Investigating how neuronal activity state governs the decline of plasticity with age in C. elegans

Neural plasticity, which is the basis or learning and memory formation, declines continuously and progressively over the course of life. However, the molecular mechanisms underlying neuronal ageing and the decline of neural plasticity with age are not well understood. Sensory input and neural excitation have been shown to regulate organismal ageing processes and control lifespan, but how they drive the ageing of cognitive function and plasticity remains obscure. To study the mechanisms of how neuronal activity affects the decline of neural plasticity with age, I have established an assay in C. elegans based on its robust and reproducible behavioral responses to O2. Animals show O2 experience-dependent behavioral plasticity, where an overnight shift of the O2 concentration in the culture environment reprograms worms’ O2-evoked speed responses. I show that long-term high neural activity of the O2-sensing neurons accelerates the decline of plasticity with age at both the neuronal and behavioral level. By gene expression profiling of O2- sensing neurons in ageing animals, I show that neuronal activity alters age-related changes in transcription, and the data suggest that neuronal resources undergo a redistribution during ageing that depends on the neuronal activity state. In particular, the differential expression of neuronal genes that modulate Ca2+ homeostasis plays a central role in mediating activity-dependent decline. Low activity neurons require the K+-dependent Na+/Ca2+ (NCKX) exchanger to remove intracellular Ca2+ in order to sustain plasticity with age, whereas the decline of plasticity associated with high neuronal activity acts through calmodulin and the scaffold protein Kidins220 (also known as ARMS). These findings demonstrate directly that the activity of neurons alters neuronal homeostasis to govern the age-related decline of neural plasticity and throw light on the mechanisms involved

Photoacoustic Technologies beyond Medical Imaging-PASA and LGFU

The Photoacoustic (PA) effect has been extensively studied as a direct and efficient light-to-sound conversion process. The majority of previous applications of the PA effect are focused on photoacoustic imaging, where the combination of optics and acoustics ensures both optical level resolution and large penetration depth into bio-samples. This thesis aims to explore the possibilities to applying the photoacoustic effects on other fields including non-imaging PA signal spectrum analysis, therapeutic treatment and nozzle-free jetting for printing. First, in the case of fast and quantitative analysis of bio-samples, a non-imaging approach is preferable to analyze the spectrum of the PA signals. This is referred to as photoacoustic spectrum analysis. We have found a solid relationship between the morphological characteristics of the objects generating PA signals, and the polynomial fit of the measured spectrum of these PA signals. By measuring the signal with an ultra-broad-bandwidth ultrasound detector, we are able to characterize the size and shape of bio-samples in single cell level, paving the way for applications such as flow cytometry, cell counting, disease detection including blood diseases and blood freshness detection. Second, with the development of highly-efficient photoacoustic generation materials, PA transmitters that generate large amplitude, broadband and complex ultrasounds waveforms have been fabricated, extending the PA applications from pure imaging to therapeutic treatment and other areas. Our PA transmitters are fabricated with simple and inexpensive ways compared with piezoelectric ceramic film fabrication used in conventional transducers or arrays. In this thesis, a self-focusing PA lens, made from candle soot (CS)/polydimethylsiloxane (PDMS) composite has been developed and applied in laser-generated-focused-ultrasound (LGFU). A Pulsed laser illuminates the PA lens to generate a tightly focused PA wave within an ellipsoid of 90μm (minor axis) * 200μm (major axis). Compared with previously developed PA generation layers made from carbon nanotubes (CNT) and metals, candle soot can be deposited with much lower cost and simplicity. Within the focal region, a negative pressure over 27MPa is achieved, which ensures steady bubble cavitation. We demonstrate one way to enhance this cavitation with the help of a superimposed low-frequency, low-amplitude ultrasound field, and get ~30% generation rate enhancement and ~60% cavitation bubble size enhancement. The energy released from bubbles collapse are used for ablation of bio-tissues or generation of thin and high-speed streams. Taking advantages of these properties, LGFU equipped with CS/PDMS PA lens has been applied in two major areas: 1) Selective treatment, where the LGFU is used for direct ablation and dysfunction of the soft tissues less than 1mm. This treatment enjoys both selectiveness and accuracy and can treat each individual with his/her own need; 2) Nozzle-free jet printing, where the LGFU is used to generate ~10μm jets of materials with various viscosity and density. It has been demonstrated that the 2D materials like graphene and MoS2 can be printed with resolution of ~200μm. This can be applied as a potential nozzle-free high-resolution patterning modality in flexible electronics.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/149789/1/qiaochul_1.pd

Contribution à la planification d'expériences, à l'estimation et au diagnostic actif de systèmes dynamiques non linéaires : application au domaine aéronautique

In this work, we will study the uncertainty integration problem in a bounded error context for the dynamic systems, whose input and the initial state have to be optimized so that some other operation could be more easily and better obtained. This work is consisted of 6 chapters : the chapter 1 is an introduction to the general subject which we will discuss about. The chapter 2 represents the basic tools of interval analysis.The chapter 3 is dedicated to state estimation and parameter estimation. We explain at the first, how to solve the ordinary differential equation using interval analysis, which will be the basic tool for the state estimation problem given the initial condition of studied systems. On the other ride, we will look into the parameter estimation problem using interval analysis too. Based on a simple hypothesis over the uncertain variable, we calculate the system's parameter in a bounded error form, considering the operation of intervals as the operation of sets. Guaranteed results are the advantage of interval analysis, but the big time consumption is still a problem for its popularization in many non linear estimation field. We present our founding techniques to accelerate this time consuming processes, which are called contractor in constraint propagation field. At the end of this chapter, différent examples will be the test proof for our proposed methods.Chapter 4 presents the searching for optimal input in the context of interval analysis, which is an original approach. We have constructed several new criteria allow such searching. Some of them are intuitive, the other need a theoretical proof. These criteria have been used for the search of optimal initial States and le better parameter estimation results. The comparisons are done by using multiple applications and the efficiency is proved by evidence.In chapter 5, we applied the approaches proposed above in diagnosis by state estimation and parameter estimation. We have developed a complete procedure for the diagnosis. The optimal input design has been reconsidered in an active diagnosis context. Both state and parameter estimation are implemented using an aeronautical application in literature.The last chapter given a brief summary over the realized subject, some further research directions are given in the perspective section.All the algorithms are written in C/C++ on a Linux based operation system.Dans ce travail de thèse, nous nous focalisons sur le problème de l'intégration d'incertitude à erreurs bornées pour les systèmes dynamiques, dont les entrées et les états initiaux doivent être optimaux afin de réaliser certaines fonctionnalités.Le document comporte 5 chapitres: le premier est une introduction présentant le panorama du travail. Le deuxième chapitre présente les outils de base de l'analyse par intervalle. Le chapitre 3 est dédié à l'estimation d'états et de paramètres. Nous décrivons d'abord une procédure pour résoudre un système d'équations différentielles ordinaires avec l'aide de cet outil. Ainsi, une estimation des états à partir des conditions initiales peut être faite. Les systèmes différentiels considérés dépendent de paramètres qui doivent être estimés. Ce problème inverse pourra être résolu via l'inversion ensembliste. L'approche par intervalle est une procédure déterministe naturelle sans incertitude, tous les résultats obtenus sont garantis. Néanmoins, cette approche n'est pas toujours efficace, ceci est dû au fait que certaines opérations ensemblistes conduisent à des temps de calcul important. Nous présentons quelques techniques, par cela, nous nous plaçons dans un contexte à erreurs bornées permettant d'accélérer cette procédure. Celles-ci utilisent des contracteurs ciblés qui permettent ainsi une réduction de ce temps. Ces algorithmes ont été testés et ont montré leur efficacité sur plusieurs applications: des modèles pharmacocinétiques et un modèle du vol longitudinal d'avion en atmosphère au repos.Le chapitre 4 présente la recherche d'entrées optimales dans le cadre analyse par intervalle, ce qui est une approche originale. Nous avons construit plusieurs critères nouveaux permettant cette recherche. Certains sont intuitifs, d'autres ont nécessité un développement théorique. Ces critères ont été utilisés pour la recherche d'états initiaux optimaux. Des comparaisons ont été faites sur plusieurs applications et l'efficacité de certains critères a été mise en évidence.Dans le chapitre 5, nous appliquons les approches présentées précédemment au diagnostic via l'estimation de paramètres. Nous avons développé un processus complet pour le diagnostic et aussi formulé un processus pour le diagnostic actif avec une application en aéronautique. Le dernier chapitre résume les travaux réalisés dans cette thèse et essaye de donner des perspectives à la recherche.Les algorithmes proposés dans ce travail ont été développés en C++ et utilisent l'environnement du calcul ensembliste

Analysis and application of safety risks for gas pipelines in karst sinkhole-prone areas based on the D/I-MICMAC-VS integrated method

To mitigate the risk of gas pipelines in karst sinkhole-prone areas, this study employs the DEMATEL/ISM method to elucidate the hierarchical structure and causal relationships among various factors in the system, considering four categories of accident causes: human, material, environment and management. Additionally, the MICMAC method is utilized to analyze the dependence and driving force of risk factors. Utilizing the Visual Studio platform, the software for risk analysis of gas pipelines in karst sinkhole-prone areas is developed. This research introduces the D/I-MICMAC-VS integrated risk analysis method and provides an example analysis. The results demonstrate that: (1) The risk factors for gas pipelines in karst sinkhole-prone areas are distributed across six levels. The possibility of risk accidents can be reduced in the short term by rigorously managing surface-level direct factors, while middle-level indirect factors play an intermediary role in the system. Effective control of gas pipeline accidents can only be achieved by addressing deep-rooted factors fundamentally. (2) The spontaneous cluster serves as a key element for risk management and control of gas pipeline accidents, and prioritized intervention significantly aids in accident prevention. The independent cluster directly influences the system’s risk level through its own changes and development. The linkage cluster plays a pivotal role in transmitting and promoting the evolution and development of accidents. Effective risk management and control can be achieved by discerning the deep root factors that inducing changes in the dependency cluster

Efficient Photoacoustic Conversion in Optical Nanomaterials and Composites

Photoacoustic pulses generated by pulsed laser irradiation have the characteristics of high frequency and wide bandwidth, which are desirable for imaging and sensing. Efficient photoacoustic composites have been developed for fabricating photoacoustic transmitters capable of generating high‐amplitude ultrasound. Here, recent advances in photoacoustic transmitters are reviewed from an application perspective, starting with the fundamental aspects of photoacoustic generation. The topics discussed include various composite materials for photoacoustic generation, and their applications such as high‐amplitude therapy, imaging and sensing, and photoacoustic waveform control.Photoacoustic transmitters using pulsed laser irradiation onto optical nanomaterials have been developed for generating strong photoacoustic pulses, enabling interesting applications. Recent advances in photoacoustic transmitters are reviewed from an application perspective, starting with the fundamental aspects of photoacoustic generation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147165/1/adom201800491_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147165/2/adom201800491.pd

Towards Spontaneous Style Modeling with Semi-supervised Pre-training for Conversational Text-to-Speech Synthesis

The spontaneous behavior that often occurs in conversations makes speech more human-like compared to reading-style. However, synthesizing spontaneous-style speech is challenging due to the lack of high-quality spontaneous datasets and the high cost of labeling spontaneous behavior. In this paper, we propose a semi-supervised pre-training method to increase the amount of spontaneous-style speech and spontaneous behavioral labels. In the process of semi-supervised learning, both text and speech information are considered for detecting spontaneous behaviors labels in speech. Moreover, a linguistic-aware encoder is used to model the relationship between each sentence in the conversation. Experimental results indicate that our proposed method achieves superior expressive speech synthesis performance with the ability to model spontaneous behavior in spontaneous-style speech and predict reasonable spontaneous behavior from text.Comment: Accepted by INTERSPEECH 202

Designing dynamic mechanics in self-healing nanocomposite hydrogels

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2018.Cataloged from PDF version of thesis.Includes bibliographical references (pages 127-136).The functional versatility and endurable self-healing capacity of soft materials in nature is found to originate from the dynamic supramolecular scaffolds assembled via reversible interactions. To mimic this strategy, extensive efforts have been made to design polymer networks with transient crosslinks, which lays the foundation for synthetic self-healing hydrogels. Towards the development of stronger and faster self-healing hydrogels, understanding and controlling the gel network dynamics is of critical importance, since it provides design principles for key properties such as dynamic mechanics and self-healing performance. For this purpose, a universal strategy independent of exact crosslinking chemistry would be regulating the polymer material's dynamic behavior by optimal network design, yet current understanding of the relationship between network structure and macroscopic dynamic mechanics is still limited, and implementation of complex network structure has always been challenging. In this thesis, we show how the dynamic mechanical properties in a hydrogel can be controlled by rational design of polymer network structures. Using mussel-inspired reversible catechol coordination chemistry, we developed a nanocomposite hydrogel network (NP gel) with hierarchical assembly of polymer chains on iron oxide (Fe3O4) nanoparticles as network crosslinks. With NP gel as a model system, we first investigated its unique dynamic mechanics in comparison with traditional permanent and dynamic gels, and discovered a general approach to manipulate the network dynamics by controlling the crosslink structural functionality. Then we further explored the underlying relationship between polymer network structure and two key parameters in relaxation mechanics, which elucidated universal approaches for designing relaxation patterns in supramolecular transient gel network. Finally, by utilizing these design principles, we designed a hybrid gel network using two crosslinking structures with distinct relaxation timescales. By simply adjusting the ratio of two crosslinks, we can precisely tune the material's dynamic mechanics from a viscoelastic fluid to a rigid solid. Such controllability in dynamic mechanics enabled performance optimization towards mechanically rigid and fast self-healing hydrogel materials.by Qiaochu Li.Ph. D

Common magnitude representation of fractions and decimals is task dependent.

Although several studies have compared the representation of fractions and decimals, no study has investigated whether fractions and decimals, as two types of rational numbers, share a common representation of magnitude. The current study aimed to answer the question of whether fractions and decimals share a common representation of magnitude and whether the answer is influenced by task paradigms. We included two different number pairs, which were presented sequentially: fraction-decimal mixed pairs and decimal-fraction mixed pairs in all four experiments. Results showed that when the mixed pairs were very close numerically with the distance 0.1 or 0.3, there was a significant distance effect in the comparison task but not in the matching task. However, when the mixed pairs were further apart numerically with the distance 0.3 or 1.3, the distance effect appeared in the matching task regardless of the specific stimuli. We conclude that magnitudes of fractions and decimals can be represented in a common manner, but how they are represented is dependent on the given task. Fractions and decimals could be translated into a common representation of magnitude in the numerical comparison task. In the numerical matching task, fractions and decimals also shared a common representation. However, both of them were represented coarsely, leading to a weak distance effect. Specifically, fractions and decimals produced a significant distance effect only when the numerical distance was larger

Efficacy of HuaDan Anshen Mistura for treating insomnia: a randomized, double-blind, placebo-controlled, multi-center clinical trial

AbstractObjectiveTo evaluate the effect of HuaDan Anshen Mistura (mistura) in clinical treatment of Chinese patients with insomnia.MethodsIn this randomized, double-blind, placebo-controlled, multi-center study, 244 patients with insomnia were randomly assigned to a placebo group, a low-dose (10 mL/day), or a high-dose (20 mL/day) mistura group. Efficacy was assessed by using the sleep dysfunction rating scale (SDRS) and Clinical Global Impression-Improvement (CGI-I) scores. Safety and tolerability assessments included emergent adverse events, laboratory tests, and electrocardiograms.ResultsTotal SDRS scores decreased in all three groups, and there were significant differences between the placebo group and the low- and high-dose mistura groups (P=0.000). CGI-I ratings in the low- and high-dose mistura groups were significantly better than that of the placebo group (P=0.000). Incidences of rebound insomnia were similar in all three groups (placebo group: 6.94%, low-dose mistura group: 12.99%, and high-dose mistura group: 10.96%; P=0.475). The efficacy of HuaDan Anshen Mistura in the low- or high-dose group was significantly better than that of the placebo group (P=0.000), but with no significant difference found between the low- and high-dose mistura groups (P=0.887). The rates of adverse events were similar in the three groups (placebo 2.44%, low-dose mistura 0%, and high-dose mistura 5%; P=0.088).ConclusionHuaDan Anshen Mistura is an effective and generally well-tolerated hypnotic medicine for the treatment of Chinese patients with insomnia