pluralism. Current approaches to value alignment, which rely on centralized, top-down definitions, lack the mechanisms for meaningful contestability. This leaves users and communities unable to challenge or shape the values embedded in the systems that govern their digital lives, creating a crisis of legitimacy and trust. This paper introduces Community-Defined AI Value Pluralism (CDAVP), a socio-technical framework that addresses this gap. It reframes the design problem from achieving a single aligned state to infrastructuring a dynamic ecosystem for value deliberation and application. At its core, CDAVP enables diverse, self-organizing communities to define and maintain explicit value profiles - rich, machine-readable representations that can encompass not only preferences but also community-specific rights and duties. These profiles are then contextually activated by the end-user, who retains ultimate control (agency) over which values guide the AI's behavior. AI applications, in turn, are designed to transparently interpret these profiles and moderate conflicts, adhering to a set of non-negotiable, democratically-legitimated meta-rules. The designer's role shifts from crafting static interfaces to becoming an architect of participatory ecosystems. We argue that infrastructuring for pluralism is a necessary pathway toward achieving robust algorithmic accountability and genuinely contestable, human-centric AI.

cs.HC↗

arXiv2024

Impact of local structure on melt dynamics in Cu-Ti alloys: Insights from ab-initio molecular dynamics simulations

First-principle based molecular-dynamics simulations have been performed for binary Cu$_x$Ti$_{1-x}$ (x = 0.31, 0.50, and 0.76) alloys to investigate the relationship between local structure and dynamical properties in the liquid and undercooled melt. The undercooled melts show a pronounced short-range order, majorly a five-fold symmetry (FFS) around the Cu atoms, which competes with bcc ordering. This complex SRO is also reflected in the partial coordination numbers, where mainly a Z12 coordination is present around Cu, which corresponds to an icosahedral ordering. Higher coordination numbers were obtained for Ti compatible with Frank-Kasper polyhedra. The increasing Frank-Kasper polyhedra coordination scenario around Ti impacts on the interatomic distances of Ti atoms, which increase with increasing Ti content. The Cu$_{50}$Ti$_{50}$ composition exhibits the highest FFS ordering and amount of Frank-Kasper polyhedra, which explains the slowest melt dynamics, found experimentally and in simulations for this composition. Thus, our results suggest that the high undercooling degree and glass-forming ability of binary CuTi alloys, originates from the high complexity of the local structure rather than due to the preferred formation of Cu-Ti pairs, as Cu-Ti interactions were found to be weak.

cond-mat.mtrl-sci↗

arXiv2023

SSO-Monitor: Fully-Automatic Large-Scale Landscape, Security, and Privacy Analyses of Single Sign-On in the Wild

Single Sign-On (SSO) shifts the crucial authentication process on a website to to the underlying SSO protocols and their correct implementation. To strengthen SSO security, organizations, such as IETF and W3C, maintain advisories to address known threats. One could assume that these security best practices are widely deployed on websites. We show that this assumption is a fallacy. We present SSO-MONITOR, an open-source fully-automatic large-scale SSO landscape, security, and privacy analysis tool. In contrast to all previous work, SSO-MONITOR uses a highly extensible, fully automated workflow with novel visual-based SSO detection techniques, enhanced security and privacy analyses, and continuously updated monitoring results. It receives a list of domains as input to discover the login pages, recognize the supported Identity Providers (IdPs), and execute the SSO. It further reveals the current security level of SSO in the wild compared to the security best practices on paper. With SSO-MONITOR, we automatically identified 1,632 websites with 3,020 Apple, Facebook, or Google logins within the Tranco 10k. Our continuous monitoring also revealed how quickly these numbers change over time. SSO-MONITOR can automatically login to each SSO website. It records the logins by tracing HTTP and in-browser communication to detect widespread security and privacy issues automatically. We introduce a novel deep-level inspection of HTTP parameters that we call SMARTPARMS. Using SMARTPARMS for security analyses, we uncovered URL parameters in 5 Client Application (Client) secret leakages and 337 cases with weak CSRF protection. We additionally identified 447 cases with no CSRF protection, 342 insecure SSO flows and 9 cases with nested URL parameters, leading to an open redirect in one case. SSO-MONITOR reveals privacy leakages that deanonymize users in 200 cases.

cs.CR↗

arXiv2022

How different are self and nonself?

Biological and artificial networks routinely make reliable distinctions between similar inputs, and the rules for making these distinctions are learned. In some ways, self/nonself discrimination in the immune system is similar, being both reliable and (partly) learned through thymic selection. In contrast to other examples, we show that the distributions of self and nonself peptides are nearly identical but strongly inhomogeneous. Reliable discrimination is possible only because self-peptides are a particular finite sample drawn out of this distribution, and T cells can target the spaces in between these samples. In conventional learning problems, this would constitute overfitting and lead to disaster. Here, the strong inhomogeneities imply instead that the immune system gains by targeting peptides which are similar to self, with maximum sensitivity for sequences just one or two substitutions away. This prediction from the structure of the underlying distribution in sequence space agrees, for example, with the observed responses to mutation derived cancer neoantigens.

q-bio.CB↗

arXiv2021

Heterologous autoimmunity and prokaryotic immune defense

Some prokaryotes possess CRISPR-Cas systems that provide adaptive immunity to viruses guided by DNA segments called spacers acquired from invading phage. However, the patchy incidence and limited memory breadth of CRISPR-Cas systems suggest that their fitness benefits are offset by costs. Here, we propose that cross-reactive CRISPR targeting can lead to heterologous autoimmunity, whereby foreign spacers guide self-targeting in a spacer-length dependent fashion. Balancing antiviral defense against autoimmunity predicts a scaling relation between spacer length and CRISPR repertoire size. We find evidence for this scaling through comparative analysis of sequenced prokaryotic genomes, and show that this association also holds at the level of CRISPR types. In contrast, the scaling is absent in strains with nonfunctional CRISPR loci. Finally, we demonstrate that stochastic spacer loss can explain variations around the scaling relation, even between strains of the same species. Our results suggest that heterologous autoimmunity is a selective factor shaping the evolution of CRISPR-Cas systems.

q-bio.PE↗

arXiv2020

Tregs self-organize into a "computing ecosystem" and implement a sophisticated optimization algorithm for mediating immune response

Regulatory T cells (Tregs) play a crucial role in mediating immune response. Yet an algorithmic understanding of the role of Tregs in adaptive immunity remains lacking. Here, we present a biophysically realistic model of Treg mediated self-tolerance in which Tregs bind to self-antigens and locally inhibit the proliferation of nearby activated T cells. By exploiting a duality between ecological dynamics and constrained optimization, we show that Tregs tile the potential antigen space while simultaneously minimizing the overlap between Treg activation profiles. We find that for sufficiently high Treg diversity, Treg mediated self-tolerance is robust to fluctuations in self-antigen concentrations but lowering the Treg diversity results in a sharp transition -- related to the Gardner transition in perceptrons -- to a regime where changes in self-antigen concentrations can result in an auto-immune response. We propose a novel experimental test of this transition in immune-deficient mice and discuss potential implications for autoimmune diseases.

q-bio.PE↗

arXiv2020

Early life imprints the hierarchy of T cell clone sizes

The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, through mathematical modeling and statistical analyses of T cell receptor sequencing data we demonstrate that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire. We demonstrate how the empirical scaling law relating the rank of the largest clones to their size can emerge from clonal growth during repertoire formation. We statistically identify early founded clones and find that they are indeed highly enriched among the largest clones. This enrichment persists even after decades of human aging, in a way that is quantitatively predicted by a model of fluctuating clonal selection. Our work presents a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization and provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity.

q-bio.PE↗

arXiv2018

How a well-adapting immune system remembers

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.

q-bio.PE↗

arXiv2018

Receptor crosstalk improves concentration sensing of multiple ligands

Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems leading to crosstalk between different receptors. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of non-cognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the non-cognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing.

q-bio.SC↗

arXiv2018

Regulation of T cell expansion by antigen presentation dynamics

An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number of T cells. Here, we show that such a relationship arises naturally from a model in which T cell expansion is limited by decaying levels of presented antigen. The same model also accounts for the observed dependence of T cell expansion on affinity for antigen and on the kinetics of antigen administration. Extending the model to address expansion of multiple T cell clones competing for antigen, we find that higher affinity clones can suppress the proliferation of lower affinity clones, thereby promoting the specificity of the response. Employing the model to derive optimal vaccination protocols, we find that exponentially increasing antigen doses can achieve a nearly optimized response. We thus conclude that the dynamics of presented antigen is a key regulator of both the size and specificity of the adaptive immune response.

q-bio.PE↗

arXiv2017

Transitions in optimal adaptive strategies for populations in fluctuating environments

Biological populations are subject to fluctuating environmental conditions. Different adaptive strategies can allow them to cope with these fluctuations: specialization to one particular environmental condition, adoption of a generalist phenotype that compromise between conditions, or population-wise diversification (bet-hedging). Which strategy provides the largest selective advantage in the long run depends on the range of accessible phenotypes and the statistics of the environmental fluctuations. Here, we analyze this problem in a simple mathematical model of population growth. First, we review and extend a graphical method to identify the nature of the optimal strategy when the environmental fluctuations are uncorrelated. Temporal correlations in environmental fluctuations open up new strategies that rely on memory but are mathematically challenging to study: we present here new analytical results to address this challenge. We illustrate our general approach by analyzing optimal adaptive strategies in the presence of trade-offs that constrain the range of accessible phenotypes. Our results extend several previous studies and have applications to a variety of biological phenomena, from antibiotic resistance in bacteria to immune responses in vertebrates.

q-bio.PE↗

arXiv2017

Population dynamics of immune repertoires

The evolution of the adaptive immune system is characterized by changes in the relative abundances of the B- and T-cell clones that make up its repertoires. To fully capture this evolution, we need to describe the complex dynamics of the response to pathogenic and self-antigenic stimulations, as well as the statistics of novel lymphocyte receptors introduced throughout life. Recent experiments, ranging from high-throughput immune repertoire sequencing to quantification of the response to specific antigens, can help us characterize the effective dynamics of the immune response. Here we describe mathematical models informed by experiments that lead to a picture of clonal competition in a highly stochastic context. We discuss how different types of competition, noise and selection shape the observed clone-size distributions, and contrast them with predictions of a neutral theory of clonal evolution. These mathematical models show that memory and effector immune repertoire evolution is far from neutral, and is driven by the history of the pathogenic environment, while naive repertoire dynamics are consistent with neutral theory and competition in a fixed antigenic environment. Lastly, we investigate the effect of long-term clonal selection on repertoire aging.

q-bio.PE↗

arXiv2016

Search for systemic mass loss in Algols with bow shocks

Aims. Various studies indicate that interacting binary stars of Algol type evolve non-conservatively. However, direct detections of systemic mass loss in Algols have been scarce so far. We study the systemic mass loss in Algols by looking for the presence of infrared excesses originating from the thermal emission of dust grains, which is linked to the presence of a stellar wind. Methods. In contrast to previous studies, we make use of the fact that stellar and interstellar material is piled up at the edge of the astrosphere where the stellar wind interacts with the interstellar medium. We analyse WISE W3 $12\,μ$m and WISE W4 $22\,μ$m data of Algol-type binary Be and B[e] stars and the properties of their bow shocks. From the stand-off distance of the bow shock we are able to determine the mass-loss rate of the binary system. Results. Although the velocities of the stars with respect to the interstellar medium are quite low, we find bow shocks present in two systems, namely $π$ Aqr, and $φ$ Per; a third system, CX Dra, shows a more irregular circumstellar environment morphology which might somehow be related to systemic mass loss. The properties of the two bow shocks point to mass-loss rates and wind velocities typical of single B stars, which do not support an enhanced systemic mass loss.

astro-ph.SR↗

arXiv2015

Diversity of immune strategies explained by adaptation to pathogen statistics

Biological organisms have evolved a wide range of immune mechanisms to defend themselves against pathogens. Beyond molecular details, these mechanisms differ in how protection is acquired, processed and passed on to subsequent generations -- differences that may be essential to long-term survival. Here, we introduce a mathematical framework to compare the long-term adaptation of populations as a function of the pathogen dynamics that they experience and of the immune strategy that they adopt. We find that the two key determinants of an optimal immune strategy are the frequency and the characteristic timescale of the pathogens. Depending on these two parameters, our framework identifies distinct modes of immunity, including adaptive, innate, bet-hedging and CRISPR-like immunities, which recapitulate the diversity of natural immune systems.

q-bio.PE↗

arXiv2014

How a well-adapted immune system is organized

The repertoire of lymphocyte receptors in the adaptive immune system protects organisms from diverse pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. We develop a general framework for predicting the optimal repertoire that minimizes the cost of infections contracted from a given distribution of pathogens. The theory predicts that the immune system will have more receptors for rare antigens than expected from the frequency of encounters; individuals exposed to the same infections will have sparse repertoires that are largely different, but nevertheless exploit cross-reactivity to provide the same coverage of antigens; and the optimal repertoires can be reached via the dynamics of competitive binding of antigens by receptors, and selective amplification of stimulated receptors. Our results follow from a tension between the statistics of pathogen detection, which favor a broader receptor distribution, and the effects of cross-reactivity, which tend to concentrate the optimal repertoire onto a few highly abundant clones. Our predictions can be tested in high throughput surveys of receptor and pathogen diversity.

q-bio.PE↗