Towards Poisoning Fair Representations

Fair machine learning seeks to mitigate model prediction bias against certain demographic subgroups such as elder and female. Recently, fair representation learning (FRL) trained by deep neural networks has demonstrated superior performance, whereby representations containing no demographic information are inferred from the data and then used as the input to classification or other downstream tasks. Despite the development of FRL methods, their vulnerability under data poisoning attack, a popular protocol to benchmark model robustness under adversarial scenarios, is under-explored. Data poisoning attacks have been developed for classical fair machine learning methods which incorporate fairness constraints into shallow-model classifiers. Nonetheless, these attacks fall short in FRL due to notably different fairness goals and model architectures. This work proposes the first data poisoning framework attacking FRL. We induce the model to output unfair representations that contain as much demographic information as possible by injecting carefully crafted poisoning samples into the training data. This attack entails a prohibitive bilevel optimization, wherefore an effective approximated solution is proposed. A theoretical analysis on the needed number of poisoning samples is derived and sheds light on defending against the attack. Experiments on benchmark fairness datasets and state-of-the-art fair representation learning models demonstrate the superiority of our attack

Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice

: Homologous recombination (HR)-based gene therapy using adeno-associated viruses (AAV-HR) without nucleases has several advantages over classic gene therapy, especially the potential for permanent transgene expression. However, the low efficiency of AAV-HR remains a major limitation. Here, we tested a series of small-molecule compounds and found that ribonucleotide reductase (RNR) inhibitors substantially enhance AAV-HR efficiency in mouse and human liver cell lines approximately threefold. Short-term administration of the RNR inhibitor fludarabine increased the in vivo efficiency of both non-nuclease- and CRISPR/Cas9-mediated AAV-HR two- to sevenfold in the murine liver, without causing overt toxicity. Fludarabine administration induced transient DNA damage signaling in both proliferating and quiescent hepatocytes. Notably, the majority of AAV-HR events occurred in non-proliferating hepatocytes in both fludarabine-treated and control mice, suggesting that the induction of transient DNA repair signaling in non-dividing hepatocytes was responsible for enhancing AAV-HR efficiency in mice. These results suggest that use of a clinically approved RNR inhibitor can potentiate AAV-HR-based genome-editing therapeutics

Evaluation of flight efficiency for Stockholm Arlanda Airport arrivals

Analysis of punctuality of airport arrivals, as well as identification of causes of the delays within transition airspace, is an important step in evaluating performance of the Terminal Maneuvering Area (TMA) Air Navigation Services: without knowing the current performance levels, it is difficult to identify which areas could be improved. Deviations from the flight plans is one of the major reasons for arrival delays. In this work, we quantified the impact of the deviations from the flight plans on the fuel burn. One of the main reasons of fuel waste is non- optimal vertical profiles during the descent phase. We calculated how much extra fuel is wasted due to vertical flight inefficiency within Stockholm TMA.Peer ReviewedPostprint (published version

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Gas exchange characteristics and their influencing factors for halophytic plant communities on west coast of Bohai Sea.

Water-salt stress and nutrient limitation may affect leaf economic spectrum of halophytes and confuse our understanding on plant physiological principles in a changing world. In this study, three halophytic plant communities of Phragmites australis, Suaeda salsa, and Tamarix chinensis, were selected in two sites (sites 1 and 2) on the west coast of Bohai Sea. The net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), leaf vapor pressure deficit (VPDleaf) and their influencing factors were studied to test the possible carbon assimilation strategies of the halophytes. P. australis had higher Pn, Tr, and Gs than S. salsa and T. chinensis in both sites. Similar trends were found for leaf P and photosynthetic N and P efficiency (PNUE and PPUE, respectively) in one or both sites. By contrast, the leaf dry mass per area (LMA) increased in the order of P. australis < S. salsa < T. chinensis in both sites. For identical species in different sites, Pn, leaf P, and PNUE were lower but Tr, VPDleaf, leaf N, leaf N:P, and PPUE were higher in site 1 than in site 2 for one or more halophytes. Although soil physicochemical properties in different sites explained several variations among the halophytes, two-way ANOVA indicated that the species can explain most of the leaf traits compared with the site. LMA also had significant nonlinear relationships with Pn, Tr, Gs, and VPDleaf. PNUE and PPUE showed positive correlation with Pn in both sites, but they decreased in the power-law function with increasing LMA. Overall, the redundancy analysis showed that the gas exchange capacity of the halophytic plant communities was significantly affected by PPUE (60.0% of explanation), PNUE (57.1%), LMA (35.0%), leaf P (22.0%), and soil N (15.8%)

Food-Derived Pharmacological Modulators of the Nrf2/ARE Pathway: Their Role in the Treatment of Diseases

Oxidative stress, which refers to unbalanced accumulation of reactive oxygen species (ROS) levels in cells, has been linked to acute and chronic diseases. Nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays a vital role in regulating cytoprotective genes and enzymes in response to oxidative stress. Therefore, pharmacological regulation of Nrf2/ARE pathway is an effective method to treat several diseases that are mainly characterized by oxidative stress and inflammation. Natural products that counteract oxidative stress by modulating Nrf2 have contributed significantly to disease treatment. In this review, we focus on bioactive compounds derived from food that are Nrf2/ARE pathway regulators and describe the molecular mechanisms for regulating Nrf2 to exert favorable effects in experimental models of diseases