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Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders.

Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs. Here we summarize small-group discussions in tables of circuits and biomarkers categorized by (a) sensorimotor, (b) behavioral medicine and (c) integrated approaches (e.g., physiological responses). In total, hundreds of biomarkers have been identified and are summarized herein by the respective group leads. We hope the meeting proceedings become a rich resource for NASAs Human Research Program (HRP) and the community of researchers.

Zi-Qiang Li,1,&ast; Ye Qin,2,&ast; Wen-Peng Cai,1,&ast; Si-Qi Deng,3 Xiao-Fei Mao,1 Jian-Guo Zhang,1 Tian-Ya Hou,1 Yu Pan,4 Yi Cui,1 Ying-Nan Ge,5 Wei Dong,1,&ast; Yun-Xiang Tang1,&ast; 1Faculty of Psychology, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The School of Mechanical Engineering, Changzhou University, Changzhou, 210046, People’s Republic of China; 3Department of Clinical Psychological Counseling, Shanghai Tongxinjici Health Couseling Center, Shanghai, 200433, People’s Republic of China; 4Department of Medical Psychology, Chinese PLA General Hospital, Beijing, 100830, People’s Republic of China; 5Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Dong; Yun-Xiang Tang, Faculty of Psychology, Naval Medical University, No. 800 Xiangyin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-13524435414 ; +86-13386271042, Email sophiedongwei@163.com; tangyun7633@sina.comPurpose: This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm.Methods: A randomized pretest-posttest control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later.Results: Mean valence ratings of SD group were more negative than SC group’s (p < 0.05) and mean arousal ratings of SD group were higher than SC group’s (p < 0.01).Conclusion: Sleep deprivation may impa

Qing-Wei Gu,&ast; Qi Sun,&ast; Jie Wang, Wen-Sha Gu, Wei Wang, Xiao-Ming Mao Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Ming Mao, Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, 68 ChangLe Street, Nanjing, Jiangsu, 210006, People’s Republic of China, Tel +86-18951670295, Email maoxming@163.comPurpose: To investigate the pathogenesis of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM), we evaluated the effects of short-term glycemic variability (GV) on the profile of T cell subpopulations.Methods: A total of 47 T2DM patients with normoalbuminuria, 47 microalbuminuria, and 49 macroalbuminuria were enrolled. The continuous glucose monitoring (CGM) determined the GV of enrolled patients. Flow cytometry was used to determine the proportion of T cell subpopulations.Results: The frequency of T helper (Th) 17 and Th1 cells significantly increased while regulatory T cells (Tregs) significantly decreased in the macroalbuminuria group compared to normoalbuminuria and microalbuminuria groups (P < 0.01). The suppressive function of Tregs was significantly lower in the macroalbuminuria group than the normoalbuminuria group (P < 0.05). Compared with the normoalbuminuria group, the mean amplitude of glucose excursions (MAGE) of the macroalbuminuria group was significantly higher (P< 0.05). Furthermore, there were negative associations between the proportion of Tregs and MAGE.Conclusions: Increased GV could decrease the proportion of Tregs and may impair their function. This may lead to increases in Th1 and Th17 cells, and some inflammatory cytokines, which might contribute to the development and progression of DKD in T2DM.Keywords: type 2 diabetes mellitus, diabetic kidney disease, glycemic variability, regulatory T cells, inflammatory cytokines

Knapsack and Partition are two important additive problems whose fine-grained complexities in the $(1-\varepsilon)$-approximation setting are not yet settled. In this work, we make progress on both problems by giving improved algorithms. - Knapsack can be $(1 - \varepsilon)$-approximated in $\tilde O(n + (1/\varepsilon) ^ {2.2} )$ time, improving the previous $\tilde O(n + (1/\varepsilon) ^ {2.25} )$ by Jin (ICALP'19). There is a known conditional lower bound of $(n+\varepsilon)^{2-o(1)}$ based on $(\min,+)$-convolution hypothesis. - Partition can be $(1 - \varepsilon)$-approximated in $\tilde O(n + (1/\varepsilon) ^ {1.25} )$ time, improving the previous $\tilde O(n + (1/\varepsilon) ^ {1.5} )$ by Bringmann and Nakos (SODA'21). There is a known conditional lower bound of $(1/\varepsilon)^{1-o(1)}$ based on Strong Exponential Time Hypothesis. Both of our new algorithms apply the additive combinatorial results on dense subset sums by Galil and Margalit (SICOMP'91), Bringmann and Wellnitz (SODA'21). Such techniques have not been explored in the context of Knapsack prior to our work. In addition, we design several new methods to speed up the divide-and-conquer steps which naturally arise in solving additive problems., Comment: To appear in SODA 2023. Corrects minor mistakes in Lemma 3.3 and Lemma 3.5 in the proceedings version of this paper

Chun-Hui Zhao,1 Ya-Hong Sun,1 Xiao-Min Mao2 1Department of Respiratory Medicine, Haining People’s Hospital, Haining, Zhejiang, 314400, People’s Republic of China; 2Department of Infectious Diseases, Haining People’s Hospital, Haining, Zhejiang, 314400, People’s Republic of ChinaCorrespondence: Xiao-Min Mao, Department of Infectious Diseases, Haining People’s Hospital, No. 2, Qianjiang West Road, Haining, Zhejiang, 314400, People’s Republic of China, Email maoxiaomin2022@163.comObjective: To compare the effect of diaphragmatic breathing and volume incentive spirometry (VIS) on hemodynamics, pulmonary function, and blood gas in patients following open abdominal surgery under general anesthesia.Methods: A total of 58 patients who received open abdominal surgery were randomly assigned to the control group (n=29) undergoing diaphragmatic breathing exercises and the VIS group (n=29) undergoing VIS exercises. All the participants performed the six-minute walk test (6MWT) preoperatively to evaluate their functional capacity. Hemodynamic indexes, pulmonary function tests, and blood gas indexes were recorded before surgery and on the 1st, 3rd, and 5th postoperative day.Results: The functional capacity was not significantly different between the two groups during the preoperative period (P > 0.05). At 3 days and 5 days postoperatively, patients in the VIS group had a significantly higher SpO2 than that in the control group (P < 0.05). Pulmonary function test values were reduced in both two groups postoperatively when compared to the preoperative values but improved for three and five days afterward (P < 0.05). Of note, the significantly elevated levels of peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were observed on the 1st, 3rd, and 5th postoperative days in the VIS group compared with those in the control group (P < 0.05). Besides, bass excess (BE), and pH values were

The All-Pairs Shortest Paths (APSP) problem is one of the fundamental problems in theoretical computer science. It asks to compute the distance matrix of a given $n$-vertex graph. We revisit the classical problem of maintaining the distance matrix under a fully dynamic setting undergoing vertex insertions and deletions with a fast worst-case running time and efficient space usage. Although an algorithm with amortized update-time $\tilde O(n ^ 2)$ has been known for nearly two decades [Demetrescu and Italiano, STOC 2003], the current best algorithm for worst-case running time with efficient space usage runs is due to [Gutenberg and Wulff-Nilsen, SODA 2020], which improves the space usage of the previous algorithm due to [Abraham, Chechik, and Krinninger, SODA 2017] to $\tilde O(n ^ 2)$ but fails to improve their running time of $\tilde O(n ^ {2 + 2 / 3})$. It has been conjectured that no algorithm in $O(n ^ {2.5 - \epsilon})$ worst-case update time exists. For graphs without negative cycles, we meet this conjectured lower bound by introducing a Monte Carlo algorithm running in randomized $\tilde O(n ^ {2.5})$ time while keeping the $\tilde O(n ^ 2)$ space bound from the previous algorithm. Our breakthrough is made possible by the idea of ``hop-dominant shortest paths,'' which are shortest paths with a constraint on hops (number of vertices) that remain shortest after we relax the constraint by a constant factor., Comment: Preprint

Knapsack is one of the most fundamental problems in theoretical computer science. In the $(1 - \epsilon)$-approximation setting, although there is a fine-grained lower bound of $(n + 1 / \epsilon) ^ {2 - o(1)}$ based on the $(\min, +)$-convolution hypothesis ([K{\"u}nnemann, Paturi and Stefan Schneider, ICALP 2017] and [Cygan, Mucha, Wegrzycki and Wlodarczyk, 2017]), the best algorithm is randomized and runs in $\tilde O\left(n + (\frac{1}{\epsilon})^{11/5}/2^{\Omega(\sqrt{\log(1/\epsilon)})}\right)$ time [Deng, Jin and Mao, SODA 2023], and it remains an important open problem whether an algorithm with a running time that matches the lower bound (up to a sub-polynomial factor) exists. We answer the question positively by showing a deterministic $(1 - \epsilon)$-approximation scheme for knapsack that runs in $\tilde O(n + (1 / \epsilon) ^ {2})$ time. We first extend a known lemma in a recursive way to reduce the problem to $n \epsilon$-additive approximation for $n$ items with profits in $[1, 2)$. Then we give a simple efficient geometry-based algorithm for the reduced problem.

Exploiting unmanned aerial vehicles (UAVs) to execute tasks is gaining growing popularity recently. To solve the underlying task scheduling problem, the deep reinforcement learning (DRL) based methods demonstrate notable advantage over the conventional heuristics as they rely less on hand-engineered rules. However, their decision space will become prohibitively huge as the problem scales up, thus deteriorating the computation efficiency. To alleviate this issue, we propose a double-level deep reinforcement learning (DL-DRL) approach based on a divide and conquer framework (DCF), where we decompose the task scheduling of multi-UAV into task allocation and route planning. Particularly, we design an encoder-decoder structured policy network in our upper-level DRL model to allocate the tasks to different UAVs, and we exploit another attention based policy network in our lower-level DRL model to construct the route for each UAV, with the objective to maximize the number of executed tasks given the maximum flight distance of the UAV. To effectively train the two models, we design an interactive training strategy (ITS), which includes pre-training, intensive training and alternate training. Experimental results show that our DL-DRL performs favorably against the learning-based and conventional baselines including the OR-Tools, in terms of solution quality and computation efficiency. We also verify the generalization performance of our approach by applying it to larger sizes of up to 1000 tasks. Moreover, we also show via an ablation study that our ITS can help achieve a balance between the performance and training efficiency., Comment: 13 pages, 7 figures

Unbounded SubsetSum is a classical textbook problem: given integers $w_1,w_2,\cdots,w_n\in [1,u],~c,u$, we need to find if there exists $m_1,m_2,\cdots,m_n\in \mathbb{N}$ satisfying $c=\sum_{i=1}^n w_im_i$. In its all-target version, $t\in \mathbb{Z}_+$ is given and answer for all integers $c\in[0,t]$ is required. In this paper, we study three generalizations of this simple problem: All-Target Unbounded Knapsack, All-Target CoinChange and Residue Table. By new combinatorial insights into the structures of solutions, we present a novel two-phase approach for such problems. As a result, we present the first near-linear algorithms for CoinChange and Residue Table, which runs in $\tilde{O}(u+t)$ and $\tilde{O}(u)$ time deterministically. We also show if we can compute $(\min,+)$ convolution for $n$-length arrays in $T(n)$ time, then All-Target Unbounded Knapsack can be solved in $\tilde{O}(T(u)+t)$ time, thus establishing sub-quadratic equivalence between All-Target Unbounded Knapsack and $(\min,+)$ convolution.

The (unweighted) tree edit distance problem for $n$ node trees asks to compute a measure of dissimilarity between two rooted trees with node labels. The current best algorithm from more than a decade ago runs in $O(n ^ 3)$ time [Demaine, Mozes, Rossman, and Weimann, ICALP 2007]. The same paper also showed that $O(n ^ 3)$ is the best possible running time for any algorithm using the so-called decomposition strategy, which underlies almost all the known algorithms for this problem. These algorithms would also work for the weighted tree edit distance problem, which cannot be solved in truly sub-cubic time under the APSP conjecture [Bringmann, Gawrychowski, Mozes, and Weimann, SODA 2018]. In this paper, we break the cubic barrier by showing an $O(n ^ {2.9546})$ time algorithm for the unweighted tree edit distance problem. We consider an equivalent maximization problem and use a dynamic programming scheme involving matrices with many special properties. By using a decomposition scheme as well as several combinatorial techniques, we reduce tree edit distance to the max-plus product of bounded-difference matrices, which can be solved in truly sub-cubic time [Bringmann, Grandoni, Saha, and Vassilevska Williams, FOCS 2016]., Comment: Accepted to FOCS'21. Fixed some minor typos

Many NP-Hard problems on general graphs, such as maximum independence set, maximal cliques and graph coloring can be solved efficiently on chordal graphs. In this paper, we explore the problem of non-separating st-paths defined on edges: for a connected undirected graph and two vertices, a non-separating path is a path between the two vertices such that if we remove all the edges on the path, the graph remains connected. We show that on general graphs, checking the existence of non-separating st-paths is NP-Hard, but the same problem can be solved in linear time on chordal graphs. In the case that such path exists, we introduce an algorithm that finds the shortest non-separating st-path on a connected chordal graph of $n$ vertices and $m$ edges with positive edge lengths that runs in $O(n\log{n} + m)$ time., Comment: Fixed one misleading typo as well as some other minor issues in section 6.1.1 Some further polishment for submission to ICALP 2021

We study a natural extension to the well-known convex hull problem by introducing multiplicity: if we are given a set of convex polygons, and we are allowed to partition the set into multiple components and take the convex hull of each individual component, what is the minimum total sum of the perimeters of the convex hulls? We show why this problem is intriguing, and then introduce a novel algorithm with a run-time cubic in the total number of vertices. In the case that the input polygons are disjoint, we show an optimization that achieves a run-time that, in most cases, is cubic in the total number of polygons, within a logarithmic factor., Comment: The result is non-original and inferior compared to https://dl.acm.org/doi/pdf/10.1145/3188745.3188878

Xiao-Mei Mao,1,* Pan Zhou,1,* Si-Yang Li,2,* Xiao-Yun Zhang,2 Jin-Xing Shen,2 Qing-Xi Chen,1 Jiang-Xing Zhuang,3 Dong-Yan Shen2 1School of Life Sciences, Xiamen University, Xiamen 361102, People’s Republic of China; 2Biobank, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People’s Republic of China; 3Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian 361102, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong-Yan ShenBiobank, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen 361003, People’s Republic of ChinaTel +86 592 213 7507Fax +86 592 213 7509Email shendongyan@163.comJiang-Xing ZhuangFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian 361102, People’s Republic of ChinaEmail jiangxingzhuang@xmu.edu.cnPurpose: Diosgenin (DSG) is the precursor of steroid hormones and plays a crucial part in the proliferation of various carcinomas including human colorectal cancer and gastric carcinoma. Nevertheless, its specific features and mechanisms in human cholangiocarcinoma (CCA) remain unknown.Methods: MTS assay, colony-forming assay, and EdU assay were performed to determine the role of DSG on the progression of human CCA cells. The distributions of cell cycle, the ratio of apoptosis, and the mitochondrial membrane potential (ΔΨm) were studied by flow cytometry (FCM). AO/EB and Hoechst 33258 staining were performed to observe the morphological features of cell apoptosis. TEM was performed to observe the ultrastructures of QBC939 and HuCCT1 cells. The mRNA and protein expression of mitochondrial apoptotic pathway and GSK3β/β-catenin pathway were further confirmed by

While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.

Ke He,1,2,* Yun Hu,2,* Jun-Cheng Shi,2 Yun-Qing Zhu,2 Xiao-Ming Mao2 1Department of Endocrinology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China; 2Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Background: Urinary tract infections (UTIs) occur more frequently in diabetic patients. This study was conducted to investigate the prevalence, risk factors and microorganisms of UTIs in Chinese patients with type 2 diabetes (T2D).Patients and methods: A total of 3,652 Chinese inpatients with T2D were reviewed and data on their clinical characteristics, symptoms of UTIs, random blood glucose, HbA1c, glutamic acid decarboxylase antibody, insulin autoantibody, albumin excretion rate in 24-hour urine, urine culture and susceptibility to antibiotics, and so on were collected. Binary logistic analysis was performed to look for risk factors of UTIs.Results: There were 409 (11.2%) patients suffering from UTIs. Gender, age, random blood glucose, insulin autoantibody and albumin excretion rate in 24-hour urine were the risk factors of UTIs in diabetic patients. The percentage of positive urine cultures was higher in the asymptomatic bacteriuria patients than in symptomatic patients (P<0.001). The incidence of septicemia was considerable in the UTIs and asymptomatic bacteriuria groups. Escherichia coli was the most common pathogenic microorganism isolated in diabetic patients with UTIs, and one-half of the E. coli infections were multidrug resistant. Furthermore, meropenem was the most effective antibiotic on E. coli.Conclusion: We suggest that a routine urine analysis or urine culture should be conducted in patients with T2D diabetes who have the identified risk factors. The UTIs might affect the islet function or blood glucose control in patients with T2D. Before a doctor decides to prescribe antibioti

While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.

Unsupervised pre-training was a critical technique for training deep neural networks years ago. With sufficient labeled data and modern training techniques, it is possible to train very deep neural networks from scratch in a purely supervised manner nowadays. However, unlabeled data is easier to obtain and usually of very large scale. How to make use of them better to help supervised learning is still a well-valued topic. In this paper, we investigate convolutional denoising auto-encoders to show that unsupervised pre-training can still improve the performance of high-level image related tasks such as image classification and semantic segmentation. The architecture we use is a convolutional auto-encoder network with symmetric shortcut connections. We empirically show that symmetric shortcut connections are very important for learning abstract representations via image reconstruction. When no extra unlabeled data are available, unsupervised pre-training with our network can regularize the supervised training and therefore lead to better generalization performance. With the help of unsupervised pre-training, our method achieves very competitive results in image classification using very simple all-convolution networks. When labeled data are limited but extra unlabeled data are available, our method achieves good results in several semi-supervised learning tasks.

Image restoration, including image denoising, super resolution, inpainting, and so on, is a well-studied problem in computer vision and image processing, as well as a test bed for low-level image modeling algorithms. In this work, we propose a very deep fully convolutional auto-encoder network for image restoration, which is a encoding-decoding framework with symmetric convolutional-deconvolutional layers. In other words, the network is composed of multiple layers of convolution and de-convolution operators, learning end-to-end mappings from corrupted images to the original ones. The convolutional layers capture the abstraction of image contents while eliminating corruptions. Deconvolutional layers have the capability to upsample the feature maps and recover the image details. To deal with the problem that deeper networks tend to be more difficult to train, we propose to symmetrically link convolutional and deconvolutional layers with skip-layer connections, with which the training converges much faster and attains better results., Comment: 17 pages. A journal extension of the version at arXiv:1603.09056

In this paper, we propose a very deep fully convolutional encoding-decoding framework for image restoration such as denoising and super-resolution. The network is composed of multiple layers of convolution and de-convolution operators, learning end-to-end mappings from corrupted images to the original ones. The convolutional layers act as the feature extractor, which capture the abstraction of image contents while eliminating noises/corruptions. De-convolutional layers are then used to recover the image details. We propose to symmetrically link convolutional and de-convolutional layers with skip-layer connections, with which the training converges much faster and attains a higher-quality local optimum. First, The skip connections allow the signal to be back-propagated to bottom layers directly, and thus tackles the problem of gradient vanishing, making training deep networks easier and achieving restoration performance gains consequently. Second, these skip connections pass image details from convolutional layers to de-convolutional layers, which is beneficial in recovering the original image. Significantly, with the large capacity, we can handle different levels of noises using a single model. Experimental results show that our network achieves better performance than all previously reported state-of-the-art methods., Comment: Accepted to Proc. Advances in Neural Information Processing Systems (NIPS'16). Content of the final version may be slightly different. Extended version is available at http://arxiv.org/abs/1606.08921

The cross-correlation between the 21 cm emission from the high-redshift intergalactic medium and the near-infrared (NIR) background light from the high-redshift galaxies promises to be a powerful probe of cosmic reionization. In this paper, we investigate the cross power spectrum during the epoch of reionization. We employ an improved halo approach to derive the distribution of the density field and consider two stellar populations in the star formation model: metal-free stars and metal-poor stars. The reionization history is further generated to be consistent with the electron-scattering optical depth from cosmic microwave background measurements. Then the intensity of NIR background is estimated by collecting emission from stars in the first-light galaxies. On large scales, we find the 21 cm and NIR radiation backgrounds are positively correlated during the very early stages of reionization. However, these two radiation backgrounds quickly become anti-correlated as reionization proceeds. The maximum absolute value of the cross power spectrum is $|\Delta^2_{\rm{21,NIR}}|\sim10^{-4}$ mK nW $\rm{m}^{-2}$ $\rm{sr}^{-1}$ reached at $\ell\sim1000$, when the mean fraction of ionized hydrogen is $\bar{x}_{i}\sim0.9$. We find that SKA can measure the 21 cm-NIR cross power spectrum in conjunction with mild extensions to the existing CIBER survey, provided that the integration time independently adds up to 1000 and 1 hours for 21 cm and NIR observations, and that the sky coverage fraction of CIBER survey is extended from $4\times10^{-4}$ to 0.1. Measuring the cross-correlation signal as a function of redshift provides valuable information on reionization and helps confirm the origin of the "missing" NIR background., Comment: 12 pages, 7 figures. Minor revisions to match to the published version

The cross-correlation between the 21 cm emission from the high-redshift intergalactic medium and the near-infrared (NIR) background light from the high-redshift galaxies promises to be a powerful probe of cosmic reionization. In this paper, we investigate the cross power spectrum during the epoch of reionization. We employ an improved halo approach to derive the distribution of the density field and consider two stellar populations in the star formation model: metal-free stars and metal-poor stars. The reionization history is further generated to be consistent with the electron-scattering optical depth from cosmic microwave background measurements. Then the intensity of NIR background is estimated by collecting emission from stars in the first-light galaxies. On large scales, we find the 21 cm and NIR radiation backgrounds are positively correlated during the very early stages of reionization. However, these two radiation backgrounds quickly become anti-correlated as reionization proceeds. The maximum absolute value of the cross power spectrum is $|\Delta^2_{\rm{21,NIR}}|\sim10^{-4}$ mK nW $\rm{m}^{-2}$ $\rm{sr}^{-1}$ reached at $\ell\sim1000$, when the mean fraction of ionized hydrogen is $\bar{x}_{i}\sim0.9$. We find that SKA can measure the 21 cm-NIR cross power spectrum in conjunction with mild extensions to the existing CIBER survey, provided that the integration time independently adds up to 1000 and 1 hours for 21 cm and NIR observations, and that the sky coverage fraction of CIBER survey is extended from $4\times10^{-4}$ to 0.1. Measuring the cross-correlation signal as a function of redshift provides valuable information on reionization and helps confirm the origin of the "missing" NIR background., Comment: 12 pages, 7 figures. Minor revisions to match to the published version

Ke He*, Jun-Cheng Shi*, Xiao-Ming Mao Department of Endocrinology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China *These authors contributed equally to this work Abstract: Acarbose is an α-glucosidase inhibitor that is commonly used to control postprandial blood glucose. It functions as a competitive and reversible inhibitor of small intestinal brush border glucosidase, blocks the degradation of starch and sucrose, and delays the absorption of glucose and fructose in the alimentary tract. The starch content of a diet might alter the hypoglycemic effects of acarbose because of its mechanism of action. Chinese individuals consume a typical Eastern diet, which is characterized by a high intake of whole grains, legumes, vegetables, fruits, and fish. These dietary habits allow acarbose to be used extensively in the People's Republic of China. Several Chinese-based studies have demonstrated that the use of acarbose as a monotherapy had similar effects on other anti-diabetes agents in decreasing glycosylated hemoglobin (HbA1c) and blood glucose levels, and acarbose in combination with other anti-diabetic drugs could further reduce blood glucose and decrease the mean amplitude of glycemic excursions. Importantly, acarbose is safe and well tolerated, with a low incidence of adverse effects. This article provides a comprehensive review of the safety and efficacy of acarbose for the treatment of diabetes in Chinese patients. Keywords: acarbose, α-glucosidase inhibitor, efficacy, safety

Using scanning tunneling microscopy, the coordination self-assembly of a series of peripheral bromo-phenyl and pyridyl substituted porphyrins with Fe was studied on an Au(111) surface. The porphyrins functionalized with two trans-pyridyl groups afford extended hexagonal frameworks and the porphyrins functionalized with three pyridyl groups generate discrete rosette and extended chiral kagome framework structures. The self-assembly of the porphyrin derivatives in which phenyl groups are substituted by bromo-phenyl results in coordination networks exhibiting identical structures to that of the parent compounds. These structures contain nanocavities decorated with Br, which provide potential for covalent functionalization.

Using scanning tunneling microscopy, the coordination self-assembly of a series of peripheral bromo-phenyl and pyridyl substituted porphyrins with Fe was studied on an Au(111) surface. The porphyrins functionalized with two trans-pyridyl groups afford extended hexagonal frameworks and the porphyrins functionalized with three pyridyl groups generate discrete rosette and extended chiral kagome framework structures. The self-assembly of the porphyrin derivatives in which phenyl groups are substituted by bromo-phenyl results in coordination networks exhibiting identical structures to that of the parent compounds. These structures contain nanocavities decorated with Br, which provide potential for covalent functionalization.

Using scanning tunneling microscopy, the coordination self-assembly of a series of peripheral bromo-phenyl and pyridyl substituted porphyrins with Fe was studied on an Au(111) surface. The porphyrins functionalized with two trans-pyridyl groups afford extended hexagonal frameworks and the porphyrins functionalized with three pyridyl groups generate discrete rosette and extended chiral kagome framework structures. The self-assembly of the porphyrin derivatives in which phenyl groups are substituted by bromo-phenyl results in coordination networks exhibiting identical structures to that of the parent compounds. These structures contain nanocavities decorated with Br, which provide potential for covalent functionalization.

After reionization, emission in the 21 cm hyperfine transition provides a direct probe of neutral hydrogen distributed in galaxies. Different from galaxy redshift surveys, observation of baryon acoustic oscillations in the cumulative 21 cm emission may offer an attractive method for constraining dark energy properties at moderate redshifts. Keys to this program are techniques to extract the faint cosmological signal from various contaminants, such as detector noise and continuum foregrounds. In this paper, we investigate the possible systematic and statistical errors in the acoustic scale estimates using ground-based radio interferometers. Based on the simulated 21 cm interferometric measurements, we analyze the performance of a Fourier-space, light-of-sight algorithm in subtracting foregrounds, and further study the observing strategy as a function of instrumental configurations. Measurement uncertainties are presented from a suite of simulations with a variety of parameters, in order to have an estimate of what behaviors will be accessible in the future generation of hydrogen surveys. We find that 10 separate interferometers, each of which contains $\sim 300$ dishes, observes an independent patch of the sky and produces an instantaneous field-of-view of $\sim 100$ $\rm deg^2$, can be used to make a significant detection of acoustic features over a period of a few years. Compared to optical surveys, the broad bandwidth, wide field-of-view and multi-beam observation are all unprecedented capabilities of low-frequency radio experiments., Comment: 13 pages, 11 figures, published version

After reionization, emission in the 21 cm hyperfine transition provides a direct probe of neutral hydrogen distributed in galaxies. Different from galaxy redshift surveys, observation of baryon acoustic oscillations in the cumulative 21 cm emission may offer an attractive method for constraining dark energy properties at moderate redshifts. Keys to this program are techniques to extract the faint cosmological signal from various contaminants, such as detector noise and continuum foregrounds. In this paper, we investigate the possible systematic and statistical errors in the acoustic scale estimates using ground-based radio interferometers. Based on the simulated 21 cm interferometric measurements, we analyze the performance of a Fourier-space, light-of-sight algorithm in subtracting foregrounds, and further study the observing strategy as a function of instrumental configurations. Measurement uncertainties are presented from a suite of simulations with a variety of parameters, in order to have an estimate of what behaviors will be accessible in the future generation of hydrogen surveys. We find that 10 separate interferometers, each of which contains $\sim 300$ dishes, observes an independent patch of the sky and produces an instantaneous field-of-view of $\sim 100$ $\rm deg^2$, can be used to make a significant detection of acoustic features over a period of a few years. Compared to optical surveys, the broad bandwidth, wide field-of-view and multi-beam observation are all unprecedented capabilities of low-frequency radio experiments., Comment: 13 pages, 11 figures, published version

The ability to subtract foreground contamination from low-frequency observations is crucial to reveal the underlying 21 cm signal. The traditional line-of-sight methods can deal with the removal of diffuse emission and unresolved point sources, but not bright point sources. In this paper, we introduce a foreground cleaning technique in Fourier space, which allows us to handle all such foregrounds simultaneously and thus sidestep any special treatments to bright point sources. Its feasibility is tested with a simulated data cube for the 21 CentiMeter Array experiment. This data cube includes more realistic models for the 21 cm signal, continuum foregrounds, detector noise and frequency-dependent instrumental response. We find that a combination of two weighting schemes can be used to protect the frequency coherence of foregrounds: the uniform weighting in the uv plane and the inverse-variance weighting in the spectral fitting. The visibility spectrum is therefore well approximated by a quartic polynomial along the line of sight. With this method, we demonstrate that the huge foreground contamination can be cleaned out effectively with residuals on the order of \sim10 mK, while the spectrally smooth component of the cosmological signal is also removed, bringing about systematic underestimate in the extracted power spectrum primarily on large scales., Comment: 9 pages, 9 figures. Final published version

The ability to subtract foreground contamination from low-frequency observations is crucial to reveal the underlying 21 cm signal. The traditional line-of-sight methods can deal with the removal of diffuse emission and unresolved point sources, but not bright point sources. In this paper, we introduce a foreground cleaning technique in Fourier space, which allows us to handle all such foregrounds simultaneously and thus sidestep any special treatments to bright point sources. Its feasibility is tested with a simulated data cube for the 21 CentiMeter Array experiment. This data cube includes more realistic models for the 21 cm signal, continuum foregrounds, detector noise and frequency-dependent instrumental response. We find that a combination of two weighting schemes can be used to protect the frequency coherence of foregrounds: the uniform weighting in the uv plane and the inverse-variance weighting in the spectral fitting. The visibility spectrum is therefore well approximated by a quartic polynomial along the line of sight. With this method, we demonstrate that the huge foreground contamination can be cleaned out effectively with residuals on the order of \sim10 mK, while the spectrally smooth component of the cosmological signal is also removed, bringing about systematic underestimate in the extracted power spectrum primarily on large scales., Comment: 9 pages, 9 figures. Final published version

The baryon acoustic oscillations (BAO) prior to recombination should be imprinted onto the 21cm emission background from the epoch of reionization through the underlying density perturbations. Using an analytical approach for both matter power spectrum (CDM+baryons) and reionization process, we demonstrate the BAO induced signatures on the power spectrum of 21cm emission fluctuations. Future low-frequency radio telescopes such as LOFAR and MWA should be able to detect these weak BAO wiggles with an integration time of $\sim1$ year. A combination of the BAO measurements at different redshifts $z\approx1000$ (CMB), $z\approx10$ (epoch of reionization) and $z\approx0$ (clustering of galaxies) may allow one to set more robust constraints on the determinations of cosmological parameters including dark energy and its equation of state., Comment: 4 pages, 5 figures, accepted for publication in ApJ Lett. References updated

The baryon acoustic oscillations (BAO) prior to recombination should be imprinted onto the 21cm emission background from the epoch of reionization through the underlying density perturbations. Using an analytical approach for both matter power spectrum (CDM+baryons) and reionization process, we demonstrate the BAO induced signatures on the power spectrum of 21cm emission fluctuations. Future low-frequency radio telescopes such as LOFAR and MWA should be able to detect these weak BAO wiggles with an integration time of $\sim1$ year. A combination of the BAO measurements at different redshifts $z\approx1000$ (CMB), $z\approx10$ (epoch of reionization) and $z\approx0$ (clustering of galaxies) may allow one to set more robust constraints on the determinations of cosmological parameters including dark energy and its equation of state., Comment: 4 pages, 5 figures, accepted for publication in ApJ Lett. References updated

The baryon acoustic oscillations (BAO) prior to recombination should be imprinted onto the 21cm emission background from the epoch of reionization through the underlying density perturbations. Using an analytical approach for both matter power spectrum (CDM+baryons) and reionization process, we demonstrate the BAO induced signatures on the power spectrum of 21cm emission fluctuations. Future low-frequency radio telescopes such as LOFAR and MWA should be able to detect these weak BAO wiggles with an integration time of $\sim1$ year. A combination of the BAO measurements at different redshifts $z\approx1000$ (CMB), $z\approx10$ (epoch of reionization) and $z\approx0$ (clustering of galaxies) may allow one to set more robust constraints on the determinations of cosmological parameters including dark energy and its equation of state., Comment: 4 pages, 5 figures, accepted for publication in ApJ Lett. References updated

Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury. This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO). Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R. Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might be mediated through alterations in NO production. Accordingly, we measured neurogenesis in dentate gyrus (DG) and subventricular zone (SVZ) of CB1R-knockout (KO) and wild-type mice, some of whom were treated with the cannabinoid agonist R(+)-Win 55212-2 [(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone] or the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI). NOS activity was increased by approximately 25%, whereas bromodeoxyuridine (BrdU) labeling of newborn cells in DG and SVZ was reduced by approximately 50% in CB1R-KO compared with wild-type mice. 7-NI increased BrdU labeling in both DG and SVZ and to a greater extent in CB1R-KO than in wild-type mice. In addition, R(+)-Win 55212-2 and 7-NI enhanced BrdU incorporation into neuron-enriched cerebral cortical cultures to a similar maximal extent and in nonadditive fashion, consistent with a shared mechanism of action. Double-label confocal microscopy showed coexpression of BrdU and the neuronal lineage marker doublecortin (Dcx) in DG and SVZ of untreated and 7-NI-treated CB1R-KO mice, and 7-NI increased the number of Dcx- and BrdU/Dcx-immunoreactive cells in SVZ and DG. Thus, cannabinoids appear to stimulate adult neurogenesis by opposing the antineurogenic effect of NO., Journal Article, Research Support, N.I.H. Extramural, info:eu-repo/semantics/published

Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury. This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO). Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R. Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might be mediated through alterations in NO production. Accordingly, we measured neurogenesis in dentate gyrus (DG) and subventricular zone (SVZ) of CB1R-knockout (KO) and wild-type mice, some of whom were treated with the cannabinoid agonist R(+)-Win 55212-2 [(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone] or the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI). NOS activity was increased by approximately 25%, whereas bromodeoxyuridine (BrdU) labeling of newborn cells in DG and SVZ was reduced by approximately 50% in CB1R-KO compared with wild-type mice. 7-NI increased BrdU labeling in both DG and SVZ and to a greater extent in CB1R-KO than in wild-type mice. In addition, R(+)-Win 55212-2 and 7-NI enhanced BrdU incorporation into neuron-enriched cerebral cortical cultures to a similar maximal extent and in nonadditive fashion, consistent with a shared mechanism of action. Double-label confocal microscopy showed coexpression of BrdU and the neuronal lineage marker doublecortin (Dcx) in DG and SVZ of untreated and 7-NI-treated CB1R-KO mice, and 7-NI increased the number of Dcx- and BrdU/Dcx-immunoreactive cells in SVZ and DG. Thus, cannabinoids appear to stimulate adult neurogenesis by opposing the antineurogenic effect of NO., Journal Article, Research Support, N.I.H. Extramural, info:eu-repo/semantics/published

The results of an investigation into the processing of middle- to low-grade bauxite with an alumina:silica (A:S) ratio of about 5 showed that the optimum conditions for the first stage were a sintering temperature of 1 100 degrees C and sintering time of 40 minutes. The leaching recovery of Al2O3 was up to 87.99 % under optimum conditions and leaching at 90 degrees C gave an A:S ratio in the leaching solution of over 400. The optimum conditions for the second stage were a sintering temperature of 1 200 degrees C and a sintering time of 40 min. Al2O3 recovery reached 86.04 %. The final recovery of Al2O3 was 98.23 % and the consumption of Na2CO3 was about 11.20 kg/t Al2O3., The results of an investigation into the processing of middle- to low-grade bauxite with an alumina:silica (A:S) ratio of about 5 showed that the optimum conditions for the first stage were a sintering temperature of 1 100 degrees C and sintering time of 40 minutes. The leaching recovery of Al2O3 was up to 87.99 % under optimum conditions and leaching at 90 degrees C gave an A:S ratio in the leaching solution of over 400. The optimum conditions for the second stage were a sintering temperature of 1 200 degrees C and a sintering time of 40 min. Al2O3 recovery reached 86.04 %. The final recovery of Al2O3 was 98.23 % and the consumption of Na2CO3 was about 11.20 kg/t Al2O3.

The ignition of iron ore in sintering by microwave heat in an airflow was studied experimentally and its mechanism analysed by calculating the oxygen content under different airflow conditions. It was shown that the ignition temperature is much lower than in conventional sintering. Microwave power of 8kW, ignition time 1.5 minutes and air preheated to 350 degrees C gave a sintered ore with satisfactory properties. Calculations showed that the oxygen content at ignition is 21% for microwave heat and 8.59% for gas heat. The higher oxygen content means the coke burns at lower temperature and completely, thus improving the properties of the sintered ore., The ignition of iron ore in sintering by microwave heat in an airflow was studied experimentally and its mechanism analysed by calculating the oxygen content under different airflow conditions. It was shown that the ignition temperature is much lower than in conventional sintering. Microwave power of 8kW, ignition time 1.5 minutes and air preheated to 350 degrees C gave a sintered ore with satisfactory properties. Calculations showed that the oxygen content at ignition is 21% for microwave heat and 8.59% for gas heat. The higher oxygen content means the coke burns at lower temperature and completely, thus improving the properties of the sintered ore.