A coherent Ising machine for 2000-node optimization problems

The analysis and optimization of complex systems can be reduced to mathematical problems collectively known as combinatorial optimization. Many such problems can be mapped onto ground-state search problems of the Ising model, and various artificial spin systems are now emerging as promising approaches. However, physical Ising machines have suffered from limited numbers of spin-spin couplings because of implementations based on localized spins, resulting in severe scalability problems. We report a 2000-spin network with all-to-all spin-spin couplings. Using a measurement and feedback scheme, we coupled time-multiplexed degenerate optical parametric oscillators to implement maximum cut problems on arbitrary graph topologies with up to 2000 nodes. Our coherent Ising machine outperformed simulated annealing in terms of accuracy and computation time for a 2000-node complete graph

A coherent Ising machine for 2000-node optimization problems

The analysis and optimization of complex systems can be reduced to mathematical problems collectively known as combinatorial optimization. Many such problems can be mapped onto ground-state search problems of the Ising model, and various artificial spin systems are now emerging as promising approaches. However, physical Ising machines have suffered from limited numbers of spin-spin couplings because of implementations based on localized spins, resulting in severe scalability problems. We report a 2000-spin network with all-to-all spin-spin couplings. Using a measurement and feedback scheme, we coupled time-multiplexed degenerate optical parametric oscillators to implement maximum cut problems on arbitrary graph topologies with up to 2000 nodes. Our coherent Ising machine outperformed simulated annealing in terms of accuracy and computation time for a 2000-node complete graph

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

An Efficient Monte Carlo Approach to Compute PageRank for Large Graphs on a Single PC

This paper describes a novel Monte Carlo based random walk to compute PageRanks of nodes in a large graph on a single PC. The target graphs of this paper are ones whose size is larger than the physical memory. In such an environment, memory management is a difficult task for simulating the random walk among the nodes. We propose a novel method that partitions the graph into subgraphs in order to make them fit into the physical memory, and conducts the random walk for each subgraph. By evaluating the walks lazily, we can conduct the walks only in a subgraph and approximate the random walk by rotating the subgraphs. In computational experiments, the proposed method exhibits good performance for existing large graphs with several passes of the graph data

An Experimental Survey of Extended Resolution Effects for SAT Solvers on the Pigeonhole Principle

It has been proven that extended resolution (ER) has more powerful reasoning than general resolution for the pigeonhole principle in Cook’s paper. This fact indicates the possibility that a solver based on extended resolution can exceed Boolean satisfiability problem solvers (SAT solvers for short) based on general resolution. However, few studies have provided practical evidence of this assumption. This paper explores how extended resolution can improve SAT solvers by using the pigeonhole principle, which was the first problem solved by ER in polynomial steps. In fact, although Cook’s paper introduced how to add auxiliary variables, there is no evidence that these variables are really useful for practical solvers. We try to answer the question: If the SAT solver can add appropriate auxiliary variables as proposed in Cook’s paper, can the solver enhance its performance by utilizing these variables? Experimental results show that if the solver properly prioritizes the extended variables in the search, the solver can end the search in a shorter time

Understand Restart of SAT Solver Using Search Similarity Index (Student Abstract)

SAT solvers are widely used to solve many industrial problems because of their high performance, which is achieved by various heuristic methods. Understanding why these methods are effective is essential to improving them. One approach to this is analyzing them using qualitative measurements. In our previous study, we proposed search similarity index (SSI), a metric to quantify the similarity between searches. SSI significantly improved the performance of the parallel SAT solver. Here, we apply SSI to analyze the effect of restart, a key SAT solver technique. Experiments using SSI reveal the correlation between the difficulty of instances and the search change effect by restart, and the reason behind the effectiveness of the state-of-the-art restart method is also explained

Exact Clustering via Integer Programming and Maximum Satisfiability

We consider the following general graph clustering problem: given a complete undirected graph G=(V,E,c) with an edge weight function c:E->Q, we are asked to find a partition C of V that maximizes the sum of edge weights within the clusters in C. Owing to its high generality, this problem has a wide variety of real-world applications, including correlation clustering, group technology, and community detection. In this study, we investigate the design of mathematical programming formulations and constraint satisfaction formulations for the problem. First, we present a novel integer linear programming (ILP) formulation that has far fewer constraints than the standard ILP formulation by Groetschel and Wakabayashi (1989). Second, we propose an ILP-based exact algorithm that solves an ILP problem obtained by modifying our above ILP formulation and then performs simple post-processing to produce an optimal solution to the original problem. Third, we present maximum satisfiability (MaxSAT) counterparts of both our ILP formulation and ILP-based exact algorithm. Computational experiments using well-known real-world datasets demonstrate that our ILP-based approaches and their MaxSAT counterparts are highly effective in terms of both memory efficiency and computation time

T cell function is dispensable for intracranial aneurysm formation and progression

Given the social importance of intracranial aneurysm as a major cause of a lethal subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis of this disease is essential for improving poor prognosis once after rupture. Previous histopathological analyses of human aneurysm walls have revealed the presence of T cells in lesions suggesting involvement of this type of cell in the pathogenesis. However, it remains unclear whether T cell actively participates in intracranial aneurysm progression. To examine whether T cell is involved in aneurysm progression, intracranial aneurysm model of rat was used. In this model, aneurysm is induced by increase in hemodynamic force loaded on bifurcation site of intracranial arteries where aneurysms are developed. Deficiency in T cells and pharmacological inhibition of T cell function were applied to this model. CD3-positive T cells were present in human aneurysm walls, whose number was significantly larger compared with that in control arterial walls. Deficiency in T cells in rats and pharmacological inhibition of T cell function by oral administration of Cyclosporine A both failed to affect intracranial aneurysm progression, degenerative changes of arterial walls and macrophage infiltration in lesions. Although T cells are detectable in intracranial aneurysm walls, their function is dispensable for macrophage-mediated inflammation and degenerative changes in arterial walls, which presumably leads to intracranial aneurysm progression