Addition is a key fundamental function for many error-tolerant applications. Approximate addition is considered to be an efficient technique for trading off energy against performance and accuracy. ...This paper proposes a carry-maskable adder whose accuracy can be configured at runtime. The proposed scheme can dynamically select the length of the carry propagation to satisfy the quality requirements flexibly. Compared with a conventional ripple carry adder and a conventional carry look-ahead adder, the proposed 16-bit adder reduced the power consumption by 54.1% and 57.5%, respectively, and the critical path delay by 72.5% and 54.2%, respectively. In addition, results from an image processing application indicate that the quality of processed images can be controlled by the proposed adder. Good scalability of the proposed adder is demonstrated from the evaluation results using a 32-bit length.
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The initial attachment of influenza virus to cells is the binding of hemagglutinin (HA) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the ...sugar–protein interaction are promising as HA inhibitors to prevent the infection. We herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus HA. In order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptide library was performed with the HAs of the H1 and H3 strains, and two kinds of the HA-binding peptides were identified. The binding of the peptides to HAs was inhibited in the presence of sialic acid, and plaque assays indicated that the corresponding N-stearoyl peptide strongly inhibited infections by the A/Aichi/2/68 (H3N2) strain of the virus. Alanine scanning of the peptides indicated that arginine and proline were responsible for binding. The affinities of several mutant peptides with single-amino-acid substitutions against H3 HA were determined, and corresponding docking studies were performed. A Spearman analysis revealed a correlation between the affinity of the peptides and the docking study. These results provide a practicable method to design of peptide-based HA inhibitors that are promising as anti-influenza drugs.
Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue ...maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a “heat shock metabolite (HSM)” by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50 concentrations.
Glycosphingolipids are major components of the membrane raft, and several kinds of viruses and bacterial toxins are known to bind to glycosphingolipids in the membrane raft. Since the viral genes and ...pathogenic proteins that are taken into cells are directly delivered to their target organelles, caveolae/raft-mediated endocytosis represents a promising pathway for specific delivery. In the present study, we demonstrated the ability of an artificial pentadecapeptide, which binds to ganglioside GM3, to deliver protein into cells by caveolae/raft-mediated endocytosis. The cellular uptake of a biotinylated GM3-binding peptide (GM3BP)–avidin complex into HeLa cells was observed, and the cellular uptake of this complex was inhibited by an incubation with sialic acid or endocytic inhibitors such as methyl-ß-cyclodextrin, and also by an incubation at 4 °C. These results indicate that the GM3BP-avidin complex bind to GM3 in membrane raft, and are taken into cell through caveolae/raft-mediated endocytosis. The GM3BP-avidin complex was transported into cells and localized around the nucleus more slowly than a human immunodeficiency virus type 1 TAT peptide. Furthermore, the uptake of a green fluorescent protein (GFP) linked with GM3BP into HeLa cells was similar to that of the GM3BP–avidin complex, and the localization of the GM3BP-GFP fusion protein was markedly different with that of the TAT-GFP fusion protein. The uptake and trafficking of GM3BP were distinguished from conventional cell-penetrating peptides. GM3BP has potential as a novel peptide for the selective delivery of therapeutic proteins and materials into cells in addition to being a cell-penetrating peptide.
Izenamides A, B, and C (1–3), new linear depsipeptides, were isolated from a taxonomically distinct marine cyanobacterium. Izenamides A and B contain a statine moiety ...(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid and inhibited the activity of cathepsin D, an aspartic peptidase. Meanwhile, izenamides did not show growth-inhibitory activity against HeLa, HL60, or MCF-7 cells at up to 10 μM.
Most studies of afterslip distribution consider only elastic media. However, the effects of poroelastic rebound in the upper crust and viscoelastic relaxation in the asthenosphere are part of the ...observed post-seismic deformation. Therefore, these effects should be removed to give a more reliable and correct afterslip distribution. We developed a method for calculating an afterslip distribution in elastic, poroelastic and viscoelastic media, and we applied this method to the case of the 2007 southern Sumatra earthquake (M
w 8.5). To estimate the coseismic slip and time evolution of the afterslip distribution, we applied Akaike's Bayesian Information Criterion (ABIC) inversion method of coseismic displacement, and analysed 15 months of GPS post-seismic deformation data in 3-month observation periods. To calculate afterslip in each period, we considered not only viscoelastic responses to coseismic slip but also viscoelastic responses to afterslip in the preceding periods. We used viscoelastic model to compute post-seismic deformation models every 3 months during the 15 months after the earthquake. The viscosity value for the asthenosphere layer is a crucial unknown parameter. To overcome this problem, we used a grid search method to determine the best-viscosity value, and we found that the best viscosity for the Sumatra subduction zone was 2.5 × 1018 Pa·s. After removing the poroelastic and viscoelastic responses, we obtained maximum afterslip of 0.5 m during the 15-month investigation (the same as maximum afterslip estimated using the elastic medium only), but the poroelastic and viscoelastic responses brought the afterslip distribution to a shallower depth than the main coseismic rupture area. The results showed that the poroelastic and viscoelastic responses added significant corrections to the afterslip distribution. Compared with the traditional method, this method improved the determination of the afterslip distribution. We conclude that consideration of poroelastic and viscoelastic behaviours is essential for calculating the afterslip distribution. We propose that these parameters should be considered to obtain more reliable and correct afterslip distribution models following earthquakes.
Approximate computing is a promising paradigm to realize fast, small, and low power characteristics, which are essential for modern applications, such as Internet of Things (IoT) devices. This paper ...proposes the Carry-Predicting Adder (CPredA), an approximate adder that is scalable relative to accuracy and power consumption. The proposed CPredA improves the accuracy of a previously studied adder by performing carry prediction. Detailed simulations reveal that, compared to the existing approximate adder, accuracy is improved by approximately 50% with comparable energy efficiency. Two application-level evaluations demonstrate that the proposed approximate adder is sufficiently accurate for practical use.
Hoshinoamides A (1) and B (2), new acyclic lipopeptides, were isolated from the marine cyanobacterium Caldora penicillata. Their structures were elucidated by spectroscopic analyses and degradation ...reactions. Hoshinoamides A (1) and B (2) did not exhibit any cytotoxicity against HeLa cells at 10 μM, but inhibited the in vitro growth of the malarial parasite Plasmodium falciparum (IC50 = 0.52 and 1.0 μM, respectively).
The development of a simple detection method with high sensitivity is essential for the diagnosis and surveillance of infectious diseases. Previously, we constructed a sensitive biosensor for the ...detection of pathological human influenza viruses using a boron-doped diamond electrode terminated with a sialyloligosaccharide receptor-mimic peptide that could bind to hemagglutinins involved in viral infection. Circulation of influenza induced by the avian virus in humans has become a major public health concern, and methods for the detection of avian viruses are urgently needed. Here, peptide density and dendrimer generation terminated on the electrode altered the efficiency of viral binding to the electrode surface, thus significantly enhancing charge-transfer resistance measured by electrochemical impedance spectroscopy. The peptide-terminated electrodes exhibited an excellent detection limit of less than one plaque-forming unit of seasonal H1N1 and H3N2 viruses. Furthermore, the improved electrode was detectable for avian viruses isolated from H5N3, H7N1, and H9N2, showing the potential for the detection of all subtypes of influenza A virus, including new subtypes. The peptide-based electrochemical architecture provided a promising approach to biosensors for ultrasensitive detection of pathogenic microorganisms.
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