A rational approach to selective pharmacophore designing: an innovative strategy for specific recognition of Gsk3β

We propose a novel cheminformatics approach that combines structure and ligand-based design to identify target-specific pharmacophores with well-defined exclusion ability. Our strategy includes the prediction of selective interactions, developing structure, and knowledge-based selective pharmacophore models, followed by database screening and molecular docking. This unique strategy was employed in addressing the off-target toxicity of Gsk3β and CDKs. The connections of Gsk3β in eukaryotic cell apoptosis and the extensive potency of Gsk3β inhibitors to block cell death have made it a potential drug-discovery target for many grievous human disorders. Gsk3β is phylogenetically very closely related to the CDKs, such as CDK1 and CDK2, which are suggested to be the off-target proteins of Gsk3β inhibitors. Here, we have employed novel computational approaches in designing the ligand candidates that are potentially inhibitory against Gsk3β, with well-defined the exclusion ability to CDKs. A structure-ligand -based selective pharmacophore was modeled. This model was used to retrieve molecules from the zinc database. The hits retrieved were further screened by molecular docking and protein-ligand interaction fingerprints. Based on these results, four molecules were predicted as selective Gsk3β antagonists. It is anticipated that this unique approach can be extended to investigate any protein-ligand specificity.     

The discovery of polyacetylene film – the dawning of an era of conducting polymers

This lecture is not directly related to our discovery and development of conducting polymers to which the Nobel Prize in Chemistry 2000 was awarded. However, I would like to present my previous work that I had carried out just before we reached the discovery of chemical doping. I do hope my talk will be of use for you the audience to deepen your understandings by learning what had happened before and how we did reach the idea of chemical doping.     

Laser-induced ablation of polymers using a patterned dopant generated from a leuco-dye precursor via flood exposure: A “portable conformable mask” approach to laser ablation of PMMA at 351 nm

A two-stage laser ablation process is described, which initially generates a laser-light absorbing image from a conventional photolithographic mask via a UV-flood exposure step. For this purpose a colorless precursor of a dye, i.e., itsleuco form, is imbedded into the polymer to be ablated as a dopant. For poly(methyl methacrylate) as such a polymer, triphenylmethanol, the leuco precursor for the corresponding triphenylmethyl dye represents a good choice for ablation with excimer lasers operating at the wavelength 351 nm. In this fashion conventional masks and exposure tools of UV-photolithography may be used in combination with laser ablation. The resulting images are characterized by a good contrast and reasonably sharp contours. The photochemical mechanism and additional aspects of this two-step process, which resembles the portable conformal mask approach of photolithography, are outlined.     

Chemical and physical surface modification of PTFE films—an approach to produce stable electrets

The thermal stability of positive charge has been investigated in chemically and physically treated polytetrafluoroethylene (PTFE) films. It has been found that virgin films, oriented by the manufacturer, display an increase in thermal stability of positive charge with an increase of the initial value of surface potential. Such an anomalous behavior is explained by the influence of a negative tribocharge, trapped some small distance below the surface. In PTFE samples treated with orthophosphoric acid and with tetraethoxysilane, a?considerable improvement of positive charge stability has been achieved, but no influence of the initial value of surface potential has been observed. However, this influence should be kept in mind when comparing charge stability in virgin and modified samples. In nonoriented PTFE films, no influence of the initial value of surface potential on charge stability has been observed. This could be due to the fact that these films did not possess a noticeable negative tribocharge. After the treatment in glow-discharge defluorination, oxidation and appearance of polar groups have been detected on the surface. These changes in chemical composition of a PTFE surface resulted in a noticeable improvement in thermal stability of positively charged electrets. This improvement is attributed to the formation of deeper traps on the modified surface.     

A variational approach to the modulational-oscillatory instability of Bose–Einstein condensates in an optical potential

We use the time-dependent variational approach to demonstrate how the modulational and oscillatory instabilities can be generated in Bose–Einstein condensates (BECs) trapped in a periodic optical lattice with weak driving harmonic potential. We derive and analyze the ordinary differential equations for the time evolution of the amplitude and phase of the modulational perturbation, and obtain the instability condition of the condensates through the effective potential. The effect of the optical potential on the dynamics of the BECs is shown. We perform direct numerical simulations to support our theoretical findings, and good agreement is found.     

“Polarized Fusion”: New Aspects of an Old Project

A few new considerations with respect to energy production by low-energy nuclear fusion reactions will be discussed. A summary of the present status of nuclear fusion is given with emphasis on utilizing spin-polarized particles as fuel. The reactions considered are those concerning the four- and five-nucleon systems and especially the D + D reactions for which the status of the theory and the experimental data are presented. Recent progress has been achieved by microscopic calculations of the D + D reactions. New aspects concern the increased cross sections at very low energies by electron screening as well as the dynamics of the implosion scenario in inertial-fusion pellets with polarized fuel. The need to get more experimental data is pointed out.     

“Synthetic metals”: a novel role for organic polymers

Since the initial discovery in 1977, that polyacetylene (CH)_x, now commonly known as the prototype conducting polymer, could be p- or n-doped either chemically or electronically to the metallic state, the development of the field conducting polymers, “synthetic metals”, has continued to accelerate at an unexpectedly rapid rate and a variety of other conducting polymers and their derivatives have been discovered. Potential new science/technology has been developed by combining the now well established field of electronic polymers (intrinsically conducting polymers – “synthetic metals”, when doped) with the emerging field of nanoscience (one dimension <100 nm). A simple and inexpensive method is described for producing conducting patterns of electronic polymers on plastic and paper from computer-designed patterns. This method, “Line Patterning”, does not involve printing of the conducting polymers. The difference in hydrophobicity/hydrophilicity between a substrate and a line of regular toner printed on it by a non-modified, standard ofiice laser printer results in conducting polymer areas separated by insulating toner lines.     

Analytic extrapolation inL ∞-norm: An alternative approach to “QCD Sum Rules”

In view of physical applications (especially to QCD Sum Rules), the following problem, pertaining to analytic extrapolation techniques, is studied. We are considering amplitudes, which are (real) analytic functions in the complex plane cut along=[s ₀, ). A modelF ₀(s) of the amplitude is given through the values ofF ₀(s) on some interval=[s ₂,s ₁] (withs ₁<s ₀) and the values of its discontinuity on. These values are approximate, and are supplemented by prescribed error channels, measured inL -norm (both on and). Investigating the compatibility between these data leads to an extremum problem which is solved up to a point where numerical methods can be implemented.Unité Associée au CNRS n^o040768     

Reply to Comment on “Permanent Electric Dipole Moment of an Rb Atom”

The result of our experiment on Rb atoms is interesting and surprising .To affirm or to refuse the result should not be by conjectures but by experiments.     

Padé approximant approach to singular properties of quantum gases: the ideal cases

In this paper, we show how to recover the low-temperature and high-density information of ideal quantum gases from the high-temperature and low-density approximation by the Padéapproximant. The virial expansion is a high-temperature and low-density expansion and in practice, often, only the first several virial coefficients can be obtained. For Bose gases, we determine the BEC phase transition from a truncated virial expansion. For Fermi gases, we recover the low-temperature and high-density result from the virial expansion.     

Combined primary–secondary system approach to the design of an equipment isolation system with High-Damping Rubber Bearings

Isolating acceleration-sensitive equipment from the motion of the supporting structure represents an effective protection from earthquake damage. In this paper, a passive equipment isolation system composed of High-Damping Rubber Bearings (HDRB) is designed by adopting a coupled approach in which the supporting structure and the isolated equipment are considered as parts of a combined primary–secondary system and analyzed together. This allows for taking into account their dynamic interaction when significant and non-negligible according to the mass ratio and to the frequency ratio. The design methodology is developed by resorting to a reduced-order 2-DOF model of the combined system, a linear visco-elastic constitutive model of the isolation system and to a modal damping constraint depending upon the damping properties of the HDRB and their rubber compound. A 1:5 scale experimental model, consisting of a two-storey steel frame and a heavy block-type mass isolated from the second floor, is subsequently used to exemplify the design methodology and to perform shaking table tests. The dynamic properties of the experimental model are identified and the seismic performance of the equipment isolation system is discussed under a wide selection of seismic inputs, both artificial and natural.     

On the Decay of an “Isolated” Oscillator Nonlinearly Coupled to a Damped Oscillator

JETP Letters - Mechanisms of pumping and decay of an “isolated” oscillator which can nonlinearly interact with a neighboring oscillator having a different frequency have been discussed....     

Logical inference approach to relativistic quantum mechanics: Derivation of the Klein–Gordon equation

The logical inference approach to quantum theory, proposed earlier De Raedt et al. (2014), is considered in a relativistic setting. It is shown that the Klein–Gordon equation for a massive, charged, and spinless particle derives from the combination of the requirements that the space–time data collected by probing the particle is obtained from the most robust experiment and that on average, the classical relativistic equation of motion of a particle holds.     

Topological approach to examine the singularity of the axial-vector current in an Abelian gauge field theory （QED）

A topological way to distinguish divergences of the Abelian axial-vector current in quantum field theory is proposed. By using the properties of the Atiyah-Singer index theorem, the nomtrivial Jacobian factor of the integration measure in the path-integral formulation of the theory is connected with the topological properties of the gauge field. The singularity of the fermion current related to the topological character can be correctly examined in a gauge background.