Efficient Suppression of Abdominal Aortic Aneurysm Expansion in Rats through Systemic Administration of Statin-Loaded Nanomedicine

Abdominal aortic aneurysm (AAA) is a life-threatening disease. However, no systemically injectable drug has been approved for AAA treatment due to low bioavailability. Polymeric micelles are nanomedicines that have the potential to improve therapeutic efficacy by selectively delivering drugs into disease sites, and research has mainly focused on cancer treatments. Here, we developed a statin-loaded polymeric micelle to treat AAAs in rat models. The micelle showed medicinal efficacy by preventing aortic aneurysm expansion in a dose-dependent manner. Furthermore, the micelle-injected group showed decreased macrophage infiltration and decreased matrix metalloproteinase-9 activity in cases of AAA.     

Role of Neuroinflammation and Blood-Brain Barrier Permutability on Migraine

Currently, migraine is treated mainly by targeting calcitonin gene-related peptides, although the efficacy of this method is limited and new treatment strategies are desired. Neuroinflammation has been implicated in the pathogenesis of migraine. In patients with migraine, peripheral levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α, are known to be increased. Additionally, animal models of headache have demonstrated that immunological responses associated with cytokines are involved in the pathogenesis of migraine. Furthermore, these inflammatory mediators might alter the function of tight junctions in brain vascular endothelial cells in animal models, but not in human patients. Based on clinical findings showing elevated IL-1β, and experimental findings involving IL-1β and both the peripheral trigeminal ganglion and central trigeminal vascular pathways, regulation of the Il-1β/IL-1 receptor type 1 axis might lead to new treatments for migraine. However, the integrity of the blood-brain barrier is not expected to be affected during attacks in patients with migraine.     

Synthetic Biomarker Design by Using Analyte‐Responsive Acetaminophen

The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy that uses analyte‐responsive acetaminophen (APAP) to expand the catalogue of analytes available for synthetic biomarker development. As proof‐of‐concept, we designed hydrogen peroxide (H₂O₂)‐responsive APAP (HR‐APAP) and succeeded in H₂O₂ detection with cellular and animal experiments. In fact, for blood samples following HR‐APAP injection, we demonstrated that the plasma concentration ratio [APAP+APAP conjugates]/[HR‐APAP] accurately reflects in vivo differences in H₂O₂ levels. We anticipate that our practical methodology will be broadly useful for the preparation of various synthetic biomarkers.     

Sparse event-triggered control of linear systems

In event-triggered control, a situation where the control input must be sparse often arises. Therefore, in this study, we propose sparse event-triggered control, meaning that the control input is sparse and updated in an event-triggered manner. First, we present a model-based method for sparse event-triggered control of linear systems, where the event condition is defined by a Lyapunov function. The resulting control input is proven to be sparse and the control system is confirmed to be asymptotically stable. Second, we extend it to a data-driven version, where the event condition is adaptively updated from online data on the state trajectory. Finally, we discuss the possibility of extending our framework to two cases of disturbance and nonlinear dynamics.     

Modulation‐Doped Multiple Quantum Wells of Aligned Single‐Wall Carbon Nanotubes

Heterojunctions, quantum wells, and superlattices with precise doping profiles are behind today's electronic and photonic devices based on III–V compound semiconductors such as GaAs. Currently, there is considerable interest in constructing similar artificial 3D architectures with tailored electrical and optical properties by using van der Waals junctions of low‐dimensional materials. In this study, the authors have fabricated a novel structure consisting of multiple thin (≈20 nm) layers of aligned single‐wall carbon nanotubes with dopants inserted between the layers. This “modulation‐doped” multiple‐quantum‐well structure acts as a terahertz polarizer with an ultra‐broadband working frequency range (from ≈0.2 to ≈200 THz), a high extinction ratio (20 dB from ≈0.2 to 1 THz), and a low insertion loss (<2.5 dB from ≈0.2 to 200 THz). The individual carbon nanotube films—highly aligned, densely packed, and large (2 in. in diameter)—were produced using vacuum filtration and then stacked together in the presence of dopants. This simple, robust, and cost‐effective method is applicable to the fabrication of a variety of devices relying on macroscopically 1D properties of aligned carbon nanotube assemblies.     

A method of estimating entropies of coals and coal liquids

A method for estimating entropies of both solid and liquid fuels is proposed. An example showing calculation of availability of coal is presented. Entropy and availability of coal calculated are compared with those obtained by other methods. Deviations among different methods examined are discussed.     

Carnitine/organic cation transporter OCTN2-mediated transport of carnitine in primary-cultured epididymal epithelial cells

Carnitine is essential for the acquisition of motility and maturation of spermatozoa in the epididymis, and is accumulated in epididymal fluid. In this study, carnitine transport into primary-cultured rat epididymal epithelial cells was characterized to clarify the nature of the transporter molecules involved. Uptake of carnitine by primary-cultured epididymal epithelial cells was time, Na(+) and concentration dependent. Kinetic analysis of carnitine uptake by the cells revealed the involvement of high- and low-affinity transport systems with Km values of 21 microM and 2.2 mM respectively. The uptake of carnitine by the cells was significantly reduced by inhibitors of carnitine/organic cation transporter (OCTN2), such as carnitine analogues and cationic compounds. In RT-PCR analysis, OCTN2 expression was detected. These results demonstrated that the high-affinity carnitine transporter OCTN2, which is localized at the basolateral membrane of epididymal epithelial cells, mediates carnitine supply into those cells from the systemic circulation as the first step of permeation from blood to spermatozoa.     

Transport of carnitine and acetylcarnitine by carnitine/organic cation transporter (OCTN) 2 and OCTN3 into epididymal spermatozoa

Carnitine and acetylcarnitine are important for the acquisition of motility and maturation of spermatozoa in the epididymis. In this study, we examined the involvement of carnitine/organic cation transporter (OCTN) in carnitine and acetylcarnitine transport in epididymal spermatozoa of mice. Uptake of both compounds by epididymal spermatozoa was time-dependent and partially Na(+)-dependent. Kinetic analyses revealed the presence of a high-affinity transport system in the spermatozoa, with K(m) values of 23.6 and 6.57 muM for carnitine and acetylcarnitine respectively in the presence of Na(+). Expression of OCTN2 and OCTN3 in epididymal spermatozoa was confirmed by immunofluorescence analysis. The involvement of these two transporters in carnitine and acetylcarnitine transport was supported by a selective inhibition study. We conclude that both Na(+)-dependent and -independent carnitine transporters, OCTN2 and OCTN3, mediate the supply of carnitine and acetylcarnitine to epididymal spermatozoa in mice.     

Emergence of [GAR+] cells in yeast from sake brewing affects the fermentation properties

In the traditional (kimoto) method of sake (Japanese rice wine) brewing, Saccharomyces cerevisiae yeast cells are exposed to lactate, which is produced by lactic acid bacteria in the seed mash. Lactate promotes the appearance of glucose-repression-resistant [GAR⁺] cells. Herein, we compared the resistance to glucose repression among kimoto, industrial, and laboratory yeast strains. We observed that the frequencies of the spontaneous emergence of [GAR⁺] cells among the kimoto strains were higher than those among the industrial and laboratory strains. The fermentation ability of a kimoto yeast (strain U44) was lower than that of an industrial strain (K701), as [GAR⁺] cells generally showed slower ethanol production. The addition of lactate decreased the fermentation abilities of the K701 strain by increasing the number of [GAR⁺] cells, but it did not affect those of the U44 strain. These results suggest that lactate controlled fermentation by promoting the appearance of [GAR⁺] cells in the industrial sake strains but not in the kimoto strains.