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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert j.Thomas m.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage mark L.Dell’Acqua Brian m.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Stress Corrosion Crack Growth Behavior of Titanium Alloy/Bioactive Glasses Sandwiches in Simulated Human Physiological Environment

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journal of materials Science & Technology 2002年第5期18卷 387-391页

作者： DaCHEN j.m.mcNaney E.Saiz A.P.Tomsia R.O.ritchie Dept. of mat. Sci. Shanghai Jiaotong Univ. Shanghai 200030 China Dept. of mat. Sci. and Eng. Univ. of California Berkeley CA 94720 United States mat. Sci. Div. Lawrence Berkeley Natl. Lab. Berkeley CA 94720 United States

Based on a series of newly developed bioactive glasses having suitable thermo-mechanical properties to allow application as fixation agents between bone and titanium alloy biomedical implants, the stress corrosion crack growth (SCCG) behavior of their interfaces with Ti6AI4V was investigated in simulated body fluid (SBF) with the objective of discerning the salient mechanisms of crack advance and to assess the reliability of the bonds. Results indicated that crack growth rates in Ti6AI4V/glass/Ti6AI4V sandwich specimens were nearly the same as or slightly lower than those in the bulk glasses at comparable stress intensities; indeed, cracks would prefer to propagate off the interface, suggesting that the Ti6AI4V/glass interface has relatively good crack-growth resistance. mechanistically, interfacial crack growth appears to be controlled by the classic stress corrosion mechanisms for silicate glasses, with no discernible effect of bioactivity on the SCCG behavior being observed.

关键词： Stress corrosion Titanium alloy Bioactive glass Crack growth

Biomarkers of Aging: Changes in Circadian Rhythms Related to the modulation of metabolic Output

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Biomedical and Environmental Sciences 1991年第1期4卷 182-191页

作者： PETER H.DUFFY ritchie j.FEUERS Food and Drug Administration Natiomd Center Jbr Toxicological Research JeffersonFood and Drug Administration Natiomd Center Jbr Toxicological Research Jefferson Arkansas 72079 To whom correspondence should be addressedArkansas 72079

Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) many variables that are related to the modulation of metabolic output vary dramatically at different times of the day; (2) various experimental variable and treatment groups must be synchronized with environmental cues that control circadian rhythms; and (3) multiple circadian variables may interact together to modulate the rate of aging. The rhythm for physiological factors such as whole animal metabolic output, body temperature, heart rate, urine flow, potassium, etc. were found to be dissociated or altered by the senescence process; behavioral variables such as spontaneous activity, wheel running, feeding and drinking, verbal performance, as well as sleep-wakefulness rhythms, seem to be accurate predictors of biological age. Circadian rhythms for a variety of enzymes of intermediary metabolism which are directly associated with energy metabolism have been well documented. These well-defined rhythms of enzyme activity have also been shown to degenerate with aging. Rhythms tend to lose amplitude as activity falls with age and as a general loss of regulation (especially time of day where maximal activity might be found) of activity across the 24-h span occurs. As with behavioral variables, changes in enzyme rhythms appear to accurately predict aging. Generally speaking, the loss of temporal organization with age, characterized by decreased circadian amplitude, loose internal synchronization, and poor response to external environmental time queues, is associated with poor health states and decreased longevity. Temporal rhythms for whole animal parameters are highly correlated with molecular events, such as regulation of cellular metabolism. DNA repair, and gene expression. Automated data acquisition and process control systems will be required for future C

关键词： Biomarkers of Aging Changes in Circadian Rhythms Related to the modulation of metabolic Output

Variation in sexual dimorphism and assortative mating do not predict genetic divergence in the sexually dimorphic Goodeid fish Girardinichthys multiradiatus

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Current Zoology 2012年第3期58卷 440-452页

作者： C. mACIAS GARCIA G SmITH C. GONZALEZ ZUARTH j. A. GRAVES m. G. ritchie Departamento de Ecologia Evolutiva Instituto de Ecologia UNAM A. E 70-275 C. E 04510 M6xico DE M6xico School of Biology University of St Andrews St Andrews Fife KY16 9TH Scotland UK

Sexual dimorphism is often used as a proxy for the intensity of sexual selection in comparative studies of sexual selection and diversification. The mexican Goodeinae are a group of livebearing freshwater fishes with large variation between species in sexual dimorphism in body shape. Previously we found an association between variation in morphological sexual dimorphism between species and the amount of gene flow within populations in the Goodeinae. Here we have examined if mor- phological differentiation within a single dimorphic species is related to assortative mating or gene flow between populations. In the Amarillo fish Girardinichthys multiradiatus studies have shown that exaggerated male fins are targets of female preferences. We find that populations of the species differ in the level of sexual dimorphism displayed due to faster evolution of differences in male than female morphology. However, this does not predict variation in assortative mating tests in the laboratory; in fact dif- ferences in male morphology are negatively correlated with assortative mating. microsatellite markers reveal significant genetic differences between populations. However, gene flow is not predicted by either morphological differences or assortative mating. Rather, it demonstrates a pattern of isolation by distance with greater differentiation between watersheds. We discuss the caveats of predicting behavioural and genetic divergence from so-called proxies of sexual selection [Current Zoology 58 （3）： 440-452, 2012].

关键词： Sexual dimorphism Assortative mating Genetic distance Speciation Viviparous fish

Immersion in the Design: Design-for-assembly of Cable Harnesses

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厦门大学学报（自然科学版） 2002年第S1期41卷 205-206页

作者： j E L Simmons j m ritchie P O'B Holt G T Russell manufacturing Systems Research Group Manufacturing Systems Research Group Image Systems Engineering LaboratoryHeriot-Watt UniversityImage Systems Engineering LaboratoryHeriot-Watt University Edinburgh UKEdinburgh UK

Approaches to efficiency in manufacturing and assem bl y over the past 100 years have concentrated frequently on the twin themes of div iding jobs done by people into defined segments and to automating as many of tho se segments as possible. This approach to manufacturing engineering may be char acterised as one of deconstruction and replacement so far as the role of the hum an being is concerned. more recently design engineering has been approached in a similar light with research into ’intelligent’ methods involving, for example, expert systems or genetic algorithms to handle an increasing proportion of desi gn tasks. Expert systems are predicated on the idea that it is possible to capture and systemise significant amounts of professional knowledge: a task that has proved with experience to be much more difficult than when such systems wer e first proposed. Genetic algorithms, notwithstanding considerable research eff ort, have yet to make significant inroads into the practise of design and manufa cture. This paper will draw on new and previous experimental work carried out with supp ort from industry to propose an alternative approach that is enabled by the prod ucts of modern information technology. In this paradigm it is recognised that t he involvement of the human design expert is, for the time being at least, inevi table. Rather than seeking to reduce or even eliminate the " expert" with his or her tacit knowledge, the aim is to provide the expert with interactive to ols including immersive virtual reality so that implicit, human expertise can be applied effectively in the design cycle. The proposed approach is considered in the context of a particularly costly and difficult task, namely the design and planning for manufacture and assembly of c able harnesses for use in electro-mechanical artefacts. The efficient and reli able manufacture of cabling systems for many such products in the aerospace, aut omotive and IT sectors provides diverse challenges to des

关键词： Immersion in the Design

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi mātai medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

Arctic sea-ice extent: No record minimum in 2023 or recent years

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 52-55页

作者： Ola m.johannessen Tor I.Olaussen Nansen Scientific Society BergenNorway Nansen Environmental and Remote Sensing Center BergenNorway

Arctic sea-ice extent reaches its minimum each year in September. On 11 September 2023 the minimum was 4.969 million square kilometers(***^(2)). This was not a record low, which occurred in 2012, when the minimum was 4.175 ***^(2), 0.794 ***^(2) less than the minimum in 2023. However, the ice extent had decreased by 0.432 ***^(2) compared with 2022. Nevertheless, the summer melting in 2023 was remarkably less than expected when considering the strong heat waves in the atmosphere and ocean, with record temperatures set around the world. In general, there is a high correlation between the long-term decrease in sea-ice extent and the increasing CO_(2) in the atmosphere, where the increase of CO_(2) in recent decades explains about 80% of the decrease in sea ice in September, while the remainder is caused by natural variability.

关键词： Sea ice Arctic minimum ice Climate

Biomarkers of Aging: Changes in Circadian Rhythms Related to the modulation of metabolic Output

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Biomedical and Environmental Sciences 1991年第Z1期 182-191页

作者： PETER H.DUFFY,ritchie j.FEUERS Food and Drug Administration Natiomd Center jbr Toxicological Research jefferson Food and Drug Administration Natiomd Center jbr Toxicological Research jefferson Arkansas 72079 To whom correspondence should be addressed Arkansas 72079

关键词： Biomarkers of Aging Changes in Circadian Rhythms Related to the modulation of metabolic Output