Pairwise classification using quantum support vector machine with Kronecker kernel

We investigated the potential application of quantum computing using the Kronecker kernel to pairwise classification and have devised a way to apply the Harrow-Hassidim-Lloyd (HHL)-based quantum support vector machine algorithm. Pairwise classification can be used to predict relationships among data and is used for problems such as link prediction and chemical interaction prediction. However, in pairwise classification using a Kronecker kernel, it is very costly to calculate the Kronecker product of the kernel matrices when there is a large amount of data. We found that the Kronecker product of kernel matrices can be represented more efficiently in time and space in quantum computing than that in classical computing. We also found that a pairwise classifier can be effectively trained by applying the HHL-based quantum support vector machine algorithm to the Kronecker kernel matrix. In an experiment comparing a classical algorithm with a quantum support vector machine with a Kronecker kernel run on a quantum computing simulator, the misclassification rate of the latter was almost the same as that of the former for the same pairwise classification problem in some cases. This indicates that a quantum support vector machine with a Kronecker kernel algorithm can achieve accuracy equivalent to that of the classical algorithm more efficiently and scalably. This finding paves the way for applying quantum machine learning to predicting relationships in large-scale data

Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells

Airway mucus hyperproduction and fluid imbalance are important hallmarks of cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians. Dysregulated expression and/or function of airway ion transporters, including cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC), have been implicated as causes of CF-associated mucus hypersecretory phenotype. However, the contributory roles of other substances and transporters in the regulation of CF airway pathogenesis remain unelucidated. Here, we identified a novel connection between CFTR/ENaC expression and the intracellular Zn2+ concentration in the regulation of MUC5AC, a major secreted mucin that is highly expressed in CF airway. CFTR-defective and ENaC-hyperactive airway epithelial cells specifically and highly expressed a unique, alternative splice isoform of the zinc importer ZIP2/SLC39A2 (ΔC-ZIP2), which lacks the C-terminal domain. Importantly, ΔC-ZIP2 levels correlated inversely with wild-type ZIP2 and intracellular Zn2+ levels. Moreover, the splice switch to ΔC-ZIP2 as well as decreased expression of other ZIPs caused zinc deficiency, which is sufficient for induction of MUC5AC; while ΔC-ZIP2 expression per se induced ENaC expression and function. Thus, our findings demonstrate that the novel splicing switch contributes to CF lung pathology via the novel interplay of CFTR, ENaC, and ZIP2 transporters

Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females