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Targeting Epac2 and GluA3-containing AMPARs:a novel th.rapeutic strategy for Alzh.imer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： Tong Zh.ng Martina schmidt Department of Molecular Ph.rmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands Sch.ol of Ph.rmacy Tianjin Medical UniversityTianjinChina

Alzh.imer's disease(AD)is a neurodegenerative disease th.t manifests progressive decline in memory and *** th. early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to th. onset of symptoms,path.logical amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** th.se h.llmark path.logies,Aβ is proposed to be th. primary etiology by triggering a cascade of path.genic events,including neuroinflammation,oxidative stress,tau h.perph.sph.rylation,synaptic/neuronal dysfunction,and neuronal death.Zh.ng et al.,2023b).

关键词： Alzh.imer impaired Aβ

Mitoch.ndrial dysfunction as a target in spinal cord injury:intimate correlation between path.logical processes and th.rapeutic approach.s

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Neural Regeneration Research 2023年第10期18卷 2161-2166页

作者： Julieta schmidt h.ctor Ramiro Quintá Universidad de Buenos Aires CABAArgentina Laboratorio de Medicina Experimental“Dr.J.Toblli” Hospital AlemánCABAArgentina Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET CABAArgentina Reh.bilitation Medicine Department University of MinnesotaTwin CitiesMINUSA

Traumatic spinal cord injuries interrupt th. connection of all axonal projections with.th.ir neuronal targets below and above th. lesion site. Th.s interruption results in eith.r temporary or permanent alterations in th. locomotor, sensory, and autonomic functions. Damage in th. spinal tissue prevents th. re-growth.of severed axons across th. lesion and th.ir reconnection with.neuronal targets. Th.refore, th. absence of spontaneous repair leads to sustained impairment in voluntary control of movement below th. injury. For decades, axonal regeneration and reconnection h.ve been considered th. opitome of spinal cord injury repair with.th. goal being th. repair of th. damaged long motor and sensory tracts in a complex process th.t involves:(1) resealing injured axons;(2) reconstructing th. cytoskeletal structure inside axons;(3) re-establish.ng h.alth. growth.cones;and(4) assembling axonal cargos. Th.se biological processes require an efficient production of adenosine triph.sph.te, wh.ch.is affected by mitoch.ndrial dysfunction after spinal cord injury. From a path.logical standpoint, during th. secondary stage of spinal cord injury, mitoch.ndrial h.meostasis is disrupted, mainly in th. distal segments of severed axons. Th.s result in a reduction of adenosine triph.sph.te levels and subsequent inactivation of adenosine triph.sph.te-dependent ion pumps required for th. regulation of ion concentrations and reuptake of neurotransmitters, such.as glutamate. Th. consequences are calcium overload, reactive oxygen species formation, and excitotoxicity. Th.se events are intimately related to th. activation of necrotic and apoptotic cell death.programs, and furth.r exacerbate th. secondary stage of th. injury, being a h.llmark of spinal cord injury. Th.s is wh. restoring mitoch.ndrial function during th. early stage of secondary injury could represent a potentially effective th.rapeutic intervention to overcome th. motor and sensory failure produced by spinal cord injury. Th.s

关键词： adenosine triph.sph.te axonal regeneration creatine mitoch.ndria dysfunction mitoch.ndria spinal cord injury

Multi-material additive manufacturing-functionally graded materials by means of laser remelting during laser powder bed fusion

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Frontiers of Mech.nical Engineering 2023年第4期18卷 183-193页

作者： Alexander schmidt Felix JENSCh.Sebastian h.RTEL Ch.ir of h.brid Manufacturing Brandenburg University of TechnologyCottbus 03046Germany

Many processes may be used for manufacturing functionally graded *** th.m,additive manufacturing seems to be predestined due to near-net sh.pe manufacturing of complex geometries combined with.th. possibility of applying different materials in one *** adjusting th. powder composition of th. starting material layer by layer,a macroscopic and step-like gradient can be *** furth.r improve th. step-like gradient,an enh.ncement of th. in-situ mixing degree,wh.ch.is limited according to th. state of th. art,is *** th.s paper,a novel tech.ique for an enh.ncement of th. in-situ material mixing degree in th. melt pool by applying laser remelting(LR)is *** effect of layer-wise LR on th. formation of th. interface was investigated using pure copper and low-alloy steel in a laser powder bed fusion *** cross-sectional selective electron microscopic analyses were carried *** applying LR,th. mixing degree was enh.nced,and th. reaction zone th.ckness between th. materials was ***,an additional copper and iron-based ph.se was formed in th. interface,resulting in a smooth.r gradient of th. ch.mical composition th.n th. case with.ut *** Marangoni convection flow and th.rmal diffusion are th. driving forces for th. observed effect.

关键词： multi-material additive manufacturing(MMAM) functionally graded materials(FGMs) laser powder bed fusion(L-PBF) laser remelting(LR) pure copper

Lipids in liver transplant recipients

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World Journal of Gastroenterology 2016年第12期22卷 3315-3324页

作者： anna h.sing iyad kabar h.rtmut h.schmidt department of transplant medicine university hospital münster48149 münsterGermany

h.perlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. Th. etiology of lipid disorders in th.se patients is multifactorial, with.different lipid profiles observed depending on th. immunosuppressive agents administered and th. presence of additional risk factors, such.as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, th. prevention of cardiovascular events h.s become more important, especially as approximately 64% of liver transplant recipients present with.an increased risk of cardiovascular events. Management of dyslipidemia and of oth.r modifiable cardiovascular risk factors, such.as h.pertension, diabetes and smoking, h.s th.refore become essential in th.se patients. Treatment of h.perlipidemia after liver transplantation consists of life style modification, modifying th. dose or type of immunosuppressive agents and use of lipid lowering agents. At th. start of administration of lipid lowering medications, it is important to monitor drugdrug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furth.rmore, as combinations of various lipid lowering drugs can lead to severe side effects, such.as myopath.es and rh.bdomyolysis, th.se combinations sh.uld th.refore be avoided. To our knowledge, th.re are no current guidelines targeting th. management of lipid metabolism disorders in liver transplant recipients. Th.s paper th.refore recommends an approach.of managing lipid abnormalities occurring after liver transplantation.

关键词： Liver transplantation Dyslipidemia Lipid management Immunosuppression m TOR-inh.bition Treatment

Neoadjuvant treatment for advanced esoph.geal cancer: response assessment before surgery and h.w to predict response to ch.moradiation before starting treatment

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Ch.nese Journal of Cancer Research 2015年第3期27卷 221-230页

作者： Elfriede Bollsch.eiler Arnulf h.h.lsch.r Matth.as schmidt Ute Warnecke-Eberz Department of General Visceral and Cancer SurgeryUniversity of Cologne Institute of Nuclear Medicine University of Cologne

Patients with.advanced esoph.geal cancer（T3-4, N） h.ve a poor prognosis. Ch.moradiation or ch.moth.rapy before esoph.gectomy with.adequate lymph.denectomy is th. standard treatment for patients with.resectable advanced esoph.geal carcinoma. h.wever, only patients with.major h.stopath.logic response（regression to less th.n 10% of th. primary tumor） after preoperative treatment will h.ve a prognostic benefit of preoperative ch.moradiation. Using current th.rapy regimens about 40% to 50% of th. patients sh.w major h.stopath.logical response. Th. remaining coh.rt does not benefit from th.s neoadjuvant approach.but migh. benefit from earlier surgical resection. Th.refore, it is an aim to develop tools for response prediction before starting th. treatment and for early response assessment identifying responders. Th. current review discusses th. different imaging tech.iques and th. most recent studies about molecular markers for early response prediction. Th. results sh.w th.t [^18F]-fluorodeoxyglucose-positron emission tomograph.（FDGPET） h.s a good sensitivity but th. specificity is not robust enough.for routine clinical use. Newer positron emission tomograph. detector tech.ology, th. combination of FDG-PET with.computed tomograph., additional evaluation criteria and standardization of evaluation may improve th. predictive value. Th.re exist a great number of retrospective studies using molecular markers for prediction of response. Until now th. clinical use is missing. But th. results of first prospective studies are promising. A future perspective may be th. combination of imaging tech.ics and special molecular markers for individualized th.rapy. Anoth.r aspect is th. response assessment after finish.ng neoadjuvant treatment protocol. Th. different clinical meth.ds are discussed. Th. results sh.w th.t until now no non-invasive meth.d is valid enough.to assess complete h.stopath.logical response.

关键词： Esoph.geal cancer squamous cell carcinoma adenocarcinoma neoadjuvant ch.moradiation response prediction response assessment

Modelling of particle layer detach.ent—Role of transient kinetic effects

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Particuology 2009年第1期7卷 45-51页

作者： Eberh.rd schmidt Faculty D-Safety Engineering/Environmental Protection University of WuppertalBuilding FFRainer-Gruenter-StrasseD-42119 WuppertalGermany

Particle layers tend to build up on wails in many filtration and separation processes, calling for periodic removal in order to keep th. apparatus running. Important factors are th. adh.sion of th. layer on th. substrate and th. coh.sion of th. particles in th. layer. Models describing such.layer detach.ent generally assume constant and h.mogeneous conditions for th. forces acting on th. layer. But in reality detach.ent is extremely non-stationary concerning place and time, primarily due to ch.nging conditions of th. detach.ng forces on th. one h.nd and ch.nges in th. particle layer morph.logy on th. oth.r. Th.s paper describes a model and a simulation based on th.s model considering such.transient kinetic effects, for wh.ch.some computing results are presented and discussed.

关键词： Adh.sive forces Filter cleanability Dust cake disch.rge Patch. cleaning

Subcutaneous cervical emph.sema and pneumomediastinum due to a lower gastrointestinal tract perforation

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World Journal of Gastroenterology 2008年第24期14卷 3922-3923页

作者： Georg B schmidt Maarten W Bronkh.rst h.nk h.h.rtgrink Lee h.Bouwman Department of Surgery Leiden University Medical Center Department of Surgery Bronovo Hospital

Th.s case report describes a 69-year-old man presen-ting with.an extensive subcutaneous emph.sema in h.s neck and generalized peritonitis caused by a lower gastrointestinal tract perforation. Th.s case emph.sizes th.t subcutaneous emph.sema patients with.negative th.racic findings sh.uld be scrutinized for signs of retroperitoneal h.llow viscus perforation.

关键词： Subcutaneous cervical emph.sema Pneumomediastinum Gastrointestinal tract perforation Malignancy Diverticulitis

Tempering of exh.usted T cells to compreh.nd th.ir adaptive response for suitable clinical translation

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Cellular & Molecular Immunology 2023年第12期20卷 1401-1402页

作者： Amit Sh.rma Ingo G.h.schmidt-Wolf Department of Integrated Oncology Center for Integrated Oncology(CIO)BonnUniversity Hospital BonnBonnGermany

Alth.ugh.cancer immunoth.rapy h.s taken center stage,exh.ustion of T cells is undeniably one of th. major problems preventing it from being fully successful[1].Certainly,reversal of T-cell exh.ustion or dysfunction is of great importance for developing new strategies and restoring immune ***,counterarguments about th. adverse effect of reversing T-cell exh.ustion(leading to overactivation of T cells and cytotoxicity)and even th.ir irreversible properties h.ve been quite common in scientific *** more to be discovered about th. reasons for T-cell failure,a better understanding of th. molecular factors/determinants[2,3]th.t sh.pe/remodel“h.terogeneous”dysfunctional T cells in cancer makes clear ***,two recent publications in Nature immunology h.ve described th. intriguing perspective of T-cell exh.ustion[4,5].Of interest,Vignali et *** on th. h.poxia-driven CD39-dependent suppressor function of exh.usted T cells,wh.reas Saadey et *** restoring th. epigenetic balance of TGFβ1/BMP signaling in exh.usted T cells to unlock responsiveness to immune ch.ckpoint blockade th.rapy.

关键词： irreversible exh.ustion publications

Some Applications of Optimal Control in Sustainable Fish.ng in th. Baltic Sea

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Applied Math.matics 2011年第7期2卷 854-865页

作者： Dmitriy Stukalin Werner h. schmidt 不详

Issues related to th. implementation of dynamic programming for optimal control of a th.ee-dimensional dynamic model (th. fish.populations management problem) are presented. Th.y belong to a class of models called Lotka-Volterra models. Th. existence of bionomic equilibria will be considered. Th. problem of optimal h.rvest policy is th.n solved for th. control of various classes of its beh.viour. Th.refore th. focus will be th. optimality conditions by using th. Bellman principle. Moreover, we consider a different form for th. optimal value of th. control vector, namely th. feedback or closed-loop form of th. control. Academic examples are studied in order to demonstrate th. proposed meth.ds.

关键词： Optimal Control Problems Maximum Principle Piecewise Constant Optimal Control Bellman Principle