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Retinal prostheses use periodic repetition of electrical stimuli to form artificial vision. To enhance the reliability of evoked visual percepts, repeating stimuli need to evoke consistent spiking activity in individual retinal ganglion cells (RGCs). However, it is not well known whether outer retinal degeneration alters the consistency of RGC responses. Hence, here we systematically investigated the trial-to-trial variability in network-mediated responses as a function of the degeneration level. We patch-clamp recorded spikes in ON and OFF types of alpha RGCs from r d10 mice at four different postnatal days (P15, P19, P31, and P60), representing distinct stages of degeneration. To assess the consistency of responses, we analyzed variances in spike count and timing across repeats of the same stimulus delivered multiple times. We found the trial-to-trial variability of network-mediated responses increased considerably as the disease progressed. Compared to responses taken before degeneration onset, those of degenerate retinas showed up to ~70% higher variability (Fano Factor) in spike counts (p < 0.001) and ~95% lower correlation level in spike timing (p < 0.001). These results indicate consistency weakens significantly in electrically-evoked network-mediated responses and therefore raise concerns about the ability of microelectronic retinal implants to elicit consistent visual percepts at advanced stages of retinal degeneration.

All-inorganic perovskite nanocrystals (PeNCs), CsPbX 3 (X = Cl, Br, or I), have been considered as one of the prospective emissive materials for display applications, which showed superior photoluminescence quantum yield and high color purity with narrow spectral line width. Recently, high-performance green and red perovskite light-emitting diodes (PeLEDs) were introduced; however, the efficiency of blue PeLEDs still lagged owing to PeNCs' deep HOMO energy level (∼6.0 eV), which is in discord with the adjacent organic interlayer. In this work, we demonstrated an interfacial engineering strategy with conjugated polyelectrolytes, functionalized PFN (poly[(9,9-bis(3'-( N , N -dimethylamino)propyl)-2,7-fluorene)- alt -2,7-(9,9-dioctylfluorene)]) with halide anions, between the hole injection layer and PeNCs. By introducing PFN-X (X = Cl, Br, or I), they exhibit well-balanced charge carriers and resultant effective radiative recombination in the PeNC layer with reduced hole injection barrier and electron blocking behavior. Among them, in particular, the PFN-Cl-treated PeLEDs display a maximum external quantum efficiency of 1.34% at 470 nm electroluminescence emission with enhanced spectral operating stability.

Many of the recessive virus-resistance genes in plants encode eukaryotic translation initiation factors (eIFs), including eIF4E, eIF4G, and related proteins. Notably, eIF4E and its isoform eIF(iso)4E are pivotal for viral infection and act as recessive resistance genes against various potyviruses in a wide range of plants. In this study, we used Clustered Regularly Interspaced Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated targeted mutagenesis to test whether novel sequence-specific mutations at eIF4E1 in Solanum lycopersicum (tomato) cv. Micro-Tom could confer enhanced resistance to potyviruses. This approach produced heritable homozygous mutations in the transgene-free E 1 generation. Sequence analysis of eIF4E1 from E 0 transgenic plants expressing Cas9 and eIF4E-sgRNA transcripts identified chimeric deletions ranging from 11 to 43 bp. Genotype analysis of the eIF4E1 -edited lines in E 0 , E 1 , and E 2 transgenic tomato plants showed that the mutations were transmitted to subsequent generations. When homozygous mutant lines were tested for resistance to potyviruses, they exhibited no resistance to tobacco etch virus (TEV). Notably, however, several mutant lines showed no accumulation of viral particles upon infection with pepper mottle virus (PepMoV). These results indicate that site-specific mutation of tomato eIF4E1 successfully conferred enhanced resistance to PepMoV. Thus, this study demonstrates the feasibility of the use of CRISPR/Cas9 approach to accelerate breeding for trait improvement in tomato plants., (Copyright © 2020 Yoon, Venkatesh, Lee, Kim, Lee, Kim and Kang.)

Pulvomycins B-D ( 1 - 3 ) were discovered from an estuarine Streptomyces strain along with the known pulvomycin ( 4 ). The 22-membered macrocyclic lactone structures of 1 - 3 were determined based on the interpretation of NMR, UV, and MS data, the modified Mosher's method, and Kishi's bidentate chiral solvent NMR spectroscopy. Genomic analysis of the bacterial strain revealed the biosynthetic gene cluster of pulvomycin and enabled us to propose the trans -acyltransferase polyketide biosynthetic pathway. Pulvomycin D displayed potent cytotoxic activity against various cancer cell lines.

Inorganic lead halide perovskite nanocrystals (PeNCs) have intensively drawn attention as efficient light-emitting materials for optoelectronic applications due to their fine optoelectronic properties with a high photoluminescence quantum yield and easily tunable saturated emission color. However, the poor stability of the red-emitting PeNCs has become an obstacle because of the uncontrollable iodine substitution from the PeNCs due to weak Pb-I bonding. In this work, we have demonstrated a ligand-mediated post-treatment (LMPT) method using a halide ion-pair ligand, tridodecylmethyl ammonium iodide (TrDAI), for the air stable and high-quality red-emitting PeNCs. Through the LMPT method, the optoelectronic properties of red-emitting PeNCs are dramatically improved resulting in a PLQY of 88.7% at 637 ± 2 nm emission with an increased carrier lifetime from 20.77 to 31.52 ns. We achieve highly efficient red perovskite light-emitting diodes exhibiting a maximum current efficiency of 7.69 cd A -1 and an external quantum efficiency of 6.36% at 637 ± 2 nm electroluminescence emission with a sharp full-width at half maximum of 31 nm.

Micromixers are critical components in the lab-on-a-chip or micro total analysis systems technology found in micro-electro-mechanical systems. In general, the mixing performance of the micromixers is determined by characterising the mixing time of a system, for example the time or number of circulations and vibrations guided by tracers (i.e., fluorescent dyes). Our previous study showed that the mixing performance could be detected solely from the electrical measurement. In this paper, we employ electromagnetic micromixers to investigate the correlation between electrical and mechanical behaviours in the mixer system. This work contemplates the "anti-reciprocity" concept by providing a theoretical insight into the measurement of the mixer system; the work explains the data interdependence between the electrical point impedance (voltage per unit current) and the mechanical velocity. This study puts the electromagnetic micromixer theory on a firm theoretical and empirical basis.

The development of new aminoglycoside (AG) antibiotics has been required to overcome the resistance mechanism of AG-modifying enzymes (AMEs) of AG-resistant pathogens. The AG acetyltransferase, AAC(6')-APH(2″), one of the most typical AMEs, exhibiting substrate promiscuity towards a variety of AGs and acyl-CoAs, was employed to enzymatically synthesize new 6'- N -acylated isepamicin (ISP) analogs, 6'- N -acetyl/-propionyl/-malonyl ISPs. They were all active against the ISP-resistant Gram-negative bacteria tested, and the 6'- N -acetyl ISP displayed reduced toxicity compared to ISP in vitro. This study demonstrated the importance of the modification of the 6'-amino group in circumventing AG-resistance and the potential of regioselective enzymatic modification of AG scaffolds for the development of more robust AG antibiotics.

Boron nitride nanotubes (BNNTs) have attracted significant interest because of the remarkable difference in their physical properties compared with carbon nanotubes and their far-reaching potential applications, including electrical insulators; thermally conducting, catalytic, and piezoelectric materials; and neutron absorbers. Despite their unique physical properties, the bundling and insolubility of BNNTs in water because of its substantial van der Waals attraction and hydrophobicity, respectively, give rise to many limitations in practical applications. Here, we present a new way to produce a highly stable BNNT dispersion by the noncovalent functionalization of the BNNT surface in water. The noncovalently functionalized BNNTs (p-BNNTs) have been found to be highly stable in water for a long time (>1 year) and easily water-redispersible by mild vortex mixing for a few minutes even after freeze-drying at -45 °C. The p-BNNTs were cylindrically encapsulated with polymerizable surfactants (BNNT diameter = ca. 3 nm and surfactant thickness = 0.8 nm).

Little is known about predictors of breast cancer literacy among immigrant women. A cross-sectional survey investigated predisposing, enabling, and need factors of breast cancer literacy among 233 Korean American women living in a southeastern U.S. city. Breast cancer literacy was measured by questions that asked awareness of cancer screening methods and a 5-item questionnaire derived from the American Cancer Society's breast cancer screening guidelines and risk factors. Annual checkup was an enabling factor of awareness of Clinical Breast Exam (CBE) and mammogram, and also for breast cancer literacy covering the knowledge of breast cancer screening guidelines and risk factors. Health status was a need factor of CBE awareness. Marital status was a predisposing factor of mammogram awareness, and age and years of residence in the US were predisposing factors of breast cancer literacy. The findings of the study illuminate probable avenues of intervention to promote breast health knowledge for Korean American women.

Indoor pollutants are important problems to public health. Among indoor pollutants, indoor dust contains extracellular vesicles (EVs), which are associated with pulmonary inflammation. However, it has not been reported whether indoor dust EVs affect the cancer lung metastasis. In this study, we isolated indoor dust EVs and investigated their roles in cancer lung metastasis. Upon intranasal administration, indoor dust EVs enhanced mouse melanoma lung metastasis in a dose-dependent manner in mice. Pre-treatment or co-treatment of indoor dust EVs significantly promoted melanoma lung metastasis, whereas post-treatment of the EVs did not. In addition, the lung lysates from indoor dust EV-treated mice significantly increased tumour cell migration in vitro . We observed that tumour necrosis factor-α played important roles in indoor dust EV-mediated promotion of tumour cell migration in vitro and cancer lung metastasis in vivo . Furthermore, Pseudomonas EVs, the main components of indoor dust EVs, and indoor dust EVs showed comparable effects in promoting tumour cell migration in vitro and cancer lung metastasis in vivo . Taken together, our results suggest that indoor dust EVs, at least partly contributed by Pseudomonas EVs, are potential promoting agents of cancer lung metastasis., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.)

Two-dimensional molybdenum disulfide (MoS 2 ) has emerged as a promising material for optoelectronic applications because of its superior electrical and optical properties. However, the difficulty in synthesizing large-scale MoS 2 films has been recognized as a bottleneck in uniform and reproducible device fabrication and performance. Here, we proposed a radio-frequency magnetron sputter system, and post-treatments of electron beam irradiation and sulfurization to obtain large-scale continuous and high-quality multilayer MoS 2 films. Large-area uniformity was confirmed by no deviation of electrical performance in fabricated MoS 2 thin-film transistors (TFTs) with an average on/off ratio of 10 3 and a transconductance of 0.67 nS. Especially, the photoresponsivity of our MoS 2 TFT reached 3.7 A W -1 , which is a dramatic improvement over that of a previously reported multilayer MoS 2 TFT (0.1 A W -1 ) because of the photogating effect induced by the formation of trap states in the band gap. Finally, we organized a 4 × 4 MoS 2 phototransistor array with high photosensitivity, linearity, and uniformity for light detection, which demonstrates the great potential of 2D MoS 2 for future-oriented optoelectronic devices.

To identify signal transducer and activator of transcription factor 3 (STAT3) inhibitors, we generated STAT3-dependent gene expression signature by analyzing gene expression profiles of DU145 cancer cells treated with STAT3 inhibitor, piperlongumine and 2-hydroxycinnamaldehyde. Then we explored gene expression signature-based strategies using a connectivity map database and identified several STAT3 inhibitors, including ethacrynic acid (EA). EA is currently used as a diuretic drug. EA inhibited STAT3 activation in DU145 prostate cancer cells and consequently decreased the levels of STAT3 target genes such as cyclin A and MCL-1. Furthermore, EA treatment inhibited tumor growth in mice xenografted with DU145 cells and decreased p-STAT3 expression in tumor tissues. Knockdown of Src homology region 2 domain-containing phosphatase-2 (SHP2) or Protein tyrosine phosphatase 1B (PTP1B) gene expression by siRNA suppressed the ability of EA to inhibit STAT3 activation. When EA was combined with an activator of SHP2 or PTP1B, p-STAT3 expression was synergistically decreased; when EA was combined with an inhibitor of SHP2 or PTP1B, p-STAT3 expression was rescued. By using an affinity pulldown assay with biotinyl-EA, EA was shown to associate with SHP2 and PTP1B in vitro. Additionally, the drug affinity responsive target stability (DARTS) assay confirmed the direct binding of EA to SHP2 and PTP1B. SHP2 is activated by EA through active phosphorylation at Y580 and direct binding to SHP2. Collectively, our results suggest that EA inhibits STAT3 activity through the modulation of phosphatases such as SHP2 and PTP1B and may be a potential anticancer drug to target STAT3 in cancer progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tripartilactam ( 1 ) is a natural macrocyclic lactam originally reported to have a unique [18,8,4]-tricyclic framework. However, the validity of this structure has been contested since niizalactam C ( 2 ), bearing a [18,6,6]-tricyclic skeleton, was proposed as an alternative structure in 2015. In the present study, a comprehensive reinvestigation of NMR spectroscopic data and a 13 C- 13 C COSY NMR experiment identified direct 13 C- 13 C coupling, thus leading to the unequivocal revision of the structure of tripartilactam as niizalactam C ( 2 ). In addition, whole-genome sequencing analysis of the tripartilactam-producing bacterial strain and subsequent bioinformatics and mutagenesis analyses identified its biosynthetic pathway, which probably utilizes one of the type I polyketide synthase (PKS) modules iteratively during its biosynthesis and exhibits spontaneous [4+2] cycloaddition from the precursor compound, sceliphrolactam, in the post-PKS process.

Covering: up to 2019 There is significant demand for new aminoglycoside antibiotics due to the widespread emergence of multidrug-resistant Gram-negative bacteria and their high toxicity, but these are not easily accessible in nature because their biosynthetic gene clusters are less commonly found in actinomycetes than are other natural products. Mining minor aminoglycoside components whose pharmacological activity has not yet been assessed could be an alternative approach for the development of next-generation antibiotics for use in the post-antibiotic era. Here, we review the biosynthetic steps responsible for the structural diversity of aminoglycosides and highlight current developments regarding the use of natural minor and semi-synthetic aminoglycosides as promising therapeutic leads or candidates.

The cultivation of a Streptomyces sp. SD53 strain isolated from the gut of the silkworm Bombyx mori produced two macrolactam natural products, piceamycin ( 1 ) and bombyxamycin C ( 2 ). The planar structures of 1 and 2 were identified by a combination of NMR, MS, and UV spectroscopic analyses. The absolute configurations were assigned based on chemical and chromatographic methods as well as ECD calculations. A new chromatography-based experimental method for determining the configurations of stereogenic centers β to nitrogen atoms in macrolactams was established and successfully applied in this report. These compounds exhibited significant bioactivities against the silkworm entomopathogen Bacillus thuringiensis and various human pathogens as well as human cancer cell lines. In particular, piceamycin potently inhibited Salmonella enterica and Proteus hauseri with MIC values of 0.083 μg/mL and 0.025 μg/mL, respectively. The biosynthetic pathway involved in the formation of the cyclopentenone moiety in piceamycin is discussed.

The complete chloroplast (cp) genome sequence of Climacium dendroides , determined using Illumina sequencing data, is presented herein. The DNA sequence of C. dendroides is 124,957 bp in length and has an overall CG content of 29.0%, including 82 protein-coding genes, 36 transfer RNA genes, and 8 ribosomal RNA genes. Phylogenetic trees were constructed based on the cp genome sequences of 10 bryophytes downloaded from GenBank and one acquired from this study., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The complete mitochondrial genome of Climacium dendroides (GenBank accession number MN942036 was 104,860 base pairs in length, containing 40 protein-coding genes, 3 ribosomal RNA (rRNA), and 24 transfer RNA (tRNA). The base composition was 29.6% A, 29.4% T, 21.0% G, and 19.8% C and its G + C content was 41.0%. The mitochondrial structure and gene order was similar to other Bryophytes. Phylogenetic tree based on the combined analysis of 33 protein-coding genes was well congruent with traditional species relationship of the moss order Hypnales., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Korean-American women experience a higher incidence of cervical cancer than non-Hispanic White women as well as other Asian-American women. A prominent cause of such a disproportional health risk among Korean-American women is a lack of awareness and knowledge of cervical cancer screening. Identifying factors related to cervical cancer screening awareness and literacy is critical for increasing cervical cancer screening among this population., Methods: Researchers surveyed 230 Korean-American women in a metro area in a Southeastern state, USA. Based on Anderson's Behavioral Model of Health Services Use, predisposing, enabling, and need factors were explored to predict cervical cancer screening awareness and literacy., Results: Monthly income, education, English proficiency, and annual checkups had significantly positive associations with cervical cancer screening awareness. Having an acquaintance giving support and receiving an annual checkup had significantly positive relationships with cervical cancer screening literacy., Discussion: This study recommends culture specific guidelines to promote annual checkups through primary care physicians and the transfer of information about cervical cancer screening through acquaintances giving support.

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

Aim: To evaluate the feasibility of conducting studies of saliva circulating tumor DNA (ctDNA) as a biomarker of metastasis or recurrence in our orthotopic head and neck cancer (HNC) mouse model., Materials and Methods: A mouse model of recurrence or metastasis after tongue cancer resection was developed. Blood and saliva were collected at baseline and at the establishment of recurrence or metastasis. Real-time polymerase chain reaction was performed to quantify human long interspersed element (hLINE) in samples to assess the amount of ctDNA., Results: In our model, salivary hLINE increased as the cancer developed and decreased after surgery. Plasma hLINE was significantly elevated in mice with metastasis. The presence of tongue cancer recurrence in mice was more correlated with hLINE concentration in saliva than in plasma., Conclusion: In our orthotopic model, salivary ctDNA better reflected tumor development and recurrence than did plasma ctDNA., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Methylated flavonoids possess improved bioactivities compared to their unmethylated counterparts. In this study, for the efficient production of O-methylated flavonoids from simple methylated phenylpropanoic acids, a recombinant Escherichia coli strain expressing 4-coumarate:coenzyme A ligase (4CL) from Oryza sativa and chalcone synthase (CHS) from Hordeum vulgare was constructed; this strain produced significant amount of homoeriodictyol (~ 52 mg/L) as well as a few amount of hesperetin (0.4 mg/L), respectively, from ferulic acid and 4-methylcaffeic acid. This demonstrates, for the first time, that the scarce but valuable methylated flavanones can be successfully produced from methylated phenylpropanoic acids in a microbial host via an artificial biosynthetic pathway consisting of 4CL and CHS that can accept O-methylated precursors.

ARPC2 is a subunit of the Arp2/3 complex, which is essential for lamellipodia, invadopodia and filopodia, and ARPC2 has been identified as a migrastatic target molecule. To identify ARPC2 inhibitors, we generated an ARPC2 knockout DLD-1 human colon cancer cell line using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system and explored gene signature-based strategies, such as a connectivity map (CMap) using the gene expression profiling data of ARPC2 knockout and knockdown cells. From the CMap-based drug discovery strategy, we identified pimozide (a clinically used antipsychotic drug) as a migrastatic drug and ARPC2 inhibitor. Pimozide inhibited the migration and invasion of various cancer cells. Through drug affinity responsive target stability (DARTS) analysis and cellular thermal shift assay (CETSA), it was confirmed that pimozide directly binds to ARPC2. Pimozide increased the lag phase of Arp2/3 complex-dependent actin polymerization and inhibited the vinculin-mediated recruitment of ARPC2 to focal adhesions in cancer cells. To validate the likely binding of pimozide to ARPC2, mutant cells, including ARPC2 F225A , ARPC2 F247A and ARPC2 Y250F cells, were prepared using ARPC2 knockout cells prepared by gene-editing technology. Pimozide strongly inhibited the migration of mutant cells because the mutated ARPC2 likely has a larger binding pocket than the wild-type ARPC2. Therefore, pimozide is a potential ARPC2 inhibitor, and ARPC2 is a new molecular target. Taken together, the results of the present study provide new insights into the molecular mechanism and target that are responsible for the antitumor and antimetastatic activity of pimozide., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The past few years have witnessed rapid advances in the synthesis of high-quality perovskite nanocrystals (PNCs). However, despite the impressive developments, the stability of PNCs remains a substantial challenge. The ability to reliably improve stability of PNCs while retaining their individual nanometer size represents a critical step that underpins future advances in optoelectronic applications. Here, we report an unconventional strategy for crafting dual-shelled PNCs (i.e., polymer-ligated perovskite/SiO 2 core/shell NCs) with exquisite control over dimensions, surface chemistry, and stabilities. In stark contrast to conventional methods, our strategy relies on capitalizing on judiciously designed star-like copolymers as nanoreactors to render the growth of core/shell NCs with controlled yet tunable perovskite core diameter, SiO 2 shell thickness, and surface chemistry. Consequently, the resulting polymer-tethered perovskite/SiO 2 core/shell NCs display concurrently a stellar set of substantially improved stabilities (i.e., colloidal stability, chemical composition stability, photostability, water stability), while having appealing solution processability, which are unattainable by conventional methods., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

In this paper, a germanium-based gate-metal-core vertical nanowire tunnel field effect transistor (VNWTFET) has been designed and optimized using the technology computer-aided design (TCAD) simulation. In the proposed structure, by locating the gate-metal as a core of the nanowire, a more extensive band-to-band tunneling (BTBT) area can be achieved compared with the conventional core-shell VNWTFETs. The channel thickness ( T ch ), the gate-metal height ( H g ), and the channel height ( H ch ) were considered as the design parameters for the optimization of device performances. The designed gate-metal-core VNWTFET exhibits outstanding performance, with an on-state current ( I on ) of 80.9 μA/μm, off-state current ( I off ) of 1.09 × 10 -12 A/μm, threshold voltage ( V t ) of 0.21 V, and subthreshold swing (SS) of 42.8 mV/dec. Therefore, the proposed device was demonstrated to be a promising logic device for low-power applications., Competing Interests: The authors declare no conflict of interest.

The cyclic depsipeptides ohmyungsamycin (OMS) A ( 1 ) and B ( 2 ), isolated from the marine-derived Streptomyces sp. SNJ042, contain two non-proteinogenic amino acid residues, β -hydroxy-l-phenylalanine ( β -hydroxy-l-Phe) and 4-methoxy-l-tryptophan (4-methoxy-l-Trp). Draft genome sequencing of Streptomyces sp. SNJ042 revealed the OMS biosynthetic gene cluster consisting of a nonribosomal peptide synthetase (NRPS) gene and three genes for amino acid modification. By gene inactivation and analysis of the accumulated products, we found that OhmL, encoding a P450 gene, is an l-Phe β -hydroxylase. Furthermore, OhmK, encoding a Trp 2,3-dioxygenase homolog, and OhmJ, encoding an O -methyltransferase, are suggested to be involved in hydroxylation and O -methylation reactions, respectively, in the biosynthesis of 4-methoxy-l-Trp. In addition, the antiproliferative and antituberculosis activities of the OMS derivatives dehydroxy-OMS A ( 4 ) and demethoxy-OMS A ( 6 ) obtained from the mutant strains were evaluated in vitro. Interestingly, dehydroxy-OMS A ( 4 ) displayed significantly improved antituberculosis activity and decreased cytotoxicity compared to wild-type OMS A.

This paper report a junctionless fin-type field-effect-transistor based capacitorless dynamic random access memory using three-dimensional technology computer-aided design simulations. The proposed 1T-DRAM is made up of a silicon germanium storage region surrounding a silicon fin. When the two materials form a heterojunction, a potential well is formed by the band discontinuity which carriers can be stored. During the program operation, band-to-band tunneling and gate-induced drain leakage occur simultaneously due to the gate and drain bias. Because of these phenomena, the electron-hole pair occurs, and generated holes are stored in the storage region by potential well. The holes formed are positively charged within the storage region, which mitigates the depletion of the channel and improves the operating current. The proposed device realizes the memory operation by the difference of the operating current depending on the presence or absence of the stored holes. In this work, the device is analyzed and optimized in detail. The proposed 1T-DRAM shows excellent performance with a retention time of 161 ms based on 50% of the maximum data margin.

We present a capacitorless one-transistor dynamic random-access memory (1T-DRAM) based on a Si/SiGe heterojunction double-gate MOSFET. In the proposed 1T-DRAM, the program process is based on band-to-band tunneling (BTBT) between gate 1 and gate 2 regions, and a sensing margin is defined by the amount of excess holes stored in the SiGe body region. Therefore, the sensing margin and retention time were affected by SiGe in the body region. The BTBT rate, enhanced by the small band-gap energy in SiGe, increased the sensing margin. The Si/SiGe heterojunction between the source/drain and body regions formed a potential barrier for hole carriers. The retention time was improved by suppressing the diffusion of hole carriers in the floating-body storage node. In addition, the retention characteristic was also enhanced by applying a gate underlap structure, which significantly reduced the electric field-induced recombination rate. The optimized device with a Si 0.7 Ge 0.3 body and underlap length (L underlap ) of 5 nm exhibited a high sensing margin of 6.16 µ A/ µ m and long retention time of 131 ms at a high temperature of 358 K.

In this work, an InGaAs/GaAsSb-based P -type gate-all-around (GAA) arch-shaped tunneling fieldeffect transistor (TFET) was designed and analyzed using technology computer-aided design (TCAD) simulations. The device performance was investigated in views of the on-state current ( I on ), subthreshold swing ( SS ), and I on / I off ratio. For high current drivability, InGaAs/GaAsSb heterojunction is used to form the broken bandgap. Owing to the GAA arch-shaped structure of the TFET, the tunneling region between source and channel extended, thus I on and SS are improved. However, it has some performance variations that are related with the height of the source region ( H source ), the epitaxially grown thickness of the channel ( t epi ), and the height of the drain region ( H drain ). Therefore, we performed a design optimization of the proposed device with the variables of H source , t epi , and H drain . The designed and optimized InGaAs/GaAsSb-based P -type GAA arch-shaped TFET demonstrated an I on of 215 μ A/ μ m SS of 18 mV/dec and I on / I off of 1.64 × 10 12 .

The effect of interface traps on InGaAs-based vertical gate-all-around (GAA) tunneling field-effect transistors (TFETs) has been investigated using technology computer-aided design (TCAD) simulation. The interface traps distributed within different energy levels ( E t ) in the energy bandgap of a semiconductor material exhibit various influences on the device performances. In this work, InGaAs-based TFETs are simulated to analyze the effects on the on-state current ( I on ), off-state current ( I off ), threshold voltage ( V th ), subthreshold swing ( SS ), and the ambipolar characteristics according to E t and type of the interface traps. We have confirmed that I off and SS are degraded by the interface traps. Further, it can be shown that I on is mainly affected by the acceptor-like traps and ambipolar behavior is affected by the donor-like traps. All the effects increase as E t becomes closer to the midgap. The effects of the interface traps with gate underlap and overlap at the source-channel region also have been investigated, considering the device fabrication. Additionally, the analysis of the effect of junction trap created at the source-channel junction has been performed.

This study investigated the antecedent factors affecting exercise preparation and performance habits and provides basic data for the development of health promotion interventions, based on what was found to be most effective in improving intention and habit. The participants were 114 university students who were willing to participate regularly in exercise and physical activities and interested in forming exercise habits. After coding, we analyzed the complete data set through frequency analysis, reliability, and latent growth model analysis. The provision of early rewards positively affected an initial exercise preparation habit. Both initial consistency and development of consistency also positively affected the development of exercise preparation, and initial behavioral complexity positively affected initial exercise preparation. However, no factors influenced an exercise performance habit. Thus, forming an exercise preparation habit requires fun, personal control, and repetitive behavior while forming an exercise performance habit is particularly challenging. These results may help construct a program for continuous exercise participation.

In this study, we have designed and analyzed the electron-hole bilayer (EHB) tunneling field-effect transistors (TFETs) based on various III-V compound semiconductor materials using two-dimensional (2-D) technology computer-aided design (TCAD) simulations. A recently proposed EHB TFET has lower subthreshold swing ( S ) and higher on-state current ( I on ) than the conventional planar TFET, using band-to-band tunneling (BTBT) across the source-to-channel junction. It uses a bias-induced BTBT across the EHB formed by an electric field between the two gates. The III-V compound semiconductors have been applied to the EHB TFETs to improve the switching performances and current drivability owing to their superior material properties such as high electron mobility and high tunneling probability. After the design and analysis of devices based on various compound semiconductors, in terms of primary DC characteristics, a lower bandgap material (InAs) has been inserted in the tunneling region of the In 0.53 Ga 0.47 As EHB TFET to enhance the tunneling rate. This paper proposes an EHB TFET that uses vertically stacked InGaAs/InAs/InGaAs layers. Moreover, the design optimization process has been performed via simulations. The simulation results of the proposed EHB TFET show remarkable performances with I on of 739.6 µ A/ µ m, S of 1.9 mV/dec, and threshold voltage ( V th ) of 7 mV at V DS 0.5 V.

In this study, the effect of an AlGaN back-barrier on the electrical characteristics of InAlGaN/GaN high electron mobility transistors (HEMTs) was investigated. The dependence of the thickness and the Al composition of the AlGaN back-barrier on the off-state current (I off ) of the devices was investigated. An InAlGaN/GaN HEMT with an Al 0.1 GaN back-barrier of thickness 20 nm exhibited lower I off because of the carrier confinement effect, which was caused by the back-barrier. The carrier confinement effect also improved the maximum output current density and the transconductance ( g m ). Thus, the obtained cut-off frequency ( f T ) and maximum oscillation frequency ( f max ) values for the InAlGaN/GaN HEMT with the 20 nm thick AlGaN back-barrier were 2.6% and 13% higher than those without the AlGaN back-barrier. In addition, the impact of the buffer trap density and GaN channel thickness were evaluated. In the case of a thickness of 20 nm for the Al 0.1 GaN back-barrier, a low I off was maintained although the trap density in the buffer layer was changed. In addition, as the gate length ( L G a) decreased to 50 nm, the InAlGaN/GaN HEMT with the 20 nm thick Al 0.1 GaN back-barrier achieved better I off characteristics, lower drain-induced barrier lowering (DIBL) of 85.8 mV/V, and subthreshold swing (S) of 269 mV/dec owing to a reduction in the short-channel effect.

Light absorption in semiconductors is a fundamental problem that has broad impact on a wide range of fields. However, it is intrinsically limited by the bandgap energy of the semiconductor. Herein, we study the enhancement of sub-bandgap light absorption in inorganic-organic hybrid perovskite semiconductor films via critical coupling. This is achieved at large incidence angles by balancing radiative and nonradiative decay rates in a planar multilayer structure. We found that a very small loss in the semiconductor layer can result in substantial light absorption. This simple but general method can be used to enhance the optical and optoelectronic responses of semiconductors below the bandgap energy.

Objective: Hepatocyte growth factor (HGF) and its receptor MET are expressed in the salivary glands during developmental stages and tumor formation; however, the function of HGF in injured salivary gland tissues remains unclear. The present study investigated the role of HGF in protecting the salivary glands against radiation-induced injury using an organotypic culture method., Materials and Methods: Acinar-like organoids were formed by means of a three-dimensional (3D) human parotid tissue-derived spheroids (hPTS) culture method. Radioprotective effects of HGF on irradiated hPTS and signaling pathways on radioprotection were investigated., Results: We detected MET expression in hPTS grown in a 3D culture. Treatment of irradiated hPTS with recombinant human HGF (rhHGF) restored salivary marker expression and secretory function of hPTS. Changes in the phosphorylation levels of apoptosis-related proteins through HGF-MET axis inhibited radiation-induced apoptosis. Treatment with PHA665752, a MET inhibitor, blocked MET-PI3K-AKT pathway, increased apoptosis, and suppressed the radioprotective effect of rhHGF against IR-induced damage of hPTS., Conclusions: These results suggest that HGF is a key effector of radioprotection and that HGF-MET-PI3K-AKT axis is involved in protecting the salivary glands from radiation-induced apoptosis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

A reduction in the strong immunosuppressive activity of FK506 ( 1 ) is essential for developing this compound as an antifungal agent. Seven new FK506 analogues modified at both the FK506-binding protein 12- and the calcineurin-binding regions were biosynthesized. 9-DeoxoFK520 ( 7 ) exhibited a >900-fold reduction in the in vitro immunosuppressive activity but maintained significant antifungal activity, indicating that the C-9 and C-21 positions are critical for separation of immunosuppressive and antifungal activities. 7 exhibited robust synergistic antifungal activity with fluconazole. FK506 ( 1 ) is a 23-membered macrolide produced by several Streptomyces species and is used as an immunosuppressive drug to prevent the rejection of transplanted organs. FK506 has also exhibited antifungal, neuroprotective, and neuroregenerative activities. In humans, FK506 binds to FK506-binding protein (FKBP) 12, and the resulting FKBP12-FK506 complex interacts with a Ca 2+ -calmodulin-dependent phosphatase, calcineurin (CaN). Inactivation of CaN by forming the FKBP12-FK506-CaN ternary complex prevents the activation of nuclear factor of activated T cells (NF-AT), inhibiting the production of interleukin-2 and subsequent T-cell proliferation. This CaN signaling pathway also plays a critical role in the growth and pathogenesis of major fungal pathogens such as Cryptococcus neoformans , Candida albicans , and Aspergillus fumigatus . Therefore, the synthesis of FK506 analogues that can discriminate human FKBP12/CaN from its fungal counterparts may separate antifungal activity from the immunosuppressive activity, thereby allowing the development of a novel antifungal agent.

The sources of primary and secondary aerosols in the Arctic are still poorly known. A number of surface seawater samples-with varying degrees of Arctic riverine and sea ice influences-were used in a sea spray generation chamber to test them for their potential to produce sea spray aerosols (SSA) and cloud condensation nuclei (CCN). Our interdisciplinary data showed that both sea salt and organic matter (OM) significantly influenced the SSA production. The number concentration of SSA in the coastal samples was negatively correlated with salinity and positively correlated with a number of OM tracers, including dissolved and chromophoric organic carbon (DOC, CDOM), marine microgels and chlorophyll a (Chl- a ) but not for viral and bacterial abundances; indicating that OM of riverine origin enhances primary aerosol production. When all samples were considered, transparent exopolymer particles (TEP) were found to be the best indicator correlating positively with the ratio number concentration of SSA/salinity. CCN efficiency was not observed to differ between the SSA from the various samples, despite differences in organic characteristics. It is suggested that the large amount of freshwater from river runoff have a substantial impact on primary aerosols production mechanisms, possibly affecting the cloud radiative forcing.

Instability of perovskite quantum dots (QDs) toward humidity remains one of the major obstacles for their long-term use in optoelectronic devices. Herein, a general amphiphilic star-like block copolymer nanoreactor strategy for in situ crafting a set of hairy perovskite QDs with precisely tunable size and exceptionally high water and colloidal stabilities is presented. The selective partition of precursors within the compartment occupied by inner hydrophilic blocks of star-like diblock copolymers imparts in situ formation of robust hairy perovskite QDs permanently ligated by outer hydrophobic blocks via coprecipitation in nonpolar solvent. These size- and composition-tunable perovskite QDs reveal impressive water and colloidal stabilities as the surface of QDs is intimately and permanently ligated by a layer of outer hydrophobic polymer hairs. More intriguingly, the readily alterable length of outer hydrophobic polymers renders the remarkable control over the stability enhancement of hairy perovskite QDs., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Neurons are highly polarized cells that can extend processes far from the cell body. As such, transport of messenger RNAs serves as a set of blueprints for the synthesis of specific proteins at distal sites. RNA localization to dendrites and axons confers the ability to regulate translation with extraordinary precision in space and time. Although the rationale for RNA localization is quite compelling, it is unclear how a neuron orchestrates such a complex task of distributing over a thousand different mRNAs to their respective subcellular compartments. Recent single-molecule imaging studies have led to insights into the kinetics of individual mRNAs. We can now peer into the transport dynamics of mRNAs in both dendrites and axons., (Copyright © 2019. Published by Elsevier Ltd.)

Genomic analysis of the clavulanic acid (CA)-high-producing Streptomyces clavuligerus strains, OL13 and OR, developed through random mutagenesis revealed a frameshift mutation in the cas1 gene-encoding clavaminate synthase 1. Overexpression of the intact cas1 in S. clavuligerus OR enhanced the CA titer by approximately 25%, producing ~ 4.95 g/L of CA, over the OR strain in the flask culture. Moreover, overexpression of the pathway-specific positive regulatory genes, ccaR and claR, in the OR strain improved CA yield by approximately 43% (~ 5.66 g/L) in the flask. However, co-expression of the intact cas1 with ccaR-claR did not further improve CA production. In the 7 L fermenter culture, maximum CA production by the OR strain expressing the wild-type cas1 and ccaR-claR reached approximately 5.52 g/L and 6.01 g/L, respectively, demonstrating that reverse engineering or simple rational metabolic engineering is an efficient method for further improvement of industrial strains.

CsPbX 3 (X = I, Br, Cl) perovskite nanocrystals (NCs) have recently emerged as emitting materials for optoelectronic and display applications owing to their easily tunable emissions, high photoluminescence quantum yield (PLQY), and vivid color purity (full width at half maximum of approximately 20 nm). However, the lagging quantum yields of blue-emitting perovskite NCs have resulted in low efficiency compared to green or red perovskite light-emitting diodes (PeLEDs); moreover, the long insulating ligands (such as oleylamine and oleic acid) inhibit charge carrier injection. In this study, we demonstrated a facile ligand-mediated post-treatment (LMPT) method for high-quality perovskite NCs with changing optical properties to allow fine-tuning of the target emission wavelength. This method involves the use of a mixed halide ion-pair ligand, di-dodecyl dimethyl ammonium bromide, and chloride, which can induce a reconstruction through a self-anion exchange. Using the LMPT method, the PLQY of the surface-passivated blue-emitting NCs was dramatically enhanced to over 70% within the 485 nm blue emission region and 50% within the 467 nm deep-blue emission region. Through this treatment, we achieved highly efficient blue-PeLED maximum external quantum efficiencies of 0.44 and 0.86% within the 470 and 480 ± 2 nm electroluminescence emission regions, respectively.

Introduction: Hyoid bone movement can be useful for diagnosing oropharyngeal dysphagia. In most clinical settings, the movement can be evaluated by a video fluoroscopic swallowing study (VFSS) that induces radiation exposure. In contrast with the hyoid bone, the thyroid cartilage is easily seen through the anterior neck surface. We hypothesized that the movement of thyroid cartilage correlates with hyoid bone movement in various axis and can be used as a parameter to evaluate swallowing. The purpose of this study was to investigate whether thyroid cartilage and hyoid bone movement were correlated and to collect basic data to determine if thyroid cartilage can be used as a parameter to evaluate swallowing., Methods: A total of 25 subjects were included, and the VFSS image with normal swallowing function was collected retrospectively. The VFSS image was analyzed by specially developed semi-automatic software. Laryngeal prominence and anterior-superior margins of the hyoid were automatically extracted during swallowing. Two-point sets of the loci during swallowing were obtained in all VFSS frames. The X-coordinates showed an anterior-posterior axis, and the Y-coordinates showed a superior-inferior axis. Pearson correlation coefficients for each X- and Y-coordinate component were computed., Results: X- and Y-coordinates of the thyroid cartilage and hyoid bones in all subjects showed movement in similar patterns, although each subject's movement differed. Pearson correlation coefficients of X- and Y-coordinate components of all subjects ranged from 0.611 to 0.981, which indicated that thyroid cartilage and hyoid bone movement was strongly correlated in anterior-posterior and superior-inferior axes, respectively., Conclusion: We analyzed thyroid cartilage and hyoid bone movement using a specifically developed semi-automatic software and concluded that the movement of thyroid cartilage and hyoid bone was strongly correlated in anterior-posterior and superior-inferior axes, respectively, during swallowing. The present study implies that analysis of thyroid cartilage movement can be used as a parameter for swallowing evaluation.

A variety of organisms, such as bacteria, fungi, and plants, produce secondary metabolites, also known as natural products. Natural products have been a prolific source and an inspiration for numerous medical agents with widely divergent chemical structures and biological activities, including antimicrobial, immunosuppressive, anticancer, and anti-inflammatory activities, many of which have been developed as treatments and have potential therapeutic applications for human diseases. Aside from natural products, the recent development of recombinant DNA technology has sparked the development of a wide array of biopharmaceutical products, such as recombinant proteins, offering significant advances in treating a broad spectrum of medical illnesses and conditions. Herein, we will introduce the structures and diverse biological activities of natural products and recombinant proteins that have been exploited as valuable molecules in medicine, agriculture and insect control. In addition, we will explore past and ongoing efforts along with achievements in the development of robust and promising microorganisms as cell factories to produce biologically active molecules. Furthermore, we will review multi-disciplinary and comprehensive engineering approaches directed at improving yields of microbial production of natural products and proteins and generating novel molecules. Throughout this article, we will suggest ways in which microbial-derived biologically active molecular entities and their analogs could continue to inspire the development of new therapeutic agents in academia and industry.

In recent years, there has been increased interest in symbolic data analysis, including for exploratory analysis, supervised and unsupervised learning, time series analysis, etc. Traditional statistical approaches that are designed to analyze single-valued data are not suitable because they cannot incorporate the additional information on data structure available in symbolic data, and thus new techniques have been proposed for symbolic data to bridge this gap. In this article, we develop a regularized convex clustering approach for grouping histogram-valued data. The convex clustering is a relaxation of hierarchical clustering methods, where prototypes are grouped by having exactly the same value in each group via penalization of parameters. We apply two different distance metrics to measure (dis)similarity between histograms. Various numerical examples confirm that the proposed method shows better performance than other competitors., (© 2019 International Biometric Society.)

The chemical analysis of a Streptomyces strain, from a Korean volcanic island, discovered new benz[ a]anthracene dimers linked by a thioether bond. The structures of donghaesulfins A and B (1 and 2) were elucidated by spectroscopic analysis including energy-dispersive X-ray. Their configurations were determined by ROESY NMR data, DP4 calculations, the modified Mosher's method, and ECD calculations. Donghaesulfins A (1) induced quinone reductase, whereas donghaesulfin B (2) displayed antiangiogenesis activity.

In the version of this article originally published, reference to another structure of GenB1 was omitted (Dow, G. T., Thoden, J. B., & Holden, H. M. The three-dimensional structure of NeoB: an aminotransferase involved in the biosynthesis of neomycin. Protein Sci. 27, 945-956 (2018)). This paper is now cited as reference 32, and "Another structure of GenB1 was also reported independently during the revision of this article 32 " was added to the text in the Discussion section. This error has been corrected in the PDF and HTML versions of the article.

Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chemical studies of gut bacteria of the carpenter ant Camponotus kiusiuensis led to the discovery of two new alkaloids, camporidines A and B (1 and 2), from Streptomyces sp. STA1. The structures of 1 and 2 were established as new polyketide alkaloids bearing a piperidine-cyclopentene-epoxide 6/5/3 tricyclic system based on NMR spectroscopic and mass spectrometric analysis. The relative configurations of the camporidines were determined by their 1 H- 1 H NOESY/ROESY and 1D NOE NMR correlations. The experimental ECD spectra of 1 and 2 were compared with their calculated ECD spectra to assign their absolute configurations. Camporidine A (1) displayed antimetastatic activity by suppression of cell invasion against the metastatic breast cancer cell line MDA-MB-231 and showed an anti-inflammatory effect by suppressing nitric oxide production induced by lipopolysaccharide. In addition, the putative biosynthetic gene cluster of the camporidines was identified, and the biosynthetic pathway of the camporidines was proposed based on bioinformatic analysis of the full genome of Streptomyces sp. STA1. Camporidines A and B (1 and 2) could be biosynthesized by a modular type I PKS containing an acyl transferase domain that accepts an unusual extender unit, which becomes the (C1'-C6') hexyl side chain. The post-PKS modification enzymes were predicted to perform an amination and an oxidation along with spontaneous Schiff base formation and generate the unique piperidine-cyclopentene-epoxide 6/5/3 tricyclic framework.

Uniform, well-ordered sub-20 nm patterns can be generated by the templated self-assembly of block copolymers (BCPs) with a high Flory-Huggins interaction parameter (χ). However, the self-assembled BCP monolayers remain limited in the possible structural geometries. Here, we introduce a multiple self-assembly method which uses di-BCPs to produce diverse morphologies, such as dot, dot-in-honeycomb, line-on-dot, double-dot, pondering, dot-in-pondering, and line-on-pondering patterns. To improve the diversity of BCP morphological structures, we employed sphere-forming and cylinder-forming poly(styrene-block-dimethylsiloxane) (PS-b-PDMS) BCPs with a high χ. The self-assembled mono-layer and double-layer SiOx dot patterns were modified at a high temperature (∼800 °C), showing hexagonally arranged (dot) and double-hexagonally arranged (pondering) SiOx patterns, respectively. We successfully obtained additional new nanostructures (big-dot, dot-in-honeycomb, line-on-dot, pondering, dot-in-pondering, and line-on-pondering types) through a second self-assembly of cylinder-forming BCPs using the dot and pondering patterns as guiding templates. This simple approach can likely be extended to the multiple self-assembly of many other BCPs with good functionality, significantly contributing to the development of various nanodevices.