Self-propagation Combustion Behavior with Varying Al/Ni Ratios in Compression-Bonded Ni-sputtered Al Foil Multilayers

Compression-bonded Ni-sputtered Al foil multilayers with various atomic ratios of Al/Ni are fabricated with various bilayer thicknesses. The microstructures that are formed after the self-propagating combustion using laser ignition result in equilibrium phases in the Al/Ni binary system. Homogeneous intermetallic compounds for Al₃Ni₂ and AlNi are obtained for the first time in the micrometer-scale multilayers through controlling the Ni layer thickness. The onset temperatures of the multilayers are below 800 K (527 °C) for all multilayer samples. The maximum temperatures correspond to the liquidus temperatures of the intermetallic compounds. The self-propagating direction is divided into a transverse propagating direction and a gross propagating direction. The measured gross propagation velocities vary widely without exhibiting a clear trend. However, the transverse propagation velocity is dependent on the measured maximum temperatures, while the effects of the bilayer thickness are not discernible. The measured transverse propagation velocities are similar to the reported propagation velocities for sputtered multilayers with similar bilayer thicknesses.     

Static analysis of JavaScript libraries in a scalable and precise way using loop sensitivity

Statically analyzing JavaScript applications often requires an analysis of JavaScript libraries because many JavaScript applications use libraries. However, static analysis techniques for JavaScript are not yet ready for analyzing libraries in a scalable and precise manner. Simply loading JavaScript libraries uses various dynamic features of JavaScript, which cause static analyzers to suffer from mutually intermingled problems of scalability and imprecision. In this paper, we present a loop‐sensitive analysis (LSA) technique, which can improve the analysis scalability when analyzing JavaScript libraries by enhancing the analysis precision of loops. The LSA technique distinguishes loop iterations when loop conditions can be determined to be either true or false precisely. We formalize LSA in the abstract interpretation framework in the presence of tricky language features such as exceptions and prove its soundness and precision theorems using Coq. We evaluate our LSA implementation with the analysis results of programs that use 5 JavaScript libraries and show that LSA significantly improves the analysis scalability and precision of an existing JavaScript static analyzer when analyzing JavaScript libraries. In addition, using the configurability of LSA, we experimentally show the correlation between scalability and precision in the analysis of JavaScript libraries. We found that even the analysis of simple programs that just load jQuery, which is the most popular JavaScript library, in a scalable way requires distinguishing not only the last 4 functions being called but also 40 iterations in each loop with 2‐level nested loops at least. Both the mechanization and implementation of LSA are publicly available.     

Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1

Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that MrgprX1 plays an essential role in CQ-induced itch. To date, a few MrgprX1 antagonists have been discovered, but they are clinically unavailable or lack selectivity. Here, a cell-based high-throughput screening was performed to identify novel antagonists of MrgprX1, and the screening of 2543 compounds revealed two novel MrgprX1 inhibitors, berbamine and closantel. Notably, berbamine potently inhibited CQ-mediated MrgprX1 activation (IC₅₀ = 1.6 μM) but did not alter the activity of other pruritogenic GPCRs. In addition, berbamine suppressed the CQ-mediated phosphorylation of ERK1/2. Interestingly, CQ-induced pruritus was significantly reduced by berbamine in a dose-dependent manner, but berbamine had no effect on histamine-induced, protease-activated receptors 2-activating peptide-induced, and deoxycholic acid-induced itch in mice. These results suggest that berbamine is a novel, potent, and selective antagonist of MrgprX1 and may be a potential drug candidate for the development of therapeutic agents to treat CQ-induced pruritus.     

Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.     

Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1

Sparstolonin B (SsnB), which is found in Sparganium stoloniferum, prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammatory responses. We determined the functions of SsnB on controlling heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). Furthermore, the distinct function of SsnB on the expression of iNOS and well-known pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were assessed in the pulmonary histological status of LPS-injected mice. SsnB upregulated the HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which lead to the reduction of STAT-1 phosphorylation. Moreover, SsnB enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and weakened IL-1β expression on LPS-treated HUVECs. SsnB-suppressed iNOS/NO synthesis was restored by the process of the RNAi inhibition of HO-1. In experiment with an LPS-injected animal model, SsnB remarkably decreased the iNOS expression in the pulmonary biostructure and TNF-α level in the bronchoalveolar lavage fluid (BALF). Therefore, these results demonstrate that SsnB is responsible for inflammation ameliorative activity by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, SsnB could be a candidate for promoting novel clinical substances to remedy pathologic inflammation.     

Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells

Arteriovenous malformation (AVM) is characterized by high-flow blood vessels connecting arteries and veins without capillaries. This disease shows increased angiogenesis and a pathophysiological hypoxic environment in proximal tissues. Here, we analyzed the effects of hypoxia on angiogenesis in the endothelial cells (ECs) of AVM and normal tissues. ECs from human normal and AVM tissues were evaluated using immunocytochemistry with CD31. In vitro tube formation under hypoxia was tested in both ECs using Matrigel. The relative expression of angiogenesis-related genes was measured using real-time PCR. Under normoxia, CD31 was significantly higher in AVM ECs (79.23 ± 0.65%) than in normal ECs (74.15 ± 0.70%). Similar results were observed under hypoxia in AVM ECs (63.85 ± 1.84%) and normal ECs (60.52 ± 0.51%). In the tube formation test under normoxic and hypoxic conditions, the junction count and total vessel length were significantly greater in AVM ECs than normal ECs. Under both normoxia and hypoxia, the angiogenesis-related gene FSTL1 showed a significantly higher expression in AVM ECs than in normal ECs. Under hypoxia, CSPG4 expression was significantly lower in AVM ECs than in normal ECs. Accordingly, the angiogenic effect was increased in AVM ECs compared with that in normal ECs. These results provide a basic knowledge for an AVM treatment strategy.     

Factors affecting production of extracellular carbohydrate complexes by Escherichia coli O157:H7

Production of extracellular carbohydrate complexes (ECC) by foodborne pathogens on raw fruits and vegetables may result in protection against removal or inactivation by sanitizers. The influence of environmental conditions on cell growth, the total amount of ECC produced, and the amount of ECC produced on a per cell basis by Escherichia coli O157:H7 strains ATCC 43895 (wild type) and 43895-exopolysaccharides (EPS) (natural mutant, extensive EPS producer) was studied. To determine the effects of pH on the production of ECC on a per cell basis, E. coli O157:H7 was grown aerobically at 12 and 22 degrees C on tryptic soy agar (TSA) acidified to pH 7.0, 6.5, 6.0, 5.5, 5.0, 4.5, and 4.0. Lettuce, alfalfa sprout, cantaloupe, tomato, and apple juice agars (pH 4.46-6.50) were also evaluated for their support of the ECC production. Conditions generally favorable for growth of E. coli O157:H7 were a rich nutrient medium (TSA) vs. heated lettuce juice agar (HLJA) or minimal salts medium (MSM), 22 degrees C compared to 12 degrees C, and an aerobic atmosphere compared to modified atmosphere (1% O(2), 10% CO(2), and 89% N(2)). Conditions favorable for production of ECC on a per cell basis were HLJA, 12 degrees C, and an aerobic atmosphere. This suggests that modified atmosphere packaging of lettuce may not only decrease the growth of E. coli O157:H7 but also its propensity to form biofilm. There was a negative relationship between cell growth and production of ECC on a per cell basis, and environmental conditions that affected the total amount of ECC produced based on initial population reflected a combination of environmental conditions influencing both cell growth and ECC production on a per cell basis. A relative growth index factor (RGIF) was calculated to better understand ECC production as affected by various environmental conditions simultaneously. The production of ECC on a per cell basis by strain 43895-EPS showed a negative linear relationship with pH of TSA at both 12 and 22 degrees C. This strain generally produced a greater amount of ECC on fresh juice agar than on TSA at the same pH, but production of ECC on alfalfa sprout juice agar (FJA, pH 6.45) at 22 degrees C was significantly less than on TSA (pH 6.50). This indicates that nutrient limitation is not based only on nutrient availability. There may be other factors that repress the production of ECC on FJA, and the effects of those factors may be temperature dependent. Further studies will be required to better understand the relationship between nutrient availability and other factors on the production of ECC by E. coli O157:H7 on raw produce.     

Single-Step Fast Tissue Clearing of Thick Mouse Brain Tissue for Multi-Dimensional High-Resolution Imaging

Recent advances in optical clearing techniques have dramatically improved deep tissue imaging by reducing the obscuring effects of light scattering and absorption. However, these optical clearing methods require specialized equipment or a lengthy undertaking with complex protocols that can lead to sample volume changes and distortion. In addition, the imaging of cleared tissues has limitations, such as fluorescence bleaching, harmful and foul-smelling solutions, and the difficulty of handling samples in high-viscosity refractive index (RI) matching solutions. To address the various limitations of thick tissue imaging, we developed an Aqueous high refractive Index matching and tissue Clearing solution for Imaging (termed AICI) with a one-step tissue clearing protocol that was easily made at a reasonable price in our own laboratory without any equipment. AICI can rapidly clear a 1 mm thick brain slice within 90 min with simultaneous RI matching, low viscosity, and a high refractive index (RI = 1.466), allowing the imaging of the sample without additional processing. We compared AICI with commercially available RI matching solutions, including optical clear agents (OCAs), for tissue clearing. The viscosity of AICI is closer to that of water compared with other RI matching solutions, and there was a less than 2.3% expansion in the tissue linear morphology during 24 h exposure to AICI. Moreover, AICI remained fluid over 30 days of air exposure, and the EGFP fluorescence signal was only reduced to ~65% after 10 days. AICI showed a limited clearing of brain tissue >3 mm thick. However, fine neuronal structures, such as dendritic spines and axonal boutons, could still be imaged in thick brain slices treated with AICI. Therefore, AICI is useful not only for the three-dimensional (3D) high-resolution identification of neuronal structures, but also for the examination of multiple structural imaging by neuronal distribution, projection, and gene expression in deep brain tissue. AICI is applicable beyond the imaging of fluorescent antibodies and dyes, and can clear a variety of tissue types, making it broadly useful to researchers for optical imaging applications.     

Novel preparation and high electrical performance effect of Mn-doped ultra-high surface area activated carbon (USAC) as an additive for Ni hybrid capacitors

This paper reports the synthesis of various molar concentrations of manganese (Mn)-doped Ultra-High Surface area Activated Carbon (USAC) additives and their efficient use as cathode materials for supercapacitors. We synthesized the nanoparticles via a novel and facile dip-coating process and characterized them in detail by various analytical techniques. The SEM, EDAX, and XPS results showed that the Mn ions were successfully substituted on the USAC additives’ layered structure without any structural changes. The long cyclic stability of the as-prepared Mn-doped USAC additives was tested as a cathode material for supercapacitors at different current densities. The detailed experimental results showed that the Mn dopant content crucially determines the electrochemical performances of the USAC additives. Electrochemical measurements showed that the MnCEP-S600HTT with 0.10 mol% molar concentration of Mn dopant gives the best cycling performances. It delivers a discharge capacity of 262.9 mAh g^?1 after 100 cycles. Further increasing the current density to 1000 mA g^?1 allowed it to still maintain 253.6 mAh g^?1 after 200 cycles. We confirmed that the structure of Mn-doped USAC additives is an important pole to improve the structural stability and electrochemical properties.