基于ALS抑制剂药效团模型的数据库搜索

以ALS抑制剂药效团模型为基础建立了提问结构,将药效团模型中的生物结构信息输入到多种小分子三维结构数据库中(NCI-3D和ACD-3D数据库),借助分子三维结构搜索软件(3DFS和ISIS/3D软件)和多种搜索方法(POW-ELL方法和遗传算法)分别搜寻出100多个符合特征结构信息的全新结构候选化合物。这些命中结构的分子特征信息为我们下一步进行分子设计,确定先导化合物结构明确了方向,并提供了重要依据。     

机载三维激光成像系统点云数据滤波与地面点提取算法研究

使用原始的las标准格式的雷达数据,首先根据激光的回波次数和反射强度信息进行滤波,经过初步滤波之后根据角度限制法则和窗口移动法进行地面点提取工作,使用Delphi编程语言实现了该算法,并使用不同的阈值对不同的数据进行了结果的对比。     

MPEG-4 ALS无损音频编码

介绍了一种有代表的无损音频标准MPEG4ALS的算法,给出与其它的无损音频编码算法性能的比较结果。     

A single‐cell‐gap transflective LCD using active‐level‐shift technology

Abstract— A single‐cell‐gap transflective LCD using active‐level‐shift (ALS) technology has been developed and is presented. An efficient pixel architecture has recently been designed to apply different voltages on transmissive and reflective subpixels through two separated storage capacitors, formed by a boosting electrode and pixel electrodes. A 2.2‐in. vertical‐alignment‐mode (VA) transflective LCD prototype with a similar gamma for both the transmissive and reflective areas was obtained. Compared to a conventional dual‐cell‐gap design, the new single‐cell‐gap design achieves a 17% higher aperture ratio and the contrast increased from 200:1 to 500:1.     

基于Spark和微服务架构的电影推荐系统设计与实现

推荐系统广泛应用于人们生活的多个领域,日常生活中常见的有电商、电影、音乐和新闻推荐等。推荐系统根据用户的历史偏好主动推送相关的信息,节约了用户的时间,极大地提升了用户的体验。随着大数据技术的发展成熟,数据处理的速度变得更快。该文选取MovieLens电影数据集,并基于大数据分布式处理框架Spark和交替最小二乘法ALS等算法搭建数据处理平台,然后再结合Spring Boot和Spring Cloud等搭建电影后台服务,实现一个基于微服务架构的电影推荐系统。     

Immune Signaling Kinases in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder of motor neurons in adults, with a median survival of 3–5 years after appearance of symptoms, and with no curative treatment currently available. Frontotemporal dementia (FTD) is also an adult-onset neurodegenerative disease, displaying not only clinical overlap with ALS, but also significant similarities at genetic and pathologic levels. Apart from the progressive loss of neurons and the accumulation of protein inclusions in certain cells and tissues, both disorders are characterized by chronic inflammation mediated by activated microglia and astrocytes, with an early and critical impact of neurodegeneration along the disease course. Despite the progress made in the last two decades in our knowledge around these disorders, the underlying molecular mechanisms of such non-cell autonomous neuronal loss still need to be clarified. In particular, immune signaling kinases are currently thought to have a key role in determining the neuroprotective or neurodegenerative nature of the central and peripheral immune states in health and disease. This review provides a comprehensive and updated view of the proposed mechanisms, therapeutic potential, and ongoing clinical trials of immune-related kinases that have been linked to ALS and/or FTD, by covering the more established TBK1, RIPK1/3, RACK I, and EPHA4 kinases, as well as other emerging players in ALS and FTD immune signaling.     

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.     

The Involvement of RAGE and Its Ligands during Progression of ALS in SOD1 G93A Transgenic Mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive degeneration of upper and lower motor neurons that causes paralysis and muscle atrophy. The pathogenesis of the disease is still not elucidated. Receptor for Advanced Glycation End Product (RAGE) is a major component of the innate immune system and has implications in ALS pathogenesis. Multiple studies suggest the role of RAGE and its ligands in ALS. RAGE and its ligands are overexpressed in human and murine ALS motor neurons, astrocytes, and microglia. Here, we demonstrated the expression of RAGE and its ligands during the progression of the disease in the transgenic SOD1 G93A mouse lumbar spinal cord. We observed the highest expression of HMGB1 and S100b proteins at ALS onset. Our results highlight the potential role of RAGE and its ligands in ALS pathogenesis and suggest that some of the RAGE ligands might be used as biomarkers in early ALS diagnosis and potentially be useful in targeted therapeutic interventions at the early stage of this devastating disease.     

Optimized Protocol for Proportionate CNS Cell Retrieval as a Versatile Platform for Cellular and Molecular Phenomapping in Aging and Neurodegeneration

Efficient purification of viable neural cells from the mature CNS has been historically challenging due to the heterogeneity of the inherent cell populations. Moreover, changes in cellular interconnections, membrane lipid and cholesterol compositions, compartment-specific biophysical properties, and intercellular space constituents demand technical adjustments for cell isolation at different stages of maturation and aging. Though such obstacles are addressed and partially overcome for embryonic premature and mature CNS tissues, procedural adaptations to an aged, progeroid, and degenerative CNS environment are underrepresented. Here, we describe a practical workflow for the acquisition and phenomapping of CNS neural cells at states of health, physiological and precocious aging, and genetically provoked neurodegeneration. Following recent, unprecedented evidence of post-mitotic cellular senescence (PoMiCS), the protocol appears suitable for such de novo characterization and phenotypic opposition to classical senescence. Technically, the protocol is rapid, efficient as for cellular yield and well preserves physiological cell proportions. It is suitable for a variety of downstream applications aiming at cell type-specific interrogations, including cell culture systems, Flow-FISH, flow cytometry/FACS, senescence studies, and retrieval of omic-scale DNA, RNA, and protein profiles. We expect suitability for transfer to other CNS targets and to a broad spectrum of engineered systems addressing aging, neurodegeneration, progeria, and senescence.     

Strength evaluation of a steam distribution device in the Ignalina NPP accident localisation system

The Ignalina NPP has a pressure suppression type of confinement, which is referred to as the accident localization system (ALS). The ALS prevents the release of the radioactive material from the NPP to the environment during a loss-of-coolant accident (LOCA). Ten water pools are located in the two ALS towers (five pools in each tower), which separate the dry well from the wet well. These water pools condense the accident-generated steam and prevent high overpressures in the compartments.The steam distribution device (SDD), with the vertical vent pipes (nozzles) that are inserted under the water of the condensing pools, connects the dry well and the wet well. In case of an accident, these components must be capable of withstanding the dynamic loads generated by a LOCA for successful pressure suppression function.This paper presents the transient analysis of the SDD and their connections to the vertical steam corridors following a LOCA. A thermo-hydraulic analysis of the SDD was performed using the state-of-the-art COCOSYS code to determine pressure and temperature histories resulting from a LOCA. The finite element code NEPTUNE was used to evaluate the structural integrity of the SDD and its supporting reinforced concrete wall. Results show that, although portions of the SDD undergo plastic response and the outside surface of the vertical steam corridor reinforced concrete wall cracks, the structural integrity of the SDD and wall are maintained during a LOCA.