Subthreshold Conduction of Disordered ZnO-Based Thin-Film Transistors.

This study presents the disorderedness effects on the subthreshold characteristics of atomically deposited ZnO thin-film transistors (TFTs). Bottom-gate ZnO TFTs show n-type enhancement-mode transfer characteristics but a gate-voltage-dependent, degradable subthreshold swing. The charge-transport characteristics of the disordered semiconductor TFTs are severely affected by the localized trap states. Thus, we posit that the disorderedness factors, which are the interface trap capacitance and the diffusion coefficient of electrons, would result in the degradation. Considering the factors as gate-dependent power laws, we derive the subthreshold current-voltage relationship for disordered semiconductors. Notably, the gate-dependent disorderedness parameters are successfully deduced and consistent with those obtained by the gm/Ids method, which was for the FinFETs. In addition, temperature-dependent current-voltage analyses reveal that the gate-dependent interface traps limit the subthreshold conduction, leading to the diffusion current. Thus, we conclude that the disorderedness factors of the ZnO films lead to the indefinable subthreshold swing of the ZnO TFTs.

Threshold-Voltage Extraction Methods for Atomically Deposited Disordered ZnO Thin-Film Transistors.

In this paper, we present a threshold-voltage extraction method for zinc oxide (ZnO) thin-film transistors (TFTs). Bottom-gate atomic-layer-deposited ZnO TFTs exhibit typical n-type enhancement-mode transfer characteristics but a gate-voltage-dependent, unreliable threshold voltage. We posit that this obscure threshold voltage is attributed to the localized trap states of ZnO TFTs, of which the field-effect mobility can be expressed as a gate-bias-dependent power law. Hence, we derived the current-voltage relationship by dividing the drain current with the transconductance to rule out the gate-bias-dependent factors and successfully extract the reliable threshold voltage. Furthermore, we investigated the temperature-dependent characteristics of the ZnO TFTs to validate that the observed threshold voltage was genuine. Notably, the required activation energies from the low-temperature measurements displayed an abrupt decrease at the threshold voltage, which was attributed to the conduction route change from diffusion to drift. Thus, we conclude that the reliable threshold voltage of accumulation-mode ZnO TFTs can be determined using a gate-bias-dependent factor-removed current-voltage relationship with a low-temperature analysis.

All-Natural Moss-Based Microstructural Composites in Deformable Form for Use as Graffiti and Artificial-Porous-Material Replacement.

Although artificial porous materials are useful for dissipating acoustic waves, they pose a major environmental threat as most are non-recyclable. Developing sustainable structural materials with the mechanical and energy-absorption properties required to replace artificial porous materials is currently a key challenge. Here, we report, for the first time, a novel microstructure using all-natural moss with a compressive strength of up to 2.35 GPa and a sound-absorption performance of up to 90%, depending on the additives, such as yogurt, starch, and beer. In addition, the moss-based microstructure was applied as graffiti to a three-dimensionally printed house model to demonstrate improved performance against the effects of sound. By incorporating energy-absorbing materials without harmful substances, the desired structure can be decorated with the graffiti method. This work could pave the way for attenuating sound-wave and impact noise by using graffiti work on structural composite materials.

RKIP Induction Promotes Tumor Differentiation via SOX2 Degradation in NF2-Deficient Conditions.

Loss of NF2 (merlin) has been suggested as a genetic cause of neurofibromatosis type 2 and malignant peripheral nerve sheath tumor (MPNST). Previously, we demonstrated that NF2 sustained TGFß receptor 2 (TßR2) expression and reduction or loss of NF2 activated non-canonical TGFß signaling, which reduced Raf kinase inhibitor protein (RKIP) expression via TßR1 kinase activity. Here, we show that a selective RKIP inducer (novel chemical, Nf18001) inhibits tumor growth and promotes schwannoma cell differentiation into mature Schwann cells under NF2-deficient conditions. In addition, Nf18001 is not cytotoxic to cells expressing NF2 and is not disturb canonical TGFß signaling. Moreover, the novel chemical induces expression of SOX10, a marker of differentiated Schwann cells, and promotes nuclear export and degradation of SOX2, a stem cell factor. Treatment with Nf18001 inhibited tumor growth in an allograft model with mouse schwannoma cells. These results strongly suggest that selective RKIP inducers could be useful for the treatment of neurofibromatosis type 2 as well as NF2-deficient MPNST. IMPLICATIONS: This study identifies that a selective RKIP inducer inhibits tumor growth and promotes schwannoma cell differentiation under NF2-deficient conditions by reducing SOX2 and increasing SOX10 expression.

Novel chemical inhibitor against SOD1 misfolding and aggregation protects neuron-loss and ameliorates disease symptoms in ALS mouse model.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective death of motor neurons. Mutations in Cu, Zn-superoxide dismutase (SOD1) causing the gain of its toxic property are the major culprit of familial ALS (fALS). The abnormal SOD1 aggregation in the motor neurons has been suggested as the major pathological hallmark of ALS patients. However, the development of pharmacological interventions against SOD1 still needs further investigation. In this study, using ELISA-based chemical screening with wild and mutant SOD1 proteins, we screened a new small molecule, PRG-A01, which could block the misfolding/aggregation of SOD1 or TDP-43. The drug rescued the cell death induced by mutant SOD1 in human neuroblastoma cell line. Administration of PRG-A01 into the ALS model mouse resulted in significant improvement of muscle strength, motor neuron viability and mobility with extended lifespan. These results suggest that SOD1 misfolding/aggregation is a potent therapeutic target for SOD1 related ALS.

Surface Polarization Doping in Diketopyrrolopyrrole-Based Conjugated Copolymers Using Cross-Linkable Terpolymer Dielectric Layers Containing Fluorinated Functional Units.

It is essential to tune the electrical properties of inorganic semiconductors via a doping process in the fabrication of cutting-edge electronic devices; however, the doping in organic field-effect transistors (OFETs) is limited by the uncontrollable dopant diffusion and low doping efficiencies. This study proposes the use of a fluorinated functional group in a polymer dielectric layer as an effective p-type doping strategy for ambipolar diketopyrrolopyrrole (DPP)-based donor-acceptor (D-A)-type semiconducting copolymer films used in OFETs, without generating structural perturbations. To experimentally verify the surface polarization doping effect of the fluorinated group, two terpolymers─poly(pentafluorostyrene-co-3-azidopropyl-methacrylate-co-propargyl-methacrylate) (5F-SAPMA), wherein fluorinated units are included, and poly(phenyl-methacrylate-co-3-azidopropyl-methacrylate-co-propargyl-methacrylate) (PhAPMA), without fluorinated units─are designed and synthesized for use in OFETs. The synthesized 5F-SAPMA and PhAPMA films were cross-linked through the click reaction between the alkyne and azide units in the terpolymers at 150 °C to provide chemical, thermal, and mechanical stabilities and solvent resistance. The electrical characterization of the OFETs with the newly synthesized terpolymer dielectrics reveals that the surface polarization induced by the fluorinated groups of the 5F-SAPMA dielectrics leads to the generation of additional hole charges and helps minimize the broadening of the extended tail states in the vicinity of the valence band (highest occupied molecular orbital (HOMO) level). This not only enables a transition from the ambipolar to p-type dominant characteristics but also helps increase the hole mobility from 0.023 to 0.305 cm2/(V·s).

Explosive Spalling Behavior of Single-Sided Heated Concrete According to Compressive Strength and Heating Rate.

In this study, the effects of heating rate and compressive strength on the spalling behavior of single-sided heated ring-restrained concrete with compressive strengths of 60 and 100 MPa were investigated. The vapor pressure and restrained stress inside the concrete were evaluated under fast- and slow-heating conditions. Regardless of the heating rate, the concrete vapor pressure and restrained stress increased as the temperature increased, and it was confirmed that spalling occurred in the 100-MPa concrete. Specifically, it was found that moisture migration and restrained stress inside the concrete varied depending on the heating rate. Under fast heating, moisture clogging and restrained stress occurred across the concrete surface, causing continuous surface spalling for the 100-MPa concrete. Under slow heating, moisture clogging occurred, and restrained stress continuously increased in the deep area of the concrete cross-section owing to the small internal temperature difference, resulting in explosive spalling for the 100-MPa concrete with a dense internal structure. Additionally, while the tensile strength of concrete is reduced by heating, stress in the heated surface direction is generated by restrained stress. The combination of stress in the heated concrete surface and the internal vapor pressure generates spalling. The experimental results confirm that heating rate has a significant influence on moisture migration and restrained stress occurrence inside concrete, which are important factors that determine the type of spalling.

Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens.

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

Biosorption of Uranyl Ions from Aqueous Solution by Parachlorella sp. AA1.

In the present study we investigated the ability of the microalgal strain Parachlorella sp. AA1 to biologically uptake a radionuclide waste material. Batch experiments were conducted to investigate the biosorption of uranyl ions (U(VI)) in the 0.5-50.0 mg/L concentration range by strain AA1. The results showed that AA1 biomass could uptake U(VI). The highest removal efficiency and biosorption capacity (95.6%) occurred within 60 h at an initial U(VI) concentration of 20 mg/L. The optimum pH for biosorption was 9.0 at a temperature of 25 °C. X-ray absorption near edge structure analysis confirmed the presence of U(VI) in pellets of Parachlorella sp. AA1 cells. The biosorption methods investigated here may be useful in the treatment and disposal of nuclides and heavy metals in diverse wastewaters.

Human WRN is an intrinsic inhibitor of progerin, abnormal splicing product of lamin A.

Werner syndrome (WRN) is a rare progressive genetic disorder, caused by functional defects in WRN protein and RecQ4L DNA helicase. Acceleration of the aging process is initiated at puberty and the expected life span is approximately the late 50 s. However, a Wrn-deficient mouse model does not show premature aging phenotypes or a short life span, implying that aging processes differ greatly between humans and mice. Gene expression analysis of WRN cells reveals very similar results to gene expression analysis of Hutchinson Gilford progeria syndrome (HGPS) cells, suggesting that these human progeroid syndromes share a common pathological mechanism. Here we show that WRN cells also express progerin, an abnormal variant of the lamin A protein. In addition, we reveal that duplicated sequences of human WRN (hWRN) from exon 9 to exon 10, which differ from the sequence of mouse WRN (mWRN), are a natural inhibitor of progerin. Overexpression of hWRN reduced progerin expression and aging features in HGPS cells. Furthermore, the elimination of progerin by siRNA or a progerin-inhibitor (SLC-D011 also called progerinin) can ameliorate senescence phenotypes in WRN fibroblasts and cardiomyocytes, derived from WRN-iPSCs. These results suggest that progerin, which easily accumulates under WRN-deficient conditions, can lead to premature aging in WRN and that this effect can be prevented by SLC-D011.

Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome.

Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient's cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.

Enhanced Performance of Cyclopentadithiophene-Based Donor-Acceptor-Type Semiconducting Copolymer Transistors Obtained by a Wire Bar-Coating Method.

Herein, we report the fabrications of high-performance polymer field-effect transistors (PFETs) with wire bar-coated semiconducting polymer film as an active layer. For an active semiconducting material of the PFETs, we employed cyclopentadithiophene-alt-benzothiadiazole (CDT-BTZ) that is a D-A-type-conjugated copolymer consisting of a repeated electron-donating unit and an electron-accepting unit, and the other two CDT-based D-A-type copolymer analogues are cyclopentadithiophene-alt-fluorinated-benzothiadiazole (CDT-FBTZ) and cyclopentadithiophene-alt-thiadiazolopyridine (CDT-PTZ). The linear field-effect mobility values obtained from the transfer curve of the PFETs fabricated with the spin-coating were 0.04 cm2/Vs, 0.16 cm2/Vs, and 0.31 cm2/Vs, for CDT-BTZ, CDT-FBTZ, and CDT-PTZ, respectively, while the mobility values measured from the PFETs with the wire bar-coated CDT-BTZ film, CDT-FBTZ film, and CDT-PTZ film were 0.16 cm2/Vs, 0.28 cm2/Vs, and 0.95 cm2/Vs, respectively, which are about 2 to 4 times higher values than those of the PFETs with spin-coated films. These results revealed that the aligned molecular chain is beneficial for the D-A-type semiconducting copolymer even though the charge transport in the D-A-type semiconducting copolymer is known to be less critical to the degree of disorder in film.

Complementary Hybrid Semiconducting Superlattices with Multiple Channels and Mutual Stabilization.

An organic-inorganic hybrid superlattice with near perfect synergistic integration of organic and inorganic constituents was developed to produce properties vastly superior to those of either moiety alone. The complementary hybrid superlattice is composed of multiple quantum wells of 4-mercaptophenol organic monolayers and amorphous ZnO nanolayers. Within the superlattice, multichannel formation was demonstrated at the organic-inorganic interfaces to produce an excellent-performance field effect transistor exhibiting outstanding field-effect mobility with band-like transport and steep subthreshold swing. Furthermore, mutual stabilizations between organic monolayers and ZnO effectively reduced the performance degradation notorious in exclusively organic and ZnO transistors.

ZnO composite nanolayer with mobility edge quantization for multi-value logic transistors.

A quantum confined transport based on a zinc oxide composite nanolayer that has conducting states with mobility edge quantization is proposed and was applied to develop multi-value logic transistors with stable intermediate states. A composite nanolayer with zinc oxide quantum dots embedded in amorphous zinc oxide domains generated quantized conducting states at the mobility edge, which we refer to as "mobility edge quantization". The unique quantized conducting state effectively restricted the occupied number of carriers due to its low density of states, which enable current saturation. Multi-value logic transistors were realized by applying a hybrid superlattice consisting of zinc oxide composite nanolayers and organic barriers as channels in the transistor. The superlattice channels produced multiple states due to current saturation of the quantized conducting state in the composite nanolayers. Our multi-value transistors exhibited excellent performance characteristics, stable and reliable operation with no current fluctuation, and adjustable multi-level states.

p53 induces senescence through Lamin A/C stabilization-mediated nuclear deformation.

p53-mediated cellular senescence has been intensively investigated, because it is important for tumor suppressive function. In addition, p16/INK4A is well known to be critical for cellular senescence. However, detailed molecular mechanism or relevance between p53 and p16-mediated senescence has not been demonstrated yet. Here we show that p53 induces p16 through Lamin A/C stabilization via direct interaction. Stabilized Lamin A/C promotes degradation of BMI-1 and MEL-18 (Polycomb repressor complex 1, PRC1), which sequesters p16 promotor. Increased p53 can reduce BMI-1/MEL-18 and induce p16 expression via Lamin A/C. Elimination of Lamin A/C can abolish p53-induced p16 expression and BMI-1/MEL-18 reduction. As Lamin A/C expression is increased during cell differentiation, this mechanism seems to be very useful for selective induction of senescence in non-stem cells. Our results suggest that Lamin A/C-p53 network is important for p16/INK4A-mediated cellular senescence.

Loss of NF2 Induces TGFß Receptor 1-mediated Noncanonical and Oncogenic TGFß Signaling: Implication of the Therapeutic Effect of TGFß Receptor 1 Inhibitor on NF2 Syndrome.

Neurofibromatosis type 2 (NF2) syndrome is a very rare human genetic disease, and there has been no proper treatment for it until now. In our recent study, it has been reported that the loss of NF2 activates MAPK signaling through reduction of RKIP in a mesothelioma model. Here, we show that loss of NF2 induces reduction of the TGFß receptor 2 (TßR2) expression, and an overwhelming expression of TGFß receptor 1 (TßR1) is activated by physical stimuli such as pressure or heavy materials. Activated TßR1 induces the phosphorylation and degradation of RKIP. RKIP reduction consequently results in MAPK activation as well as Snail-mediated p53 suppression and occurrence of EMT in NF2-deficient cells by physical stimuli. Thus, TßR1 kinase inhibitors restore cell differentiation and induce growth suppression in NF2-deficient Schwannoma cell line and MEF. Moreover, TEW7197, a specific TßR1 kinase inhibitor, reduces tumor formation in the NF2-model mouse (Postn-Cre;NF2f/f). Gene expression profiling reveals that TEW7197 treatment induces the expression of lipid metabolism-related gene set, such as NF2-restored cells in HEI-193 (NF2-deficient Schwannoma). Our results indicate that reduction or deletion of TßR2 or NF2 induces the TßR1-mediated oncogenic pathway, and therefore inhibition of the unbalanced TGFß signaling is a putative strategy for NF2-related cancers (NF2 syndrome and mesothelioma) and TßR2-mutated advanced cancers. Mol Cancer Ther; 17(11); 2271-84. ©2018 AACR.

Shellac Films as a Natural Dielectric Layer for Enhanced Electron Transport in Polymer Field-Effect Transistors.

Shellac, a natural polymer resin obtained from the secretions of lac bugs, was evaluated as a dielectric layer in organic field-effect transistors (OFETs) on the basis of donor (D)-acceptor (A)-type conjugated semiconducting copolymers. The measured dielectric constant and breakdown field of the shellac layer were ∼3.4 and 3.0 MV/cm, respectively, comparable with those of a poly(4-vinylphenol) (PVP) film, a commonly used dielectric material. Bottom-gate/top-contact OFETs were fabricated with shellac or PVP as the dielectric layer and one of three different D-A-type semiconducting copolymers as the active layer: poly(cyclopentadithiophene- alt-benzothiadiazole) with p-type characteristics, poly(naphthalene-bis(dicarboximide)- alt-bithiophene) [P(NDI2OD-T2)] with n-type characteristics, and poly(dithienyl-diketopyrrolopyrrole- alt-thienothiophene) [P(DPP2T-TT)] with ambipolar characteristics. The electrical characteristics of the fabricated OFETs were then measured. For all active layers, OFETs with a shellac film as the dielectric layer exhibited a better mobility than those with PVP. For example, the mobility of the OFET with a shellac dielectric and n-type P(NDI2OD-T2) active layer was approximately 2 orders of magnitude greater than that of the corresponding OFET with a PVP insulating layer. When P(DPP2T-TT) served as the active layer, the OFET with shellac as the dielectric exhibited ambipolar characteristics, whereas the corresponding OFET with the PVP dielectric operated only in hole-accumulation mode. The total density of states was analyzed using technology computer-aided design simulations. The results revealed that compared with the OFETs with PVP as the dielectric, the OFETs with shellac as the dielectric had a lower trap-site density at the polymer semiconductor/dielectric interface and much fewer acceptor-like trap sites acting as electron traps. These results demonstrate that shellac is a suitable dielectric material for D-A-type semiconducting copolymer-based OFETs, and the use of shellac as a dielectric layer facilitates electron transport at the interface with D-A-type copolymer channels.

Laminopathies; Mutations on single gene and various human genetic diseases.

Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucleus, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy. In this review, we briefly overview the relevance of genetic mutations of Lamin A, human disorders and laminopathies. We also discuss a mouse model for genetic diseases. Finally, we describe the current treatment for laminopathies. [BMB Reports 2018; 51(7): 327-337].