Adding backbone to protein folding: why proteins are polypeptides

It is argued that the chemical nature of the polypeptide backbone is the central determinant of the three-dimensional structures of proteins. The requirement that buried polar groups form intramolecular hydrogen bonds limits the fold of the backbone to the well known units of secondary structure while the amino acid sequence chooses among the set of conformations available to the backbone. ‘Sidechain-only’ models, based for example on hydrophobicity patterns, fail to account for the properties of the backbone and thus will have difficulty capturing essential features of a folding pathway. This is evident from the incorrect predictions they make for the conformations of the limiting cases of all-hydrophobic or all-polar sequences

Numerical Analysis of Solid Rocket Motor Instabilities With AP Composite Propellants

A non-steady model for the combustion of ammonium perchlorate composite propellants has been developed in order to be incorporated into a comprehensive gasdynamics model of solid rocket motor flow fields. The model including the heterogeneous combustion and turbulence mechanisms is applied to nonlinear combustion instability analyses. This paper describes the essential mechanisms and features of the model and discusses the methodology of non-steady calculations of the combustion instabilities of solid rocket motors

Gait Transitions for Quasi-Static Hexapedal Locomotion on Level Ground

As robot bodies become more capable, the motivation grows to better coordinate them—whether multiple limbs attached to a body or multiple bodies assigned to a task. This paper introduces a new formalism for coordination of periodic tasks, with specific application to gait transitions for legged platforms. Specifically, we make modest use of classical group theory to replace combinatorial search and optimization with a computationally simpler and conceptually more straightforward appeal to elementary algebra. We decompose the space of all periodic legged gaits into a cellular complex indexed using “Young Tableaux”, making transparent the proximity to steady state orbits and the neighborhood structure. We encounter the simple task of transitioning between these gaits while locomoting over level ground. Toward that end, we arrange a family of dynamical reference generators over the “Gait Complex” and construct automated coordination controllers to force the legged system to converge to a specified cell’s gait, while assessing the relative static stability of gaits by approximating their stability margin via transit through a “Stance Complex”. To integrate these two different constructs—the Gait Complex describing possible gaits, the Stance Complex defining safe locomotion—we utilize our compositional lexicon to plan switching policies for a hybrid control approach. Results include automated gait transitions for a variety of useful gaits, shown via tests on a hexapedal robot

Analytical Solution for Pressure-Coupled Combustion Response Functions of Composite Solid Propellants

This paper extends the classical analytical solution for small perturbation analysis of the pressure-coupled response of a homogeneous propellant to any two-component composite propellant. The solution obtained is general and can be used with any particular model for propellant combustion. As an example, the Cohen and Strand ammonium perchlorate propellant model for a single ammonium perchlorate particle size was used in this work. The results and their mechanistic significance are presented and discussed. It is shown that, for a two-component composite propellant, two forms of pressure exponents arise from the analysis. The significance of the second exponent is that it enables the composite propellant to be viewed as a homogeneous propellant with a frequency-dependent exponent via the coupling coefficients. It is found that the ammonium perchlorate is the main source of instability because of its condensed phase exothermicity and monopropellant flame kinetics. This will be a problem with energetic materials in general. The inert binder provides a stabilizing influence because of its endothermicity and the diffusion flame formed with the ammonium perchlorate. Effects of ammonium perchlorate particle size and pressure stem from the changing flame structure and its effect on burning rate

Automatic Extraction of Protein Point Mutations Using a Graph Bigram Association

Protein point mutations are an essential component of the evolutionary and experimental analysis of protein structure and function. While many manually curated databases attempt to index point mutations, most experimentally generated point mutations and the biological impacts of the changes are described in the peer-reviewed published literature. We describe an application, Mutation GraB (Graph Bigram), that identifies, extracts, and verifies point mutations from biomedical literature. The principal problem of point mutation extraction is to link the point mutation with its associated protein and organism of origin. Our algorithm uses a graph-based bigram traversal to identify these relevant associations and exploits the Swiss-Prot protein database to verify this information. The graph bigram method is different from other models for point mutation extraction in that it incorporates frequency and positional data of all terms in an article to drive the point mutation–protein association. Our method was tested on 589 articles describing point mutations from the G protein–coupled receptor (GPCR), tyrosine kinase, and ion channel protein families. We evaluated our graph bigram metric against a word-proximity metric for term association on datasets of full-text literature in these three different protein families. Our testing shows that the graph bigram metric achieves a higher F-measure for the GPCRs (0.79 versus 0.76), protein tyrosine kinases (0.72 versus 0.69), and ion channel transporters (0.76 versus 0.74). Importantly, in situations where more than one protein can be assigned to a point mutation and disambiguation is required, the graph bigram metric achieves a precision of 0.84 compared with the word distance metric precision of 0.73. We believe the graph bigram search metric to be a significant improvement over previous search metrics for point mutation extraction and to be applicable to text-mining application requiring the association of words

Variability Tests for Intrinsic Absorption Lines in Quasar Spectra

Quasar spectra have a variety of absorption lines whose origins range from energetic winds expelled from the central engines to unrelated, intergalactic clouds. We present multi-epoch, medium resolution spectra of eight quasars at z~2 that have narrow ``associated'' absorption lines (AALs, within $\pm$5000 km s^{-1} of the emission redshift). Two of these quasars were also known previously to have high-velocity mini-broad absorption lines (mini-BALs). We use these data, spanning ~17 years in the observed frame with two to four observations per object, to search for line strength variations as an identifier of absorption that occurs physically near (``intrinsic'' to) the central AGN. Our main results are the following: Two out of the eight quasars with narrow AALs exhibit variable AAL strengths. Two out of two quasars with high-velocity mini-BALs exhibit variable mini-BAL strengths. We also marginally detect variability in a high-velocity narrow absorption line (NAL) system, blueshifted \~32,900 km s^{-1}$ with respect to the emission lines. No other absorption lines in these quasars appeared to vary. The outflow velocities of the variable AALs are 3140 km s^{-1} and 1490 km s^{-1}. The two mini-BALs identify much higher velocity outflows of ~28,400 km s^{-1} and ~52,000 km s^{-1}. Our temporal sampling yields upper limits on the variation time scales from 0.28 to 6.1 years in the quasar rest frames. The corresponding minimum electron densities in the variable absorbers, based on the recombination time scale, are \~40,000 cm^{-3} to ~1900 cm^{-3}. The maximum distances of the absorbers from the continuum source, assuming photoionization with no spectral shielding, range from ~1.8 kpc to ~7 kpc.Comment: 16 pages, 4 figures, ApJ, accepte

Expression profiling of the schizont and trophozoite stages of Plasmodium falciparum with a long-oligonucleotide microarray

BACKGROUND: The worldwide persistence of drug-resistant Plasmodium falciparum, the most lethal variety of human malaria, is a global health concern. The P. falciparum sequencing project has brought new opportunities for identifying molecular targets for antimalarial drug and vaccine development. RESULTS: We developed a software package, ArrayOligoSelector, to design an open reading frame (ORF)-specific DNA microarray using the publicly available P. falciparum genome sequence. Each gene was represented by one or more long 70 mer oligonucleotides selected on the basis of uniqueness within the genome, exclusion of low-complexity sequence, balanced base composition and proximity to the 3' end. A first-generation microarray representing approximately 6,000 ORFs of the P. falciparum genome was constructed. Array performance was evaluated through the use of control oligonucleotide sets with increasing levels of introduced mutations, as well as traditional northern blotting. Using this array, we extensively characterized the gene-expression profile of the intraerythrocytic trophozoite and schizont stages of P. falciparum. The results revealed extensive transcriptional regulation of genes specialized for processes specific to these two stages. CONCLUSIONS: DNA microarrays based on long oligonucleotides are powerful tools for the functional annotation and exploration of the P. falciparum genome. Expression profiling of trophozoites and schizonts revealed genes associated with stage-specific processes and may serve as the basis for future drug targets and vaccine development

Potential Effects of Global Warming on Quail Populations

Populations of scaled quail (Callipepla squamata) and northern bobwhites (Colinus virginianus) have declined in North America coincident with global warming. We speculate on a cause-effect relation between global warming and quail declines. Quail are sensitive to operative temperatures \u3e38.7 C, which commonly occur under natural conditions in southern latitudes. Based on empirical results, the laying season for quail may be reduced by as much as 60 days because of high temperatures. We provide mechanistic models that show how reduction in length of the laying season suppresses per-capita annual production. Global warming could be associated with declining quail populations through suppression of reproduction; it also could exacerbate the effects of habitat loss and fragmentation. These possibilities should be explored in field and laboratory research