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Source/drain series resistances (Rsd) of n- and p-type double-gate fin field-effect transistors (FinFETs) were successfully extracted using the methods applicable to short channel devices. Rsd is decomposed into spreading, sheet, and contact resistances considering top and sidewall contact resistances separately. Resistivity parameters defined in the analytic model were extracted from the extracted Rsd values of FinFETs with different fin widths and spacer lengths, and the proposed model showed good agreement to the experimental data. [ABSTRACT FROM AUTHOR]

The effects of carbon incorporation on the thermal stability of the interfacial TiO2 layer and the electrical characteristics of Ti/TiO2/ n-Ge contacts were investigated. The improved thermal stability and contact characteristics of Ti/TiO2/ n-Ge contacts were characterized in terms of Schottky barrier height (SBH) and specific contact resistivity ( $\rho _{c}$ ) using the Schottky diode and circular transmission line model (CTLM). The values of SBH and $\rho _{c}$ increased after the rapid thermal annealing (RTA) above 550 °C. The current density–bias voltage ( $J-V$ ) curves of the Schottky diode showed a change of contact characteristics from Ohmic-like behavior to rectifying. This thermal instability was mainly caused by the decomposition of the interfacial TiO2 layer after high-temperature annealing. The structural degradation was confirmed by transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) analyses. When carbon ions were incorporated into the interfacial TiO2 layer, the SBH and $\rho _{c}$ values showed relatively stable characteristics as the RTA temperature increased up to 600 °C. The EELS mapping showed that the diffusion of oxygen from the interfacial TiO2 layer was effectively suppressed thanks to the incorporation of carbon. Thus, the carbon incorporation can improve the thermal stability of the interfacial TiO2 layer and the metal–insulator–semiconductor contact characteristics for Ge-based device applications.

Abstract Background Host tp53 mutations are frequently found during the early stages of colitis-associated colorectal cancer (CAC), but whether such mutations induce gut microbiota dysbiosis and chronic intestinal inflammation that contributes to the development of CAC, remains unknown. Results We found that zebrafish tp53 mutant larvae exhibited elevated intestinal inflammation, by monitoring the NFκB activity in the mid-distal intestines of zebrafish larvae using an NFκB:EGFP transgenic reporter line in vivo as well as neutrophil infiltration into the intestine. This inflammation was due to dysbiotic gut microbiota with reduced diversity, revealed using both 16S rRNA amplicon sequencing and a germfree larva model. In this dysbiosis, Aeromonas spp. were aberrantly enriched as major pathobionts and exhibited the capacity for aggressive colonization in tp53 mutants. Importantly, the ex-germfree experiments supported the causality of the host tp53 mutation for inducing the inflammation. Transcriptome and high-performance liquid chromatography analyses of the host gastrointestinal tracts identified dysregulated sialic acid (SA) metabolism concomitant with increased host Neu5Gc levels as the key determinant of aberrant inflammation, which was reversed by the sialidase inhibitors oseltamivir and Philippin A. Conclusions These results demonstrate a crucial role for host tp53 in maintaining symbiosis and immune homeostasis via SA metabolism. Disturbed SA metabolism via a tp53 mutation may be exploited by specific elements of the gut microbiome, eliciting both dysbiosis and inflammation. Manipulating sialometabolism may therefore provide an efficacious therapeutic strategy for tp53 mutation-induced dysbiosis, inflammation, and ultimately, related cancers. Video Abstract

The quantitative characteristics of traps created in the bandgap-engineered tunneling oxide (BE-TOX) layer and block layer after program/erase (P/E) stress-cycling in a 3D NAND flash memory were investigated. The trap spectroscopy by charge injection and sensing technique was used to obtain the distribution of traps in these layers. In the BE-TOX layer, significant traps were generated around 1.3 eV in the nitrogen-doped layer (N1) and increased by 48% in the fresh cell after P/E stress-cycling. The H bonds in the N1 are more likely to break during the stress-cycling and create neutral $\equiv \mathrm {SiO}^{\bullet }$ traps. In the block layer, however, trap generation was negligible after stress-cycling.

Hong et al. describe a new transgene expression system, IQ-Switch, and its variants and characterize their applications in cell culture and zebrafish systems. They show that IQ-Switch system has several advantages over the previous inducible transgene expression switches, including the low toxicity, tunability of expression levels and low levels of gene silencing.

Hyperphosphorylated Tau accumulation promotes neurodegeneration in Alzheimer’s disease. Here, the authors screen a miRNA library in Drosophila and identify a conserved ubiquitin ligase that directs Tau for autophagic degradation, uncovering a potential target to treat Tau-mediated neurodegeneration.

Si-based electrolyte-gated transistors (EGTs) have been investigated to achieve high sensitivity and a low detection limit (LOD). Here, a lumped-capacitive model was applied to analyze the influence of receptor–target conjugates on the sensing performance. The voltage-related sensitivity is mainly determined by the effective dipole potential ( $V_{DP,EFF}$ ), the effective capacitance of the functionalization layer ( $C_{FN,EFF}$ ), and the total charge density in the channel ( $Q_{S}$ ) related to the operating regime. In an n-type EGT, the sensitivity is enhanced as the device is operated in the subthreshold regime with a positive $V_{DP,EFF}$ and a small $C_{FN,EFF}$ . The influence of the $V_{DP,EFF}$ and $C_{FN,EFF}$ was experimentally evaluated by detecting the peanut allergen (PA) using the fabricated n-type Si-EGTs. A higher sensitivity and a lower LOD could be achieved in the subthreshold regimes than in the linear regime. These results suggest that the proposed model is very useful to optimize the sensing characteristics of Si-based EGT for biosensing applications.

An Asiatic lily cultivar 'Daphne' was developed in 2009 at National Institute of Horticultural and Herbal Science (NIHHS), Rural Development Administration (RDA), in Korea. A cross was made in 2000 between Asiatic lily line 'NIHHSA95- 45(Avignon x Connecticut King)', a red colored cultivar, and 'Hyanggum', yellow colored cultivar. Preliminarily selection was done in 2004 and 'A04-67' was selected. Multiplication and bulb formation, and characteristic tests were conducted from 2005 to 2008. The evaluation of this line was performed and named as 'Wongyo C1-105' in 2009 that was registered as 'Daphne'. 'Daphne' flowers at the first of June and grows average 77.8 cm. It flowers upward-facing, pink and ivory (RHS, R61D+W115B) with the size of flower 9.6 cm. Mean petal length and width is 5.8 cm and 2.2 cm, respectively. Leaves are 9 cm long and 1.4 cm wide, respectively. The weight and size of bulb is 58.9 g and 17.2 cm, respectively. Year-round flowering can be obtained by storing the bulb under -1.5°C conditions. [ABSTRACT FROM AUTHOR]

The initiation of translation is a highly regulated process that contributes to specific gene expression programs. Here the authors find that, in vertebrate, threonyl-tRNA synthetase (TRS) can act as a scaffold for the initiation machinery to stimulate the translation of a specific set of mRNAs.

tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.

The highly sensitive detection of peanut allergens (PAs) using silicon-based electrolyte-gated transistors (Si-EGTs) was demonstrated. The Si-EGT was made using a top-down technique. The fabricated Si-EGT showed excellent intrinsic electrical characteristics, including a low threshold voltage of 0.7 V, low subthreshold swing of SV) showed a constant behavior from the subthreshold regime to the linear regime. The current-related sensitivity (SI) was high in the subthreshold regime and then significantly decreased as the drain current increased. The limit of detection (LOD) was calculated to be as low as 25 pg/mL based on SI characteristics, which is the lowest value reported to date in the literature for various sensor methodologies. The Si-EGT showed selective detection of PA through a non-specific control test. These results confirm that Si-EGT is a high-sensitivity and low-power biosensor for PA detection.

Effects of carbon implantation (C-imp) on the contact characteristics of Ti/Ge contact were investigated. The C-imp into Ti/Ge system was developed to reduce severe Fermi-level pinning (FLP) and to improve the thermal stability of Ti/Ge contact. The current density (J)-voltage (V) characteristics showed that the rectifying behavior of Ti/Ge contact into an Ohmic-like behavior with C-imp. The lowering of Schottky barrier height (SBH) indicated that the C-imp could mitigate FLP. In addition, it allows a lower specific contact resistivity (ρc) at the rapid thermal annealing (RTA) temperatures in a range of 450–600 °C. A secondary ion mass spectrometry (SIMS) showed that C-imp facilitates the dopant segregation at the interface. In addition, transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) mapping showed that after RTA at 600 °C, C-imp enhances the diffusion of Ge atoms into Ti layer at the interface of Ti/Ge. Thus, carbon implantation into Ge substrate can effectively reduce FLP and improve contact characteristics.

During chronic cold stress, thermogenic adipocytes generate heat through uncoupling of mitochondrial respiration from ATP synthesis. Recent discovery of various dietary phytochemicals, endogenous metabolites, synthetic compounds, and their molecular targets for stimulating thermogenesis has provided promising strategies to treat or prevent obesity and its associated metabolic diseases. Nuclear factor E2 p45-related factor 2 (Nrf2) is a stress response protein that plays an important role in obesity and metabolisms. However, both Nrf2 activation and Nrf2 inhibition can suppress obesity and metabolic diseases. Here, we summarized and discussed conflicting findings of Nrf2 activities accounting for part of the variance in thermogenesis and energy metabolism. We also discussed the utility of Nrf2-activating mechanisms for their potential applications in stimulating energy expenditure to prevent obesity and improve metabolic deficits.

We present the fabrication and electrical characteristics of nanonet-channel (NET) low-temperature polysilicon channel (LTPS) thin-film transistors (TFTs) using a nanosphere-assisted patterning (NAP) technique. The NAP technique is introduced to form a nanonet-channel instead of the electron beam lithography (EBL) or conventional photolithography method. The size and space of the holes in the nanonet structure are well controlled by oxygen plasma treatment and a metal lift-off process. The nanonet-channel TFTs show improved electrical characteristics in terms of the ION/IOFF, threshold voltage, and subthreshold swing compared with conventional planar devices. The nanonet-channel devices also show a high immunity to hot-carrier injection and a lower variation of electrical characteristics. The standard deviation of VTH (σVTH) is reduced by 33% for a nanonet-channel device with a gate length of 3 μm, which is mainly attributed to the reduction of the grain boundary traps and enhanced gate controllability. These results suggest that the cost-effective NAP technique is promising for manufacturing high-performance nanonet-channel LTPS TFTs with lower electrical variations.

DYRK1A is a major causative gene in Down syndrome (DS). Reduced incidence of solid tumors such as neuroblastoma in DS patients and increased vascular anomalies in DS fetuses suggest a potential role of DYRK1A in angiogenic processes, but in vivo evidence is still scarce. Here, we used zebrafish dyrk1aa mutant embryos to understand DYRK1A function in cerebral vasculature formation. Zebrafish dyrk1aa mutants exhibited cerebral hemorrhage and defects in angiogenesis of central arteries in the developing hindbrain. Such phenotypes were rescued by wild-type dyrk1aa mRNA, but not by a kinase-dead form, indicating the importance of DYRK1A kinase activity. Chemical screening using a bioactive small molecule library identified a calcium chelator, EGTA, as one of the hits that most robustly rescued the hemorrhage. Vascular defects of mutants were also rescued by independent modulation of calcium signaling by FK506. Furthermore, the transcriptomic analyses supported the alterations of calcium signaling networks in dyrk1aa mutants. Together, our results suggest that DYRK1A plays an essential role in angiogenesis and in maintenance of the developing cerebral vasculature via regulation of calcium signaling, which may have therapeutic potential for DYRK1A-related vascular diseases.

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including anti-adipogenic effects. Activity-guided separation led to the identification of the anti-adipogenic functions of butein. Butein, a novel anti-adipogenic compound, robustly suppressed lipid accumulation and inhibited expression of adipogenic markers. Molecular studies showed that activated transforming growth factor-β (TGF-β) and suppressed signal transducer and activator of transcription 3 (STAT3) signaling pathways were mediated by butein. Analysis of the temporal expression profiles suggests that TGF-β signaling precedes the STAT3 in the butein-mediated anti-adipogenic cascade. Small interfering RNA-mediated silencing of STAT3 or SMAD2/3 blunted the inhibitory effects of butein on adipogenesis indicating that an interaction between two signaling pathways is required for the action of butein. Upon butein treatments, stimulation of TGF-β signaling was still preserved in STAT3 silenced cells, whereas regulation of STAT3 signaling by butein was significantly impaired in SMAD2/3 silenced cells, further showing that TGF-β acts upstream of STAT3 in the butein-mediated anti-adipogenesis. Taken together, the present study shows that butein, a novel anti-adipogenic compound from RVS, inhibits adipocyte differentiation through the TGF-β pathway followed by STAT3 and peroxisome proliferator-activated receptor γ signaling, further implicating potential roles of butein in TGF-β- and STAT3-dysregulated diseases.

SUMMARY Neurofibromatosis type 1 (NF1) is a common, dominantly inherited genetic disorder that results from mutations in the neurofibromin 1 (NF1) gene. Affected individuals demonstrate abnormalities in neural-crest-derived tissues that include hyperpigmented skin lesions and benign peripheral nerve sheath tumors. NF1 patients also have a predisposition to malignancies including juvenile myelomonocytic leukemia (JMML), optic glioma, glioblastoma, schwannoma and malignant peripheral nerve sheath tumors (MPNSTs). In an effort to better define the molecular and cellular determinants of NF1 disease pathogenesis in vivo, we employed targeted mutagenesis strategies to generate zebrafish harboring stable germline mutations in nf1a and nf1b, orthologues of NF1. Animals homozygous for loss-of-function alleles of nf1a or nf1b alone are phenotypically normal and viable. Homozygous loss of both alleles in combination generates larval phenotypes that resemble aspects of the human disease and results in larval lethality between 7 and 10 days post fertilization. nf1-null larvae demonstrate significant central and peripheral nervous system defects. These include aberrant proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), dysmorphic myelin sheaths and hyperplasia of Schwann cells. Loss of nf1 contributes to tumorigenesis as demonstrated by an accelerated onset and increased penetrance of high-grade gliomas and MPNSTs in adult nf1a+/−; nf1b−/−; p53e7/e7 animals. nf1-null larvae also demonstrate significant motor and learning defects. Importantly, we identify and quantitatively analyze a novel melanophore phenotype in nf1-null larvae, providing the first animal model of the pathognomonic pigmentation lesions of NF1. Together, these findings support a role for nf1a and nf1b as potent tumor suppressor genes that also function in the development of both central and peripheral glial cells as well as melanophores in zebrafish.

Recently, the technologies of DNA sequence variation and gene expression profiling have been used widely as approaches in the expertise of genome biology and genetics. The application to genome study has been particularly developed with the introduction of the next-generation DNA sequencer (NGS) Roche/454 and Illumina/Solexa systems, along with bioinformation analysis technologies of whole-genome de novo assembly, expression profiling, DNA variation discovery, and genotyping. Both massive whole-genome shotgun paired-end sequencing and mate paired-end sequencing data are important steps for constructing de novo assembly of novel genome sequencing data. It is necessary to have DNA sequence information from a multiplatform NGS with at least 2× and 30× depth sequence of genome coverage using Roche/454 and Illumina/Solexa, respectively, for effective an way of de novo assembly. Massive short-length reading data from the Illumina/Solexa system is enough to discover DNA variation, resulting in reducing the cost of DNA sequencing. Whole-genome expression profile data are useful to approach genome system biology with quantification of expressed RNAs from a whole-genome transcriptome, depending on the tissue samples. The hybrid mRNA sequences from Rohce/454 and Illumina/Solexa are more powerful to find novel genes through de novo assembly in any whole-genome sequenced species. The 20× and 50× coverage of the estimated transcriptome sequences using Roche/454 and Illumina/Solexa, respectively, is effective to create novel expressed reference sequences. However, only an average 30× coverage of a transcriptome with short read sequences of Illumina/Solexa is enough to check expression quantification, compared to the reference expressed sequence tag sequence.

BackgroundValvular heart surgery (VHS) utilizing cardiopulmonary bypass (CPB) is inevitably associated with ischemic-reperfusion injury, which is known to depend on oxygen tension during reperfusion. The aim of this study was to evaluate the effect of arterial oxygen tension during reperfusion on myocardial recovery in patients undergoing VHS.MethodsFifty-six patients undergoing isolated VHS were randomly exposed to an oxygen fraction of 0.7 (hyperoxic group, n = 28) or 0.5 (normoxic group, n = 28) during reperfusion. All patients received an oxygen fraction of 0.7 during CPB. In the normoxic group, the oxygen fraction was lowered to 0.5 from the last warm cardioplegia administration to 1 minute after aortic unclamping, and was then raised back to 0.7. Hemodynamic data were measured after induction of anesthesia, weaning from CPB, and sternum closure. The frequency of cardiotonic medications used during and after weaning from CPB, and the short-term outcomes during the hospital stay were also assessed.ResultsThe frequency of vasopressin and milrinone use during weaning from CPB, but not norepinephrine, was significantly less in the normoxic group. The post-operative cardiac enzyme levels and short-term outcomes were not different between the groups.ConclusionsNormoxic reperfusion from the last cardioplegia administration to 1 minute after aortic unclamping in patients undergoing VHS resulted in significantly less frequent use of vasopressin and inotropics during weaning from CPB than hyperoxic reperfusion, although it did not affect the post-operative myocardial enzyme release or short-term prognosis.

MicroRNAs (miRNAs) are a class of non-coding RNAs approximately 21 nt in length which play important roles in regulating gene expression in plants. Although many miRNA studies have focused on a few model plants, miRNAs and their target genes remain largely unknown in hot pepper (Capsicum annuum), one of the most important crops cultivated worldwide. Here, we employed high-throughput sequencing technology to identify miRNAs in pepper extensively from 10 different libraries, including leaf, stem, root, flower, and six developmental stage fruits. Based on a bioinformatics pipeline, we successfully identified 29 and 35 families of conserved and novel miRNAs, respectively. Northern blot analysis was used to validate further the expression of representative miRNAs and to analyze their tissue-specific or developmental stage-specific expression patterns. Moreover, we computationally predicted miRNA targets, many of which were experimentally confirmed using 5' rapid amplification of cDNA ends analysis. One of the validated novel targets of miR-396 was a domain rearranged methyltransferase, the major de novo methylation enzyme, involved in RNA-directed DNA methylation in plants. This work provides the first reliable draft of the pepper miRNA transcriptome. It offers an expanded picture of pepper miRNAs in relation to other plants, providing a basis for understanding the functional roles of miRNAs in pepper.

With a combination of vector magneto-optical Kerr effect magnetometry and polarized neutron reflectometry, the detailed magnetization reversal mechanism of the exchange-biased Py(30-nm)/FeMn[tAFM = (0-30)-nm]/CoFe(30-nm) trilayers was studied. We found that Py/FeMn(15-nm) and FeMn( 15-nm)/CoFe bilayers show completely different magnetization reversal modes, whereas they become very similar to each other in the corresponding Py/FeMn/CoFe trilayers. This is convincing evidence that the 15-nm FeMn layer mediates the magnetization reversal behaviors of both Py and CoFe layers through interlayer exchange bias coupling. Furthermore, magnetization reversal of Py and CoFe layers are decoupled for tAFM = 30 nm, indicating that the exchange length the magnetization reversal between two adjacent ferromagnetic layers is correlated over is less than 30 nm. This is in reasonable agreement with the theoretically predicted domain-wall width such as 28 nm for the polycrystalline FeMn/Co bilayer and 50 nm for the perfect Fe50Mn50 crystal. [ABSTRACT FROM AUTHOR]