Stochastic Optimization of Areas UnderPrecision-Recall Curves with Provable Convergence

Areas under ROC (AUROC) and precision-recall curves (AUPRC) are common metrics for evaluating classification performance for imbalanced problems. Compared with AUROC, AUPRC is a more appropriate metric for highly imbalanced datasets. While stochastic optimization of AUROC has been studied extensively, principled stochastic optimization of AUPRC has been rarely explored. In this work, we propose a principled technical method to optimize AUPRC for deep learning. Our approach is based on maximizing the averaged precision (AP), which is an unbiased point estimator of AUPRC. We cast the objective into a sum of {\it dependent compositional functions} with inner functions dependent on random variables of the outer level. We propose efficient adaptive and non-adaptive stochastic algorithms named SOAP with {\it provable convergence guarantee under mild conditions} by leveraging recent advances in stochastic compositional optimization. Extensive experimental results on image and graph datasets demonstrate that our proposed method outperforms prior methods on imbalanced problems in terms of AUPRC. To the best of our knowledge, our work represents the first attempt to optimize AUPRC with provable convergence. The SOAP has been implemented in the libAUC library at~\url{https://libauc.org/}.Comment: 24 pages, 10 figure

Increased serum lysyl oxidase-like 2 levels correlate with the degree of left atrial fibrosis in patients with atrial fibrillation

Atrial fibrillation (AF) progression is generally accompanied by increased atrial fibrosis and atrial structural remodeling. Lysyl oxidase-like 2 (LOXL2) is known to play an important role in many fibrotic conditions, including cardiac fibrosis. The present study aimed to explore the relationship between serum LOXL2 levels and AF. Fifty-four AF patients and 32 control subjects were enrolled in the study. High-density three-dimensional electroanatomic mapping was performed, and mean bipolar voltage was assessed in AF patients. LOXL2 levels were measured by enzyme-linked immunosorbent assay. All patients underwent echocardiography to assess left atrium size and left ventricle function. Serum LOXL2 levels were significantly elevated in AF patients compared with the control group (526.81 ± 316.82 vs 240.94 ± 92.51 pg/ml, P<0.01). In addition, serum LOXL2 level was significantly correlated with the size of the left atrium (LAD) (r2 = 0.38, P<0.01). Furthermore, the serum LOXL2 levels were significantly higher in AF patients with LAD ≥ 40 mm compared with those with LAD < 40 mm (664.34 ± 346.50 vs 354.90 ± 156.23 pg/ml, P<0.01). And the Spearman’s correlation analysis further revealed that the mean bipolar left atrial voltage was inversely correlated with the LOXL2 (r2 = −0.49, P<0.01) in AF patients. Multivariate regression analysis further demonstrated that serum LOXL2 [odds ratio (OR) 1.013, 95% confidence interval (CI) 1.002–1.024, P<0.05] and LAD (OR 1.704, 95% CI 1.131–2.568, P<0.01) were independent predictors of AF. In conclusion, serum LOXL2 levels were significantly elevated and were correlated with the degree of left atrial fibrosis in AF patients

Exploration of an Actin Promoter-Based Transient Expression Vector to Trace the Cellular Localization of Nucleorhabdovirus Proteins in Leafhopper Cultured Cells

Continuously cultured cell lines derived from planthopper and leafhopper have greatly facilitated the investigation of rice viruses transmitted by these insects. However, the lack of a suitable transient expression vector has limited their utility. Here, by cloning and analyzing the promoter sequence of the gene encoding cytoplasmic actin from the leafhopper Nephotettix cincticeps, we successfully developed the first efficient transient expression vector for cultured leafhopper cells, which can also be used to express exogenous proteins in other insect culture cell lines, including those derived from Recilia dorsalis leafhopper and Spodoptera frugiperda (Sf9). Furthermore, insertion of the Hr5 viral enhancer element and knockdown of the endogenous Dicer2 gene notably improved the vector’s expression efficiency in leafhopper cells. Using the optimized vector, we have for the first time traced the cellular localization of the proteins encoded by rice yellow stunt virus (RYSV) in cells of its insect vector and demonstrated that P6 protein is a component of the viroplasm

Lemur: Harmonizing Natural Language and Code for Language Agents

We introduce Lemur and Lemur-Chat, openly accessible language models optimized for both natural language and coding capabilities to serve as the backbone of versatile language agents. The evolution from language chat models to functional language agents demands that models not only master human interaction, reasoning, and planning but also ensure grounding in the relevant environments. This calls for a harmonious blend of language and coding capabilities in the models. Lemur and Lemur-Chat are proposed to address this necessity, demonstrating balanced proficiencies in both domains, unlike existing open-source models that tend to specialize in either. Through meticulous pre-training using a code-intensive corpus and instruction fine-tuning on text and code data, our models achieve state-of-the-art averaged performance across diverse text and coding benchmarks among open-source models. Comprehensive experiments demonstrate Lemur's superiority over existing open-source models and its proficiency across various agent tasks involving human communication, tool usage, and interaction under fully- and partially- observable environments. The harmonization between natural and programming languages enables Lemur-Chat to significantly narrow the gap with proprietary models on agent abilities, providing key insights into developing advanced open-source agents adept at reasoning, planning, and operating seamlessly across environments. https://github.com/OpenLemur/Lemu

Reversal of Cocaine-Conditioned Place Preference through Methyl Supplementation in Mice: Altering Global DNA Methylation in the Prefrontal Cortex

Analysis of global methylation in cells has revealed correlations between overall DNA methylation status and some biological states. Recent studies suggest that epigenetic regulation through DNA methylation could be responsible for neuroadaptations induced by addictive drugs. However, there is no investigation to determine global DNA methylation status following repeated exposure to addictive drugs. Using mice conditioned place preference (CPP) procedure, we measured global DNA methylation level in the nucleus accumbens (NAc) and the prefrontal cortex (PFC) associated with drug rewarding effects. We found that cocaine-, but not morphine- or food-CPP training decreased global DNA methylation in the PFC. Chronic treatment with methionine, a methyl donor, for 25 consecutive days prior to and during CPP training inhibited the establishment of cocaine, but not morphine or food CPP. We also found that both mRNA and protein level of DNMT (DNA methytransferase) 3b in the PFC were downregulated following the establishment of cocaine CPP, and the downregulation could be reversed by repeated administration of methionine. Our study indicates a crucial role of global PFC DNA hypomethylation in the rewarding effects of cocaine. Reversal of global DNA hypomethylation could significantly attenuate the rewarding effects induced by cocaine. Our results suggest that methionine may have become a potential therapeutic target to treat cocaine addiction

Draft genome sequence of the mulberry tree Morus notabilis

Human utilization of the mulberry–silkworm interaction started at least 5,000 years ago and greatly influenced world history through the Silk Road. Complementing the silkworm genome sequence, here we describe the genome of a mulberry species Morus notabilis. In the 330-Mb genome assembly, we identify 128 Mb of repetitive sequences and 29,338 genes, 60.8% of which are supported by transcriptome sequencing. Mulberry gene sequences appear to evolve ~3 times faster than other Rosales, perhaps facilitating the species’ spread worldwide. The mulberry tree is among a few eudicots but several Rosales that have not preserved genome duplications in more than 100 million years; however, a neopolyploid series found in the mulberry tree and several others suggest that new duplications may confer benefits. Five predicted mulberry miRNAs are found in the haemolymph and silk glands of the silkworm, suggesting interactions at molecular levels in the plant–herbivore relationship. The identification and analyses of mulberry genes involved in diversifying selection, resistance and protease inhibitor expressed in the laticifers will accelerate the improvement of mulberry plants