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Basophile:Accurate Fragment charge State Prediction Improves Peptide Identification Rates

Genomics, Proteomics & Bioinformatics 2013年第2期11卷 86-95页

作者： Dong Wang Surendra Dasari Matthew c.chambers Jerry D.Holman Kan chen daniel c.liebler daniel J.Orton Samuel O.Purvine Matthew E.Monroe chang Y.chung Kristie L.Rose David L.Tabb Department of Biomedical Informatics Vanderbilt University Medical Center Division of Biomedical Statistics and Informatics Mayo Clinic Department of Biochemistry Vanderbilt University Medical Center Biological Sciences Division and Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory Department of Pharmacology Vanderbilt University Medical Center Vanderbilt-Ingram cancer center Vanderbilt University School of Medicine

In shotgun proteomics, database search algorithms rely on fragmentation models to pre- dict fragment ions that should be observed for a given peptide sequence. The most widely used strat- egy （Naive model） is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmen- tation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during cID/higher- energy collision induced dissociation （HcD） of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% （on average） over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.

关键词： Fragmentation Basicity Fragment size Ordinal regression

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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： daniel Adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany center for Molecular Medicine cologne(cMMc) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

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Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan daniel Fulton Zubair Ahmed WMatthijs Blankesteijn Sébastien Foulquier Department of Pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands cARIM-School for cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK centre for Trauma Sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-School for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(cuadrado-Godia et al.,2018).cSVD is often associated with cognitive decline,gait problems,and dementia(cuadrado-Godia et al.,2018).

关键词： pathology becoming white

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Wafer-Scale Ag₂S-Based Memristive crossbar Arrays with Ultra-Low Switching-Energies Reaching Biological Synapses

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NANO-MIcRO LETTERS 2025年第1期17卷 1-12页

作者： Zhu, Yuan Nyberg, Tomas Nyholm, Leif Primetzhofer, daniel Shi, Xun Zhang, Zhen Uppsala Univ Dept Elect Engn Div Solid State Elect S-75121 Uppsala Sweden Uppsala Univ Dept Chem Uppsala Sweden Uppsala Univ Dept Phys & Astron Uppsala Sweden chinese Acad Sci Shanghai Inst Ceram State Key Lab High Performance Ceram & Superfine M Shanghai 200050 Peoples R China

Memristive crossbar arrays (McAs) offer parallel data storage and processing for energy-efficient neuromorphic computing. However, most wafer-scale McAs that are compatible with complementary metal-oxide-semiconductor (cMOS) technology still suffer from substantially larger energy consumption than biological synapses, due to the slow kinetics of forming conductive paths inside the memristive units. Here we report wafer-scale Ag2S-based McAs realized using cMOS-compatible processes at temperatures below 160 degrees c. Ag2S electrolytes supply highly mobile Ag+ ions, and provide the Ag/Ag2S interface with low silver nucleation barrier to form silver filaments at low energy costs. By further enhancing Ag+ migration in Ag2S electrolytes via microstructure modulation, the integrated memristors exhibit a record low threshold of approximately - 0.1 V, and demonstrate ultra-low switching-energies reaching femtojoule values as observed in biological synapses. The low-temperature process also enables McA integration on polyimide substrates for applications in flexible electronics. Moreover, the intrinsic nonidealities of the memristive units for deep learning can be compensated by employing an advanced training algorithm. An impressive accuracy of 92.6% in image recognition simulations is demonstrated with the McAs after the compensation. The demonstrated McAs provide a promising device option for neuromorphic computing with ultra-high energy-efficiency.

关键词： Wafer-scale Ag2S films Reactive sputter Silver nucleation Ag+ migration Energy-efficient neuromorphic computing

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complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez daniel Refai Gerald R.Rodts christian Mustroph David Gimbel Jonathan Grossberg daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： Mackenzie M.Spicer Jianqi Yang daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of Neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa Neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in Molecular Medicine University of Iowa Carver College of MedicineIowa CityIAUSA Neural circuits and Behavior core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

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Efects of solution chemistry on arsenic(V) removal by low-cost adsorbents

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Journal of Environmental Sciences 2013年第11期25卷 2291-2298页

作者： Yuru Wang daniel c.W.Tsang Department of civil and Environmental Engineering Hong Kong Polytechnic University Department of civil and Natural Resources Engineering University of Canterbury

Natural and anthropogenic arsenic （As） contamination of water sources pose serious health concerns, especially for small communities in rural areas. This study assessed the applicability of three industrial byproducts （coal fly ash, lignite, and green waste compost） as the low-cost adsorbents for As（V） removal under various field-relevant conditions （dissolved oxygen, As（V）/Fe ratio, solution pH, and presence of competing species）. The physico-chemical properties of the adsorbents were characterized by XRD, XRF, FT-IR, and NMR analysis. Batch experiments demonstrated that coal fly ash could provide effective As（V） removal （82.1%-95%） because it contained high content of amorphous iron/aluminium hydroxides for As（V） adsorption and dissolvable calcium minerals for calcium arsenate precipitation. However, the addition of lignite and green waste compost was found unfavourable since they hindered the As（V） removal by 10%-42% possibly due to dissolution of organic matter and ternary arsenate-iron-organic matter complexes. On the other hand, higher concentrations of dissolved iron （comparing As（V）/Fe ratios of 1：1 and 1：10） and dissolved oxygen （comparing 0.2 and 6 mg/L） only marginally enhanced the As（V） removal at pH 6 and 8. Thus, addition of dissolved iron, water aeration, or pH adjustment became unnecessary because coal fly ash was able to provide effective As（V） removal under the natural range of geochemical conditions. Moreover, the presence of low levels of background competing （0.8 or 8 mg/L of humic acid, phosphate, and silicate） imposed little influence on As（V） removal, possibly because the high adsorption capacity of coal fly ash was far from exhaustion. These results suggested that coal fly ash was a potentially promising adsorbent that warranted further investigation.

关键词： adsorption arsenic coal fly ash green waste compost lignite

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Thermal properties and high-temperature ablation of high-entropy (Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating on graphite substrate

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Journal of Advanced ceramics 2024年第8期13卷 1268-1281页

作者： Ana c.Feltrin daniel Hedman Farid Akhtar Division of Materials Science Lulea University of TechnologyLulea 97187Sweden center for Multidimensional carbon Materials(cMcM) Institute for Basic Science(IBS)Ulsan 44919Republic of Korea

An entropy-stabilized multicomponent ultrahigh-temperature ceramic(UHTc)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(SPs)from constituent transition metal diboride ***(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating had a hardness of 31.2±2.1 GPa and resisted 36.9 GPa of stress before delamination,as observed at the *** temperature-dependent thermal properties of the multicomponent diboride(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) were obtained by molecular dynamics(MD)simulations driven by a machine learning force field(MLFF)trained on density functional theory(DFT)*** thermal conductivity,density,heat capacity,and coefficient of thermal expansion obtained by the MD simulations were used in time-dependent thermal stress finite element model(FEM)*** low thermal conductivity(component diboride coupled with its similar coefficient of thermal expansion to that of graphite indicated that stresses of less than 10 GPa were generated at the interface at high temperatures,and therefore,the coating was mechanically resistant to the thermal stress induced during *** experiments at 220℃ showed that the multicomponent diboride coating was resistant to thermal stresses with no visible cracking or *** ablation mechanisms were mechanical denudation and evaporation of B_(2)O_(5) and light V-Ti oxides,which caused a decrease in the mass and thickness of the coating and resulted in mass and linear ablation rates of-0.51 mg·s^(-1) and -1.38μm·s^(-1),respectively,after 60 *** findings demonstrated the thermal and mechanical stability of multicomponent entropy-stabilized diborides as coatings for carbon materials in engineering components under extreme environments.

关键词： entropy-stabilized diborides ultrahigh temperature ceramics molecular dynamics(MD)simulations density functional theory(DFT) ablation properties

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Evolving treatment strategies for colorectal cancer: A critical review of current therapeutic options

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World Journal of Gastroenterology 2014年第4期20卷 877-887页

作者： daniel c Damin Anderson R Lazzaron Division of coloproctology Department of Surgery Hospital de Clinicas de Porto Alegre Federal University of Rio Grande do Sul Postgraduate Program in Surgery Federal University of Rio Grande do Sul

Management of rectal cancer has markedly evolved over the last two *** technologies of staging have allowed a more precise definition of tumor *** in surgical concepts and techniques have resulted in higher rates of sphincter preservation and better functional outcome for patients with this ***,preoperative chemoradiotherapy followed by total mesorectal excision has become the standard of care for locally advanced tumors,many controversial matters in management of rectal cancer still need to be *** include the feasibility of a non-surgical approach after a favorable response to neoadjuvant therapy,the ideal margins of surgical resection for sphincter preservation and the adequacy of minimally invasive techniques of tumor *** this article,after an extensive search in PubMed and Embase databases,we critically review the current strategies and the most debatable matters in treatment of rectal cancer.

关键词： Rectal cancer colorectal cancer Staging Sphincter preservation Neoadjuvant chemo-radiotherapy Surgery

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Manipulating the Interferon Signaling Pathway: Implications for HIV Infection

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Virologica Sinica 2019年第2期34卷 192-196页

作者： Krystelle Nganou-Makamdop daniel c. Douek Institute of clinical and Molecular Virology University Hospital Erlangen Erlangen 91054 Germany Human Immunology Section Vaccine Research Center National Institute of Allergy and Infectious Disease National Institutes of Health BethesdaMD 20892 USA

During human immunodeficiency virus(HIV) infection, type I interferon(IFN-I) signaling induces an antiviral state that includes the production of restriction factors that inhibit virus replication, thereby limiting the infection. As seen in other viral infections, type I IFN can also increase systemic immune activation which, in HIV disease, is one of the strongest predictors of disease progression to acquired immune deficiency syndrome(AIDS) and non-AIDS morbidity and ***, IFN-I is associated with cD4 T cell depletion and attenuation of antigen-specific T cell responses. Therefore,therapeutic manipulation of IFN-I signaling to improve HIV disease outcome is a source of much interest and debate in thefield. Recent studies have highlighted the importance of timing(acute vs. chronic infection) and have suggested that specific targeting of type I IFNs and their subtypes may help harness the beneficial roles of the IFN-I system while avoiding its deleterious activities.

关键词： Human immunodeficiency virus(HIV) Simian immunodeficiency virus(SIV) Type I interferon(IFN-I) Inflammation

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