Dielectric and piezoelectric properties of [0 0 1] and [0 1 1]-poled relaxor ferroelectric PZN–PT and PMN–PT single crystals

The properties of PZN–PT and PMN–PT single crystals of varying compositions and orientations have been investigated. Among the various compositions studied, [0 0 1]-optimally poled PZN-(6–7)%PT and PMN-30%PT exhibit superior dielectric and piezoelectric properties, with K^T ≈ 6800–8000, d₃₃ ≈ 2800 pC/N, d₃₁ ≈ −(1200–1800) pC/N for PZN-(6–7)%PT; and K^T = 7500–9000, d₃₃ = 2200–2500 pC/N and d₃₁ = −(1100–1400) pC/N for PMN-30%PT. These two compositions are also fairly resistant to over-poling. The [0 0 1]-poled electromechanical coupling factors (k₃₃, k₃₁ and k_t) are relatively insensitive to crystal composition. [0 1 1]-optimally poled PZN-7%PT single crystal also exhibits extremely high d₃₁ values of up to −4000 pC/N with k₃₁ ≈ 0.90–0.96. While [0 1 1]-poled PZN-7%PT single crystal becomes over-poled with much degraded properties when poled at and above 0.6 kV/mm, PZN-6%PT crystal shows no signs of over-poling even when poled to 2.0 kV/mm. The presence of a certain amount (i.e., 10–15%) of orthorhombic phase in a rhombohedral matrix has been found to be responsible for the superior transverse piezoelectric properties of [0 1 1]-optimally poled PZN-(6–7)%PT. The present work shows that flux-grown PZN–PT crystals exhibit superior and consistent properties and improved over-poling resistance to flux-grown PMN–PT crystals and that, for or a given crystal composition, flux-grown PMN–PT crystals exhibit superior over-poling resistance to their melt-grown counterparts.     

Doping effect of Ir(ppy)3 on white-light electrophosphorescent devices based on platinum(II) [1,3-difluoro-4,6-di(2-pyridinyl)benzene] chloride

Phosphorescent white organic light-emitting diodes (WOLEDs) based on single doped platinum(II) [1,3-difluoro-4,6-di(2-pyridinyl)benzene] chloride (Pt-4) emission layers were investigated in this paper. The devices exhibited electroluminescence spectra composed of bluish (λ_max = 480 nm) and reddish (λ_max = 660 nm) emission bands, which corresponding to monomer and excimer emission originated from Pt-4 dopants. With optimized device structures, a maximum current efficiency of 11.5 cd/A was obtained and remained above 10 cd/A even the brightness was over 6000 cd/m². Furthermore, by integrating the fac-tris(2-phenylpyridine) iridium(III) as a complementary emitter and an additional 2,2′,2″-(1,3,5-phenylene)-tris(1-phenyl-1H-benzimidazole) space layer, the device efficiency was further improved, which exhibited a maximum current efficiency of 20.4 cd/A at the luminance of 100 cd/m², and maintained the mild efficiency roll-off that similar to its single Pt-4 doped counterpart.     

Systematic profiling of substrate binding response to multidrug-resistant mutations in HIV-1 protease: Implication for combating drug resistance

Human immunodeficiency virus 1 (HIV-1) protease (PR) represents one of the primary targets for developing antiviral agents for the treatment of HIV-infected patients. However, a number of multidrug-resistant mutations in the enzyme have been observed over the past decades, largely limiting the application of PR inhibitors in antiviral therapy. A systematic investigation of the intermolecular interaction between the multidrug-resistant mutants of HIV-1 PR and its substrates would help to establish a complete profile of substrate response to PR mutations and to design new antiviral agents combating drug resistance. Here, we describe an integrative method to profile 6 clinical multidrug-resistant PR mutants against a panel of 16 substrate octapeptides that flank 12 distinct PR cleavage sites in viral precursor polyproteins. It is found that most multidrug-resistant mutations have only a modest or moderate effect on substrate peptide binding, although these mutations would cause a large free energy loss in PR inhibitor binding. Structural analysis reveals that the substrate peptides are loosely bound within PR active pocket to form a wide contact interface between them, and thus mutation of just single or few residues seems not to influence PR–substrate binding considerably. In addition, peptides derived from variable cleavage sites are generally more sensitive to the mutations as compared to those derived from conserved sites, supporting the co-evaluation mechanism of HIV-1 PR and its substrates under drug suppression. We also identify 12 functionally conserved key residues around the enzyme’s active site, which play crucial role in substrate recognition. In vitro fluorescence anisotropy assays confirm that wild-type PR can bind substrate peptides ARVL/AEAM and NLAF/PQGE with a moderately high affinity (K_D = 2 and 16 μM, respectively). In contrast, the key residue mutations N25D/D29N can completely eliminate (K_D = n.d.) or largely reduce (K_D = 32 and 120 μM, respectively) the binding capability of the two peptides, suggesting that these PR residues could be the potential target sites for developing resistance-free anti-HIV agents.     

Designing of potential inhibitors against Staphylococcus aureus sortase A: Combined analogue and structure based approach with in vitro validation

Staphylococcus aureus sortase A is an attractive target of Gram-positive bacteria that plays a crucial role in anchoring of surface proteins to peptidoglycan present in bacterial cell wall. Inhibiting sortase A is an elementary and essential effort in preventing the pathogenesis. In this context, in silico virtual screening of in-house database was performed using ligand based pharmacophore model as a filter. The developed pharmacophore model AAHR 11 consists of two acceptors, one hydrophobic and one ring aromatic feature. Top ranked molecule KKR1 was docked into the active site of the target. After profound analysis, it was analyzed and optimized based on the observations from its binding pose orientation. Upgraded version of KKR1 was KKR2 and has improved docking score, binding interactions and best fit in the binding pocket. KKR1 along with KKR2 were further validated using 100 ns molecular dynamic studies. Both KKR1 and KKR2 contain Indole-thiazolidine moiety and were synthesized. The disk diffusion assay has good initial results (ZI of KKR1, KKR2 were 24, 38 mm at 10 μg/mL and ZI of Ampicillin was 22 at 10 μg/mL) and calculated MICs of the molecules (KKR1 5.56 ± 0.28 μg/mL, KKR2 1.32 ± 0.12 μg/mL, Ampicillin 8 ± 1.1 μg/mL) were in good agreement with standard drug Ampicillin. KKR1 has shown IC₅₀ of 1.23 ± 0.14 μM whereas the optimized lead molecule KKR2 show IC₅₀ of 0.008 ± 0.07 μM. Results from in silico were validated by in vitro studies and proved that indole-thiazolidine molecules would be useful for future development as lead molecules against S. aureus sortase A.     

Red emitting MTiO3 (M = Ca or Sr) phosphors doped with Eu3+ or Pr3+ with some cations as co-dopants

Ca (or Sr)TiO₃:Eu³⁺, M (Li⁺ or Na⁺ or K⁺) and CaTiO₃:Pr³⁺, M (Li⁺ or Na⁺ or Ag⁺ or K⁺ or Gd³⁺ or La³⁺) powders were prepared by combustion synthesis method and the samples were further heated to ～1000 °C to improve the crystallinity. The structure and morphology of materials were examined by X-ray diffraction (XRD) and a scanning electron microscopy (SEM). The morphologies of SrTiO₃:Eu³⁺, CaTiO₃:Eu³⁺ or CaTiO₃:Pr³⁺ powders co-doped with other metal ions were very similar. Small and coagulated particles of nearly cubical shapes with small size distribution having smooth and regular surface were formed. Photo-luminescence spectra of CaTiO₃:Pr³⁺ and co-doped either with Li⁺, Na⁺, K⁺, Ag⁺, La³⁺ or Gd³⁺ ions showed red emissions at 613 nm due to the ¹D₂ → ³H₄ transition of Pr³⁺. The variation of intensity of emission peak with different co-doping follows the order: K⁺ > Ag⁺ > Na⁺ > Li⁺ > La³⁺ > Gd³⁺. The characteristic emissions of CaTiO₃:Eu³⁺ lattices had strong emission at 614 and 620 nm for ⁵D₀ → ⁷F₂ with other weak transitions observed at 580, 592, 654, 705 nm for ⁵D₀ → ⁷F_n transitions where n = 0, 1, 3, 4 respectively in all host lattices. Photoluminescence intensity in SrTiO₃:Eu³⁺ is more than CaTiO₃:Eu³⁺ lattices. A remarkable increase of photoluminescence intensity (in ⁵D₀ → ⁷F₂ transition) was observed if co-doped with Li⁺ ions in CaTiO₃:Eu³⁺ and SrTiO3:Eu³⁺.     

On Computations in Kummer Extensions

Let k be an algebraic number field containing a primitive m th root of unity. An extension K = k([m ] μ) of k with μ ∈ k is called a Kummer extension. These extensions have been studied extensively in the past and they play an important role in class field theory. Recently many new algorithms dealing with Kummer extensions emerged. In this paper we will give algorithms to solve two problems, which are of particular interest; the computation of the relative discriminant dK / k and the computation of Hilbert norm symbols.     

Modal analysis and modified cascade neural networks in identification of geometrical parameters of circular arches

A hybrid computational system, composed of the finite element method (FEM) and cascade neural network system (CNNs), is applied to the identification of three geometrical parameters of elastic arches, i.e. span l, height f and cross-sectional thickness h. FEM is used in the direct (forward) analysis, which corresponds to the mapping α = {l, f, h} → {ω_j}, where: α – vector of control parameters, ω_j – arch eigenfrequencies. The reverse analysis is related to the identification procedure in which the reverse mapping is performed {ω_j} → {α_i}. For the identification purposes a recurrent, three level CNNs of structure (D^k-H^k-1)_s was formulated, where: k – recurrence step, s = I, II, III-levels of cascade system. The Semi-Bayesian approach is introduced for the design of CNNs applying the MML Maximum Marginal Likelihood) criterion. The computation of hyperparameters is performed by means of the Bayesian procedure evidence. The numerical analysis proves a great numerical efficiency of the proposed hybrid approach for both the perfect (noiseless) values of eigenfrequencies and noisy ones simulated by an added artificial noise.     

A mechanistic approach to explore novel HDAC1 inhibitor using pharmacophore modeling, 3D- QSAR analysis,molecular docking,density functional and molecular dynamics simulation study

Deregulated epigenetic activity of Histone deacetylase 1 (HDAC1) in tumor development and carcinogenesis pronounces it as promising therapeutic target for cancer treatment. HDAC1 has recently captured the attention of researchers owing to its decisive role in multiple types of cancer. In the present study a multistep framework combining ligand based 3D-QSAR, molecular docking and Molecular Dynamics (MD) simulation studies were performed to explore potential compound with good HDAC1 binding affinity. Four different pharmacophore hypotheses Hypo1 (AADR), Hypo2 (AAAH), Hypo3 (AAAR) and Hypo4 (ADDR) were obtained. The hypothesis Hypo1 (AADR) with two hydrogen bond acceptors (A), one hydrogen bond donor (D) and one aromatics ring (R) was selected to build 3D-QSAR model on the basis of statistical parameter. The pharmacophore hypothesis produced a statistically significant QSAR model, with co-efficient of correlation r² = 0.82 and cross validation correlation co-efficient q² = 0.70. External validation result displays high predictive power with r² (o) value of 0.88 and r² (m) value of 0.58 to carry out further in silico studies. Virtual screening result shows ZINC70450932 as the most promising lead where HDAC1 interacts with residues Asp99, His178, Tyr204, Phe205 and Leu271 forming seven hydrogen bonds. A high docking score (−11.17 kcal/mol) and lower docking energy −37.84 kcal/mol) displays the binding efficiency of the ligand. Binding free energy calculation was done using MM/GBSA to access affinity of ligands towards protein. Density Functional Theory was employed to explore electronic features of the ligands describing intramolcular charge transfer reaction. Molecular dynamics simulation studies at 50 ns display metal ion (Zn)-ligand interaction which is vital to inhibit the enzymatic activity of the protein.     

Taylor approximation for hybrid systems

We propose a new approximation technique for Hybrid Automata. Given any Hybrid Automaton H, we call Approx(H, k) the Polynomial Hybrid Automaton obtained by approximating each formula ϕ in H with the formulae ϕ_k obtained by replacing the functions in ϕ with their Taylor polynomial of degree k. We prove that Approx(H, k) is an over-approximation of H. We study the conditions ensuring that, given any ϵ > 0, some k₀ exists such that, for all k > k₀, the “distance” between any vector satisfying ϕ_k and at least one vector satisfying ϕ is less than ϵ. We study also conditions ensuring that, given any ϵ > 0, some k₀ exists such that, for all k > k₀, the “distance” between any configuration reached by Approx(H, k) in n steps and at least one configuration reached by H in n steps is less than ϵ.     

Direct binding of microRNA-21 pre-element with Regorafenib: An alternative mechanism for anti-colorectal cancer chemotherapy?

The Regorafenib is a broad-spectrum kinase inhibitor that has been approved to treat colorectal cancer (CRC). However, evidences have shown that the agent is also implicated in drug interaction with microRNA-21 (miR-21), an oncogenic miRNA which plays a key role in resisting programmed cell death in CRC cells. Here, we supposed that, instead of kinase inhibition, Regorafenib can directly bind to and then stabilize miR-21 pre-element, thus preventing RNase Dicer-meditated cleavage of the pre-element to mature miR-21. In order to verify the notion, an in silico-in vitro integrated investigation of the direct intermolecular interaction between Regorafenib and miR-21 pre-element was performed by using active pocket identification, RNA–ligand docking, molecular dynamics (MD) simulation, binding energetic analysis, and fluorescence-based assay. It was revealed that the Regorafenib can bind at the major groove-like stem region of miR-21 pre-element through three geometrically satisfactory hydrogen bonds (H-bonds) as well as a number of hydrophobic forces and π-π stacking, conferring strong specificity and high stability to the RNA–ligand complex system (K_d = 0.73 μM). Separate inversion mutation of two base pairs (G6C, C12G) and (A13U, U4A) that are involved in the H-bonding can considerably impair the affinity of Regorafenib to miR-21 pre-element, with K_d increase to 27 and 96 μM, respectively. All these supported that Regorafenib can directly bind to miR-21 pre-element at molecular level and the binding mode can be properly modeled by using the proposed integrated strategy. This study would provide a potential, alternative mechanism for anti-colorectal cancer chemotherapy with Regorafenib.     

Curves of Genus 2 with (N,N) Decomposable Jacobians

Let C be a curve of genus 2 and ψ₁: C  −  → E ₁  a map of degree n, from C to an elliptic curveE₁ , both curves defined over C. This map induces a degree n map φ₁:P¹  −  → P ¹  which we call a Frey–Kani covering. We determine all possible ramifications for φ₁. If ψ₁:C  −  → E ₁  is maximal then there exists a maximal map ψ₂: C  −  → E ₂  , of degree n, to some elliptic curveE₂ such that there is an isogeny of degree n²from the JacobianJ_C to E₁ × E₂. We say thatJ_C is (n, n)-decomposable. If the degree n is odd the pair (ψ₂, E₂) is canonically determined. For n =  3, 5, and 7, we give arithmetic examples of curves whose Jacobians are (n, n)-decomposable.     

Computational assessment of several hydrogen-free high energy compounds

Tetrazino-tetrazine-tetraoxide (TTTO) is an attractive high energy compound, but unfortunately, it is not yet experimentally synthesized so far. Isomerization of TTTO leads to its five isomers, bond-separation energies were empolyed to compare the global stability of six compounds, it is found that isomer 1 has the highest bond-separation energy (1204.6 kJ/mol), compared with TTTO (1151.2 kJ/mol); thermodynamic properties of six compounds were theoretically calculated, including standard formation enthalpies (solid and gaseous), standard fusion enthalpies, standard vaporation enthalpies, standard sublimation enthalpies, lattice energies and normal melting points, normal boiling points; their detonation performances were also computed, including detonation heat (Q, cal/g), detonation velocity (D, km/s), detonation pressure (P, GPa) and impact sensitivity (h₅₀, cm), compared with TTTO (Q = 1311.01 J/g, D = 9.228 km/s, P = 40.556 GPa, h₅₀ = 12.7 cm), isomer 5 exhibites better detonation performances (Q = 1523.74 J/g, D = 9.389 km/s, P = 41.329 GPa, h₅₀ =  28.4 cm).     

Critical pressure for capillary valves in a Lab-on-a-Disk: CFD and flow visualization

Capillary valves are used as pressure barriers to control flow sequencing in microfluidic devices. Influence of valves height on liquid flow pattern and critical pressure are studied through flow visualization and CFD predictions (Gambit® 2.2.30 and FLUENT® 6.2.16). Both hydrophilic and hydrophobic walls are studied. Results show that the surface tension plays a major role in the liquid progress through the microchannel/valve and also in the valve filling process. Critical pressure varies linearly with the valve hydraulic diameter in the range 0.91 < D_h < 3.5 [mm] according to: P = 14.14 · D_h + 47.42 [Pa].     

Giant-grain silicon (GGS) and its application to stable thin-film transistor

We developed a giant-grain silicon (GGS) by Ni-mediated crystallization of amorphous silicon (a-Si) with a silicon-nitride (SiN_x) cap layer. Ni particles were sputtered onto the SiN_x/a-Si layer and then it was annealed at around 600 °C. The Ni diffuses through a SiN_x cap and then forms NiSi₂ crystallites in a-Si, which is able to induce crystallization. The grain size can be controlled from a few to 100 μm. The grain size can be increased with increasing the cap layer thickness or by decreasing the Ni density on the SiN_x. The p-channel GGS poly-Si TFT exhibited a field-effect mobility of 101 cm²/Vs and a threshold voltage of −3.6 V and is very stable under gate or hot carrier bias-stress. These superior performances may be due to the smooth surface of GGS poly-Si and solid-phase crystallization of a-Si.     

Linear Differential Operators for Polynomial Equations

Given a squarefree polynomial P ∈ k₀[ x,y ], k₀a number field, we construct a linear differential operator that allows one to calculate the genus of the complex curve defined by P =  0 (when P is absolutely irreducible), the absolute factorization of P over the algebraic closure of k₀, and calculate information concerning the Galois group of P over ___ k₀(x) as well as overk₀ (x).     

Computing Modular Invariants of p-groups

Let V be a finite dimensional representation of a p -group, G, over a field,k , of characteristic p. We show that there exists a choice of basis and monomial order for which the ring of invariants, k [ V ]^G, has a finite SAGBI basis. We describe two algorithms for constructing a generating set for k [ V ] G. We use these methods to analyse k [2V₃ ]^U₃where U₃is the p -Sylow subgroup ofGL₃ (F_p) and 2 V₃is the sum of two copies of the canonical representation. We give a generating set for k [2 V₃]^U₃forp =  3 and prove that the invariants fail to be Cohen–Macaulay forp >  2. We also give a minimal generating set for k [mV₂ ]^Z / pwere V₂is the two-dimensional indecomposable representation of the cyclic group Z / p.     

Development of a mercury optical sensor based on immobilization of 4-(2-pyridylazo)-resorcinol on a triacetylcellulose membrane

A new optical sensor for mercury(II) ions is developed based on immobilization of 4-(2-pyridylazo)-resorcinol (PAR) on a triacetylcellulose membrane. Chemical binding of Hg²⁺ ions in solution with a PAR immobilized on the triacetylcellulose surface could be monitored spectrophotometrically at 525 nm. The optode shows excellent response over a wide concentration range of 5–3360 μM Hg(II) with a limit of detection of 1.5 μM Hg(II). The influence of factors responsible for the improved sensitivity of the sensor were studied and identified. The response time of the optode was 20 min for a stable solution, and was 15 min for a stirrer solution. The influence of potential interfering ions on the determination of 5 × 10⁻⁵ M Hg(II) was studied. The sensor was applied for determination of Hg(II) in water samples.     

Fabrication and characterization of a thermal switch

The development of a thermal switch based on arrays of liquid–metal micro-droplets is presented. Prototype thermal switches are assembled from a silicon substrate on which is deposited an array of 1600 30-μm liquid–metal micro-droplets. The liquid–metal micro-droplet array makes and breaks contact with a second bare silicon substrate. A gap between the two silicon substrates is filled with either air at 760 Torr, air at of 0.5 Torr or xenon at 760 Torr. Heat transfer and thermal resistance across the thermal switches are measured for “on” (make contact) and “off” (break contact) conditions using guard-heated calorimetry. The figure of merit for a thermal switch, the ratio of “off” state thermal resistance over “on” state thermal resistance, R_off/R_on, is 129 ± 43 for a xenon-filled thermal switch that opens 100 μm and 60 ± 17 for an 0.5 Torr air-filled thermal switch that opens 25 μm. These thermal resistance ratios are shown to be markedly higher than values of R_off/R_on for a thermal switch based on contact between polished silicon surfaces. Transient temperature measurements for the liquid–metal micro-droplet switches indicate thermal switching times of less than 100 ms. Switch lifetimes are found to exceed one-million cycles.     

Ferroelectric properties of direct-patterned half-micron thick PZT film

Ferroelectric properties of direct-patterned PZT(PbZr_0.52Ti_0.48O₃) films with 460 μm × 460 μm size and 510 nm thick were analyzed for applying to micro-detecting devices. A photosensitive solution containing ortho-nitrobenzaldehyde was used for the preparation of direct-patterned PZT film. PZT solution was coated on Pt(1 1 1)/Ti/SiO₂/Si(1 0 0) substrate for three times to obtain half-micron thick film and three times of direct-patterning process were repeated to define a pattern on multi-layer PZT film. Through intermediate and final anneal procedure of direct-patterned PZT film, any shrinkage along horizontal direction was not observed within this experimental condition, i.e., the size of the pattern was preserved after annealing, only a thickness reduction was observed after each annealing treatment. Ferroelectric properties of direct-patterned PZT film with 460 μm × 460 μm size and 510 nm thick were compared with those of un-patterned conventional PZT film and shown to be almost the same. Through this work, the high potentiality of direct-patternable PZT film for applying to micro-devices without the introduction of physical damages from dry-etching could be confirmed.     

Identification of novel PAD4 inhibitors based on a pharmacophore model derived from transition state coordinates

1.4 Protein arginine deiminases 4 (PAD4) is an attractive target for the development of novel and selective inhibitors of Rheumatoid Arthritis (RA). F-amidine is known as mechanism-based inhibitor targeting PAD4 and used as inactivators by covalently modifying the active site Cys645. To identify novel structural inhibitors of PAD4, we investigated the flexibility of protein on basis of the transition state geometry of PAD4 inhibited by F-amidine from our previous QM/MM calculation. And a pharmacophore model was generated containing four features (ADHH) using five representative structures from molecular dynamic (MD) simulation on basis of the transition state geometry of PAD4 inhibited by F-amidine. We performed virtual screening using the pharmacophore model and molecular docking methods, resulting in the discovery of two molecules with K_D (dissociation equilibrium constant) values of 112 μM and 218 μΜ against PAD4 through Surface Plasmon Resonance (SPR) experiments. These two molecules could potentially serve as PAD4 inhibitors.