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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

Artificial intelligence in gastroenterology: A state-of-the-art review

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World Journal of Gastroenterology 2021年第40期27卷 6794-6824页

作者： Paul T Kröner Megan ML Engels benjamin s.glicksberg Kipp W Johnson Obaie Mzaik Jeanin E van Hooft Michael B Wallace Hashem B El-serag Chayakrit Krittanawong Division of Gastroenterology and Hepatology Mayo ClinicJacksonvilleFL 32224United States Cancer Center Amsterdam Department of Gastroenterology and HepatologyAmsterdam UMCLocation AMCAmsterdam 1105The Netherlands The Hasso Plattner Institute for Digital Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Gastroenterology and Hepatology Leiden University Medical CenterAmsterdam 2300The Netherlands Division of Gastroenterology and Hepatology Sheikh Shakhbout Medical CityAbu Dhabi 11001United Arab Emirates section of Gastroenterology and Hepatology Michael E.DeBakey VA Medical Center and Baylor College of MedicineHoustonTX 77030United States section of Health services Research Michael E.DeBakey VA Medical Center and Baylor College of MedicineHoustonTX 77030United States section of Cardiology Michael E.DeBakey VA Medical CenterHoustonTX 77030United States

The development of artificial intelligence(AI)has increased dramatically in the last 20 years,with clinical applications progressively being explored for most of the medical *** field of gastroenterology and hepatology,substantially reliant on vast amounts of imaging studies,is not an *** clinical applications of AI systems in this field include the identification of premalignant or malignant lesions(e.g.,identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus,pancreatic malignancies),detection of lesions(e.g.,polyp identification and classification,small-bowel bleeding lesion on capsule endoscopy,pancreatic cystic lesions),development of objective scoring systems for risk stratification,predicting disease prognosis or treatment response[e.g.,determining survival in patients post-resection of hepatocellular carcinoma),determining which patients with inflammatory bowel disease(IBD)will benefit from biologic therapy],or evaluation of metrics such as bowel preparation score or quality of endoscopic *** objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract,including the upper,middle and lower tracts;IBD;the hepatobiliary system;and the pancreas,discussing the findings and clinical applications,as well as outlining the current limitations and future directions in this field.

关键词： Artificial intelligence Machine learning Deep learning Clinical applications Gastroenterology

Asynchronous consensus for optimal power flow control in smart grid with zero power mismatch

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Journal of Modern Power systems and Clean Energy 2018年第3期6卷 412-422页

作者： benjamin s.MILLAR Danchi JIANG school of Engineering and ICT University of Tasmania

The heterogeneous nature of smart grid components and the desire for smart grids to be scalable,stable and respect customer privacy have led to the need for more distributed control paradigms. In this paper we provide a distributed optimal power flow solution for a smart distribution network with separable global costs, separable non-convex constraints, and inseparable linear constraints,while considering important aspects of network operation such as distributed generation and load mismatch, and nodal voltage constraints. An asynchronous averaging consensus protocol is developed to estimate the values of inseparable global information. The consensus protocol is then combined with a fully distributed primal dual optimization utilizing an augmented Lagrange function to ensure convergence to a feasible solution with respect to power flow and power mismatch constraints. The presented algorithm uses only local and neighbourhood communication to simultaneously find the mismatch between power generation, line loss and loads, to calculate nodal voltages,and to minimize distributed costs, leading to a completely distributed solution of the global problem. An IEEE test feeder system with a reasonable number of nodes is used to illustrate the proposed method and efficiency.

关键词： Consensus protocol Cooperative system Distributed algorithm Distributed control Optimization smart grid

Conspecific negative density dependence in American beech

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Forest Ecosystems 2017年第3期4卷 174-181页

作者： benjamin s.Ramage Isabel J.Mangana Biology Department Randolph-Macon College

Background： One of the most important drivers of forest biodiversity is conspecific negative density dependence（CNDD）, a reduction in performance when conspecific densities are high. While the majority of CNDD research has focused on tropical forests, evidence is mounting that CNDD may also play an important role in temperate *** further explore the potential reach of this phenomenon, we investigated CNDD in American beech（Fagus grandifolia）in a mature mid-Atlantic ***： We used bivariate point pattern analyses to examine spatial relationships between large beech trees and conspecific saplings, and we also contrasted these patterns with comparable patterns for heterospecifics. In addition, to address the possibility of dispersal limitation and the associated effects on spatial patterns, we analyzed seedling density as a function of adult conspecific ***： We found that beech saplings were more repel ed from large conspecifics than large heterospecifics, despite the fact that beech seedling density was positively correlated with beech basal area. However, saplings of other canopy tree species were also repel ed from adult beech trees, suggesting a general suppressive effect. Nonetheless, the discrepancy between beech seedling and sapling densities beneath adult conspecifics suggests that beech seedling survival rates were reduced in vicinity of conspecific ***： Regardless of the extent to which beech inhibits heterospecific trees, a negative effect on conspecific recruits may be critical for biodiversity maintenance. Without this conspecific suppression, a dense layer of shade-tolerant beech saplings could form beneath adult beech trees. If this were to occur, beech would have a substantial head-start fol owing canopy disturbance, and this late-successional species could potential y dominate a stand in perpetuity,through repeated disturbance cycles.

关键词： Biodiversity Disturbance Dispersal limitation Diversity Fagus grondifolia Janzen-Connell effects Mid-Atlantic Point pattern analysis Regeneration Temperate forest

Preparation and surface Modification of High-Density Chitosan/Functionalized Multi-walled Carbon Nanotubes Hollow Fibers

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Journal of Donghua University(English Edition) 2015年第4期32卷 602-608页

作者：邵梅玲杜盼杨庆 HsIAO benjamin s College of Material science and Engineering Donghua University

Functionalized multi-walled carbon nanotubes( fMWNTs) were prepared with chitosan via controlled surface deposition and crosslinking process and scanning electron microscopy( sEM),Fourier translation infrared spectroscopy( FT-IR) and Xray diffraction( XRD) are used to character properties. A novel high-density chitosan( HCs) was dissolved in f-MWNTs dispersed dilute acetic acid with a maximal concentration of 5. 8%. The hollow fibers can be made by extruding the solution into a dilute alkali solution through a wet-spinning process and the tensile properties of the materials were evaluated by universal tester. The surface property of fibers,pretreated by Helium( He) and the following grafted with gelatin was evaluated with X-ray photoelectron spectroscopy( XPs).As the hollow fibers were intended for neural tissue engineering,its suitability was evaluated in vitro using rat schwann cells( RsC96) as model cells. The cells attachment,proliferation and morphology,were studied by various microscopic techniques. Based on the results,the gelatin grafted HCs / f-MWNTs hollow fibers could be used as a potential cell carrier in neural tissue engineering.

关键词： chitosan multi-walled carbon nanotubes(MWNTs) hollow fibers wet-spinning cold plasma treatment biocompatibility

Electrospun Nanofibrous Adsorption Membranes for Wastewater Treatment:Mechanical strength Enhancement

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Chemical Research in Chinese Universities 2021年第3期37卷 355-365页

作者： XIN Rui MA Hongyang shyam Venkateswaran benjamin s.Hsiao state Key Laboratory of Organic-Inorganic Composites Beijing University of Chemical TechnologyBeijing100029China Department of Chemistry Stony Brook UniversityStony BrookNY117943400USA

Functional nanofibrous membranes fabricated by electrospinning technology have attracted much attention in the removal of heavy metal ions from contaminated *** high specific surface area,high porosity and ease of functionality create an enhanced throughput and high adsorption capacity of the nanofibrous ***,the relatively poor mechanical properties of the membrane with a non-woven nanofibrous structure are one of the major concerns,which can limit the applications in wastewater *** strategies and methodologies were explored to address the problems and were reviewed in this work,highlighting the possibilities of overcoming the poor mechanical properties of the nanofibrous membrane and to ensure the recyclability and reusability of the membrane during the adsorption process.

关键词： Electrospun nanofibrous membrane Mechanical property Heavy metal ion Wastewater treatment

Tough,conductive hydrogels with double-network based on hydrophilic polymer assistant well-dispersed carbon nanotube for innovative force sensor

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science China(Technological sciences) 2022年第5期65卷 1160-1168页

作者： CHEN GuoYin GUO Ying HsIAO s.benjamin HOU Kai ZHU MeiFang state Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai201620China Department of Chemistry Stony Brook UniversityNew York11794USA

In recent years,conductive hydrogels have become a promising candidate for application in fields such as tissue engineering and flexible electronic devices because of their conductivity,soft and wet ***,the preparation of tough and uniformly conductive hydrogels remains challenging because conductive nanofillers tend to aggregate during hydrogel ***,a hydrophilic polymer assistant dispersion strategy is proposed to fabricate a tough,conductive composite hydrogel with doublenetwork based on well-dispersed carbon nanotubes(CNTs).In particular,A@T_(2.0)/polyacrylamide(PAM)hydrogels showed a tensile strength of 332.9 kPa,elongation of 584.6%,Young’s modulus of 91.5 kPa,and conductivity of 2.765 s m^(-1),and a demonstration was performed to show the strain sensing for health monitoring and *** showed that the fabricated conductive hydrogels offer promising and broad insights in the field of wearable sensors for health monitoring,innovative electronics,and human-machine interactions.

关键词： alginate carbon nanotubes conductive hydrogel tough force sensing

Genetics in Keratoconus: where are we?

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Eye and Vision 2016年第1期3卷 121-130页

作者： Yelena Bykhovskaya benjamin Margines Yaron s.Rabinowitz Regenerative Medicine Institute and Department of surgery Cedars-Sinai Medical CenterLos AngelesUSA Cornea Genetic Eye Institute 50 N.La Cienega Blvd.Suite#340Beverly HillsCA 90211USA The Jules stein Eye Institute University of California Los AngelesLos AngelesUSA

Keratoconus(KC)is a non-inflammatory thinning and protrusion of the cornea in which the cornea assumes a conical *** etiology of this condition at present remains an *** environmental factors have been involved in KC pathogenesis,strong underlining genetic susceptibility has been *** lack of consistent findings among early genetic studies suggested a heterogeneity and complex nature of the genetic contribution to the development of ***,genome-wide linkage studies(GWLs)and genome-wide association studies(GWAs)were ***-generation sequencing(NGs)-based genomic screens are also currently being carried *** of these recently developed comprehensive genetic tools led to a much greater success and increased reproducibility of genetic findings in *** of the LOX gene identified through GWLs has been confirmed in multiple cohorts of KC patients around the *** susceptibility region located at the 2q21.3 chromosomal region near the RAB3GAP1 gene identified through GWAs was independently *** variants in the ZNF469 gene(mutated in corneal dystrophy Brittle Cornea syndrome)and in the TGFBI gene(mutated in multiple corneal epithelial–stromal TGFBI dystrophies)have been repeatedly identified in familial and sporadic KC patients of different *** comprehensive strategies using quantitative endophenotypes have been successfully employed to bring further understanding to the genetics of *** genetic determinants including the COL5A1 gene have been identified in the GWAs of KC-related trait central corneal *** recent discoveries confirmed the importance of the endophenotype approach for studying complex genetic diseases such as KC and showed that different connective tissue disorders may have the same genetic determinants.

关键词： Keratoconus Genetics Complex disease Genetic variation Linkage Genetic association sequencing Corneal dystrophy Genotyping

Radiative suppression of exciton-exciton annihilation in a two-dimensional semiconductor

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Light(science & Applications) 2023年第9期12卷 1911-1920页

作者： Luca sortino Merve Gülmüs benjamin Tilmann Leonardo de s.Menezes stefan A.Maier Chair in Hybrid Nanosystems Nanoinstitute MunichFaculty of PhysicsLudwig-Maximilians-Universität München80539 MunichGermany Center for Nanoscience Faculty of PhysicsLudwig-Maximilians-Universität München80539 MunichGermany Departamento de Física Universidade Federal de Pernambuco50670-901 Recife-PEBrazil school of Physics and Astronomy Monash UniversityClaytonVIC 3800Australia The Blackett Laboratory Department of PhysicsImperial College LondonLondon SW72BWUK

Two-dimensional(2D)semiconductors possess strongly bound excitons,opening novel opportunities for engineering light-matter interaction at the ***,their in-plane confinement leads to large non-radiative exciton–exciton annihilation(EEA)processes,setting a fundamental limit for their photonic *** this work,we demonstrate suppression of EEA via enhancement of light-matter interaction in hybrid 2D semiconductor-dielectric nanophotonic platforms,by coupling excitons in Ws2 monolayers with optical Mie resonances in dielectric *** hybrid system reaches an intermediate light-matter coupling regime,with photoluminescence enhancement factors up to *** the exciton ultrafast dynamics reveal suppressed EEA for coupled excitons,even under high exciton densities>10^(12)cm^(−2).We extract EEA coefficients in the order of 10^(−3),compared to 10^(−2)for uncoupled monolayers,as well as a Purcell factor of *** results highlight engineering the photonic environment as a route to achieve higher quantum efficiencies,for low-power hybrid devices,and larger exciton densities,towards strongly correlated excitonic phases in 2D semiconductors.

关键词： annihilation dielectric coupling