Non-Markovian Configurational Diffusion and Reaction Coordinates for Protein Folding

The non-Markovian nature of polymer motions is accounted for in folding kinetics, using frequency-dependent friction. Folding, like many other problems in the physics of disordered systems, involves barrier crossing on a correlated energy landscape. A variational transition state theory (VTST) that reduces to the usual Bryngelson-Wolynes Kramers approach when the non-Markovian aspects are neglected is used to obtain the rate, without making any assumptions regarding the size of the barrier, or the memory time of the friction. The transformation to collective variables dependent on the dynamics of the system allows the theory to address the controversial issue of what are ``good'' reaction coordinates for folding.Comment: 9 pages RevTeX, 3 eps-figures included, submitted to PR

Genetic embedded matching approach to ground states in continuous-spin systems

Due to an extremely rugged structure of the free energy landscape, the determination of spin-glass ground states is among the hardest known optimization problems, found to be NP-hard in the most general case. Owing to the specific structure of local (free) energy minima, general-purpose optimization strategies perform relatively poorly on these problems, and a number of specially tailored optimization techniques have been developed in particular for the Ising spin glass and similar discrete systems. Here, an efficient optimization heuristic for the much less discussed case of continuous spins is introduced, based on the combination of an embedding of Ising spins into the continuous rotators and an appropriate variant of a genetic algorithm. Statistical techniques for insuring high reliability in finding (numerically) exact ground states are discussed, and the method is benchmarked against the simulated annealing approach.Comment: 17 pages, 12 figures, 1 tabl

Lightweight sidewalls for aircraft interior noise control

A theoretical and experimental study was performed to devise lightweight sidewalls for turboprop aircraft. Seven concepts for new sidewalls were analyzed and tested for noise reduction using flat panels of 1.2 m x 1.8 m (4 ft x 6 ft), some of which were aircraft-type constructions and some of which were simpler, easier-to-construct panels to test the functioning of an acoustic principle. Aircraft-application sidewalls were then conceived for each of the seven concepts, and were subjectively evaluated for their ability to meet aircraft nonacoustic design requirements. As a result of the above, the following sidewall concepts were recommended for further investigation: a sidewall in which the interior cavity is vented to ceiling and underfloor areas; sidewalls with wall-mounted resonators, one having a conventional trim panel and one a limp one; and a sidewall with a stiff outer wall and a limp trim panel. These sidewalls appear to promise lower weights than conventional sidewalls adjusted to meet similar acoustic requirements, and further development may prove them to be practical

GALEX, Optical and IR Light Curves of MQ Dra: UV Excesses at Low Accretion Rates

Ultraviolet light curves constructed from NUV and FUV detectors on GALEX reveal large amplitude variations during the orbital period of the Low Accretion Rate Polar MQ Dra (SDSSJ1553+55). This unexpected variation from a UV source is similar to that seen and discussed in the Polar EF Eri during its low state of accretion, even though the accretion rate in MQ Dra is an order of magnitude lower than even the low state of EF Eri. The similarity in phasing of the UV and optical light curves in MQ Dra imply a similar location for the source of light. We explore the possibilities of hot spots and cyclotron emission with simple models fit to the UV, optical and IR light curves of MQ Dra. To match the GALEX light curves with a single temperature circular hot spot requires different sizes of spots for the NUV and FUV, while a cyclotron model that can produce the optical harmonics with a magnetic field near 60 MG requires multipoles with fields > 200 MG to match the UV fluxes.Comment: accepted for ApJ; 15 pages, 7 tables, 8 fig

Genome landscapes and bacteriophage codon usage

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference

Handling polymorphic algebraic effects

Algebraic effects and handlers are a powerful abstraction mechanism to represent and implement control effects. In this work, we study their extension with parametric polymorphism that allows abstracting not only expressions but also effects and handlers. Although polymorphism makes it possible to reuse and reason about effect implementations more effectively, it has long been known that a naive combination of polymorphic effects and let-polymorphism breaks type safety. Although type safety can often be gained by restricting let-bound expressions---e.g., by adopting value restriction or weak polymorphism---we propose a complementary approach that restricts handlers instead of let-bound expressions. Our key observation is that, informally speaking, a handler is safe if resumptions from the handler do not interfere with each other. To formalize our idea, we define a call-by-value lambda calculus that supports let-polymorphism and polymorphic algebraic effects and handlers, design a type system that rejects interfering handlers, and prove type safety of our calculus.Comment: Added the errata for the ESOP'19 paper (page 28

On the construction of model Hamiltonians for adiabatic quantum computation and its application to finding low energy conformations of lattice protein models

In this report, we explore the use of a quantum optimization algorithm for obtaining low energy conformations of protein models. We discuss mappings between protein models and optimization variables, which are in turn mapped to a system of coupled quantum bits. General strategies are given for constructing Hamiltonians to be used to solve optimization problems of physical/chemical/biological interest via quantum computation by adiabatic evolution. As an example, we implement the Hamiltonian corresponding to the Hydrophobic-Polar (HP) model for protein folding. Furthermore, we present an approach to reduce the resulting Hamiltonian to two-body terms gearing towards an experimental realization.Comment: 35 pages, 8 figure

A standardisation proof for algebraic pattern calculi

This work gives some insights and results on standardisation for call-by-name pattern calculi. More precisely, we define standard reductions for a pattern calculus with constructor-based data terms and patterns. This notion is based on reduction steps that are needed to match an argument with respect to a given pattern. We prove the Standardisation Theorem by using the technique developed by Takahashi and Crary for lambda-calculus. The proof is based on the fact that any development can be specified as a sequence of head steps followed by internal reductions, i.e. reductions in which no head steps are involved.Comment: In Proceedings HOR 2010, arXiv:1102.346

Cerebrospinal fluid biomarker panel of synaptic dysfunction in Alzheimer's disease and other neurodegenerative disorders

Introduction: Synaptic degeneration is a key part of the pathophysiology of neurodegenerative diseases, and biomarkers reflecting the pathological alterations are greatly needed. Method: Seventeen synaptic proteins were quantified in a pathology-confirmed cerebrospinal fluid cohort of patients with Alzheimer's disease (AD; n = 63), frontotemporal lobar degeneration (FTLD; n = 53), and Lewy body spectrum of disorders (LBD; n = 21), as well as healthy controls (HC; n = 48). Results: Comparisons revealed four distinct patterns: markers decreased across all neurodegenerative conditions compared to HC (the neuronal pentraxins), markers increased across all neurodegenerative conditions (14-3-3 zeta/delta), markers selectively increased in AD compared to other neurodegenerative conditions (neurogranin and beta-synuclein), and markers selectively decreased in LBD and FTLD compared to HC and AD (AP2B1 and syntaxin-1B). Discussion: Several of the synaptic proteins may serve as biomarkers for synaptic dysfunction in AD, LBD, and FTLD. Additionally, differential patterns of synaptic protein alterations seem to be present across neurodegenerative diseases. Highlights: A panel of synaptic proteins were quantified in the cerebrospinal fluid using mass spectrometry. We compared Alzheimer's disease, frontotemporal degeneration, and Lewy body spectrum of disorders. Pathology was confirmed by autopsy or familial mutations. We discovered synaptic biomarkers for synaptic degeneration and cognitive decline. We found differential patterns of synaptic proteins across neurodegenerative diseases

Compilation of extended recursion in call-by-value functional languages

This paper formalizes and proves correct a compilation scheme for mutually-recursive definitions in call-by-value functional languages. This scheme supports a wider range of recursive definitions than previous methods. We formalize our technique as a translation scheme to a lambda-calculus featuring in-place update of memory blocks, and prove the translation to be correct.Comment: 62 pages, uses pi