Dynamical Multiple-Timestepping Methods for Overcoming the Half-Period Time Step Barrier

Current molecular dynamic simulations of biomolecules using multiple time steps to update the slowingly changing force are hampered by an instability occuring at time step equal to half the period of the fastest vibrating mode. This has became a critical barrier preventing the long time simulation of biomolecular dynamics. Attemps to tame this instability by altering the slowly changing force and efforts to damp out this instability by Langevin dynamics do not address the fundamental cause of this instability. In this work, we trace the instability to the non-analytic character of the underlying spectrum and show that a correct splitting of the Hamiltonian, which render the spectrum analytic, restores stability. The resulting Hamiltonian dictates that in additional to updating the momentum due to the slowly changing force, one must also update the position with a modified mass. Thus multiple-timestepping must be done dynamically.Comment: 10 pages, 2 figures, submitted to J. Chem. Phy

Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis.

Tumor invasion and metastases represent a complex series of molecular events that portends a poor prognosis. The contribution of inflammatory pathways mediating this process is not well understood. Nod-like receptors (NLRs) of innate immunity function as intracellular sensors of pathogen motifs and danger molecules. We propose a role of NLRs in tumor surveillance and in programming tumor-infiltrating lymphocytes (TILs). In this study, we examined the downstream serine/threonine and tyrosine kinase Rip2 in a murine model of bladder cancer. In Rip2-deficient C57Bl6 mice, larger orthotopic MB49 tumors developed with more numerous and higher incidence of metastases compared to wild-type controls. As such, increased tumor infiltration of CD11b+ Gr1hi myeloid-derived suppressor cells (MDSCs) with concomitant decrease in T cells and NK cells were observed in Rip2-deficient tumor bearing animals using orthotopic and subcutaneous tumor models. Rip2-deficient tumors showed enhanced epithelial-to-mesenchymal transition, with elevated expression of zeb1, zeb2, twist, and snail in the tumor microenvironment. We found that the absence of Rip2 plays an intrinsic role in fostering the development of granulocytic MDSCs by an autocrine and paracrine effect of granulocytic colony stimulating factor (G-CSF) expression. Our findings suggest that NLR pathways may be a novel modality to program TILs and influence tumor metastases

Scalar field fluctuations in Schwarzschild-de Sitter space-time

We calculate quantum fluctuations of a free scalar field in the Schwarzschild-de Sitter space-time, adopting the planar coordinates that is pertinent to the presence of a black hole in an inflationary universe. In a perturbation approach, doing expansion in powers of a small black hole event horizon compared to the de Sitter cosmological horizon, we obtain time evolution of the quantum fluctuations and then derive the scalar power spectrum.Comment: 16 pages and 4 figures, accepted by Classical and Quantum Gravit

Fourth Order Algorithms for Solving the Multivariable Langevin Equation and the Kramers Equation

We develop a fourth order simulation algorithm for solving the stochastic Langevin equation. The method consists of identifying solvable operators in the Fokker-Planck equation, factorizing the evolution operator for small time steps to fourth order and implementing the factorization process numerically. A key contribution of this work is to show how certain double commutators in the factorization process can be simulated in practice. The method is general, applicable to the multivariable case, and systematic, with known procedures for doing fourth order factorizations. The fourth order convergence of the resulting algorithm allowed very large time steps to be used. In simulating the Brownian dynamics of 121 Yukawa particles in two dimensions, the converged result of a first order algorithm can be obtained by using time steps 50 times as large. To further demostrate the versatility of our method, we derive two new classes of fourth order algorithms for solving the simpler Kramers equation without requiring the derivative of the force. The convergence of many fourth order algorithms for solving this equation are compared.Comment: 19 pages, 2 figure

Determining Personal Evolving Topic-need to Support Information Search Activities

With the growing amount of information in the organizational memories of knowledge-intensive work environments, knowledge workers are suffering increasingly from information overload. Hence, an important aspect of effective knowledge delivery is supporting task-relevant knowledge by considering the characteristics of tasks and the nature of workers’ search behavior in organizations. The pilot research models in the information seeking (IS) research area show that workers’ information seeking activities exhibit common patterns. Based on the observations of previous studies, this work investigates the issues involved in determining the variations in task-relevant topics to support the information search process. Specifically, we provide an overview of the ISP model and theory; propose an evolving topic-needs determination method to examine the variety of a worker’s information needs for topics across task-stages; and identify a worker’s task-needs precisely by interactively mapping his/her information needs to the specific level of topics in the taxonomy. We have conducted an evaluation in a research institute which has implications for assisting workers who search the relevance information while conducting a long-term research project

Amortised resource analysis with separation logic

Type-based amortised resource analysis following Hofmann and Jost—where resources are associated with individual elements of data structures and doled out to the programmer under a linear typing discipline—have been successful in providing concrete resource bounds for functional programs, with good support for inference. In this work we translate the idea of amortised resource analysis to imperative languages by embedding a logic of resources, based on Bunched Implications, within Separation Logic. The Separation Logic component allows us to assert the presence and shape of mutable data structures on the heap, while the resource component allows us to state the resources associated with each member of the structure. We present the logic on a small imperative language with procedures and mutable heap, based on Java bytecode. We have formalised the logic within the Coq proof assistant and extracted a certified verification condition generator. We demonstrate the logic on some examples, including proving termination of in-place list reversal on lists with cyclic tails

Thermodynamical Properties and Quasi-localized Energy of the Stringy Dyonic Black Hole Solution

In this article, we calculate the heat flux passing through the horizon $. {\bf TS}|_{r_h}$ and the difference of energy between the Einstein and M{\o}ller prescription within the region ${\cal M}$, in which is the region between outer horizon ${\cal H}_+$ and inner horizon ${\cal H}_-$, for the modified GHS solution, KLOPP solution and CLH solution. The formula . E_{\rm Einstein}|_{\cal M} = . E_{\rm M{\o}ller}|_{\cal M} - \sum_{\partial {\cal M}} {\bf TS}$ is obeyed for the mGHS solution and the KLOPP solution, but not for the CLH solution. Also, we suggest a RN-like stringy dyonic black hole solution, which comes from the KLOPP solution under a dual transformation, and its thermodynamical properties are the same as the KLOPP solution