A simple protein folding algorithm using a binary code and secondary structure constraints

We describe an algorithm to predict tertiary structures of smallproteins. In contrast to most current folding algorithms, ituses very few energy parameters. Given the secondary structuralelements in the sequence—-helices and ß-strands—thealgorithm searches -the remaining conformational space of asimplified real-space representation of chains to find a minimumenergy of an exceedingly simple potential function. The potentialis based only on a single type of favorable interaction betweenhydrophobic residues, an unfavorable excluded volume term ofspatial overlaps and, for sheet proteins, an interstrand hydrogenbond interaction. Where appropriate, the known disulfide bondsare constrained by a square-law potential. Conformations aresearched by a genetic algorithm. The model predicts reasonablywell the known tertiary folds of seven out of the 10 small proteinswe consider. We draw two conclusions. First, for the proteinswe tested, this exceedingly simple potential function is noworse than others having hundreds of energy parameters in findingthe right general tertiary structures. Second, despite its simplicity,the potential function is not the weak link in this algorithm.Differences between our predicted structures and the correcttargets can be ascribed to shortcomings in our search strategy.This potential function may be useful for testing other conformationalsearch strategies.     

The spectrum of Trp- mutants isolated as 5-fluoroanthranilate-resistant clones in Saccharomyces bayanus, S. mikatae and S. paradoxus

5-Fluoroanthranilic acid (FAA)-resistant mutants were selected in homothallic diploids of three Saccharomyces species, taking care to isolate mutants of independent origin. Mutations were assigned to complementation groups by interspecific complementation with S. cerevisiae tester strains. In all three species, trp3, trp4 and trp5 mutants were recovered. trp1 mutants were also recovered if the selection was imposed on a haploid strain. Thus, FAA selection may be more generally applicable than was previously described.     

Optimal design of k-out-of-n:G subsystems subjected to imperfect fault-coverage

Systems subjected to imperfect fault-coverage may fail even prior to the exhaustion of spares due to uncovered component failures. This paper presents optimal cost-effective design policies for k-out-of-n:G subsystems subjected to imperfect fault-coverage. It is assumed that there exists a k-out-of-n:G subsystem in a nonseries-parallel system and, except for this subsystem, the redundancy configurations of all other subsystems are fixed. This paper also presents optimal design polices which maximize overall system reliability. As a special case, results are presented for k-out-of-n:G systems subjected to imperfect fault-coverage. Examples then demonstrate how to apply the main results of this paper to find the optimal configurations of all subsystems simultaneously. In this paper, we show that the optimal n which maximizes system reliability is always less than or equal to the n which maximizes the reliability of the subsystem itself. Similarly, if the failure cost is the same, then the optimal n which minimizes the average system cost is always less than or equal to the n which minimizes the average cost of the subsystem. It is also shown that if the subsystem being analyzed is in series with the rest of the system, then the optimal n which maximizes subsystem reliability can also maximize the system reliability. The computational procedure of the proposed algorithms is illustrated through the examples.     

Abuse, threat, and irritable bowel syndrome: what is the connection?

OBJECTIVE AND DESIGN: The effects of two hydroxamate inhibitors of metalloproteinase and tumor necrosis factor alpha (TNF alpha) processing on endotoxin-induced plasma TNF alpha and arthritic lesions in adjuvant-induced arthritic (AA) rats were determined. MATERIAL AND TREATMENT: BB-1101 and BB-1433 were administered orally twice daily to AA Lewis rats with an established disease (days 13 to 22). AA rats (day 16) or normal rats were injected with bacterial endotoxin and plasma levels of TNF alpha were also determined. METHODS: Hindpaw swelling was measured plethysmographically. Bone degradation was determined by radiography and bone mineral densitometry. TNF alpha was quantified using a sandwich ELISA. RESULTS: The hydroxamic-acid pseudopeptides inhibited plasma. TNF alpha levels in vivo and significantly reduced swelling and bone degradation of the tibiotarsal joints of AA rats in the range of 10-50 mg/kg given orally (p < 0.01 by Student's t-test). CONCLUSIONS: Thus, these novel compounds offer a new disease modifying therapy for arthritis and the results also suggest that inhibition of TNF alpha production may contribute, at least in part, to their anti-arthritic activity.     

Using formal specifications for functional validation of hardwaredesigns

Formal specifications can help resolve both ambiguity issues and correctness problems in verifying complex hardware designs. This new methodology shows how specifications can also help design productivity by automating many procedures that are now done manually. Input sequences, output assertions, and a simulation coverage metric for the design under verification are all generated directly from the specification     

Lipolytic activity with the membrane fraction of bovine skim milk.

Colloidal phosphate-free skim milk was subjected to gel filtration on Sepharose 4B. Lipolytic activity was observed in the membrane material eluted in the void volume fraction and in the protein fraction representing a broad range of molecular weights.     

Structure,properties and response to heat treatment of melt-spun Al-Y and Al-La alloys

Al-Y and Al-La binary alloys containing 0.7–18 wt% (0.2–6.3 at%) Y and 0.9–18 wt% (0.2–4.2 at%) La, were rapidly solidified by chill-block melt-spinning to produce ribbons between 35 and 70 m thick. Microstructures were of the classical zone A/zone B type with a notable increase in Al lattice parameter for the Al-6.3 at% Y composition, which exhibited a Knoop hardness of 430±30 kg mm^–2 as-spun. Isochronal ageing for 2 h at 200–500 °C gave significant hardening at 200 and/or 300 °C for all of the more concentrated alloys, the largest responses being produced by Al-6.3 at % Y and Al-4.2 at % La at 200 °C. X-ray diffraction asspun indicated the presence of only Al and equilibrium Al₁₁La₃ in the Al-La alloy ribbons and Al and a non-equilibrium Al₄Y/Al₁₁Y₃ in the Al-Y ribbons. This non-equilibrium Al-Y phase was identified by X-ray diffraction as isomorphous with orthorhombic or tetragonal Al₁₁ La₃ with lattice parameters determined as a _o = 0.42 ± 0.02 nm (b _o = 1.26 ± 0.06 nm) and c _o = 0.97 ± 0.05 nm. TEM showed that it was present as an intercellular network with Energy dispersive spectroscopic analysis indicating an average composition Al-46 wt% Y consistent with the Al₄Y/Al₁₁Y₃ stoichiometry and diffraction patterns consistent with an orthorhombic or tetragonal cell with these lattice parameters. While no significant change in phase constitution of the Al-La ribbons was detected by X-ray diffraction as a result of heat treatment, the Al₁₁Y₃ in Al-Y ribbons was seen to be replaced by AI₃Y on heat treatment at 400 and 500 °C.     

Atomic layer deposition onto carbon fiber fabrics

Carbon fiber fabrics, consisting of interwoven bundles of 3000 single fibers, were coated with Al₂O₃ using the atomic layer deposition (ALD) process, exposing the fabrics to alternating pulses of trimethyl aluminium and water vapors. The thickness and uniformity of the coatings were investigated using scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The obtained coatings were conformal, 84 ALD cycles gave rise to approximately 20‐nm‐thick coatings and 168 ALD cycles to approximately 40‐nm‐thick coatings. It was found, that a uniform coating can be obtained at a purge time of 40 seconds. Reducing purge times below 20 seconds gives rise to increased particle growth and thus the coating becomes inhomogeneous. Initially, the samples that were coated had a size of 2×10 cm (thickness 0.3 mm). The size of the fabric was subsequently increased up to 8×20 cm and a uniform coating of the same quality was obtained. By oxidizing the coated fabrics, fabrics composed of interwoven alumina microtubes were obtained. Infiltration of the microtubes with solutions of two distinguishable fluorescent dyes showed that interchange of the dyes between warp and weft microtubes occurs, but is absent at approximately 20% of the crossovers. Taking all our findings into account, we conclude that the majority of the fibers were separated from each other by the coating prior to the oxidation. This work demonstrates that ALD is a suitable method to produce thin, conformal coatings on the surface of carbon fiber fabrics.     

Apparent rates of production and loss of dissolved gaseous mercury (DGM) in a southern reservoir lake (Tennessee, USA)

Apparent rates of dissolved gaseous mercury (DGM) concentration changes in a southern reservoir lake (Cane Creek Lake, Cookeville, Tennessee) were investigated using the DGM data collected in a 12-month study from June 2003 to May 2004. The monthly mean apparent DGM production rates rose from January (3.2 pg L(-1)/h), peaked in the summer months (June-August: 8.9, 8.0, 8.6 pg L(-1)/h), and fell to the lowest in December (1.6 pg L(-1)/h); this trend followed the monthly insolation march for both global solar radiation and UVA radiation. The monthly apparent DGM loss rates failed to show the similar trend with no consistent pattern recognizable. The spring and summer had higher seasonal mean apparent DGM production rates than the fall and winter (6.8, 9.0, 3.9, 5.0 pg L(-1)/h, respectively), and the seasonal trend also appeared to closely follow the solar radiation variation. The seasonal apparent DGM loss featured similar rate values for the four seasons (5.5, 4.3, 3.3, and 3.9 pg L(-1)/h for spring, summer, fall, and winter, respectively). Correlation was found of the seasonal mean apparent DGM production rate with the seasonal mean morning solar radiation (r=0.9084, p<0.01) and with the seasonal mean morning UVA radiation (r=0.9582, p<0.01). No significant correlation was found between the seasonal apparent DGM loss rate and the corresponding afternoon solar radiation (r=0.5686 for global radiation and 0.6098 for UVA radiation). These results suggest that DGM production in the lake engaged certain photochemical processes, either primary or secondary, but the DGM loss was probably driven by some dark processes.