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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

Sex differences in aging and injured brain

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Neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： Jordan N.Williamson Yuan Yang University of illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA Northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

Resource Management in SAM—The D0 Data Grid

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International Conference on Computing in High Energy and Nuclear Physics 2001年第1期 730-735页

作者： Lauriloebel－Carpenter LeeLueking 等 Fermilab BataviaIL60510

One of the key components of any grid architecture is managing compute and storage resources and optimizing their *** has implemented features that allow it to exercise a "fair share" and "prioritized" policy among many groups of *** goals are as follows:1)implement th experiments policies for resource usage by research group and by data access mode,and 2) optimize the resource usage to maximize the overall throughput defined in terms of real data processing activity,At the lowest level of SAM architecture,called the station,the SAM system integrates the data delivery and cache management with the job control and scheduling of the batch *** the site-level,for example at Fermilab,requests for data from on-site stations are managed to optimize Mass Storage System resources and network throughput,Management of resources at a various geographic levels are discussed.

关键词：广域网数据管理数据存储 D0数据网格

Electromagnetic design and performance of conduction cooled superconducting magnet for spoke resonator cryomodule for Proton Improvement Plan(PIP)-II

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Superconductivity 2024年第3期11卷 14-33页

作者： Kumud Singh Janvin Itteera Mahima Vikas Tiwari Himanshu Bisht Sanjay Malhotra R.R.Singh Rajesh Jalan Sanjay Howa Rajesh Chimurkar Sunil Kumar S.Stoynev M.Turenne M.Yu B.Hanna J.Hayman C.Boffo Electromagnetic Applications&Instrumentation Division Bhabha Atomic Research CentreTrombay 400085India Fermi Accelerator National Laboratory Batavia IL 60510-5011USA

The Proton Improvement Plan(PIP)-II project is part of Fermilab’s upgrade of its proton accelerator complex,to provide a powerful,high-intensity proton beam to the laboratory’s upcoming research *** project includes an 800 MeV superconducting(SC)linear accelerator(linac),with five flavours of cavities and *** medium energy section of the linac contains two types of superconducting Single Spoke Resonator(SSR)RF cavities(SSR1 and SSR2),which are interleaved with strong solenoid focusing lenses.A unified design of the solenoid has been developed,with one solenoid design satisfying both SSR1 and SSR2 *** integral focusing strength requirement of 4.5 T^(2)m with a full width half maximum(FWHM)of 180 mm indicates the peak field strength∼6.8 T in the magnet aperture,necessitating a superconducting design within the limits of NbTi as magnet wire *** are complex combined units that include one focusing solenoid with bucking coils to minimize fringe fields and four corrector coils each,with independent current leads to produce dipole and quadrupole *** simplify the current lead design and reduce complexity,the project opted conduction cooling for these magnets,thus requiring a redesign compared to previous prototype bath cooled *** designs for high energy accelerators adopt bath cooled design of the solenoid focusing lenses for medium energy *** present design explores a unique and technically superior solution for the cryomodule operation by decoupling the magnet and cavity cooling to certain *** in cryomodule operations shall be studied after integration of magnets in the Linac *** we discuss the design requirements,challenges,electromagnetic design,superconducting wire selection and the results from magnetic measurements of the first pre-series units.

关键词： conduction module magnets

Exotic decays of the 125 GeV Higgs boson at future e^+e^-colliders

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Chinese Physics C 2017年第6期41卷 33-45页

作者：刘真王连涛张昊 Theoretical Physics Department FermilabBataviaIL 60510USA Kavli Institute for Cosmological Physics and the Enrico Fermi Institute The University of ChicagoChicagoIL 60637USA Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China

The discovery of unexpected properties of the Higgs boson would offer an intriguing opportunity to shed light on some of the most profound puzzles in particle physics. Beyond Standard Model（BSM） decays of the Higgs boson could reveal new physics in a direct manner. Future electron-positron lepton colliders operating as Higgs factories, including CEPC, FCC-ee and ilC, with the advantages of a clean collider environment and large statistics,could greatly enhance sensitivity in searching for these BSM decays. In this work, we perform a general study of Higgs exotic decays at future e^＋e^lepton colliders, focusing on the Higgs decays with hadronic final states and/or missing energy, which are very challenging for the High-Luminosity program of the Large Hadron Collider（HL-LHC）.We show that with simple selection cuts,O（10^-3-10^-5） limits on the Higgs exotic decay branching fractions can be achieved using the leptonic decaying spectator Z boson in the associated production mode e^＋e^-→ZH. We further discuss the interplay between detector performance and Higgs exotic decays, and other possibilities of exotic *** work is a first step in a comprehensive study of Higgs exotic decays at future lepton colliders, which is a key area of Higgs physics that deserves further investigation.

关键词： Higgs exotic decay BSM lepton collider Higgs factory

SAM Overview and Operation at the D0 Experiment

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International Conference on Computing in High Energy and Nuclear Physics 2001年第1期 310-314页

作者： Lauriloebel－Carpenter LeeLueking 等 Fermilab BataviaIL60510

SAM is a network-distributed data management system developed at Fermilab for use with Run II data,It is being Employed by the D0 Experiment to store,manage,deliver,and track processing of all *** describe the design and features of the system including resource management and data transfer mechanisms,We show the operational experience D0 has accumulated to date including data acquisition processing,and all levels of access and *** present various configurations of the system and describe their use in the collaboration.

关键词： SAM 数据处理系统 D0实验

Dysregulation of il-34 ligation to SDC-1 mitigates collagen-induced arthritis

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Cellular & Molecular Immunology 2022年第9期19卷 1070-1072页

作者： Anja Meyer Ryan Sienes Brian Zanotti Katrien van Raemdonck Karol Palasiewicz Daniel P.Mass Michael V.Volin Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Department of Orthopedic Surgery The University of Illinois at ChicagoChicagoILUSA

il-34 is a novel biomarker for rheumatoid arthritis(RA),as its serum levels are linked to C-reactive protein,erythrocyte sedimentation rate,rheumatoid factor(RF),il-6 and radiographic progression[1,2].il-34 reprograms naïve circulating M0 cells into glycolytic(CD14^(+)CD86^(+)GLUT1^(high))M34 macrophages(MΦs)by binding to its pathogenic receptor,SDC-1,which controls the activation of its coreceptor/M-CSFR[3].Glycolytic M34 MΦs are primed to differentiate into osteoclasts through SDC-1 ligation[3].

关键词： CD86 GLUT1 sedimentation

The CDF Date Acquisition System for Tevatron Run Ⅱ

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International Conference on Computing in High Energy and Nuclear Physics 2001年第1期 597-600页

作者： ArndMeyer FermiNationalAcceleratorLaboratory BataviaIL60510U.S.A

The CDF experiment at the Fermilab Tevatron has been significantly upgraded for the collider Run Ⅱ,which started in march 2001 and is scheduled to alst until 2006,Instantaneous luminosities of 10^32cm^-2S^-1 and above are expected.A data acquisition system capable of efficiently recording the data has been one of the most critical elements of the *** figures are the abilitity to deal with the short bunch spacing of *** sizes of the order of 250kB,and permanent logging of 20MB/s ,The design of the system and experience from the first months of data-taking operation are discussed.

关键词： CDF实验数据收集系统设计

Server-Based Data Push Architecture for Multi-Processor Environments

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Journal of Computer Science & Technology 2007年第5期22卷 641-652页

作者：孙贤和 Surendra Byna 陈勇 Department of Computer Science illinois Institute of Technology ChicagoIllinois 60616U.S.A.Computing DivisionFermi National Accelerator Laboratory.BataviaIL 60510-0500U.S.A. Department of Computer Science illinois Institute of Technology ChicagoIllinois 60616U.S.A.

Data access delay is a major bottleneck in utilizing current high-end computing （HEC） machines. Prefetching, where data is fetched before CPU demands for it, has been considered as an effective solution to masking data access delay. However, current client-initiated prefetching strategies, where a computing processor initiates prefetching instructions, have many limitations. They do not work well for applications with complex, non-contiguous data access patterns. While technology advances continue to increase the gap between computing and data access performance, trading computing power for reducing data access delay has become a natural choice. In this paper, we present a serverbased data-push approach and discuss its associated implementation mechanisms. In the server-push architecture, a dedicated server called Data Push Server （DPS） initiates and proactively pushes data closer to the client in time. Issues, such as what data to fetch, when to fetch, and how to push are studied. The SimpleScalar simulator is modified with a dedicated prefetching engine that pushes data for another processor to test DPS based prefetching. Simulation results show that L1 Cache miss rate can be reduced by up to 97% （71% on average） over a superscalar processor for SPEC CPU2000 benchmarks that have high cache miss rates.

关键词： performance measurement evaluation modeling simulation of multiple-processor system cache memory