MathNAS: If Blocks Have a Role in Mathematical Architecture Design

Neural Architecture Search (NAS) has emerged as a favoured method for unearthing effective neural architectures. Recent development of large models has intensified the demand for faster search speeds and more accurate search results. However, designing large models by NAS is challenging due to the dramatical increase of search space and the associated huge performance evaluation cost. Consider a typical modular search space widely used in NAS, in which a neural architecture consists of $m$ block nodes and a block node has $n$ alternative blocks. Facing the space containing $n^m$ candidate networks, existing NAS methods attempt to find the best one by searching and evaluating candidate networks directly.Different from the general strategy that takes architecture search as a whole problem, we propose a novel divide-and-conquer strategy by making use of the modular nature of the search space.Here, we introduce MathNAS, a general NAS framework based on mathematical programming.In MathNAS, the performances of the $m*n$ possible building blocks in the search space are calculated first, and then the performance of a network is directly predicted based on the performances of its building blocks. Although estimating block performances involves network training, just as what happens for network performance evaluation in existing NAS methods, predicting network performance is completely training-free and thus extremely fast. In contrast to the $n^m$ candidate networks to evaluate in existing NAS methods, which require training and a formidable computational burden, there are only $m*n$ possible blocks to handle in MathNAS. Therefore, our approach effectively reduces the complexity of network performance evaluation.Our code is available at https://github.com/wangqinsi1/MathNAS.Comment: NeurIPS 202

The association between urinary Alzheimer-associated neuronal thread protein and cognitive impairment in late-life depression: A controlled pilot study

Accumulation of tau protein is associated with both Alzheimer’s disease (AD) and late-life depression (LLD). Alzheimer-associated neuronal thread protein (AD7c-NTP), which is closely linked with the tau protein, is elevated in the cerebrospinal fluid and urine of AD patients. This study examined the association between urinary AD7c-NTP and late-life depression with cognitive impairment. One hundred and thirty-eight subjects were recruited into late-life depression with cognitive impairment (LLD-CI, n=52), late-life depression without cognitive impairment (LLD-NCI, n=29), AD (n=27), and healthy control (HC, n=30) groups. The level of urinary AD7c-NTP was measured using the enzyme-linked immunosorbent assay method. The Montreal Cognitive Assessment scale (MoCA), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess cognitive functions and depressive and anxiety symptoms in the AD and LLD groups. Urinary levels of AD7c-NTP in the LLD-CI group (1.0±0.7ng/ml) were significantly higher than both the LLD-NCI (0.5±0.3ng/ml) and HC groups (0.5±0.3ng/ml), but lower than in the AD group (1.6±1.7 ng/ml). No significant associations were found in the level of urinary AD7c-NTP in relation to age, gender, education and MoCA in the LLD-CI group. The level of urinary AD7c-NTP appears to be associated with cognitive impairment in late-life depression and may be a potential biomarker for early identification of cognitive impairment in LLD

A suitable method for alpine wetland delineation: An example for the headwater area of the yellow river, Tibetan Plateau

Alpine wetlands are one of the most important ecosystems in the Three Rivers Source Area, China, which plays an important role in regulating the regional hydrological cycle and carbon cycle. Accordingly, Wetland area and its distribution are of great significance for wetland management and scientific research. In our study, a new wetland classification model which based on geomorphological types and combine object-oriented and decision tree classification model (ODTC), and used a new wetland classification system to accurately extract the wetland distributed in the Headwater Area of the Yellow River (HAYR) of the Qinghai-Tibet Plateau (QTP), China. The object-oriented method was first used to segment the image into several areas according to similarity in Pixels and Textures, and then the wetland was extracted through a decision tree constructed based on geomorphological types. The wetland extracted by the model was compared with that by other seven commonly methods, such as support vector machine (SVM) and random forest (RF), and it proved the accuracy was improved by 10%–20%. The overall classification accuracy rate was 98.9%. According to our results, the HAYR’s wetland area is 3142.3 km2, accounting for 16.1% of the study area. Marsh wetlands and flood wetlands accounted for 37.7% and 16.7% respectively. A three-dimensional map of the area showed that alpine wetlands in the research region are distributed around lakes, piedmont groundwater overflow belts, and inter-mountain catchment basin. This phenomenon demonstrates that hydrogeological circumstances influence alpine wetlands’ genesis and evolution. This work provides a new approach to investigating alpine wetlands

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Background/Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. Methods: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. Results: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. Conclusion: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases