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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald P.hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

LightAD: 基于自适应采样的自动去偏框架加速方法

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中国科学技术大学学报 2024年第4期54卷 46-54,45,67页

作者：邱阳董汉德陈佳伟何向南中国科学技术大学信息科学技术学院安徽合肥230027

在推荐系统中,由于数据是从用户行为中收集而来而不是通过合理的实验得到,因此偏差问题是普遍存在的。自动去偏框架(AutoDebias)通过采用元学习寻找适当地去偏置配置(即伪标签和置信权重),已被证明是应对各种偏差的一种通用和有效的解... 详细信息

在推荐系统中,由于数据是从用户行为中收集而来而不是通过合理的实验得到,因此偏差问题是普遍存在的。自动去偏框架(AutoDebias)通过采用元学习寻找适当地去偏置配置(即伪标签和置信权重),已被证明是应对各种偏差的一种通用和有效的解决方案。然而,为每个用户-物品对设置伪标签和权重是一个极度耗时的过程。因此,自动去偏框架面临巨大的计算成本,这使其在实际应用中的适用性较差。虽然使用带有均匀采样器的随机梯度下降可以加速模型训练,但这会显著恶化模型的收敛性和稳定性。为了解决这个问题,我们提出了LightAutoDebias (简称LightAD),它为自动去偏框架配备了一种专门的权重采样策略。该采样器可以自适应地和动态地获取信息量更大的训练样本,这带来的收敛性和稳定性比标准的均匀采样器更好。在三个基准数据集上的广泛实验证明,我们的LightAD可以加速自动去偏框架的训练达几个数量级,同时保持几乎相同的精度。

关键词：推荐系统偏差去偏采样

稀土复合纳米材料改性树脂基制动片摩擦学性能

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润滑与密封 2024年第1期49卷 137-142页

作者：孙嘉晨陈爽赵运才聂佳鹏黄清华桑汉德江西理工大学机电工程学院江西赣州341000

为提升风电偏航树脂基制动片高温下的摩擦磨损性能,采用稀土和纳米材料对树脂基制动片进行改性。采用热压成型工艺制备改性树脂基制动片,对试样进行力学性能测试和摩擦磨损试验。采用SEM、EDS、XRD对试验后试样摩擦表面进行观察和分析,... 详细信息

为提升风电偏航树脂基制动片高温下的摩擦磨损性能,采用稀土和纳米材料对树脂基制动片进行改性。采用热压成型工艺制备改性树脂基制动片,对试样进行力学性能测试和摩擦磨损试验。采用SEM、EDS、XRD对试验后试样摩擦表面进行观察和分析,探究稀土和纳米材料对树脂基复合材料的作用机制。结果表明:添加稀土和纳米材料后试样的相关力学性能和摩擦学性能均有提高,其中质量分数1%的氧化铈和氧化钇、4%的纳米二氧化硅可使复合材料350℃高温下的摩擦因数提高9.09%,磨损率下降64.28%。稀土和纳米二氧化硅通过优异的界面效应,提高了高温下试样的抗热衰退性,降低了高温下试样的磨损量,使试样磨损形式从磨粒磨损为主转变为黏着磨损为主。

关键词：树脂基制动片稀土纳米材料摩擦磨损力学性能

Fast Segmentation Method of Sonar Images for Jacket Installation Environment

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Intelligent Automation & Soft Computing 2023年第5期36卷 1671-1686页

作者： hande Mao Hongzhe Yan Lei Lin Wentao Dong Yuhang Li Yuliang Liu Jing Xue COOEC-Fluor Heavy Industries Co. Ltd.Zhuhai519000China Zhejiang Ocean University Zhoushan316022China Saint Petersburg State Marine Technical University Saint Petersburg190000Russia Wenzhou Institute of Technology Wenzhou325035China Deakin University BurwoodVIC 3125430070Australia

It has remained a hard nut for years to segment sonar images of jacket installation environment,most of which are noisy images with inevitable blur after noise *** the purpose of solutions to this problem,a fast segmen-tation algorithm is proposed on the basis of the gray value characteristics of sonar *** algorithm is endowed with the advantage in no need of segmentation *** realize this goal,we follow the undermentioned steps:ﬁrst,calcu-late the gray matrix of the fuzzy image *** adjusting the gray value,the image is divided into three regions:background region,buffer region and target ***ﬁltering,we reset the pixels with gray value lower than 255 to binarize images and eliminate most ***,the remaining noise is removed by morphological *** simulation results of several sonar images show that the algorithm can segment the fuzzy sonar images quickly and ***,the stable and feasible method is testiﬁed.

关键词： Image segmentation sonar image ocean engineering morphological image

Etiology of granulomatous inflammation:A retrospective study of 174 children in a tertiary care center

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Asian Pacific Journal of Tropical Medicine 2022年第11期15卷 511-517页

作者： Ummühan Cay Derya Alabaz ÖzlemÖzgür Gündeşlioğlu Aysun Hatice Uguz hande Yanar Department of Pediatric Infectious Diseases Faculty of MedicineÇukurova UniversityAdanaTurkey Department of Pathology Faculty of MedicineÇukurova UniversityAdanaTurkey

Objective:To investigate granulomatous inflammation etiology based on clinical history and ancillary ***:Children aged<18 years with biopsy proven granulomatous lesions in any tissue specimens between January 2014 and January 2022 were included in the *** diagnosis was based on the results of immunohistochemical staining,molecular tests,culture,serology,radiological and other auxiliary laboratory *** were categorized into infectious and noninfectious ***:In total,174 patients with granulomatosis inflammation confirmed by histopathology were *** 59.2%patients were males,and the median age was 4.48(IQR 2.36-6.39)years(range:16 months-18 years).The tissues/organs that were most commonly biopsied were lymph node,bone,skin,and lung(51.1%,17.8%,9.2%,and 5.7%,respectively).Infectious and non-infectious causes were identified in 73.0%and 12.6%patients,respectively,in terms of granulomatosis inflammation etiology;however,no cause was identified in 14.4%*** most common infectious cause was tuberculosis(in 51.7%patients),followed by toxoplasmosis,aspergillosis,mucormycosis,leishmaniasis,and cat-scratch disease(in 8.6%,5.7%,1.7%,1.7%,and 1.1%patients,respectively).The common non-infectious cause was chronic granulomatous *** evaluation revealed granulomatosis inflammation in 33.3%patients,necrotizing granulomatosis inflammation in 30.5%patients,and caseating granulomatosis inflammation in 12.1%*** the pathology results of patients with and without tuberculosis were compared,the incidence of caseating granulomatosis inflammation(P=0.003)and necrotizing granulomatosis inflammation(P=0.005)was higher in patients with ***:Chronic granulomatous disease is the most common non-infectious cause in ***,primary or secondary immune deficiencies may cause granulomatosis inflammation,especially in pediatric patients.

关键词： Granulomatous Children Tuberculosis Chronic granulomatous disease

Thermal Behaviour of Some New Polyoxometalate Complexes of Ciprofloxacin with Keggin-type Heteropoly Acids

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Chemical Research in Chinese Universities 2005年第3期21卷 258-263页

作者： WANGDun-jia FANGZheng-dong hande-yan DepartmentofChemistryandEnvironmentalEngineering HubeiNormalUniversityHuangshi435002P.R.China

Four polyoxometalate complexes, (CPFX·HCl)_3H_4SiW_~12 O_~40 , (CPFX·HCl)_3H_3PW_~12 O_~40 , (CPFX·HCl)_3H_3PMo_~12 O_~40 and (CPFX·HCl)_4H_4SiMo_~12 O_~40 , were prepared from ciprofloxacin hydrochloride(CPFX·HCl) reacting with H_nXM_~12 O_~40 ·nH_2O(X=P,Si; M=W,Mo) in an aqueous solution, and characterized by elemental analysis, IR spectrometry and TG-DTA. The IR spectrum confirms the presence of Keggin-type anions of heteropoly acids and the characteristic functional groups of ciprofloxacin. The TG/DTA curves show that their thermal decomposition is a multi-step process including simultaneous collapse of the Keggin-type structure. At first, these compounds had a mass loss of water molecules, then several other mass losses occured due to the decomposition of ciprofloxacin hydrochloride and its fragments with the degradation of Keggin anions. The end product of decomposition is the mixture of WO_3(or MoO_3) and SiO_2(or P_2O_5), identified by X-ray diffraction and IR spectroscopy. The possible thermal decomposition mechanisms of these complexes are proposed. This study exemplified that the thermal stability of the complexes containing tungsten is much better than that of the complexes containing molybdenum.

关键词： Thermal decomposition Polyoxometalate complexes Keggin-type heteropoly acids Ciprofloxacin hydrochloride TG/DTA

An inherent curvature-compensated voltage reference using non-linearity of gate coupling coefficient

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Journal of Semiconductors 2015年第8期36卷 113-123页

作者： Vinayak hande Maryam Shojaei Baghini Indian Institute of Technology Bombay

A novel current-mode voltage reference circuit which is capable of generating sub- 1 V output voltage is presented. The proposed architecture exhibits the inherent curvature compensation ability. The curvature com- pensation is achieved by utilizing the non-linear behavior of gate coupling coefficient to compensate non-linear temperature dependence of base-emitter voltage. We have also utilized the developments in CMOS process to re- duce power and area consumption. The proposed voltage reference is analyzed theoretically and compared with other existing methods. The circuit is designed and simulated in 180 nm mixed-mode CMOS UMC technology which gives a reference level of 246 mV. The minimum required supply voltage is 1 V with maximum current drawn of 9.24μA. A temperature coefficient of 9 ppm/℃ is achieved over -25 to 125 ℃ temperature range. The reference voltage varies by ±11 mV across process corners. The reference circuit shows the line sensitivity of 0.9 mV/V with area consumption of 100 × ll0μm2

关键词： voltage reference gate coupling coefficient temperature coefficient curvature compensation

Risk factors and clinical responses of pneumonia patients with colistin-resistant Acinetobacter baumannii-calcoaceticus

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World Journal of Clinical Cases 2019年第10期7卷 1111-1121页

作者： hande Aydemir hande Idil Tuz Nihal Piskin Guven Celebi Canan Kulah Furuzan Kokturk Department of Infectious Diseases and Clinical Microbiology Zonguldak Bulent Ecevit UniversityFaculty of MedicineZonguldak 67100Turkey Department of Microbiology Zonguldak Bulent Ecevit UniversityFaculty of MedicineZonguldak 67100Turkey Department of Biostatistics Zonguldak Bulent Ecevit UniversityFaculty of MedicineZonguldak 67100Turkey

BACKGROUND Nosocomial infections with carbapenem-resistant Acinetobacter baumanniicalcoaceticus complex(ABC)strains are great problem for intensive care *** strains can develop resistance to all the antibiotics *** resistance is common and colistin resistance is rare in our *** the risk factors for colistin resistance is important since colistin seems to be the only remaining therapeutic option for the patients with pneumonia due to extensively drug resistant ABC for our *** To investigate the comparison of clinical responses and outcomes between pneumonia patients with colistin-susceptible and-resistant Acinetobacter *** During the study period,108 patients with pneumonia due to colistin-susceptible strains and 16 patients with colistin-resistant strains were included *** variables were compared with the Mann-Whitney U test,and categorical variables were compared using Pearson’s chi-square test or Fisher’s Exact chi-square test for two groups.A binary logistic regression model was developed to identify the potential independent factors associated with colistin resistance in patients with colistin-resistant *** High Acute Physiology and Chronic Health Evaluation II scores(OR=1.9,95%CI:1.4-2.7;P<0.001)and prior receipt of teicoplanin(OR=8.1,95%CI:1.0-63.3;P=0.045)were found to be independent risk factors for infection with colistin-resistant Acinetobacter *** combinations of antibiotics including colistin,meropenem,ampicillin/sulbactam,amikacin and trimethoprim/sulfamethoxazole were used for the treatment of patients with colistin-resistant *** the median duration of microbiological cure(P<0.001)was longer in the colistin-resistant group,clinical(P=0.703),laboratory(P=0.277),radiological(P=0.551),microbiological response(P=1.000)and infection related mortality rates(P=0.603)did not differ between the two *** the patients with infections due to c

关键词： Acinetobacter baumannii Colistin Ventilator-associated pneumonia

Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome

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International Journal of Ophthalmology(English edition) 2019年第2期12卷 258-267页

作者： hande Guclu Vuslat Pelitli Gurlu Department of Opthalmology Trakya University Faculty of Medicine

AIM: To compare safety and efficacy of intravitreal dexamethasone(IVD) implant with topical nepafenac(TN) 0.1% in previously untreated Irvine-Gass syndrome(IGS) in clinical practice. METHODS: This was a retrospective study of 62 eyes with IGS after phacoemulsification with posterior chamber intraocular lens(IOL) implantation. None of the patients used treatment before IVD or TN. Best-corrected visual acuity(BCVA) with Early Treatment Diabetic Retinopathy Study chart(ETDRS), slit-lamp, intraocular pressure(IOP) measurement, fundus examination, spectral-domain optical coherence tomography(OCT) and fundus florescein angiography were performed to all subjects at baseline, 1, 3 and 6 mo. RESULTS: The mean BCVA of the IVD group was 49.3±6.8, and the mean BCVA of the TN group was 32.9±7.3 ETDRS letters in post-treatment month 6. The mean central macular thickness(CRT) of IVD group was 266.6±53.5 μm and the mean CRT of TN group was 364.9±56.3 μm in posttreatment month 6. Baseline BCVA has correlation with final BCVA in TN group however there was no correlation between baseline BCVA and final BCVA in IVD group. CONCLUSION: IVD is found to be better than TN in controlling pseudophakic macular edema and improving visual acuity. IVD group also has significantly lower CRT however IOP is not significantly different between two groups in post-treatment month 6.

关键词： intravitreal dexamethasone implant nepafenac Irvine-Gass syndrome cystoid macular edema inflammation