Near-Optimal Scheduling for LTL with Future Discounting

We study the search problem for optimal schedulers for the linear temporal logic (LTL) with future discounting. The logic, introduced by Almagor, Boker and Kupferman, is a quantitative variant of LTL in which an event in the far future has only discounted contribution to a truth value (that is a real number in the unit interval [0, 1]). The precise problem we study---it naturally arises e.g. in search for a scheduler that recovers from an internal error state as soon as possible---is the following: given a Kripke frame, a formula and a number in [0, 1] called a margin, find a path of the Kripke frame that is optimal with respect to the formula up to the prescribed margin (a truly optimal path may not exist). We present an algorithm for the problem; it works even in the extended setting with propositional quality operators, a setting where (threshold) model-checking is known to be undecidable

Discrete-time rewards model-checked

This paper presents a model-checking approach for analyzing discrete-time Markov reward models. For this purpose, the temporal logic probabilistic CTL is extended with reward constraints. This allows to formulate complex measures – involving expected as well as accumulated rewards – in a precise and succinct way. Algorithms to efficiently analyze such formulae are introduced. The approach is illustrated by model-checking a probabilistic cost model of the IPv4 zeroconf protocol for distributed address assignment in ad-hoc networks

A model checking approach to the parameter estimation of biochemical pathways

Model checking has historically been an important tool to verify models of a wide variety of systems. Typically a model has to exhibit certain properties to be classed ‘acceptable’. In this work we use model checking in a new setting; parameter estimation. We characterise the desired behaviour of a model in a temporal logic property and alter the model to make it conform to the property (determined through model checking). We have implemented a computational system called MC2(GA) which pairs a model checker with a genetic algorithm. To drive parameter estimation, the fitness of set of parameters in a model is the inverse of the distance between its actual behaviour and the desired behaviour. The model checker used is the simulation-based Monte Carlo Model Checker for Probabilistic Linear-time Temporal Logic with numerical constraints, MC2(PLTLc). Numerical constraints as well as the overall probability of the behaviour expressed in temporal logic are used to minimise the behavioural distance. We define the theory underlying our parameter estimation approach in both the stochastic and continuous worlds. We apply our approach to biochemical systems and present an illustrative example where we estimate the kinetic rate constants in a continuous model of a signalling pathway

Jain States in a Matrix Theory of the Quantum Hall Effect

The U(N) Maxwell-Chern-Simons matrix gauge theory is proposed as an extension of Susskind's noncommutative approach. The theory describes D0-branes, nonrelativistic particles with matrix coordinates and gauge symmetry, that realize a matrix generalization of the quantum Hall effect. Matrix ground states obtained by suitable projections of higher Landau levels are found to be in one-to-one correspondence with the expected Laughlin and Jain hierarchical states. The Jain composite-fermion construction follows by gauge invariance via the Gauss law constraint. In the limit of commuting, ``normal'' matrices the theory reduces to eigenvalue coordinates that describe realistic electrons with Calogero interaction. The Maxwell-Chern-Simons matrix theory improves earlier noncommutative approaches and could provide another effective theory of the fractional Hall effect.Comment: 35 pages, 3 figure

An analysis of photoemission and inverse photoemission spectra of Si(111) and sulphur-passivated InP(001) surfaces

Photoemission (PES) and inverse-photoemission spectra (IPES) for the sulphur-passivated InP(001) surface are compared with theoretical predictions based on density-functional calculations. As a test case for our methods, we also present a corresponding study of the better known Si(111) surface. The reported spectra for InP(001)-S agree well with the calculated ones if the surface is assumed to consist of a mixture of two phases, namely, the fully S-covered $(2\times2)$-reconstructed structure, which contains four S atoms in the surface unit-cell, and a $(2\times2)$ structure containing two S and two P atoms per unit cell. The latter has recently been identified in total-energy calculations as well as in core-level spectra of S-passivated Si(111)-$(2\times1)$ is in excellent agreement with the calculations. The comparison of the experimental-PES with our calculations provides additional considerations regarding the nature of the sample surface. It is also found that the commonly-used density-of-states approximation to the photo- and inverse- photoemission spectra is not valid for these systems.Comment: Submitted to Phys. Rev. B; 6 postscript formatted pages; 7 figures in gif format; postscript figures available upon reques

p53 mutations in urinary bladder cancer

We have screened for mutations in exons 5–8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1–G2a) and 106 (56%) were highly malignant (G2b–G4 or ≥T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant. © 2001 Cancer Research Campaign http://www.bjcancer.co

Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer's and Parkinson's disease

BACKGROUND: Increasing evidence implicates dysfunctional proteostasis and the involvement of the autophagic and endo-lysosomal system and the ubiquitin-proteasome system in neurodegenerative diseases. In Alzheimer's disease (AD), there is an accumulation of autophagic vacuoles within the neurons. In Parkinson's disease (PD), susceptibility has been linked to genes encoding proteins involved in autophagy and lysosomal function, as well as mutations causing lysosomal disorders. Furthermore, both diseases are characterized by the accumulation of protein aggregates. METHODS: Proteins associated with endocytosis, lysosomal function, and the ubiquitin-proteasome system were identified in the cerebrospinal fluid (CSF) and targeted by combining solid-phase extraction and parallel reaction monitoring mass spectrometry. In total, 50 peptides from 18 proteins were quantified in three cross-sectional cohorts including AD (N = 61), PD (N = 21), prodromal AD (N = 10), stable mild cognitive impairment (N = 15), and controls (N = 68). RESULTS: A pilot study, including subjects selected based on their AD CSF core biomarker concentrations, showed increased concentrations of several targeted proteins in subjects with core biomarker levels indicating AD pathology compared to controls. Next, in a clinically characterized cohort, lower concentrations in CSF of proteins in PD were found compared to subjects with prodromal AD. Further investigation in an additional clinical study again revealed lower concentrations in CSF of proteins in PD compared to controls and AD. CONCLUSION: In summary, significantly different peptide CSF concentrations were identified from proteins AP2B1, C9, CTSB, CTSF, GM2A, LAMP1, LAMP2, TCN2, and ubiquitin. Proteins found to have altered concentrations in more than one study were AP2B1, CTSB, CTSF, GM2A, LAMP2, and ubiquitin. Interestingly, given the genetic implication of lysosomal function in PD, we did identify the CSF concentrations of CTSB, CTSF, GM2A, and LAMP2 to be altered. However, we also found differences in proteins associated with endocytosis (AP2B1) and the ubiquitin-proteasome system (ubiquitin). No difference in any peptide CSF concentration was found in clinically characterized subjects with AD compared to controls. In conclusion, CSF analyses of subjects with PD suggest a general lysosomal dysfunction, which resonates well with recent genetic findings, while such changes are minor or absent in AD