Failure rate calculation method for high power devices in space applications at low earth orbit

This paper discusses the universal calculation method for space proton induced failure rate on high power device. High energetic particles can be the reason of power device failure in both terrestrial and space. T-CAD simulation result gives a threshold charge value for the device destruction which is triggered by energetic proton from space. The amount of threshold charge depends on applied voltage for high power device. The probability of charge generation in silicon due to proton penetration is considered as well. This probability function variation depends on the thickness of device and incident energy of proton which studied before at there. Last consideration on this paper is 3.3 kV PiN diode\u27s Single Event Upset Cross section and failure rate which was calculated by proposed method in Low earth orbit environment condition

Impact on the scape of Farfugium japonicum var. japonicum (Asteraceae) under strong wind conditions based on morphological and mechanical analyses

Adaptation of Farfugium japonicum (L.) Kitam. var. japonicum (Asteraceae) to the strong wind environment of coastal areas has been shown to reduce lamina size and shorten petioles; however, their effects on other traits of this species remain unknown. Our morphological analyses showed that shortening of the scape of this species is correlated with shortening of the petiole in coastal areas. The results suggested that when the height of the scapes became higher than that of the petioles, the wind stress on the scapes became stronger and their growth was suppressed. Therefore, the populations in coastal areas with strong winds had significantly shorter scapes than inland populations, and the height of petioles and scapes in the coastal populations were correlated. Further mechanical analysis by three-point bending tests revealed that the scapes had higher strength than the petioles. This species is evergreen and can produce new leaves regardless of the season, even if it loses its leaves by strong winds; however, because scapes only develop above ground for a limited period of the year, the loss of the scapes by strong winds has a significant impact on reproduction in that year. Therefore, even though the scapes were stronger than the petiole, shortening the scapes plays an important role in reducing strong wind stress in coastal areas

Functional importance of Crenarchaea-specific extra-loop revealed by an X-ray structure of a heterotetrameric crenarchaeal splicing endonuclease

Archaeal splicing endonucleases (EndAs) are currently classified into three groups. Two groups require a single subunit protein to form a homodimer or homotetramer. The third group requires two nonidentical protein components for the activity. To elucidate the molecular architecture of the two-subunit EndA system, we studied a crenarchaeal splicing endonuclease from Pyrobaculum aerophilum. In the present study, we solved a crystal structure of the enzyme at 1.7-Å resolution. The enzyme adopts a heterotetrameric form composed of two catalytic and two structural subunits. By connecting the structural and the catalytic subunits of the heterotetrameric EndA, we could convert the enzyme to a homodimer that maintains the broad substrate specificity that is one of the characteristics of heterotetrameric EndA. Meanwhile, a deletion of six amino acids in a Crenarchaea-specific loop abolished the endonuclease activity even on a substrate with canonical BHB motif. These results indicate that the subunit architecture is not a major factor responsible for the difference of substrate specificity between single- and two-subunit EndA systems. Rather, the structural basis for the broad substrate specificity is built into the crenarchaeal splicing endonuclease itself

A simple model for magnetism in itinerant electron systems

A new lattice model of interacting electrons is presented. It can be viewed as a classical Hubbard model in which the energy associated to electron itinerance is proportional to the total number of possible electron jumps. Symmetry properties of the Hubbard model are preserved. In the half-filled band with strong interaction the model becomes the Ising model. The main features of the magnetic behavior of the model in the one-dimensional and mean-field cases are studied.Comment: 9 pages, 3 figures, to be published in Physica

Effect of Zero Modes on the Bound-State Spectrum in Light-Cone Quantisation

We study the role of bosonic zero modes in light-cone quantisation on the invariant mass spectrum for the simplified setting of two-dimensional SU(2) Yang-Mills theory coupled to massive scalar adjoint matter. Specifically, we use discretised light-cone quantisation where the momentum modes become discrete. Two types of zero momentum mode appear -- constrained and dynamical zero modes. In fact only the latter type of modes turn out to mix with the Fock vacuum. Omission of the constrained modes leads to the dynamical zero modes being controlled by an infinite square-well potential. We find that taking into account the wavefunctions for these modes in the computation of the full bound state spectrum of the two dimensional theory leads to 21% shifts in the masses of the lowest lying states.Comment: LaTeX with 5 postscript file

Superior Silencing by 2′,4′-BNA NC

The duplex stability with target mRNA and the gene silencing potential of a novel bridged nucleic acid analogue are described. The analogue, 2′,4′-BNANC antisense oligonucleotides (AONs) ranging from 10- to 20-nt-long, targeted apolipoprotein B. 2′,4′-BNANC was directly compared to its conventional bridged (or locked) nucleic acid (2′,4′-BNA/LNA)-based counterparts. Melting temperatures of duplexes formed between 2′,4′-BNANC-based antisense oligonucleotides and the target mRNA surpassed those of 2′,4′-BNA/LNA-based counterparts at all lengths. An in vitro transfection study revealed that when compared to the identical length 2′,4′-BNA/LNA-based counterpart, the corresponding 2′,4′-BNANC-based antisense oligonucleotide showed significantly stronger inhibitory activity. This inhibitory activity was more pronounced in shorter (13-, 14-, and 16-mer) oligonucleotides. On the other hand, the 2′,4′-BNANC-based 20-mer AON exhibited the highest affinity but the worst IC50 value, indicating that very high affinity may undermine antisense potency. These results suggest that the potency of AONs requires a balance between reward term and penalty term. Balance of these two parameters would depend on affinity, length, and the specific chemistry of the AON, and fine-tuning of this balance could lead to improved potency. We demonstrate that 2′,4′-BNANC may be a better alternative to conventional 2′,4′-BNA/LNA, even for “short” antisense oligonucleotides, which are attractive in terms of drug-likeness and cost-effective bulk production

Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin : ODYSSEY NIPPON study design and rationale

Background: Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). Methods: The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. Discussion: The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone)

Selective cytotoxicity of dihydroorotate dehydrogenase inhibitors to human cancer cells under hypoxia and nutrient-deprived conditions

Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine de novo biosynthesis pathway. It is located on the mitochondrial inner membrane and contributes to the respiratory chain by shuttling electrons to the ubiquinone pool. We have discovered ascofuranone (1), a natural compound produced by Acremonium sclerotigenum, and its derivatives are a potent class of HsDHODH inhibitors. We conducted a structure–activity relationship study and have identified functional groups of 1 that are essential for the inhibition of HsDHODH enzymatic activity. Furthermore, the binding mode of 1 and its derivatives to HsDHODH was demonstrated by co-crystallographic analysis and we show that these inhibitors bind at the ubiquinone binding site. In addition, the cytotoxicities of 1 and its potent derivatives 7, 8, and 9were studied using human cultured cancer cells. Interestingly, they showed selective and strong cytotoxicity to cancer cells cultured under microenvironment (hypoxia and nutrient-deprived) conditions. The selectivity ratio of 8 under this microenvironment show the most potent inhibition which was over 1000-fold higher compared to that under normal culture condition. Our studies suggest that under microenvironment conditions, cancer cells heavily depend on the pyrimidine de novo biosynthesis pathway. We also provide the first evidence that 1 and its derivatives are potential lead candidates for drug development which target the HsDHODH of cancer cells living under a tumor microenvironment