Admittance of Au/1,4-benzenedithiol/Au single-molecule junctions

Employing the admittance formula for double-barrier junctions [Fu and Dudley, Phys. Rev. Lett. 70, 65 (1993)], we have estimated an ac susceptance (imaginary part of admittance) of Au/1, 4-benzenedithiol/Au single-molecule junctions from their current-voltage characteristics. In the MHz regime, we find that the junction susceptance shows a very small ( ∼ 0.1 aF) capacitive component that can be entirely masked by a larger electrode capacitance. Direct ac signal transmission measurements up to 1 GHz reveal no molecular signals and confirm the smallness of the molecular capacitance in the MHz regime

Global understanding of deformation behavior in CoCrFeMnNi high entropy alloy under high-strain torsion deformation at a wide range of elevated temperatures

A number of recent studies have investigated deformation behavior of CoCrFeMnNi (Cantor) alloy at elevated temperatures by using plastic deformation to relatively small strains such as tensile testing. Therefore, little has been known about the deformation behavior of this typical FCC high-entropy alloy (HEA) in case that the material is subjected to ultra-high strains at various temperatures. In the present study, the equi-atomic CoCrFeMnNi HEA was successfully deformed over a wide range of strains (von Mises equivalent strains (ε) of 1∼5.5) by torsion at various temperatures ranging from 25 °C to 1100 °C. Deformation twinning was extensively activated at moderate to high strains (ε ≥ 1) and even found in the deformation at elevated temperatures as high as 600 °C where deformation twinning is not normally expected in Cantor alloy. The HEA showed outstanding deformability and the highest strains to fracture reached 4.0∼5.5 at low temperatures below 400 °C. The excellent deformability was attributed to the extensive twin activities including the formation of twin bundles and thin nanotwins as well as microbands formation. However, localized shear deformation that was promoted by the high straining at low temperatures could negatively affect the deformability. The heavy deformation led to a significant reduction of the grain sizes down to 50 nm∼150 nm. A sudden shortage of ductility occurred at intermediate temperatures, where small strains to fracture (1.2∼1.3) were realized at 600 °C∼700 °C. The embrittlement was accompanied by the formation of micro-voids at grain boundaries and intergranular fracture. The susceptibility to the embrittlement was caused by the precipitation of Cr-rich σ-phases at grain boundaries. Dynamic recrystallization (DRX) of the FCC matrix led to an accelerated softening at high temperatures above 600 °C. Nucleation and growth of DRX grains in Cantor alloy were not fundamentally different from those in conventional FCC alloys. This study gives an insight into the microstructure evolution and mechanical response in Cantor alloy under shear deformation over a wide range of strains and temperatures

Distribution of β2-adrenergic receptor mRNA expression along the hamster nephron segments

AbstractDistribution of β2-adrenergic receptor mRNA expression along the microdissected hamster nephron segments was examined by the reverse transcription-polymerase chain reaction (RT-PCR) technique. Conventional RT-PCR using a set of primers on separate exons could not be applied for the detection of β2-adrenergic receptor mRNA because of its intronless nature. We used the ‘rapid amplification of cDNA ends’ protocol [(1985) Proc. Natl. Acad. Sci. USA 85, 8998-9002] as a maneuver for RT-PCR of an intronless gene. Using this method, we successfully located hamster β2-adrenergic receptor mRNA only in glomeruli and early proximal convoluted tubule along the nephron segments tested

Distribution of Stable DnaA-Binding Sites on the Bacillus Subtilis Genome Detected using a Modified ChIP-chip Method

We developed a modified ChIP-chip method, designated ChAP-chip (Chromatin Affinity Precipitation coupled with tiling chip). The binding sites of Bacillus subtilis Spo0J determined using this technique were consistent with previous findings. A DNA replication initiator protein, DnaA, formed stable complexes at eight intergenic regions on the B. subtilis genome. Characterization of the binding sequences suggested that two factors—the local density of DnaA boxes and their affinities for DnaA—are critical for stable binding. We further showed that in addition to autoregulation, DnaA directly modulate the expression of sda in a positive, and ywlC and yydA in a negative manner. Examination of possible stable DnaA-binding sequences in other Bacillus species suggested that DnaA-dependent regulation of those genes is maintained in most bacteria examined, supporting their biological significance. In addition, a possible stable DnaA-binding site downstream of gcp is also suggested to be conserved. Furthermore, potential DnaA-binding sequences specific for each bacterium have been identified, generally in close proximity to oriC. These findings suggest that DnaA plays several additional roles, such as control of the level of effective initiator, ATP-DnaA, and/or stabilization of the domain structure of the genome around oriC for the proper initiation of chromosome replication

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice

Derivation of Human Differential Photoreceptor-like Cells from the Iris by Defined Combinations of CRX, RX and NEUROD

Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases

On the single-atom conductance of Ti

Using non-equilibrium Green's function method, we have theoretically investigated electron transmission through [0001]-, [112S0]-, and [1100]-oriented single-atom contacts (SACs) of Ti and found that all these SACs show transmission 2. 3-2. 4 at the Fermi level. The transmission sensitively varies with small perturbations of contact geometry but maintains its likeliest value at ∼2. Our results are compared with the experimental conductance histogram of Ti observed in our previous work (e-J. Surf. Sci. Nanotech. 12, 1 (2014))