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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Update on risk scoring systems for patients with upper gastrointestinal haemorrhage

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World journal of Gastroenterology 2012年第22期18卷 2739-2744页

作者： adrian j Stanley Gastrointestinal Unit Glasgow Royal Infirmary Glasgow G4 OSF United Kingdom

Upper gastrointestinal haemorrhage (UGIH) remains a common medical emergency worldwide. It is increasingly recognised that early risk assessment is an important part of management, which helps direct appropriate patient care and the timing of endoscopy. Several risk scores have been developed, most of which include endoscopic findings, although a minority do not. These scores were developed to identify various end-points including mortality, rebleeding or clinical intervention in the form of transfusion, endoscopic therapy or surgery. Recent studies have reported accurate identification of a very low risk group on presentation, using scores which require simple clinical or laboratory parameters only. This group may not require admission, but could be managed with early out-patient endoscopy. This article aims to describe the existing pre- and post-endoscopy risk scores for UGIH and assess the published data comparing them in the prediction of outcome. Recent data assessing their use in clinical practice, in particular the early identification of low-risk patients, are also discussed.

关键词： Upper gastrointestinal haemorrhage Bleeding Endoscopy Risk assessment Scoring systems Bla-tchford Rockall

Endoscopic ultrasound-guided elastography in the nodal staging of oesophageal cancer

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World journal of Gastroenterology 2012年第9期18卷 889-895页

作者： Stuart Paterson Fraser Duthie adrian j Stanley Department of Gastroenterology Forth Valley Royal Hospital Department of Pathology Glasgow Royal Infirmary Department of Gastroenterology Glasgow Royal Infirmary

AIM： To assess quantitative endoscopic ultrasound （EUS）- guided elastography in the nodal staging of oesophago- gastric cancers.METHODS： This was a single tertiary centre study as- sessing 50 patients with established oesophago-gastric cancer undergoing EUS-guided fine needle aspiration biopsy （FNAB） of lymph nodes between july 2007 and july 2009. EUS-guided elastography of lymph nodes was performed before EUS-FNAB. Standard EUS charac- teristics were also described. Cytological determination of whether a lymph node was malignant or benign was used as the gold standard for this study. Comparisons of elastography and standard EUS characteristics were made between the cytologically benign and malignant nodes. The main outcome measure was the accuracy of elastography in differentiating between benign and malignant lymph nodes in oesophageal cancers.

关键词： Endoscopic ultrasound Oesophageal cancerLymph nodes Elastography Tumour staging

Relating thermal conductivity of soil skeleton with soil texture by the concept of“local thermal conductivity fluctuation”

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journal of Rock Mechanics and Geotechnical Engineering 2022年第1期14卷 262-271页

作者： adrian Rózanski Faculty of Civil Engineering Wroclaw University of Science and TechnologyWybrzeze Wyspia_nskiego 2750-370WrocławPoland

The thermal conductivity of the soil skeletonλ;is an essential parameter from the point of view of the correct assessment of soil overall/effective *** work introduces the concept of“local thermal conductivity fluctuation”which characterizes the microscale variation of conductivity within the solid *** is proposed to link the“local fluctuation”of thermal conductivityλwith the soil texture-the information that is available at the scale of engineering *** was possible to relate the skeleton thermal conductivity with the grain size distribution of the ***,based on a large series of numerical simulations,the paper provides four triangle diagrams(at different organic matter contents:0%,2%,4%and 6%)relating the value ofλ;with volume fraction of individual soil *** result is extremely important from the practical point of *** can quickly evaluateλ;value provided that information on the grain size distribution and organic matter content is available.

关键词： Soil skeleton Probability density function(PDF) Computational micromechanics Local fluctuation Soil texture

Gene therapy and genome editing for primary immunodeficiency diseases

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Genes & Diseases 2020年第1期7卷 38-51页

作者： Zhi-Yong Zhang adrian j.Thrasher Fang Zhang Molecular and Cellular Immunology Great Ormond Street Institute of Child HealthUniversity Colleage LondonUK Department of Immunology and Rheumatology Children’s Hospital of Chongqing Medical UniversityChina

In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells(HSCs)transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases(PIDs).Despite of some pitfalls at early stage clinical trials,the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety,preparatory regime for manufacturing high quality virus,automated CD34 cell ***,the overall outcome from the clinical trials for the different PIDs has been very *** addition to the viral vector based gene therapy,the recent fast moving forward developments in genome editing using engineered nucleases in HSCs has provided a new promising platform for the treatment of *** review provides an overall outcome and progress in gene therapy clinical trials for SCID-X,ADA-SCID,WAS,X-CGD,and the recent developments in genome editing technology applied in HSCs for developing potential therapy,particular in the key studies for PIDs.

关键词： Adenosine deaminase deficient Chronic granulomatous disease Gene therapy Genome editing Hematopoietic progenitor stem cells Primary immunodeficiency diseases Wiskott-Aldrich syndrome X-liked severe combined immunodeficiency

Design considerations and behavior of reinforced concrete core dams during construction and impounding

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Water Science and Engineering 2016年第3期9卷 212-218页

作者： Peter Tschernutter adrian Kainrath Institute of Hydraulic Engineering and Water Resources Management Vienna University of Technology

Reinforced concrete core dams can be an alternative solution to conventional dam designs either for permanent impounded reservoirs or flood protection and flood-retaining dams. Dams of this type have been constructed in Austria for various reasons and have shown good behavior during operation. For a better understanding of the load-deformation behavior of this type of dams during construction and impounding, numerical simulations were carried out. The interaction between the thin reinforced concrete core and the dam fill material as well as the influence of fill material properties and other main parameters, such as the roughness of the concrete surface and bedding conditions of the concrete core,on the deformation behavior of dams were examined. The results show that high compressive stress is mainly induced by arching effects in the dam body during construction. During the reservoir impounding, the compressive stresses in the core are reduced significantly while the bending moment in the core footing increases. The results also show that the maximum bending moments occur at the core footing and can be significantly reduced by design improvements. The findings in this study can provide general design recommendations for small dams with a central concrete core as a sealing blanket.

关键词： Embankment dam Concrete diaphragm sealing Numerical analysis Concrete core Structural force

AI and freedom for evolution in energy science

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Energy and AI 2020年第1期1卷 131-132页

作者： adrian Bejan Duke University DurhamNCUnited States

Artifacts such as AI,written language,science and technology are ob-jects(devices,processes,methods)that,when added to the homo sapi-ens,enhance the effect of human *** we are a“human and machine species”that is mon... 详细信息

关键词： such freedom AI

On sustaining the ecology and livestock industry of the Bayanbuluk Grasslands

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journal of Arid Land 2010年第1期2卷 57-63页

作者： adrian R WILLIAMS Pendragon Dryland Management Services

A short visit to the Bayanbuluk Grassland in the Tianshan Mountains, Xinjiang, PRC, revealed a number of environmental and livestock production problems, including grassland degradation, loss of grassland biodiversity, soil erosion and flash flooding downstream, decreased pasture productivity, and poor livestock nutrition (especially in winter) leading to stock losses and flocks and herds of low productivity. This paper describes those problems and then suggests some solutions. Short duration, high intensity grazing could be one of the solutions to both improving grassland condition and improving livestock nutrition. Local production of fodder crops for feeding in winter and spring deserves testing, using adapted strains of Alfalfa (Medicago sativa) and trialling fodder root crop production. It is important to realise that the land management objectives of scientists, administrators, herders and farmers may be similar, and that there are opportunities for land improvement through working together.

关键词： Bayanbuluk Grasslands Tianshan Mountains reversing grassland degradation improving livestock productivity

The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： Robert Sulak Xiaonan Liu adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2j mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells