De Novo Design of Molecules with Low Hole Reorganization Energy Based on a Quarter-Million Molecule DFT Screen: Part 2.

Organic semiconductors have many desirable properties including improved manufacturing and flexible mechanical properties. Due to the vastness of chemical space, it is essential to efficiently explore chemical space when designing new materials, including through the use of generative techniques. New generative machine learning methods for molecular design continue to be published in the literature at a significant rate but successfully adapting methods to new chemistry and problem domains remains difficult. These challenges necessitate continual method evaluation to probe method viability for use in alternative applications not covered in the original works. In continuation of our previous work, we evaluate four additional machine-learning-based de novo methods for generating molecules with high predicted hole mobility for use in semiconductor applications. The four generative methods evaluated here are (1) Molecule Deep Q-Networks (MolDQN), which utilizes Deep-Q learning to directly optimize molecular structure graphs for desired properties instead of generating SMILES, (2) Graph-based Genetic Algorithm (GraphGA), which uses a genetic algorithm for optimization where crossovers and mutations are defined in terms of RDKit's reaction SMILES, (3) Generative Tensorial Reinforcement Learning (GENTRL), which is a variational autoencoder (VAE) with a learned prior distribution and optimized using reinforcement learning, and (4) Monte Carlo tree search exploration of chemical space in conjunction with a recurrent neural network (RNN) decoder (ChemTS). The generated molecules were evaluated using density functional theory (DFT) and we discovered better performing molecules with the GraphGA method compared to the other approaches.

Fabrication of bioresorbable hydroxyapatite bone grafts through the setting reaction of calcium phosphate cement.

We prepared hydroxyapatite (HAp) bone grafts by the setting reaction of calcium phosphate cement, and investigated the effects of the porosity and crystallinity on the osteoconductivity and bioresorbability. We examined the effect of the water-mixing ratio, pressure, and post-heat treatment temperature during preparation on the crystallite size and porosity of the HAp blocks. The quantity of protein adsorption increased with increasing porosity and specific surface area (SSA) of the HAp blocks, whereas the initial cell attachment was similar despite the different porosities and crystallinities. In in vitro dissolution tests with a pH 5.5 buffer, which mimics an osteoclast-created Howship's lacuna, both the porosity and SSA of the HAp blocks affected the solubility; most likely due to the increased contact area with the buffer. Thus, HAp blocks prepared by the setting reaction of calcium phosphate cement could be applicable for bioresorbable HAp bone grafts because of the high porosity and SSA.

De Novo Design of Molecules with Low Hole Reorganization Energy Based on a Quarter-Million Molecule DFT Screen.

Materials exhibiting higher mobilities than conventional organic semiconducting materials such as fullerenes and fused thiophenes are in high demand for applications in printed electronics. To discover new molecules in the heteroacene family that might show improved hole mobility, three de novo design methods were applied. Machine learning (ML) models were generated based on previously calculated hole reorganization energies of a quarter million examples of heteroacenes, where the energies were calculated by applying density functional theory (DFT) and a massive cloud computing environment. The three generative methods applied were (1) the continuous space method, where molecular structures are converted into continuous variables by applying the variational autoencoder/decoder technique; (2) the method based on reinforcement learning of SMILES strings (the REINVENT method); and (3) the junction tree variational autoencoder method that directly generates molecular graphs. Among the three methods, the second and third methods succeeded in obtaining chemical structures whose DFT-calculated hole reorganization energy was lower than the lowest energy in the training dataset. This suggests that an extrapolative materials design protocol can be developed by applying generative modeling to a quantitative structure-property relationship (QSPR) utility function.

Machine-Learning Guided Quantum Chemical and Molecular Dynamics Calculations to Design Novel Hole-Conducting Organic Materials.

Materials exhibiting higher mobilities than conventional organic semiconducting materials such as fullerenes and fused thiophenes are in high demand for applications such as printed electronics, organic solar cells, and image sensors. In order to discover new molecules that might show improved charge mobility, combined density functional theory (DFT) and molecular dynamics (MD) calculations were performed, guided by predictions from machine learning (ML). A ML model was constructed based on 32 values of theoretically calculated hole mobilities for thiophene derivatives, benzodifuran derivatives, a carbazole derivative and a perylene diimide derivative with the maximum value of 10-1.96 cm2/(V s). Sequential learning, also known as active learning, was applied to select compounds on which to perform DFT/MD calculation of hole mobility to simultaneously improve the mobility surrogate model and identify high mobility compounds. By performing 60 cycles of sequential learning with 165 DFT/MD calculations, a molecule having a fused thioacene structure with its calculated hole mobility of 10-1.86 cm2/(V s) was identified. This values is higher than the maximum value of mobility in the initial training data set, showing that an extrapolative discovery could be made with the sequential learning.

Massive Theoretical Screen of Hole Conducting Organic Materials in the Heteroacene Family by Using a Cloud-Computing Environment.

Materials exhibiting higher mobilities than conventional organic semiconducting materials such as fullerenes and fused thiophenes are in high demand for applications in printed electronics. To discover new molecules in the heteroacene family that might show improved charge mobility, a massive theoretical screen of hole conducting properties of molecules was performed by using a cloud-computing environment. Over 7 000 000 structures of fused furans, thiophenes and selenophenes were generated and 250 000 structures were randomly selected to perform density functional theory (DFT) calculations of hole reorganization energies. The lowest hole reorganization energy calculated was 0.0548 eV for a fused thioacene having 8 aromatics rings. Hole mobilities of compounds with the lowest 130 reorganization energy were further processed by applying combined DFT and molecular dynamics (MD) methods. The highest mobility calculated was 1.02 and 9.65 cm2/(V s) based on percolation and disorder theory, respectively, for compounds containing selenium atoms with 8 aromatic rings. These values are about 20 times higher than those for dinaphthothienothiophene (DNTT).

Reciprocal expression of Slug and Snail in human oral cancer cells.

Snail, also called Snai1, is a key regulator of EMT. Snail plays crucial roles in cancer progression, including resistance to anti-tumor drugs and invasion by various cancer cells. Slug, also known as Snai2, is also involved in the aggravation of certain tumors. In this study, we examined the roles of Slug in human oral squamous cell carcinoma (OSCC) cells. Slug is highly expressed in these cells, and Slug siRNA effectively represses anti-tumor drug resistance and invasive properties. In addition, transforming growth factor (TGF)-ß upregulates the expression of Snail and Slug and promotes resistance to anti-tumor drugs in OSCC cells. Surprisingly, Slug siRNA appears to upregulate Snail expression considerably in OSCC cells. Snail siRNA also appears to upregulate Slug expression. Thus, either Slug or Snail siRNA alone partially mitigates malignant phenotypes in the presence of TGF-ß, whereas both Slug and Snail siRNAs together dramatically suppress them. Therefore, Slug and Snail in tandem, but not alone, are potential therapeutic targets for nucleic acid medicines to treat oral cancer.

High electromechanical strain and enhanced temperature characteristics in lead-free (Na,Bi)TiO3-BaTiO3 thin films on Si substrates.

Here, we demonstrate the high electromechanical strain and enhanced temperature characteristics in the c-axis-oriented lead-free (Na,Bi)TiO3-BaTiO3 (NBT-BT) polycrystalline thin film prepared on Si substrates by rf magnetron sputtering. The effective transverse piezoelectric coefficient, e31*, estimated from the electromechanical strain measured under high electric field, reaches a high level of -12.5 C/m2, and is comparable to those of conventional Pb(Zr,Ti)O3 films. In-situ X-ray diffraction measurement and electron diffraction analysis revealed the electromechanical strain of the NBT-BT film to originate predominantly in elongation of the tetragonal (P4bm) crystal lattice in the c-axis direction. In addition to the large e31*, the NBT-BT film exhibits enhanced permittivity maximum temperature, Tm, of ~400 °C and no depolarization below Tm, as compared to bulk NBT-BT having Tm ≈ 300 °C and a depolarization temperature of ~100 °C. We conclude that the enhancement of temperature characteristics is associated with the distorted P4bm crystal lattice formed by deposition-induced stress and defects. We believe that the present study paves the way for practical applications of lead-free piezoelectric thin films in electromechanical devices.

Conductivity Modulation of Gold Thin Film at Room Temperature via All-Solid-State Electric-Double-Layer Gating Accelerated by Nonlinear Ionic Transport.

We demonstrated the field-effect conductivity modulation of a gold thin film by all-solid-state electric-double-layer (EDL) gating at room temperature using an epitaxially grown oxide fast lithium conductor, La2/3-xLi3xTiO3 (LLT), as a solid electrolyte. The linearly increasing gold conductivity with increasing gate bias demonstrates that the conductivity modulation is indeed due to carrier injection by EDL gating. The response time becomes exponentially faster with increasing gate bias, a result of the onset of nonlinear ionic transportation. This nonlinear dynamic response indicates that the ionic motion-driven device can be much faster than would be estimated from a linear ionic transport model.

Preparation and in vitro cytocompatibility of chitosan-siloxane hybrid hydrogels.

Injectable systems can be used in minimally invasive surgical applications. Although chitosan-glycerophosphate hydrogel systems are biodegradable and biocompatible, the long periods of time required for their effective gelation have severely limited their clinical application. The challenges currently facing researchers in this field are therefore focused on shortening the gelation time and biocompatibility of these materials to develop hydrogels suitable for clinical application. Chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS) hybrids have recently demonstrated good cytocompatibility with respect to human osteoblastic cells (MG63) and human bone marrow cells. Although these precursor sols could form gels under physiological conditions, they required neutralization with a sodium hydroxide solution. In this study, the chitosan-GPTMS hybrid systems were neutralized with glycerophosphate to prepare injectable hydrogels. The results revealed that the gelation time of the hydrogels could be controlled by the amount of GPTMS in the precursor sols. The in vitro cytocompatibility of the hydrogels were evaluated in terms of the proliferation of MG63 cells cultured either directly onto the hydrogels or indirectly onto the cell culture plate under a hydrogel insert. In the former case, the cells showed good attachment and proliferated for up to 7 days. Similar results were observed in the in direct culture. These results suggest that this new chitosan-GPTMS hydrogel could potentially be used as an injectable biomaterial in clinical applications.

Photoinduced underwater superoleophobicity of TiO2 thin films.

The photoinduced wettabilities of water, n-hexadecane, dodecane, and n-heptane on a flat TiO2 surface prepared by a sol-gel method-based coating were investigated. An amphiphilic surface produced by UV irradiation exhibited underwater superoleophobicity with an extremely high static oil contact angle (CA) of over 160°. The TiO2 surface almost completely repelled the oil droplet in water. A robust TiO2 surface with no fragile nanomicrostructure was fabricated on a Ti mesh with a pore size of approximately 150 µm. The fabricated mesh was found to be applicable as an oil/water separation filter.

Heterogeneous structure and in vitro degradation behavior of wet-chemically derived nanocrystalline silicon-containing hydroxyapatite particles.

Nanocrystalline hydroxyapatite (HAp) and silicon-containing hydroxyapatite (SiHAp) particles were synthesized by a wet-chemical procedure and their heterogeneous structures involving a disordered phase were analyzed in detail by X-ray diffractometry (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and solid-state magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. The effects of heterogeneous structure on in vitro biodegradability and the biologically active Ca(II)- and Si(IV)-releasing property of SiHAp particles were discussed. The (29)Si NMR analysis revealed that the Si(IV) was incorporated in the HAp lattice in the form of Q(0)(SiO(4)(4-)orHSiO(4)(3-)) species, accompanied by the formation of condensed silicate units outside the HAp lattice structure, where the fraction and amount of Q(0) species in the HAp lattice depends on the Si content. The (31)P and (1)H NMR results agreed well with the XRD, TEM and FTIR results. NMR quantitative analysis results were explained by using a core-shell model assuming a simplified hexagonal shape of HAp covered with a disordered layer, where Si(IV) in Q(0) was incorporated in the HAp lattice and a disordered phase consisted of hydrated calcium phosphates involving polymeric silicate species and carbonate anions. With the increase in the Si content in the HAp lattice, the in vitro degradation rate of the SiHAps increased, while their crystallite size stayed nearly unchanged. The biologically active Ca(II)- and Si(IV)-releasing ability of the SiHAps was remarkably enhanced at the initial stage of reactions by an increase in the amount of Si(IV) incorporated in the HAp lattice but also by an increase of the amount of polymeric silicate species incorporated in the disordered phase.

Analysis of two gene clusters involved in 2,4,6-trichlorophenol degradation by Ralstonia pickettii DTP0602.

Ralstonia pickettii DTP0602 utilizes 2,4,6-trichlorophenol (2,4,6-TCP) as sole source of carbon and energy. We have characterized hadABC which is involved in the degradation of 2,4,6-TCP. To identify the other genes involved in 2,4,6-TCP degradation, the DNA sequence around hadABC was determined. A regulatory gene, hadR, homologous to the LysR-type transcriptional regulator was located upstream of hadA, but no maleylacetate (MA) reductase gene was located near hadABC. An 8.4-kb DNA fragment containing a MA reductase gene, hadD, was cloned using a DNA probe designed from the N-terminal sequence of purified MA reductase. hadD was located upstream of an open reading frame, hadS, which codes for a homolog of the LysR-type transcriptional regulator. A hadS insertion mutant, DTP62S, constitutively expressed MA reductase when grown on aspartate in the absence of 2,4,6-TCP. MA reductase was repressed in DTP62S supplemented with hadS. HadR and HadS are proposed to be a positive and a negative regulator, respectively. A draft genome sequence analysis revealed that the hadRXABC and hadSYD clusters were separated by 146-kb on the 8.1-Mb chromosome.

Preparation of nanometer-scale rod array of hydroxyapatite crystal.

Fabrication of nano- or micro-structured scaffolds to mimic structural and three-dimensional details of natural bone or teeth has been the subject of much interest, and this study proposes a new strategy for self-assembling one-dimensional hydroxyapatite (HAp) nanorods into organized superstructures. A nanometer-scale rod array of HAp having preferred orientation to the c-axis was successfully prepared simply by soaking calcium-containing silicate glass substrates in Na(2)HPO(4) aqueous solution at 80 degrees C for various periods. Those HAp rods grew perpendicularly to the glass surface, and the crystallites covered the glass surface uniformly, resulting in a "dental enamel-like" rod array structure consisting of "pine-leaf-like" structure units.

Preparation of (001)-oriented Pb(Zr,Ti)O3 thin films and their piezoelectric applications.

Preparation of (001)-oriented Pb(Zr,Ti)O(3) (PZT) thin films and their applications to a sensor and actuators were investigated. These thin films, which have a composition close to the morphotropic phase boundary, were epitaxially grown on (100)MgO single-crystal substrates by RF magnetron sputtering. These (001)-oriented PZT thin films could be obtained on various kinds of substrates, such as glass and Si, by introducing (100)-oriented MgO buffer layers. In addition, the (001) oriented PZT thin films could be obtained on Si substrates without buffer layers by optimizing the sputtering conditions. All of these thin films showed excellent piezoelectric properties without the need for poling treatment. The PZT thin films on the MgO substrates had a high piezoelectric coefficient, d(31), of -100 pm/V, and an extremely low relative dielectric constant, epsilon(r), of 240. The PZT thin films on Si substrate had a very high d(31) of -150 pm/V and an epsilon(r) = 700. These PZT thin films were applied to an angular rate sensor with a tuning fork in a car navigation system, to a dual-stage actuator for positioning the magnetic head of a high-density hard disk drive, and to an actuator for an inkjet printer head for industrial on-demand printers.

Selective protein adsorption property and characterization of nano-crystalline zinc-containing hydroxyapatite.

Nano-crystalline Zn-containing hydroxyapatite (ZnHAp) was prepared by the wet-chemical method and the selective adsorption of essential proteins was examined, taking bovine serum albumin (BSA) and pathogenic protein such as beta(2)-microglobulin (beta(2)-MG) as model proteins. Transmission electron microscopy observation and X-ray diffraction analysis indicated that the increase of Zn content led to smaller crystallites and their specific surface area of ZnHAps increased with increasing Zn content, accordingly. Furthermore, the amounts of BSA adsorption on ZnHAp particles decreased with increasing Zn content in spite of the increase in the specific surface area. It is thus concluded that nano-crystalline ZnHAps had a highly selective adsorption property with regard to beta(2)-MG.

Sarcomas of the oral and maxillofacial region: a review of 32 cases in 25 years.

Thirty-two cases of sarcomas involving the oral and maxillofacial region over a period of 25 years were reviewed. The age range was from 5 months to 77 years with a mean age of 42. The male to female ratio was 3:1. The sarcomas were located in the maxilla including the maxillary sinus (n= 13), mandible (n= 13), buccal mucosa (n= 3), temporomandibular fossa (n= 2), and submandibular region (n= 1). Histologically sarcomas were classified as osteosarcoma (n= 9), malignant fibrous histiocytoma (n= 7), rhabdomyosarcoma (n= 5), fibrosarcoma (n= 3), plasmacytoma (n= 2), leiomyosarcoma (n= 2), angiosarcoma (n= 2), liposarcoma (n= 1), and ameloblastic fibrosarcoma (n= 1). Surgical resection was performed in 29 cases. Local recurrence was found in 10 patients and metastasis in 11 patients. Metastases included five regional lymph node metastases and eight distant metastases. The survival of patients with local recurrence or metastasis was poor. Surgery is the most reliable treatment for sarcomas of the oral and maxillofacial region. Adequate excision with safety surgical margin as the initial therapy is important for better survival. The value of radiation therapy and/or chemotherapy is uncertain. The 5-year survival rate of primary cases was 61%.

Application of an absorption-based surface plasmon resonance principle to the development of SPR ammonium ion and enzyme sensors.

Two new types of surface plasmon resonance (SPR) sensors that can determine the concentration of ammonium cations and urea were realized based on the previously reported theory of the absorption-based SPR measurement method. The change of the dielectric constant caused by the change of the light absorption characteristics of dyes incorporated in a sensing membrane phase is utilized in these SPR sensors. The determination of ions using the SPR sensor was realized by detecting the SPR signals of the minimum reflectance related to the change of absorption spectra of the dye in the ion optode membrane consisting of an ammonium-selective ionophore (TD19C6) and a lipophilic cationic dye (KD-M11) that shows absorption spectral changes due to protonation and deprotonation. A SPR enzyme sensor that can determine the concentration of urea was prepared by the combination of this ion optode membrane and an enzyme membrane based on urease. With the newly developed SPR sensors, the intensity changes of the reflectance at the fixed SPR resonance angle are monitored, which is different from conventional SPR sensors where usually the change of the SPR resonance angles is detected. In a continuous-flow experiment using the SPR ion sensor for NH4+ ion determination, a dynamic measurement range from 10(-5) to 10(-2) M was achieved. In the case of the enzyme-based SPR urea sensor, a dynamic range from 10(-4) to 10(-1) M was observed in a stopped-flow batch arrangement. It is expected that this sensing technique can be applied for the SPR-based detection of a wide range of low molecular weight analytes.