Leukocyte telomere length variability as a potential biomarker in patients with polyQ diseases

SCA1, SCA2, and SCA3 are the most common forms of SCAs among the polyglutamine disorders, which include Huntington's Disease (HD). We investigated the relationship between leukocyte telomere length (LTL) and the phenotype of SCA1, SCA2, and SCA3, comparing them with HD. The results showed that LTL was significantly reduced in SCA1 and SCA3 patients, while LTL was significantly longer in SCA2 patients. A significant negative relationship between LTL and age was observed in SCA1 but not in SCA2 subjects. LTL of SCA3 patients depend on both patient's age and disease duration. The number of CAG repeats did not affect LTL in the three SCAs. Since LTL is considered an indirect marker of an inflammatory response and oxidative damage, our data suggest that in SCA1 inflammation is present already at an early stage of disease similar to in HD, while in SCA3 inflammation and impaired antioxidative processes are associated with disease progression. Interestingly, in SCA2, contrary to SCA1 and SCA3, the length of leukocyte telomeres does not reduce with age. We have observed that SCAs and HD show a differing behavior in LTL for each subtype, which could constitute relevant biomarkers if confirmed in larger cohorts and longitudinal studies

Model Checking Probabilistic Pushdown Automata

We consider the model checking problem for probabilistic pushdown automata (pPDA) and properties expressible in various probabilistic logics. We start with properties that can be formulated as instances of a generalized random walk problem. We prove that both qualitative and quantitative model checking for this class of properties and pPDA is decidable. Then we show that model checking for the qualitative fragment of the logic PCTL and pPDA is also decidable. Moreover, we develop an error-tolerant model checking algorithm for PCTL and the subclass of stateless pPDA. Finally, we consider the class of omega-regular properties and show that both qualitative and quantitative model checking for pPDA is decidable

Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case–control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (<60 years) who survived a first MI and 653 age-matched controls from North and South Europe. Additionally, from the UK, 413 coronary artery bypass graft (CABG) patients and two groups of 367 and 94 FH patients, of whom 145 and 17 respectively had premature CHD, were recruited. Leukocyte telomere length (LTL) was measured using a real-time polymerase chain reaction-based method. In HIFMECH, LTL was significantly shorter in subjects from the North (7.99 kb, SD 4.51) compared to the South (8.27 kb, SD 4.14; p = 0.02) and in cases (7.85 kb, SD 4.01) compared to controls (8.04 kb, SD 4.46; p = 0.04). In the CABG study, LTL was significantly shorter (6.89 kb, SD 4.14) compared to the HIFMECH UK controls (7.53, SD 5.29; p = 0.007). In both samples of FH patients, LTL was shorter in those with CHD (overall 8.68 kb, SD 4.65) compared to the non-CHD subjects (9.23 kb, SD 4.83; p = 0.012). Apart from a consistent negative correlation with age, LTL was not associated across studies with any measured CHD risk factors. The present data confirms that subjects with CHD have shorter telomeres than controls and extends this to those with monogenic and polygenic forms of CHD

PALS-Based Analysis of an Airplane Multirate Control System in Real-Time Maude

Distributed cyber-physical systems (DCPS) are pervasive in areas such as aeronautics and ground transportation systems, including the case of distributed hybrid systems. DCPS design and verification is quite challenging because of asynchronous communication, network delays, and clock skews. Furthermore, their model checking verification typically becomes unfeasible due to the huge state space explosion caused by the system's concurrency. The PALS ("physically asynchronous, logically synchronous") methodology has been proposed to reduce the design and verification of a DCPS to the much simpler task of designing and verifying its underlying synchronous version. The original PALS methodology assumes a single logical period, but Multirate PALS extends it to deal with multirate DCPS in which components may operate with different logical periods. This paper shows how Multirate PALS can be applied to formally verify a nontrivial multirate DCPS. We use Real-Time Maude to formally specify a multirate distributed hybrid system consisting of an airplane maneuvered by a pilot who turns the airplane according to a specified angle through a distributed control system. Our formal analysis revealed that the original design was ineffective in achieving a smooth turning maneuver, and led to a redesign of the system that satisfies the desired correctness properties. This shows that the Multirate PALS methodology is not only effective for formal DCPS verification, but can also be used effectively in the DCPS design process, even before properties are verified.Comment: In Proceedings FTSCS 2012, arXiv:1212.657

A Metric Encoding for Bounded Model Checking (extended version)

In Bounded Model Checking both the system model and the checked property are translated into a Boolean formula to be analyzed by a SAT-solver. We introduce a new encoding technique which is particularly optimized for managing quantitative future and past metric temporal operators, typically found in properties of hard real time systems. The encoding is simple and intuitive in principle, but it is made more complex by the presence, typical of the Bounded Model Checking technique, of backward and forward loops used to represent an ultimately periodic infinite domain by a finite structure. We report and comment on the new encoding technique and on an extensive set of experiments carried out to assess its feasibility and effectiveness

Bounded Model Checking for Linear Time Temporal-Epistemic Logic

We present a novel approach to the verification of multi-agent systems using bounded model checking for specifications in LTLK, a linear time temporal-epistemic logic. The method is based on binary decision diagrams rather than the standard conversion to Boolean satisfiability. We apply the approach to two classes of interpreted systems: the standard, synchronous semantics and the interleaved semantics. We provide a symbolic algorithm for the verification of LTLK over models of multi-agent systems and evaluate its implementation against MCK, a competing model checker for knowledge. Our evaluation indicates that the interleaved semantics can often be preferable in the verification of LTLK

Genetic algorithms for DNA sequence assembly

This paper describes a genetic algorithm application to the DNA fragment assembly problems. The genetic algorithm uses a random key representation for representing the orderings of fragments. Two different fitness functions, both based on pairwise overlap strengths between fragments, were tested. The paper concludes that the genetic algorithm is a promising method for fragment assembly problems, achieving usable solutions quickly, but that the current fitness functions are flawed and that other representations might be more appropriate

Assembly and analysis of fragmentation data for liquid propellant vessels

Fragmentation data was assembled and analyzed for exploding liquid propellant vessels. These data were to be retrieved from reports of tests and accidents, including measurements or estimates of blast yield, etc. A significant amount of data was retrieved from a series of tests conducted for measurement of blast and fireball effects of liquid propellant explosions (Project PYRO), a few well-documented accident reports, and a series of tests to determine auto-ignition properties of mixing liquid propellants. The data were reduced and fitted to various statistical functions. Comparisons were made with methods of prediction for blast yield, initial fragment velocities, and fragment range. Reasonably good correlation was achieved. Methods presented in the report allow prediction of fragment patterns, given type and quantity of propellant, type of accident, and time of propellant mixing