While prolactin is most well known for its role in lactation and suppression of reproduction, its physiological functions are quite diverse. There are many etiologies of hyperprolactinemia, including ...physiologic as well as pathologic causes. Physiologic causes include pregnancy, lactation, sleep-associated, nipple stimulation and sexual orgasm, chest wall stimulation, or trauma. Stress is also an important physiologic cause of hyperprolactinemia, and its clinical significance is still being explored. This review will provide an overview of prolactin physiology, the role of stress in prolactin secretion, as well as the general clinical approach to hyperprolactinemia.
•In-situ irradiations performed on nanoprecipitates in Eurofer97 and AM-Grade91.•The M23C6 carbides are highly susceptible to radiation induced amorphization.•MX type nanoprecipitates are highly ...amorphization resistant.•Crystalline-to-amorphous transformation temperature of M23C6 is ∼812 K.•Cation chemistry of M23C6 seems to have little effect on the amorphization behavior.
In-situ irradiations using 1 MeV Kr2+ ions in a transmission electron microscope were performed on extraction replica samples containing M23C6 carbides and MX carbonitrides from two ferritic-martensitic (FM) steels: (i) 9%Cr-1%W-TaV based Eurofer97 and (ii) 9%Cr-1%Mo-VNb (all in wt.%) based additively manufactured (AM) Grade91 steel. The irradiations were performed between 100 and 773 K up to a maximum dose of ∼2.4 displacements per atom (dpa). The M23C6 carbides are highly susceptible to radiation induced amorphization (RIA), while the MX type nanoprecipitates are highly amorphization resistant across the entire irradiation temperature range. Between 100 and 423 K, RIA of M23C6 carbides occurs very rapidly with critical amorphization doses ranging between ∼0.35 and 0.9 dpa, increasing to higher doses at 573 K. Complete amorphization of the M23C6 carbides up to doses of ∼2.4 dpa is not possible at 773 K under the present irradiation conditions. The critical amorphization dose of M23C6 carbides increases nearly exponentially with irradiation temperature. The critical temperature for the crystalline-to-amorphous phase transformation (Tc→a) of M23C6 carbides irradiated as replica samples, i.e. without the surrounding metal matrix, was estimated to be ∼812 K. Comparing the present results with neutron irradiation data on bulk samples reveals a decrease in the critical amorphization dose for M23C6 and an increase of Tc→a, highlighting the effect of dose rate on the amorphization behavior that is qualitatively consistent with literature on other non-metals. Changes in the minor chemistry of M23C6, such as presence or absence of W, V, Nb, Mo, seems to have little effect on the amorphization behavior. In-situ irradiations on extraction replica samples provide a novel pathway to explore radiation tolerance of nanoprecipitates in nuclear structural materials
Abstract
Reduced activation ferritic martensitic (RAFM) and oxide dispersion strengthened (ODS) steels are the most promising candidates for fusion first-wall/blanket (FW/B) structures. The ...performance of these steels will deteriorate during service due to neutron damage and transmutation-induced gases, such as helium/hydrogen, at elevated operating temperatures. Here, after highlighting the operating conditions of fusion reactor concepts and a brief overview, the main irradiation-induced degradation challenges associated with RAFM/ODS steels are discussed. Their long-term degradation scenarios such as (a) low-temperature hardening embrittlement (LTHE)—including dose-temperature dependent yield stress, tensile elongations, necking ductility, test temperature effect on hardening, Charpy impact ductile-to-brittle transition temperature and fracture toughness, (b) intermediate temperature cavity swelling, (c) the effect of helium on LTHE and cavity swelling, (d) irradiation creep and (e) tritium management issues are reviewed. The potential causes of LTHE are discussed, which highlights the need for advanced characterisation techniques. The mechanical properties, including the tensile/Charpy impact of RAFM and ODS steels, are compared to show that the current generation of ODS steels also suffers from LTHE, and shows irradiation hardening up to high temperatures of ∼400 °C–500 °C. To minimise this, future ODS steel development for FW/B-specific application should target materials with a lower Cr concentration (to minimise
α
′), and minimise other elements that could form embrittling phases under irradiation. RAFM steel-designing activities targeting improvements in creep and LTHE are reviewed. The need to better understand the synergistic effects of helium on the thermo-mechanical properties in the entire temperature range of FW/B is highlighted. Because fusion operating conditions will be complex, including stresses due to the magnetic field, primary loads like coolant pressure, secondary loads from thermal gradients, and due to spatial variation in damage levels and gas production rates, an experimentally validated multiscale modelling approach is suggested as a pathway to future reactor component designing such as for the fusion neutron science facility.
The data presented in this article is supplementary to the research article “Phase instabilities in austenitic steels during particle bombardment at high and low dose rates” (Levine et al.) 5. ...Needle-shaped samples were prepared with focused ion beam milling from a 304L stainless steel that was irradiated with fast neutrons (E > 0.1 MeV) in the BOR-60 reactor at 318 °C to 47.5 dpa. Atom probe tomography (APT) experiments in voltage mode were then conducted on a Cameca LEAP 5000X HR. Atom position, range, and mass spectrum files after reconstruction with Cameca’s IVAS software are included. Cu- and Ni-Si-Mn-rich solute nanoclusters were identified and analyzed using the Open Source Characterization of APT Reconstructions (OSCAR) program. Python code for OSCAR 4, information on the program’s underlying algorithm, and sample output files are provided. A proximity histogram of a Ni-Si-Mn-rich cluster and a 1D density/solute concentration profile of a Cu-rich cluster are given to demonstrate OSCAR’s analytical functionalities. The provided APT dataset is valuable for benchmarking phase instabilities in neutron-irradiated austenitic stainless steels that occur at high doses. The OSCAR program can be reused to process other APT data sets where solute nanoclustering is of interest.
In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity ...theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy.
We used MT to include multiple bioactive properties that allows for the identification of multi-functional single agent compounds, in this case, the dual functions of β-amyloid (Aβ) -lowering and anti-oligomerization. Using this technology, we identified and designed novel compounds in chemical classes unrelated to current anti-AD agents that exert dual Aβ lowering and anti-Aβ oligomerization activities in animal models of AD. AD is a multifaceted disease with different pathological features.
Our study, for the first time, demonstrated that MT can provide novel strategy for discovering drugs with Aβ lowering and anti-aggregation dual activities for AD.
Human intravenous immunoglobulin (IVIG) has been indicated as a potential therapy for autoimmune neurological disorders, as well as in many neurodegenerative diseases, with various underlying ...therapeutic mechanisms such as regulation of T-cell trafficking, cytokines, Fc receptor blocking, and interruption of complement activation cascade. In Alzheimer's disease (AD), IVIG presents naturally occurring antibodies against amyloid-beta (Aβ) aggregation, thus IVIG immunotherapy may increase the clearance of Aβ and protect brain function. Recently, we and others reported that besides Aβ clearance, IVIG specifically regulates the levels of complement-derived anaphylatoxins, such as C5a and C3, which play an important role in the regulation of AMPA and NMDA receptor expression in the brain and further upregulate the AMPA-PKA-CREB signaling pathway and synaptic function in AD mouse models. Since down-regulation of complement components has been linked with deficits of cognitive function in age-related dementia following the decline of innate immunity during aging, the IVIG immunotherapy could be an attractive novel AD therapeutic through its local regulation of C3, C5a component levels in brain.
In the 1960s, the Molten Salt Reactor Experiment demonstrated the feasibility of molten salt reactors for civil applications. The Molten Salt Reactor Experiment used a nuclear graphite grade known as ...CGB in the core as the fast neutron moderator. For application in this purpose, CGB graphite underwent additional impregnation steps that are not typically used in conventional nuclear graphites. These additional impregnations significantly lowered the permeability and reduced the size of pore openings in CGB graphite, for the purpose of inhibiting molten salt ingression into the graphite. Although several publications report the mechanical properties and irradiation response of CGB graphite, little information has been published about the microstructure or sealant used for this graphite grade. Here the results of multiple advanced microscopy techniques are presented with the objective to investigate the unique microstructure and sealing technology of legacy material from the Molten Salt Reactor Experiment so it can be potentially readopted for modern reactors. The microstructural characterization shows that some pores were fully sealed by the impregnation whereas other regions contained foam-like materials that partially filled the void content. This manuscript also investigates and documents the nature and possible source of the sealant material. The pore sealing methods used for CGB are discussed and compared with other common technologies used to reduce the impregnation of molten salts into graphite components. Knowledge of CGB graphite's microstructure can enable development of new pore infiltration technologies to improve in operando behavior advancing the next generation of molten salt reactors.
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The preparation of transmission electron microscopy (TEM) samples is a critical step in the characterization of materials, and the focused ion beam (FIB) technique is a commonly used method. However, ...a significant limitation of this technique is the FIB-induced damages on the foil surfaces, which can obscure the real features of interest, particularly in radiation effects studies. To overcome this limitation, this study presents a detailed description of the flash electropolishing technique, which can be used to remove the FIB damage from samples. The flash electropolishing technique has been successfully applied to a range of materials, including Fe, Fe-based model alloys, commercial Fe-Cr alloys, and advanced Fe-Cr alloys, both in their as-received and ion-irradiated states. Furthermore, the parameters used for Fe-Cr model alloys can be adjusted for commercial and advanced alloys with minimal modifications. Further, the study also examined the effects of electropolishing variables, such as perchloric acid concentration, electropolishing temperature, Cr concentration, and voltage. Qualitatively, a general trend and scoping test strategy is explored in our experiments. Overall, the flash electropolishing technique offers a promising solution to the challenges posed by FIB-induced damages in the preparation of TEM samples.
The preparation of transmission electron microscopy (TEM) samples is a critical step in the characterization of materials, and the focused ion beam (FIB) technique is a commonly used method. However, ...a significant limitation of this technique is the FIB-induced damages on the foil surfaces, which can obscure the real features of interest, particularly in radiation effects studies. To overcome this limitation, this study presents a detailed description of the flash electropolishing technique, which can be used to remove the FIB damage from samples. The flash electropolishing technique has been successfully applied to a range of materials, including Fe, Fe-based model alloys, commercial Fe-Cr alloys, and advanced Fe-Cr alloys, both in their as-received and ion-irradiated states. Furthermore, the parameters used for Fe-Cr model alloys can be adjusted for commercial and advanced alloys with minimal modifications. The study also examined the effects of electropolishing variables, such as perchloric acid concentration, electropolishing temperature, Cr concentration, and voltage. Qualitatively, a general trend and scoping test strategy is explored in our experiments. Overall, the flash electropolishing technique offers a promising solution to the challenges posed by FIB-induced damages in the preparation of TEM samples.
STEM-BF of Fe-8Cr irradiated at 10−4 dpa/s and 450 °C to 0.35 dpa. The irradiation-induced small dots in the right micrograph are revealed after flash electropolishing, which are fully masked by the FIB damages in the left micrograph. Display omitted
SCOPE: Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age‐related neurodegenerative ...disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE‐derived phenolic acid in the brain. METHODS AND RESULTS: We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3‐hydroxybenzoic acid and 3‐(3´‐hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3‐hydroxybenzoic acid and 3‐(3´‐hydroxyphenyl)propionic acid potently interfere with the assembly of β‐amyloid peptides into neurotoxic β‐amyloid aggregates that play key roles in AD pathogenesis. CONCLUSION: Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.
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