Explore the vast range of titles available.

Plasma glial fibrillary acidic protein (GFAP) is an emerging biomarker of Alzheimer’s disease (AD), with higher blood GFAP levels linked to faster cognitive decline, particularly among individuals with high brain amyloid burden. However, few studies have examined brain GFAP expression to clarify if peripheral associations reflect brain changes. This study aimed to correlate region-specific GFAP mRNA expression ( n  = 917) and protein abundance (n=386) with diverse neuropathological measures at autopsy in the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) and to characterize the interaction between brain GFAP and brain amyloid burden on downstream outcomes. We assessed GFAP gene expression in the dorsolateral prefrontal cortex, caudate nucleus, and posterior cingulate cortex with respect to core AD pathology (amyloid-β and tau), cerebrovascular (microinfarcts, macroinfarcts, and cerebral amyloid angiopathy [CAA]), proteinopathic (TDP-43, Lewy bodies), and cognitive outcomes. These associations were further examined at the protein level using tandem-mass tag proteomic measurements from the dorsolateral prefrontal cortex. We also assessed GFAP interactions with AD neuropathology on downstream outcomes. Cortical GFAP gene and protein expression were significantly upregulated in participants with a neuropathologically confirmed AD diagnosis at autopsy (all P FDR  < 3.5e−4), but not in individuals positive for tau pathology and negative for amyloid pathology (all P FDR  > 0.05). Higher cortical GFAP levels were associated with increased amyloid pathology, CAA pathology, and faster cognitive decline (all P FDR  < 3.3e−3). GFAP’s associations with phosphorylated tau burden and cognition were influenced by amyloid burden, being most pronounced among amyloid-positive individuals, confirming previous in vivo biomarker observations. No associations were observed between GFAP gene expression and outcomes in the caudate nucleus. Our results support previous biomarker findings and suggest that higher brain GFAP levels are associated with higher brain amyloid burden and faster cognitive decline among amyloid-positive individuals.

Spin crossover complexes are a route toward designing molecular devices with a facile readout due to the change in conductance that accompanies the change in spin state. Because substrate effects are important for any molecular device, there are increased efforts to characterize the influence of the substrate on the spin state transition. Several classes of spin crossover molecules deposited on different types of surface, including metallic and non-metallic substrates, are comprehensively reviewed here. While some non-metallic substrates like graphite seem to be promising from experimental measurements, theoretical and experimental studies indicate that 2D semiconductor surfaces will have minimum interaction with spin crossover molecules. Most metallic substrates, such as Au and Cu, tend to suppress changes in spin state and affect the spin state switching process due to the interaction at the molecule–substrate interface that lock spin crossover molecules in a particular spin state or mixed spin state. Of course, the influence of the substrate on a spin crossover thin film depends on the molecular film thickness and perhaps the method used to deposit the molecular film.

The exchange coupling between two ferromagnetic thin films, one with magnetically hard and the other with soft phases, separated by a thin non-magnetic layer, is studied. Nd-Fe-B/Ti/Fe thin film heterostructures were fabricated using DC magnetron sputtering on Si substrates, which were heated in situ at 650 °C using a house-built vacuum-compatible heater. The effect of the thickness of the Ti buffer layer and the annealing temperature on the formation of various phases of Nd-Fe-B was investigated. The effect of the thickness of the non-magnetic Ti spacer layer on the exchange coupling strength between the hard phase Nd-Fe-B ferromagnetic thin layer and the soft phase transition metal Fe layer was experimentally investigated. Hysteresis loops of multilayer thin films indicate an antiferromagnetic coupling was observed when the thickness of the spacer layer was 2 nm. This is within the range of an antiferromagnetic coupling calculation based on RKKY theory predictions.

[...]the Arkansas transplant became interested in local politics and concerned with the impact that people like Edd Jeffords, a journalist and outspoken member of the back-to-the-land (BTL) movement, would have on his tourist business, especially after Jeffords and others began advocating the cleanup of the town's famous water supply.2 The local newspaper, the Times-Echo, shared Smith and Cross's fears and called on the citizens of Eureka Springs to stand against the onslaught of moral laxity. First published in 1980, Milton Rafferty's The Ozarks suggested that members of \"the drug culture,\" finding their way to the region, knew \"more about the federal assistance programs\" than their neighbors and were not reluctant to use such handouts.5 Rafferty presented the in-migrants as \"escapists\" who \"rejected twentieth-century city life, preferring to live a back-to-the-land communal lifestyle.\\n59 The work of the OI was not the only instance of the BTL community actively working to become an asset to their adopted home.

This work details the construction and optimization of a fully automated, custom-built, remote controlled vibrating sample magnetometer for use in spintronics related research and teaching. Following calibration by a standard 6 mm diameter Ni disc sample with known magnetic moment, hysteresis measurements of Nd-Fe-B thin films acquired by this built vibrating sample magnetometer were compared to the data taken using a commercial superconducting quantum interference device and showed very similar results. In plane and out of plane magnetic hysteresis data acquired for 25 nm Fe thin films are also presented. The developed vibrating sample magnetometer is able to achieve a sensitivity approaching 1 × 10−5 emu. Further alterations to the design that may improve beyond this limit are also discussed.

Molecular materials exhibiting bistability between two states are intriguing candidates for next generation electronic devices. Two similar classes of materials, known as spin crossover (SCO) and valence tautomers (VT) respectively, are of particular interest due to their multifunctional properties, which are controllable via several external parameters, such as temperature, light irradiation, pressure, magnetic field, and electric field. In recent years, considerable research has been dedicated to better understanding the underlying principles that govern the behavior of these materials, so that their implementation into nano-based devices might be achieved.In this report, a systematic study of the valence tautomer molecule [Co(sq)(cat)(3-tpp)2] is presented. In the first chapter, the phenomenon of valence tautomerism (VT) occurring in coordination compounds is introduced and described from the perspective of Crystal Field Theory (CFT). Further, the molecular structure and physical properties of the [Co(sq)(cat)(3-tpp)2] molecule are explored. The properties of the ferroelectric material Polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP), and the 2-D Mxene Ti3C2 are also discussed.The next section details equipment development and experimental methods. Thin films of VT molecules were prepared from solution via a drop-casting approach. For thin film analysis, we have developed a custom made, fully automated Vibrating Sample Magnetometer (VSM) with a sensitivity on the order of 1 × 10-5 emu, as well as a fully automated, variable temperature, under vacuum electron transport stage, and a magneto-optic Kerr effect apparatus (MOKE). Additional experimental methods used to characterize the VT thin films include X-ray Absorption Spectroscopy (XAS), UV-visible Spectrometry (UV-Vis) and Differential Scanning Calorimetry. Experimental results obtained from these techniques are discussed and analyzed in the third section. PVDF-HFP polarization dependent isothermal spin state switching of [Co(sq)(cat)(3-tpp)2] is also discussed as well as the effects of doping [Co(sq)(cat)(3-tpp)2] with Ti3C2, followed by a conclusion and an outline of future work.

RationaleThe serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Our previous data show that stressors can inhibit 5-HT neuronal activity and release by stimulating the release of the stress neurohormone corticotropin-releasing factor (CRF) within the serotonergic dorsal raphe nucleus (DRN). The inhibitory effects of CRF on 5-HT DRN neurons are indirect, mediated by CRF-R1 receptors located on GABAergic afferents.ObjectivesWe tested the hypothesis that DRN CRF-R1 receptors contribute to stress-induced reinstatement of morphine-conditioned place preference (CPP). We also examined the role of this circuitry in stress-induced negative affective state with 22-kHz distress ultrasonic vocalizations (USVs), which are naturally emitted by rats in response to environmental challenges such as pain, stress, and drug withdrawal.MethodsFirst, we tested if activation of CRF-R1 receptors in the DRN with the CRF-R1-preferring agonist ovine CRF (oCRF) would reinstate morphine CPP and then if blockade of CRF-R1 receptors in the DRN with the CRF-R1 antagonist NBI 35965 would attenuate swim stress–induced reinstatement of morphine CPP. Second, we tested if intra-DRN pretreatment with NBI 35965 would attenuate foot shock stress–induced 22-kHz USVs.ResultsIntra-DRN injection of oCRF reinstated morphine CPP, while intra-DRN injection of NBI 35965 attenuated swim stress–induced reinstatement. Moreover, intra-DRN pretreatment with NBI 35965 significantly reduced 22-kHz distress calls induced by foot shock.ConclusionsThese data provide evidence that stress-induced negative affective state is mediated by DRN CRF-R1 receptors and may contribute to reinstatement of morphine CPP.

Background Platelet activation may be a central mediator of a chain of events leading to microinfarcts, leakage of thrombin and fibrin through the blood‐brain barrier and chronic neuroinflammation that typify Alzheimer’s Disease (AD). The platelet thrombin receptor Protease Activated Receptor 4 (PAR4) is responsible for platelet activation and amplification of thrombin generation. Thrombin cleaves fibrinogen to fibrin, and pathologic fibrin deposition in the cerebral microvasculature is itself a risk factor for Alzheimer’s disease. Fibrin interaction with vascular amyloid β (Aβ) leads to degradation‐resistant blood clots. This process initiates inflammation both in the vessel and adjacent parenchyma. Inflammation in general has been reported to turn on expression of PAR4 in endothelial cells not typically expressing PAR4. Method 1) Data were acquired from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP) to study the correlation of the PAR4 gene expression or methylation with AD diagnosis and longitudinal cognitive decline. 2) 5xFAD amyloid model mice were crossed with PAR4KO mice to test for pathology and markers of inflammation. Result 1) PAR4 gene F2RL3 mRNA was elevated in AD cases and was associated with worse retrospective longitudinal cognitive performance. We also report a significant association of F2RL3 epigenetic demethylation with cognitive decline. 2) 5xFAD mice exhibit increased PAR4 protein expression on vascular endothelial cells. 5xFAD mice exhibit increased vascular fibrin deposits compared to WT mice, and this fibrin deposition is reduced in 5xFAD/PAR4KO compared to 5xFAD. Conclusion In a human study the PAR4 gene F2RL3 mRNA expression is associated with multiple AD‐relevant outcomes and its encoded product, PAR4, may play a role in disease pathogenesis. PAR4 is a platelet receptor that functions upstream of fibrin deposition in 5xFAD amyloid mice, leading to misexpression in the microvasculature. Fibrin deposits have been reported to be inflammatory in 5xFAD and future work will focus on teasing apart the contribution of PAR4 mediated fibrin deposits in inflammation and microglial activation.

Platelet activation may be a central mediator of a chain of events leading to microinfarcts, leakage of thrombin and fibrin through the blood-brain barrier and chronic neuroinflammation that typify Alzheimer's Disease (AD). The platelet thrombin receptor Protease Activated Receptor 4 (PAR4) is responsible for platelet activation and amplification of thrombin generation. Thrombin cleaves fibrinogen to fibrin, and pathologic fibrin deposition in the cerebral microvasculature is itself a risk factor for Alzheimer's disease. Fibrin interaction with vascular amyloid β (Aβ) leads to degradation-resistant blood clots. This process initiates inflammation both in the vessel and adjacent parenchyma. Inflammation in general has been reported to turn on expression of PAR4 in endothelial cells not typically expressing PAR4. 1) Data were acquired from the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP) to study the correlation of the PAR4 gene expression or methylation with AD diagnosis and longitudinal cognitive decline. 2) 5xFAD amyloid model mice were crossed with PAR4KO mice to test for pathology and markers of inflammation. 1) PAR4 gene F2RL3 mRNA was elevated in AD cases and was associated with worse retrospective longitudinal cognitive performance. We also report a significant association of F2RL3 epigenetic demethylation with cognitive decline. 2) 5xFAD mice exhibit increased PAR4 protein expression on vascular endothelial cells. 5xFAD mice exhibit increased vascular fibrin deposits compared to WT mice, and this fibrin deposition is reduced in 5xFAD/PAR4KO compared to 5xFAD. In a human study the PAR4 gene F2RL3 mRNA expression is associated with multiple AD-relevant outcomes and its encoded product, PAR4, may play a role in disease pathogenesis. PAR4 is a platelet receptor that functions upstream of fibrin deposition in 5xFAD amyloid mice, leading to misexpression in the microvasculature. Fibrin deposits have been reported to be inflammatory in 5xFAD and future work will focus on teasing apart the contribution of PAR4 mediated fibrin deposits in inflammation and microglial activation.

A Tangled Hope: America, China, and Human Rights at the End of the Cold War, 1976-2000, discusses the evolution of both the international and American understanding of human rights. Beginning with a discussion of the philosophical and cultural frameworks concerning \"rights\" that developed in Europe and the Americas throughout the 18th and 19th centuries, this work moves into the post-World War II climate that shaped Jimmy Carter and his unique understanding of human rights and America's role in the Cold War world. In particular, I argue that the existing narrative concerning Carter's foreign policy is lacking in a nuanced understanding of his beliefs and experiences and how he subsequently brought them to bear on his development and application of a moral foreign policy. Jimmy Carter established a system of ethically rigid, yet pragmatically applied, human rights structures in diplomacy, allowing constructive engagement across the world, and especially with China. Contrary to existing scholarship, I argue that Carter developed a policy of moral pragmatism that allowed for flexible implementation of his human rights agenda across varied fronts. In the case of normalization between Beijing and Washington, I challenge the existing narrative on Carter's application of his human rights policies to Sino-American relations. While Betty Glad, Warren Cohen, Michael Hunt, and others have argued that human rights played little to no role in Sino-American relations during the 1970s, newly declassified documentation shows human rights were discussed at every step and ultimately were placed within Carter's understanding of the Cold War and Christian Pragmatism.