Synthesis and Evaluation of Novel 1,2,6-Thiadiazinone Kinase Inhibitors as Potent Inhibitors of Solid Tumors

A focused series of substituted 4H-1,2,6-thiadiazin-4-ones was designed and synthesized to probe the anti-cancer properties of this scaffold. Insights from previous kinase inhibitor programs were used to carefully select several different substitution patterns. Compounds were tested on bladder, prostate, pancreatic, breast, chordoma, and lung cancer cell lines with an additional skin fibroblast cell line as a toxicity control. This resulted in the identification of several low single digit micro molar compounds with promising therapeutic windows, particularly for bladder and prostate cancer. A number of key structural features of the 4H-1,2,6-thiadiazin-4-one scaffold are discussed that show promising scope for future improvement.     

Fine-structure effects in relativistic calculations of the static polarizability of the helium atom

We use the relativistic configuration-interaction method and the model potential method to calculate the scalar and tensor components of the dipole polarizabilities for the excited states 1s3p ³ P ₀ and 1s3p ³ P ₂ of the helium atom. The calculations of the reduced matrix elements for the resonant terms in the spectral expansion of the polarizabilities are derived using two-electron basis functions of the relativistic Hamiltonian of the atom, a Hamiltonian that incorporates the Coulomb and Breit electron-electron interactions. We formulate a new approach to determining the parameters of the Fuss model potential. Finally, we show that the polarizability values are sensitive to the choice of the wave functions used in the calculations. Zh. éksp. Teor. Fiz. 115, 494–504 (February 1999)     

Observation of superdeformed states in 88Mo

High-spin states in ⁸⁸Mo were studied using the Gammasphere germanium detector array in conjunction with the Microball CsI(Tl) charged-particle detector system. Three γ-ray cascades with dynamic moments of inertia showing similar characteristics to superdeformed rotational bands observed in the neighbouring A= 80 region have been identified and assigned to the nucleus ⁸⁸Mo. The quadrupole moment of the strongest band, deduced by the Residual Doppler Shift Method, corresponds to a quadrupole deformation of β₂≈ 0.6. This confirms the superdeformed nature of this band. The experimental data are interpreted in the framework of total routhian surface calculations. All three bands are assigned to two-quasi-particle proton configurations at superdeformed shape. Received: 20 May 1999 / Revised version: 25 August 1999     

A tour construction heuristic for the travelling salesman problem

The tour construction heuristic that generates initial tours for the tour improvement heuristics plays an important role in solving the travelling salesman problem (TSP). With the help of an effective tour construction heuristic, the performance of a heuristic can be improved. In this study we present a new tour construction algorithm, the construction priority (CP). We incorporate the performance of the CP into metaheuristics such as tabu search, genetic algorithm, space smoothing, and noising methods. The performance of the CP is empirically compared with the nearest neighbour (NN) approach. Extensive computational comparison shows that the CP is considerably more effective compared to NN.     

Affine Approximation of Lipschitz Functions and Nonlinear Quotients

New concepts related to approximating a Lipschitz function between Banach spaces by affine functions are introduced. Results which clarify when such approximations are possible are proved and in some cases a complete characterization of the spaces X, Y for which any Lipschitz function from X to Y can be so approximated is obtained. This is applied to the study of Lipschitz and uniform quotient mappings between Banach spaces. It is proved, in particular, that any Banach space which is a uniform quotient of L _p , 1 < p < , is already isomorphic to a linear quotient of L _p . Submitted: June 1998, revised: December 1998.     

Nonlinear Dynamics of Motivational Flow

Motivational flow is the experience of intrinsic motivation, which is in turn the result of the levels of challenge and skill involvement for a particular task. The level of flow is predictive of the amount of time a person will spend in that task, and it is thought to form a basis for an individual's time allocation between occupational and leisure activities. In this study, 28 university students, many of whom were employed, completed a 7-day log of their daily activities, their duration, and provided ratings of the level of skills and challenges inherent in the task. The logs provided a time series of several hundred points for each participant, which were each subjected to nonlinear dynamical analysis through nonlinear regression. Principal results were: (1) Flow was chaotic for all subjects. (2) The average R ² for the nonlinear models was .22, compared to .02 for the linear counterpart. (3) R ² was higher for people who spent more time at paying jobs. Evidence for individual differences in dynamical character were uncovered.     

Positive Definite Toeplitz Completions

The problem of completing a partially prescribed Toeplitz matrixto a positive definite Toeplitz matrix is considered. The mainresult is a characterization of the patterns of specified entriesthat guarantee the existence of a positive definite Toeplitzcompletion of a partial positive definite Toeplitz matrix. Thischaracterization resolves affirmatively a conjecture of C. R.Johnson and L. Rodman.     

The neutron flux of a252Cf neutron activation analysis device using the MCNP code

This report presents results from the application of the Monte Carlo N-Particle (MCNP) computer code to the²⁵²Cf neutron activation analysis (NAA) Device in the Technical Physics Institute of the Heilongjiang Science Academy of the People's Republic of China. The thermal and epithermal neutron flux at the sample positions and the neutron and photon fluxes on the surfaces of the device were calculated. A comparison between the calculated and experimental thermal and epithermal neutron fluxes at sample positions yield relative errors of less than 10% for the thermal neutron flux.     

Decentralized Interaction and Co-Adaptation in the Repeated Prisoner&2018;s Dilemma

A Prisoner&2018;s dilemma that is repeated indefinitely has many equilibria; the problem of selecting among these is often approached using evolutionary models. The background of this paper is a number of earlier studies in which a specific type of evolutionary model, a genetic algorithm (GA), was used to investigate which behavior survives under selective pressure. However, that normative instrument searches for equilibria that may never be attainable. Furthermore, it aims for optimization and, accordingly, says what people should do to be successful in repeated prisoner&2018;s dilemma (RPD) type situations. In the current paper, I employ simulation to find out what people would do, whether this makes them successful or not. Using a replication of Miller&2018;s (1988) GA study for comparison, a model is simulated in which the population is spatially distributed across a torus. The agents only interact with their neighbors and locally adapt their strategy to what they perceive to be successful behavior among those neighbors. Although centralized GA-evolution may lead to somewhat better performance, this goes at the cost of a large increase in required computations while a population with decentralized interactions and co-adaptation is almost as successful and, additionally, endogenously learns a more efficient scheme for adaptation. Finally, when the agents&2018; perceptive capabilities are limited even further, so that they can only perceive how their neighbors are doing against themselves, rather than against all those neighbors&2018; opponents&2014;which essentially removes reputation as a source of information&2014;cooperation breaks down.