Legally grounded fairness objectives

Recent work has identified a number of formally incompatible operational measures for the unfairness of a machine learning (ML) system. As these measures all capture intuitively desirable aspects of a fair system, choosing "the one true" measure is not possible, and instead a reasonable approach is to minimize a weighted combination of measures. However, this simply raises the question of how to choose the weights. Here, we formulate Legally Grounded Fairness Objectives (LGFO), which uses signals from the legal system to non-arbitrarily measure the social cost of a specific degree of unfairness. The LGFO is the expected damages under a putative lawsuit that might be awarded to those who were wrongly classified, in the sense that the ML system made a decision different to that which would have be made under the court's preferred measure. Notably, the two quantities necessary to compute the LGFO, the court's preferences about fairness measures, and the expected damages, are unknown but well-defined, and can be estimated by legal advice. Further, as the damages awarded by the legal system are designed to measure and compensate for the harm caused to an individual by an unfair classification, the LGFO aligns closely with society's estimate of the social cost

Sialic Acid Mutarotation Is Catalyzed by the Escherichia coli β-Propeller Protein YjhT

The acquisition of host-derived sialic acid is an important virulence factor for some bacterial pathogens, but in vivo this sugar acid is sequestered in sialoconjugates as the {alpha}-anomer. In solution, however, sialic acid is present mainly as the β-anomer, formed by a slow spontaneous mutarotation. We studied the Escherichia coli protein YjhT as a member of a family of uncharacterized proteins present in many sialic acid-utilizing pathogens. This protein is able to accelerate the equilibration of the {alpha}- and β-anomers of the sialic acid N-acetylneuraminic acid, thus describing a novel sialic acid mutarotase activity. The structure of this periplasmic protein, solved to 1.5Å resolution, reveals a dimeric 6-bladed unclosed β-propeller, the first of a bacterial Kelch domain protein. Mutagenesis of conserved residues in YjhT demonstrated an important role for Glu-209 and Arg-215 in mutarotase activity. We also present data suggesting that the ability to utilize {alpha}-N-acetylneuraminic acid released from complex sialoconjugates in vivo provides a physiological advantage to bacteria containing YjhT

Activation Addition: Steering Language Models Without Optimization

Reliably controlling the behavior of large language models (LLMs) is a pressing open problem. Existing methods include supervised finetuning, reinforcement learning from human feedback (RLHF), prompt engineering and guided decoding. We instead investigate activation engineering: modifying activations at inference time to predictably alter model behavior. In particular, we bias the forward pass with an added 'steering vector' implicitly specified through natural language. Unlike past work which learned these steering vectors (Subramani, Suresh, and Peters 2022; Hernandez, Li, and Andreas 2023), our Activation Addition (ActAdd) method computes them by taking the activation differences that result from pairs of prompts. We demonstrate ActAdd on GPT-2 on OpenWebText and ConceptNet. Our inference-time approach yields control over high-level properties of output and preserves off-target model performance. It involves far less compute and implementation effort compared to finetuning or RLHF, allows users to provide natural language specifications, and its overhead scales naturally with model size

Seasonal variation in SARS-CoV-2 transmission in temperate climates: a Bayesian modelling study in 143 European regions

Although seasonal variation has a known influence on the transmission of several respiratory viral infections, its role in SARS-CoV-2 transmission remains unclear. While there is a sizable and growing literature on environmental drivers of COVID-19 transmission, recent reviews have highlighted conflicting and inconclusive findings. This indeterminacy partly owes to the fact that seasonal variation relates to viral transmission by a complicated web of causal pathways, including many interacting biological and behavioural factors. Since analyses of specific factors cannot determine the aggregate strength of seasonal forcing, we sidestep the challenge of disentangling various possible causal paths in favor of a holistic approach. We model seasonality as a sinusoidal variation in transmission and infer a single Bayesian estimate of the overall seasonal effect. By extending two state-of-the-art models of non-pharmaceutical intervention (NPI) effects and their datasets covering 143 regions in temperate Europe, we are able to adjust our estimates for the role of both NPIs and mobility patterns in reducing transmission. We find strong seasonal patterns, consistent with a reduction in the time-varying reproduction number R(t) (the expected number of new infections generated by an infectious individual at time t) of 42.1% (95% CI: 24.7%—53.4%) from the peak of winter to the peak of summer. These results imply that the seasonality of SARSCoV-2 transmission is comparable in magnitude to the most effective individual NPIs but less than the combined effect of multiple interventions

Characterization of the l-arabinofuranose-specific GafABCD ABC transporter essential for l-arabinose-dependent growth of the lignocellulose-degrading bacterium Shewanella sp. ANA-3

Microbes that have evolved to live on lignocellulosic biomass face unique challenges in the effective and efficient use of this material as food. The bacterium Shewanella sp. ANA-3 has the potential to utilize arabinan and arabinoxylan, and uptake of the monosaccharide, l-arabinose, derived from these polymers, is known to be mediated by a single ABC transporter. We demonstrate that the substrate binding protein of this system, GafASw, binds specifically to l-arabinofuranose, which is the rare furanose form of l-arabinose found in lignocellulosic biomass. The structure of GafASw was resolved to 1.7 Å and comparison to Escherichia coli YtfQ (GafAEc) revealed binding site adaptations that confer specificity for furanose over pyranose forms of monosaccharides, while selecting arabinose over another related monosaccharide, galactose. The discovery of a bacterium with a natural predilection for a sugar found abundantly in certain lignocellulosic materials suggests an intimate connection in the enzymatic release and uptake of the sugar, perhaps to prevent other microbes scavenging this nutrient before it mutarotates to l-arabinopyranose. This biological discovery also provides a clear route to engineer more efficient utilization of plant biomass components in industrial biotechnology

Mask wearing in community settings reduces SARS-CoV-2 transmission

The effectiveness of mask wearing at controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been unclear. While masks are known to substantially reduce disease transmission in healthcare settings [D. K. Chu et al., Lancet 395, 1973–1987 (2020); J. Howard et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2014564118 (2021); Y. Cheng et al., Science eabg6296 (2021)], studies in community settings report inconsistent results [H. M. Ollila et al., medRxiv (2020); J. Brainard et al., Eurosurveillance 25, 2000725 (2020); T. Jefferson et al., Cochrane Database Syst. Rev. 11, CD006207 (2020)]. Most such studies focus on how masks impact transmission, by analyzing how effective government mask mandates are. However, we find that widespread voluntary mask wearing, and other data limitations, make mandate effectiveness a poor proxy for mask-wearing effectiveness. We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior ([Formula: see text] 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses