Experimental exploration over a quantum control landscape through nuclear magnetic resonance

The growing successes in performing quantum control experiments motivated the development of control landscape analysis as a basis to explain these findings.When a quantum system is controlled by an electromagnetic field, the observable as a functional of the control field forms a landscape. Theoretical analyses have revealed many properties of control landscapes, especially regarding their slopes, curvatures, and topologies. A full experimental assessment of the landscape predictions is important for future consideration of controlling quantum phenomena. Nuclear magnetic resonance (NMR) is exploited here as an ideal laboratory setting for quantitative testing of the landscape principles. The experiments are performed on a simple two-level proton system in a H$_2$O-D$_2$O sample. We report a variety of NMR experiments roving over the control landscape based on estimation of the gradient and Hessian, including ascent or descent of the landscape, level set exploration, and an assessment of the theoretical predictions on the structure of the Hessian. The experimental results are fully consistent with the theoretical predictions. The procedures employed in this study provide the basis for future multispin control landscape exploration where additional features are predicted to exist

Integrated GANs: Semi-Supervised SAR Target Recognition

With the advantage of working in all weathers and all days, synthetic aperture radar (SAR) imaging systems have a great application value. As an efficient image generation and recognition model, generative adversarial networks (GANs) have been applied to SAR image analysis and achieved promising performance. However, the cost of labeling a large number of SAR images limits the performance of the developed approaches and aggravates the mode collapsing problem. This paper presents a novel approach namely Integrated GANs (I-GAN), which consists of a conditional GANs, an unconditional GANs and a classifier, to achieve semi-supervised generation and recognition simultaneously. The unconditional GANs assist the conditional GANs to increase the diversity of the generated images. A co-training method for the conditional GANs and the classifier is proposed to enrich the training samples. Since our model is capable of representing training images with rich characteristics, the classifier can achieve better recognition accuracy. Experiments on the Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset proves that our method achieves better results in accuracy when labeled samples are insufficient, compared against other state-of-the-art techniques

Regulatory Mechanisms of the Wnt/β-Catenin Pathway in Diabetic Cutaneous Ulcers

Skin ulcers are a serious complication of diabetes. Diabetic patients suffer from vascular lesions and complications such as peripheral neuritis, peripheral vascular lesions, and collagen abnormalities, which result in skin wounds that are refractory and often develop into chronic ulcers. The healing of skin ulcers requires an inflammatory reaction, wound proliferation, remodeling regulation, and control of stem cells. Studies investigating diabetic cutaneous ulcers have focused on cellular and molecular levels. Diabetes can cause nerve and blood vessel damage, and persistent high blood sugar levels can cause systemic multisite nerve damage based on peripheral neuropathy. The long-term hyperglycemia state enables the polyol glucose metabolism pathway to be activated, increasing the accumulation of toxic substances in the vascular injured nerve tissue cells. Sustained hyperglycemia leads to dysfunction of epithelial cells, leading to a decrease in pro-angiogenic signaling and nitric oxide production. In addition, due to impaired leukocyte function in hyperglycemia, immune function is impaired and the immune response at relevant sites is insufficient, making diabetic foot more difficult to heal. The Wnt/β-catenin pathway is a highly conserved signal transduction pathway involved in a variety of biological processes, such as cell proliferation, apoptosis, and differentiation. It is considered an important pathway involved in the healing of skin wounds. This article summarizes the mechanism of action of the Wnt/β-catenin pathway involved in the inflammatory responses to diabetic ulcers, wound proliferation, wound remodeling, and stem cells. The interactions between the Wnt signal pathway and other metabolic pathways are also discussed

The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability

人类与其他动物相比的重要区别在于人类拥有高等认知能力，这种能力集中体现在学习记忆和语言表达方面。厦门大学医学院神经科学研究所王鑫教授团队发现人科动物特异性基因USP6作为一个新的NMDA受体调控因子，可通过去泛素化途径调节NMDA型谷氨酸受体的降解和稳定性，进而调控突触可塑性和学习记忆能力。 本研究工作由王鑫教授指导完成，博士生曾凡伟、马学海与硕士生朱琳为共同第一作者，王鑫教授为通讯作者。Ubiquitin-specific protease (USP) 6 is a hominoid deubiquitinating enzyme previously implicated in intellectual disability and autism spectrum disorder. Although these findings link USP6 to higher brain function, potential roles for USP6 in cognition have not been investigated. Here, we report that USP6 is highly expressed in induced human neurons and that neuron-specific expression of USP6 enhances learning and memory in a transgenic mouse model. Similarly, USP6 expression regulates N-methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation and long-term depression in USP6 transgenic mouse hippocampi. Proteomic characterization of transgenic USP6 mouse cortex reveals attenuated NMDAR ubiquitination, with concomitant elevation in NMDAR expression, stability, and cell surface distribution with USP6 overexpression. USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells. Together, these results indicate that USP6 enhances NMDAR stability to promote synaptic function and cognition.This work was partially supported by the National Natural Science Foundation of China (31871077, 81822014, 81571176 to XW; 81701349 to Hongfeng Z.; 81701130 to QZ; and 81471160 to HS), the National Key R&D Program of China (2016YFC1305900 to XW and HS), the Natural Science Foundation of Fujian Province of China (2017J06021 to XW), the Fundamental Research Funds for the Chinese Central Universities (20720150061 to XW and 20720180040 to ZS), Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University (SKLCSB2019KF012 to QZ), and China Postdoctoral Science Foundation (2017M612130 to QZ).该研究得到了国家自然科学基金面上项目和优秀青年基金项目的支持

SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate

共济失调是一类以运动协调性紊乱为主要特征的神经系统症状，临床表现包括步态不稳、丧失平衡、吞咽困难、眼球运动异常、肌张力受损等。厦门大学医学院神经科学研究所王鑫教授团队首次从轴突线粒体运输这一全新视角揭示了一类遗传性共济失调的发病机制，并发现抗癫痫药--丙戊酸大幅度减缓模型小鼠的疾病进程，具有较强的转化应用价值，有望为共济失调提供新的治疗手段。 该研究工作由王鑫教授指导完成，厦门大学医学院助理教授张洪峰和博士生洪育娟共同完成主要实验工作。Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.We thank Tim Huang for helpful discussion, Wei Mo for sharing mouse lines, Li Zhong for sharing reagents, Aidong Han, Luming Yao, Caiming Wu, Mingxia Zhu, Qingfeng Liu, Lin Zhu, Shuo Zhang, Haiping Zheng, and Changchuan Xie for technical assistance, and Cui Li for providing bioinformatics software. We also thank Novogene Co., Ltd. and PTM Biolab Co., Ltd. for technical assistance in the transcriptomic and proteomic analyses, respectively. 厦门大学医学院许华曦、赵颖俊、张云武、杜丹教授在研究过程中给予大力帮助和支持。本研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

Trisomy 21-induced Dysregulation of Microglial Homeostasis in Alzheimer’s Brains is Mediated by USP25

阿尔茨海默病（Alzheimer’s disease, AD）是一种最为常见的与记忆、认知能力退化相关的渐进性神经退行性疾病。唐氏综合征（Down’s syndrome, DS）是早发型阿尔茨海默病的一个重要风险因素，作为最常见的智力障碍遗传疾病，厦门大学医学院神经科学研究所王鑫教授团队揭示了治疗阿尔茨海默病和唐氏综合征新的治疗靶点，并且在小鼠模型上利用USP25小分子抑制剂成功地改善了阿尔茨海默病小鼠的认知功能，缓解了神经退行性病变的病理进程。该研究工作由王鑫教授指导完成，厦门大学医学院助理教授郑秋阳和博士生李桂林完成主要实验工作，王世华、朱琳、高月、邓青芳、张洪峰、张丽珊、吴美玲、狄安洁参与了部分研究工作。厦门大学医学院许华曦、赵颖俊和孙灏教授在研究过程中给予大力帮助和支持，清华大学董晨教授提供了Usp25基因敲除小鼠，厦门大学附属妇女儿童医院周裕林教授和郑良楷博士帮助收集了脑组织样品。Down syndrome (DS), caused by trisomy of chromosome 21, is the most significant risk factor for early-onset Alzheimer’s disease (AD); however, underlying mechanisms linking DS and AD remain unclear. Here, we show that triplication of homologous chromosome 21 genes aggravates neuroinflammation in combined murine DS-AD models. Overexpression of USP25, a deubiquitinating enzyme encoded by chromosome 21, results in microglial activation and induces synaptic and cognitive deficits, whereas genetic ablation of Usp25 reduces neuroinflammation and rescues synaptic and cognitive function in 5×FAD mice. Mechanistically, USP25 deficiency attenuates microglia-mediated proinflammatory cytokine overproduction and synapse elimination. Inhibition of USP25 reestablishes homeostatic microglial signatures and restores synaptic and cognitive function in 5×FAD mice. In summary, we demonstrate an unprecedented role for trisomy 21 and pathogenic effects associated with microgliosis as a result of the increased USP25 dosage, implicating USP25 as a therapeutic target for neuroinflammation in DS and AD.This work was supported by the National Natural Science Foundation of China (31871077, 81822014, and 81571176 to X.W.; 81701130 to Q.Z.), the National Key R&D Program of China (2016YFC1305900 to X.W.), the Natural Science Foundation of Fujian Province of China (2017J06021 to X.W.), the Fundamental Research Funds for the Chinese Central Universities (20720150061 to X.W.), and the BrightFocus Foundation (A2018214F to Yingjun Zhao). 该研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

Quantum control landscape analysis including its application in NMR experiments

Scientists have attempted for decades to efficiently control the dynamics of quantum systems on the atomic and molecular scale with modulated electromagnetic fields, such as femtosecond laser pulses. The success of such experiments in achieving specified control objectives will rely on finding the optimal pulse shapes. The search for optimal solutions in such a high-dimensional control parameter space is usually accomplished by learning algorithms. The success of quantum optimal control in a wide range of applications motivated the analysis of the underlying control landscape, defined by the objective value as a functional of the control field, whose topology (e.g., local optima and saddle points) will dictate the ease of finding globally optimal control fields by iterative searches with gradient-based algorithms. Based on some assumptions theoretical analysis revealed many topological properties of the landscapes, which are both experimentally assessed and theoretically developed in this dissertation. The experimental works focus on the landscapes in controlling nuclear spins by pulsed magnetic fields, with nuclear magnetic resonance (NMR) spectroscopy as a testbed. We choose this type of experimental settings because of its desirable physical properties and potential application in realizing quantum computation. A set of methodology for control landscape studies in NMR systems is constructed, leading to the first observation of landscape saddles in the laboratory. The dissertation also discusses a variety of theoretical topics about the control landscape in general, including (i) measuring “distances” from the landscape saddle points and driving to locate them; (ii) simultaneous optimization of multiple control objectives in the same quantum system; and (iii) generalizing the landscape concept from the semiclassical setting to the full quantum setting. All these works aim to further enrich and develop the landscape theory in quantum optimal control, and apply it to physical systems with practical importance

Pareto-front shape in multiobservable quantum control

Many scenarios in the sciences and engineering require simultaneous optimization of multiple objective functions, which are usually conflicting or competing. In such problems the Pareto front, where none of the individual objectives can be further improved without degrading some others, shows the tradeoff relations between the competing objectives. This paper analyzes the Pareto-front shape for the problem of quantum multiobservable control, i.e., optimizing the expectation values of multiple observables in the same quantum system. Analytic and numerical results demonstrate that with two commuting observables the Pareto front is a convex polygon consisting of flat segments only, while with noncommuting observables the Pareto front includes convexly curved segments. We also assess the capability of a weighted-sum method to continuously capture the points along the Pareto front. Illustrative examples with realistic physical conditions are presented, including NMR control experiments on a 1 H − 13 C two-spin system with two commuting or noncommuting observables

Searching for an optimal control in the presence of saddles on the quantum-mechanical observable landscape

Physical Review A. Volume 95, Issue 6, 22 June 2017, Article number 063418.© 2017 American Physical Society. The broad success of theoretical and experimental quantum optimal control is intimately connected to the topology of the underlying control landscape. For several common quantum control goals, including the maximization of an observable expectation value, the landscape has been shown to lack local optima if three assumptions are satisfied: (i) the quantum system is controllable, (ii) the Jacobian of the map from the control field to the evolution operator is full rank, and (iii) the control field is not constrained. In the case of the observable objective, this favorable analysis shows that the associated landscape also contains saddles, i.e., critical points that are not local suboptimal extrema. In this paper, we investigate whether the presence of these saddles affects the trajectories of gradient-based searches for an optimal control. We show through simulations that both the detailed topology of the control landscape and the parameters of the system Hamiltonian influence whether the searches are attracted to a saddle. For some circumstances with a special initial state and target observable, optimizations may approach a saddle very closely, reducing the efficiency of the gradient algorithm. Encounters with such attractive saddles are found to be quite rare. Neither the presence of a large number of saddles on the control landscape nor a large number of system states increases the likelihood that a search will closely approach a saddle. Even for applications that encounter a saddle, well-designed gradient searches with carefully chosen algorithmic parameters will readily locate optimal controls

Increased death and exhaustion of CD69high T cells and NK cells are associated with PD-1 antibody application in the in vitro co-culture system

Background The application of PD-1 monoclonal antibody (mAb) helps to treat non-small cell lung cancer, but acquired resistance has emerged in clinical practice. We tested the hypothesis that acquired resistance of anti-PD-1 immunotherapy is linked to death and exhaustion of activated T and NK cell. Methods The co-culture system of HCC827 cells and peripheral mononuclear cells (PBMCs) was established to evaluate the effect of PD-1 mAb on the death rate and exhaustion of T and NK cell. The predisposing role of CD69 for death and exhaustion was validated by using PHA-activated PBMCs of CD69low NSCLC patients. The 10-colour/three laser flow cytometer was used to test related markers for cell activation, death and exhaustion. Results We found that PD-1 mAb increase the death and exhaustion of T cells and NK cells in a dose-dependent way when PBMCs from NSCLC patients whose the percentages of CD69+ cells in peripheral blood T cells were greater than 5% (CD69high NSCLC patients). By analyzing PBMCs from healthy volunteers and CD69low NSCLC patients, we found that T cells and NK cells can be induced to die by PD-1 mAb after PHA activation, and had a tendency to raise the rate of cell exhaustion. Conclusions Our findings imply that increased death and exhaustion of CD69high T cells and NK cells are associated with ineffective anti-PD-1 immunotherapy in lung cancer. The CD69 expression of T cells and NK cells may be developed as a potential predictor for acquired resistance of anti-PD-1 immunotherapy. These data may provide ideas to guide individualized medication of PD-1 mAb in NSCLC patients