Design of novel FLT-3 inhibitors based on dual-layer 3D-QSAR model and fragment-based compounds in silico

FMS-like tyrosine kinase 3 (FLT-3) is strongly correlated with acute myeloid leukemia, but no FLT-3-inhibitor cocomplex structure is available to assist the design of therapeutic inhibitors. Hence, we propose a dual-layer 3D-QSAR model for FLT-3 that integrates the pharmacophore, CoMFA, and CoMSIA. We then coupled the model with the fragment-based design strategy to identify novel FLT-3 inhibitors. In the first layer, the previously established model, Hypo02, was evaluated in terms of its correlation coefficient (r), RMS, cost difference, and configuration cost, with values of 0.930, 1.24, 106.45, and 16.44, respectively. Moreover, Fischer's cross-validation test of data generated by Hypo02 yielded a 98% confidence level, and the validation of the testing set yielded a best r value of 0.87. The features of Hypo02 were separated into two parts and then used to screen the MiniMaybridge fragment compound database. Nine novel FLT-3 inhibitors were generated in this layer. In the second layer, Hypo02 was subjected to an alignment rule to generate CoMFA- and CoMSIA-based models, for which the partial least-squares validation method was utilized. The values of q(2), r(2), and predictive r(2) were 0.58, 0.98, and 0.76, respectively, derived from the CoMFA model with steric and electrostatic fields. The CoMSIA model with five different fields yielded values of 0.54, 0.97, and 0.76 for q(2), r(2), and predictive r(2), respectively. The CoMFA and CoMSIA models were used to constrain 3D structures of the nine novel FLT-3 inhibitors. This dual-layer 3D-QSAR model constitutes a valuable tool to easily and quickly screen and optimize novel potential FLT-3 inhibitors for the treatment of acute myeloid leukemia.     

Preparation of polymer/silica hybrid hard coatings with enhanced hydrophobicity on plastic substrates

In this study, an easy method to increase hydrophobicity of the polymer/silica hybrid coating was demonstrated. UV-curable nano-sized colloidal silica was synthesized and surface-modified both by a coupling agent, 3-(trimethoxysilyl)propyl methacrylate (MSMA), and a capping agent, trimethyethoxysiliane (TMES). The formed particles were introduced into the poly(2-hydroxyethyl methacrylate) (PHEMA) matrix to yield PHEMA/silica hybrid hard coatings on plastic substrates via a UV-curing process. Differential scanning calorimetric (DSC) analyses of the hybrids indicated increases of the glass transition temperature (T_g) with increasing silica content in the hybrids; in general, an increase of 23 °C could be achieved for hybrids doped with 15 wt.% silica. Thermal decomposition temperature (T_d), as measured by the thermal gravimetric analyzer (TGA), was found to depend on the silica content in a trend similar to that on T_g. Specifically, a large increase of 25 °C was observed when the sample contained 15 wt.% silica. The pencil hardness of the PHEMA/silica hybrids coated on poly(methyl methacrylate) (PMMA) substrates can reach 5H, in comparison with 2H for pure PHEMA coating. Abrasion resistance was enhanced when silica nanoparticles were incorporated. Furthermore, due to the incorporation of TMES, hydrophobicity of the hybrid coating increased considerably as the TMES content was increased. In the extreme case, a hard surface with a water contact angle (92°) has been obtained.     

Which subnormal Toeplitz operators are either normal or analytic?

We study subnormal Toeplitz operators on the vector-valued Hardy space of the unit circle, along with an appropriate reformulation of P.R. Halmos?s Problem 5: Which subnormal block Toeplitz operators are either normal or analytic? We extend and prove Abrahamse?s theorem to the case of matrix-valued symbols; that is, we show that every subnormal block Toeplitz operator with bounded type symbol (i.e., a quotient of two bounded analytic functions), whose analytic and co-analytic parts have the “left coprime factorization”, is normal or analytic. We also prove that the left coprime factorization condition is essential. Finally, we examine a well-known conjecture, of whether every subnormal Toeplitz operator with finite rank self-commutator is normal or analytic.     

Ultrafast photovoltaic response in ferroelectric nanolayers

We show that light drives large-amplitude structural changes in thin films of the prototypical ferroelectric PbTiO3 via direct coupling to its intrinsic photovoltaic response. Using time-resolved x-ray scattering to visualize atomic displacements on femtosecond time scales, photoinduced changes in the unit-cell tetragonality are observed. These are driven by the motion of photogenerated free charges within the ferroelectric and can be simply explained by a model including both shift and screening currents, associated with the displacement of electrons first antiparallel to and then parallel to the ferroelectric polarization direction.     

Controlled Deterministic Secure Quantum Communication Based on Quantum Search Algorithm

In this study, we propose a controlled deterministic secure quantum communication (CDSQC) protocol based on the idea of Grover’s quantum search algorithm (QSA). The proposed protocol has the following two advantages over the existing CDSQC protocols: (1) high qubit frequency and (2) less quantum memory. Moreover, the security analysis of the proposed protocol shows that any eavesdropper will be detected with a very high probability under both ideal and noisy quantum channel conditions.     

Transport properties of Co<Subscript>2</Subscript>CrAl Heusler alloy films

The effect of atomic disorder on the electron transport and the magnetoresistance (MR) of Co₂CrAl Heusler alloy (HA) films has been investigated. We show that Co₂CrAl films with L2₁ order exhibit a negative value for the temperature coefficient of resistivity (TCR) in a temperature range of 10 < T < 290 K, and the temperature dependence of electric conductivity varies as T ^3/2 similarly to that of the zero-gap semiconductors. The atomic or the site disorder on the way of L2₁ → B2 → A2 → amorphous state in Co₂CrAl HA films causes the deviation from this dependence: reduction in the absolute value of TCR as well as decrease in the resistivity down to ?(T = 293 K) ～ 200 μΩ cm in comparison to ?(T = 293 K) ～ 230 μΩ cm typical for the Co₂CrAl films with L2₁ order. The magnetic-field dependence of MR of the Co₂CrAl films with L2₁ order is determined by two competing contributions: a positive Lorentz scattering and a negative s-d scattering. The atomic disorder in Co₂CrAl films drastically changes MR behavior due to its strong influence on the magnetic properties.     

Chemical vapor sensing properties of graphene based on geometrical evaluation

Graphene is a promising candidate for chemical vapor sensing. We prepared graphene sheets from highly oriented pyrolytic graphite through mechanical cleavage in order to investigate their responses to NH₃ and NO₂ as electron donors and acceptors, respectively. We investigated how the geometric characteristics of graphene, such as length-to-width (L/w) ratio and number of layers, affect chemical sensing properties at room temperature and ambient atmosphere. In this study, the L/w ratio of an individual graphene sheet, which is related to graphene conductivity, dominated the NH₃ sensing characteristics, while the number of graphene layers had no significant effect. We also studied the effects of various thermal treatments on graphene sensitivity and recovery time in an ambient atmosphere. This study confirms the effects of geometry, operation temperature and gas concentration on the NH₃ and NO₂ sensing performances of graphene.     

Postbuckling analysis and its application to stretchable electronics

A versatile strategy for fabricating stretchable electronics involves controlled buckling of bridge structures in circuits that are configured into open, mesh layouts (i.e. islands connected by bridges) and bonded to elastomeric substrates. Quantitative analytical mechanics treatments of the responses of these bridges can be challenging, due to the range and diversity of possible motions. Koiter (1945) pointed out that the postbuckling analysis needs to account for all terms up to the 4th power of displacements in the potential energy. Existing postbuckling analyses, however, are accurate only to the 2nd power of displacements in the potential energy since they assume a linear displacement–curvature relation. Here, a systematic method is established for accurate postbuckling analysis of beams. This framework enables straightforward study of the complex buckling modes under arbitrary loading, such as lateral buckling of the island-bridge, mesh structure subject to shear (or twist) or diagonal stretching observed in experiments. Simple, analytical expressions are obtained for the critical load at the onset of buckling, and for the maximum bending, torsion (shear) and principal strains in the structure during postbuckling.     

High spin states in neutron-rich 106Tc nucleus

The high spin states of the neutron-rich odd-odd 106Tc nucleus have been reinvestigated by observing prompt γ-rays from the spontaneous fission of 252Cf. A previously known collective band is confirmed and expanded, and a new collective band is newly identified. Several levels in previous report in 106Tc are reexamined and they belong to the members of a band in 107Tc. The total Routhian surface (TRS) calculations show that the 106Tc has triaxial shape. The spins and parities as well as the configurations for these bands have been tentatively assigned according to the analysis of the angular momentum alignments.     

Effect of DC bias on microstructural rearrangement of a-SiN:H films on PET substrate

Hydrogenated amorphous silicon nitride (a-SiN:H) films were deposited on flexible polyethylene terephthalate substrates at temperature as low as 100 °C by hot-wire chemical vapor deposition using SiH₄, H₂ and NH₃ precursors. Field emission scanning emission microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and small angle X-ray scattering were employed to study structural and microstructural properties of a-SiN:H films. The rms surface roughness increased with increase of positive bias to substrate. Intermediate range order, porosity and interface inhomogeneity in amorphous of a-SiN:H films evaluated by acoustic and optical phonon of silicon network, Guinier plot and correlated length from Raman and SAXS characterizations. The fractal behavior of a-SiN:H domains approached the perfect symmetry and the intermediate range order of a-SiN:H films deteriorate with increase of the positive substrate bias. Both correlation length and void size of the a-SiN:H amorphous domain increased with increase of the substrate bias from 0 to +200 V.