The homeostasis of intracellular inorganic phosphate is essential for eukaryotic metabolism and is regulated by the INPHORS signalling pathway, which employs inositol pyrophosphates (IPPs) as key intermediary messengers. This study investigates the metabolic pathways of inositol pyrophosphates (IPPs) in the yeast cell line PhoΔSPX and the human tumor cell line HCT116. Utilizing pulse-labelling experiments with 18O water and ordinary differential equation (ODE) models, we explore the synthesis and turnover of the highly phosphorylated IPP, 1,5-InsP8. Our findings challenge the notion that 1,5-InsP8 can be synthesized through distinct routes, revealing a linear reaction sequence in both systems. Employing model reduction via the profile likelihood method, we achieved statistically concise identifiability analysis that led to significant biological insights. In yeast, we determined that 1,5-InsP8 production primarily occurs through the phosphorylation of 5-InsP7, with the pathway involving 1-InsP7 deemed unnecessary as its removal did not compromise model accuracy. Crucially, this prediction of altered IPP concentrations was validated experimentally in vip1Δ and kcs1Δ knockout strains, providing orthogonal biological support for the reduced model. In HCT116 cells, 1,5-InsP8 synthesis is mainly driven by 1-InsP7, with variations observed across different experimental conditions. These results underscore the utility of model reduction in enhancing our understanding of metabolic pathways, coupling predictive modeling with experimental validation, and providing a framework for future investigations into the regulation and implications of linear IPP pathways in eukaryotic cells.

Today, Single Sign-On (SSO) is omnipresent on the Internet. Every day, millions of users utilize SSO protocols such as OAuth 2.0 (OAuth) or OpenID Connect 1.0 (OIDC). These protocols allow users to log in to multiple websites or services, called Relying Partys (RPs), using their accounts from major Identity Providers (IdPs) such as Apple, Facebook, and Google. Consequently, these IdPs gain the ability to track their users across the Internet. In return, RPs gain access to an enriched set of the user’s personal data stored at the IdP, including names, email addresses, and profile pictures.In this paper, we present three novel SSO privacy leaks found in the wild. Contrary to prior work, our leaks occur automatically as soon as the user visits the RP, without their consent or awareness, in a non-transparent manner. To prove their prevalence, we conducted a large-scale study on the Tranco top 1M websites. Our measurement shows that 10,931 RPs automatically leak the user’s identity, the currently visited RP, and other metadata (e.g., time of access) to the IdPs (partial leak). Additionally, 2,947 RPs silently deanonymize users, logging them into their accounts without their awareness (full leak). Even worse, 6 RPs leak the user’s identity to third parties (escalated leak). Besides 4 major IdPs, including Facebook and Google, we identified privacy leaks affecting 1,032 additional, less-popular IdPs. Conversely, 7 IdPs, including Apple and Github, are exemplary in avoiding these leaks.To protect users, we present our browser extension called SSO Privacy Guard. We demonstrate its effectiveness in preventing all the identified leaks. Furthermore, we discuss if and how emerging initiatives by major browser vendors related to tracking prevention can also improve privacy in the SSO ecosystem. To promote reproducibility, we publicly release the source code and all artifacts, and we plan to release SSO Privacy Guard in the official Chrome and Firefox extension stores.

Single Sign-On (SSO) with OAuth 2.0 and OpenID Connect 1.0 is essential for user authentication and autho-rization on the Internet. Billions of users rely on SSO services provided by Google, Facebook, and Apple. For large-scale measurements on the security of SSO, researchers need to reliably detect SSO implementations in the wild. In this paper, we survey the current state of 36 SSO measurement tools from prior work and discover gaps leading to blind spots in the SSO landscape that hinder the community from improving large-scale research. We observe unreliable measurements and a lack of reproducibility, making comparisons between studies difficult, if not impossible. We fill these gaps with SSO-MONITOR, our open-source, modular, and highly extensible framework for large-scale SSO landscape and security measurements. SSO-MONITOR achieves a high accuracy of 93% and, compared to pre-vious tools, significantly improves the reliability of SSO measurements by 19 %. It continuously takes snapshots of SSO implementations on the top 1M web sites to compose an SSO archive that is reproducible by design. Therefore, it passively monitors the SSO flows and provides an extensive set of landscape and security insights on sso-monitor.me. Our SSO archive allows researchers to perform comprehensive measurements over time and even beyond the scope of SSO. We use the data in our SSO archive to measure the security of 89k SSO authentication flows on the top 1M websites. Thereby, we discover 33k violations of OAuth Security Best Current Practices and 339 severe security vulnerabilities. They include 30 username and password leaks and 28 token leaks that allow full account takeovers.

SUMMARY: Despite the continuous discovery of new transcript isoforms, fueled by the recent increase in accessibility and accuracy of long-read RNA sequencing data, functional differences between isoforms originating from the same gene often remain obscure. To address this issue and enable researchers to assess potential functional consequences of transcript isoform variation on the proteome, we developed IsoTV. IsoTV is a versatile pipeline to process, predict and visualize the functional features of translated transcript isoforms. Attributes such as gene and isoform expression, transcript composition and functional features are summarized in an easy-to-interpret visualization. IsoTV is able to analyze a variety of data types from all eukaryotic organisms, including short- and long-read RNA-seq data. Using Oxford Nanopore long read data, we demonstrate that IsoTV facilitates the understanding of potential protein isoform function in different cancer cell types. AVAILABILITY AND IMPLEMENTATION: IsoTV is available at https://github.molgen.mpg.de/MayerGroup/IsoTV, with the corresponding documentation at https://isotv.readthedocs.io/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hosts diverge widely in how, and how well, they defend themselves against infection and immunopathology. Why are hosts so heterogeneous? Both epidemiology and life history are commonly hypothesized to influence host immune strategy, but the relationship between immune strategy and each factor has commonly been investigated in isolation. Here, we show that interactions between life history and epidemiology are crucial for determining optimal immune specificity and sensitivity. We propose a demographically-structured population dynamics model, in which we explore sensitivity and specificity of immune responses when epidemiological risks vary with age. We find that variation in life history traits associated with both reproduction and longevity alters optimal immune strategies-but the magnitude and sometimes even direction of these effects depends on how epidemiological risks vary across life. An especially compelling example that explains previously-puzzling empirical observations is that depending on whether infection risk declines or rises at reproductive maturity, later reproductive maturity can select for either greater or lower immune specificity, potentially illustrating why studies of lifespan and immune variation across taxa have been inconclusive. Thus, the sign of selection on the life history-immune specificity relationship can be reversed in different epidemiological contexts. Drawing on published life history data from a variety of chordate taxa, we generate testable predictions for this facet of the optimal immune strategy. Our results shed light on the causes of the heterogeneity found in immune defenses both within and among species and the ultimate variability of the relationship between life history and immune specificity.

Mobile user equipments supporting Long Term Evolution (LTE) - carrier aggregation (CA) face several new unpredicted issues when operating in frequency division duplex mode. This paper addresses the transmit (Tx) modulated spur problem, a new issue, that appears in LTE-CA transceivers. Due to the presence of several mixers and dividers to support different bands and CA scenarios, many harmonics are generated on the chip. Unavoidable crosstalk between these harmonics can generate an unwanted continuous wave spur around the Tx frequency. Once this spur appears at the chip area where the receive (Rx) local oscillator resides, it downconverts the undesired portion of the Tx signal which leaked through the duplexer to the Rx baseband. This interference, referred to as Tx modulated spur, causes a severe degradation of the signal-to-noise ratio (SNR) of the wanted signal. To mitigate such, we propose an active digital cancellation architecture which utilizes the known information of the Tx signal. An equivalent baseband model of the Tx modulated spur is presented from which the digital cancellation architecture is derived. Simulations show that the proposed architecture cancels the Tx interference and improves the SNR of the wanted signal significantly.

The Cognitive Radio (CR) concept relies on observing the surrounding radio spectrum, sensing changes and reacting accordingly. therefore a CR-enabled User Equipment (UE) demands enhanced strategies for efficient interference detection, rapid spectrum evaluation and a highly flexible, reconfigurable architecture to be able to support the multitude of today's as well as future radio access technologies (RATs). It is shown that classical methods of spectrum analysis like the Fast Fourier Transformation (FFT) have critical shortcomings in fullfilling the requirements of CR and how analog keyblocks like the wideband ΣΓ-ADC can be implemented. The pivotal focus of this paper is to propose alternative approaches suitable for integration into the Digital Front-End (DFE) and the UE.