Learning Generative Models across Incomparable Spaces

Generative Adversarial Networks have shown remarkable success in learning a distribution that faithfully recovers a reference distribution in its entirety. However, in some cases, we may want to only learn some aspects (e.g., cluster or manifold structure), while modifying others (e.g., style, orientation or dimension). In this work, we propose an approach to learn generative models across such incomparable spaces, and demonstrate how to steer the learned distribution towards target properties. A key component of our model is the Gromov-Wasserstein distance, a notion of discrepancy that compares distributions relationally rather than absolutely. While this framework subsumes current generative models in identically reproducing distributions, its inherent flexibility allows application to tasks in manifold learning, relational learning and cross-domain learning.Comment: International Conference on Machine Learning (ICML

Distributionally Robust Bayesian Optimization

Robustness to distributional shift is one of the key challenges of contemporary machine learning. Attaining such robustness is the goal of distributionally robust optimization, which seeks a solution to an optimization problem that is worst-case robust under a specified distributional shift of an uncontrolled covariate. In this paper, we study such a problem when the distributional shift is measured via the maximum mean discrepancy (MMD). For the setting of zeroth-order, noisy optimization, we present a novel distributionally robust Bayesian optimization algorithm (DRBO). Our algorithm provably obtains sub-linear robust regret in various settings that differ in how the uncertain covariate is observed. We demonstrate the robust performance of our method on both synthetic and real-world benchmarks.Comment: Accepted at AISTATS 202

Toothache, tooth brushing frequency and dental check-ups in children and adolescents with and without disabilities

According to international studies, children and adolescents with disabilities have more tooth decay, brush their teeth less often twice a day and use preventive dental services less often than children and adolescents without disabilities. With data from the second follow-up to the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Wave 2, 2014–2017), toothache, tooth brushing frequency and dental check-ups are examined in children and adolescents with and without disabilities. It was found that children and adolescents with disabilities had more toothache in the three months before the survey (23.5% and 15.9%, respectively) and brushed or got their teeth brushed twice a day less often (33.5% and 22.2%, respectively) than children and adolescents without disabilities. Differences in the utilisation of dental check-ups could not be determined. Overall, the results point to the importance of measures to promote tooth brushing frequency in order to improve the oral health of children and adolescents with disabilities. In addition, further opportunities should be created to collect data on the oral health of people with disabilities at the population level in health or participation studies

Validation of salt intake measurements: comparisons of a food record checklist and spot-urine collection to 24-hour-urine collection.

OBJECTIVE Monitoring population salt intake is operationally and economically challenging. We explored whether a questionnaire assessment and a prediction of Na intake from spot-urine could replace or complement the recommended measurement of Na in 24-hour urine (24hU). DESIGN Compare the agreement of a Na-specific food record checklist (FRCL) and a late afternoon spot-urine measurement (PM-spot) with 24hU measurement in estimating Na intake at group level. Each participant's use of these methods extended over three days. Agreement was assessed using mean (95% CI) differences, linear regression models, and Bland-Altman plots. SETTING The validation study was part of a one-year workplace intervention trial to lower salt intake in Switzerland. PARTICIPANTS 70 women and 71 men, 21-61 years, completed three FRCLs, and acceptable PM-spot and 24hU samples at baseline (April-October 2015). RESULTS Mean Na intake estimates varied slightly across methods (3.5-3.9 g/d). Mean Na intake differences from 24hU were 0.2 (95% CI 0, 0.5) g/d for FRCL, and 0.4 (95% CI 0.2, 0.6) g/d for PM-spot. Linear regression models and Bland-Altmann plots more clearly depicted differences by sex and discretionary salt use. CONCLUSIONS Although 24hU remains the best reference method for monitoring Na intake at the population level, PM-spot and FRCL might be more practical instruments for frequent, periodic Na intake assessments. Population specific prediction models to estimate 24hU could be developed and evaluated

Quantitative analysis of the human T cell palmitome

Palmitoylation is a reversible post-translational modification used to inducibly compartmentalize proteins in cellular membranes, affecting the function of receptors and intracellular signaling proteins. The identification of protein “palmitomes” in several cell lines raises the question to what extent this modification is conserved in primary cells. Here we use primary T cells with acyl-biotin exchange and quantitative mass spectrometry to identify a pool of proteins previously unreported as palmitoylated in vivo

LMNA Co-Regulated Gene Expression as a Suitable Readout after Precise Gene Correction

LMNA-related muscular dystrophy is an autosomal-dominant progressive disorder caused by mutations in LMNA. LMNA missense mutations are becoming correctable with CRISPR/Cas9-derived tools. Evaluating the functional recovery of LMNA after gene editing bears challenges as there is no reported direct loss of function of lamin A/C proteins in patient-derived cells. The proteins encoded by LMNA are lamins A/C, important ubiquitous nuclear envelope proteins but absent in pluripotent stem cells. We induced lamin A/C expression in induced pluripotent stem cells (iPSCs) of two patients with LMNA-related muscular dystrophy, NM_170707.4 (LMNA): c.1366A > G, p.(Asn456Asp) and c.1494G > T, p.(Trp498Cys), using a short three-day, serum-induced differentiation protocol and analyzed expression profiles of co-regulated genes, examples being COL1A2 and S100A6. We then performed precise gene editing of LMNA c.1366A > G using the near-PAMless (PAM: protospacer-adjacent motif) cytosine base editor. We show that the mutation can be repaired to 100% efficiency in individual iPSC clones. The fast differentiation protocol provided a functional readout and demonstrated increased lamin A/C expression as well as normalized expression of co-regulated genes. Collectively, our findings demonstrate the power of CRISPR/Cas9-mediated gene correction and effective outcome measures in a disease with, so far, little perspective on therapies