Time-lagged independent component analysis of random walks and protein dynamics

Time-lagged independent component analysis (tICA) is a widely used dimension reduction method for the analysis of molecular dynamics (MD) trajectories and has proven particularly useful for the construction of protein dynamics Markov models. It identifies those ‘slow’ collective degrees of freedom onto which the projections of a given trajectory show maximal autocorrelation for a given lag time. Here we ask how much information on the actual protein dynamics and, in particular, the free energy landscape that governs these dynamics the tICA-projections of MD-trajectories contain, as opposed to noise due to the inherently stochastic nature of each trajectory. To answer this question, we have analyzed the tICA-projections of high dimensional random walks using a combination of analytical and numerical methods. We find that the projections resemble cosine functions and strongly depend on the lag time, exhibiting strikingly complex behaviour. In particular, and contrary to previous studies of principal component projections, the projections change non-continuously with increasing lag time. The tICA-projections of selected 1 μs protein trajectories and those of random walks are strikingly similar, particularly for larger proteins, suggesting that these trajectories contain only little information on the energy landscape that governs the actual protein dynamics. Further the tICA-projections of random walks show clusters very similar to those observed for the protein trajectories, suggesting that clusters in the tICA-projections of protein trajectories do not necessarily reflect local minima in the free energy landscape. We also conclude that, in addition to the previous finding that certain ensemble properties of non-converged protein trajectories resemble those of random walks, this is also true for their time correlations. Due to the higher complexity of the latter, this result also suggests tICA analyses as a more sensitive tool to test MD simulations for proper convergence

Voltage-current and voltage-flux characteristics of asymmetric high TC DC SQUIDs

We report measurements of transfer functions and flux shifts of 20 on-chip high T$_C$ DC SQUIDs half of which were made purposely geometrically asymmetric. All of these SQUIDs were fabricated using standard high T$_C$ thin film technology and they were single layer ones, having 140 nm thickness of YBa$_2$Cu$_3$O$_{7-x}$ film deposited by laser ablation onto MgO bicrystal substrates with 24$^0$ misorientation angle. For every SQUID the parameters of its intrinsic asymmetry, i. e., the density of critical current and resistivity of every junction, were measured directly and independently. We showed that the main reason for the on-chip spreading of SQUIDs' voltage-current and voltage-flux characteristics was the intrinsic asymmetry. We found that for SQUIDs with a relative large inductance ($L>120$ pH) both the voltage modulation and the transfer function were not very sensitive to the junctions asymmetry, whereas SQUIDs with smaller inductance ($L\simeq 65-75$ pH) were more sensitive. The results obtained in the paper are important for the implementation in the sensitive instruments based on high T$_C$ SQUID arrays and gratings.Comment: 11 pages, 4 tables, 17 figures This version is substantially modified. The Introduction and Section 2 are completely rewritten, while experimental part is mainly the same as in previous versio

Automated quantitative analysis of single and double label autoradiographs

A method for the analysis of silver grain content in both single and double label autoradiographs is presented. The total grain area is calculated by counting the number of pixels at which the recorded light intensity in transmission dark field illumination exceeds a selected threshold. The calibration tests included autoradiographs with low (3H- thymidin) and high (3H-desoxyuridin) silver grain density. The results are proportional to the customary visual grain count. For the range of visibly countable grain densities in single labeled specimens, the correlation coefficient between the computed values and the visual grain counts is better than 0.96. In the first emulsion of the two emulsion layer autoradiographs of double labeled specimens (3H-14C- thymidin) the correlation coefficient is 0.919 and 0.906. The method provides a statistical correction for the background grains not due to the isotope. The possibility to record 14C tracks by shifting the focus through the second emulsion of the double labeled specimens is also demonstrated. The reported technique is essentially independent of size, shape and density of the grains

Amphicarpic Legumes for Tropical Pasture Persistence

Amphicarpy, by which a plant produces underground seeds in addition to aerial fruits, is found in many plant families and in species of at least 15 legume genera. First studies on the tropical Centrosema rotundifolium and subtropical Macroptilium panduratum revealed for both species, besides their stoloniferous growth habit, two important mechanisms for survival under unfavorable conditions: (1) Underground meristems and reserve organs, and (2) regeneration from a soil seed reserve based on underground, aerial-flowering independent, seed production. Underground seed production was for both species particularly high on very sandy soils, but amphicarpy enables the plants to exhibit a plasticity response to unfavourable soil conditions by changing resource allocation from underground to above-ground reproduction. The latter, which seems to be influenced by cross-pollination and thus aids gene-recombination, favours spreading of plant populations whereas underground reproduction ensures population survival on-site. Preliminary information on the agronomic potential of both species is given and several research needs are highlighted

Scale morphology and specialized dorsal scales of a new teleosteomorph fish from the Aptian of West Gondwana

Scales of a new species of Teleosteomorpha from the continental Aptian of the south of South America are studied. These neopterygians are from the La Cantera Formation in central Argentina, and were previously identified as Pholidophoriformes. They present ganoid scales; most of them are rhombic with well-developed peg-and-socket articulations and possessing a smooth surface. They have a straight posterior margin, but occasionally, some scales of the flank have a sinuous posterior margin with one or two serrations. The shape of the scales varies along the body from large, rectangular and deeper than long scales behind the head to the preanal region to smaller and rhomboidal scales in the caudal region. There are a few horizontal rows along the flank and about 32 lateral line scales. Thick, round ganoid scales are present in the prepelvic region close to the ventral margin. The round and rhombic scales present growth lines, which form concentric ridges on the external side. A characteristic row of deep scales forms the dorsal margin on each side of the body; a row of median ridge scales is not present. This is a unique feature of the studied fishes. Scutes covered with unornamented ganoine precede the pelvic, dorsal, and anal fins, as well as the dorsal and ventral margins of the caudal fin. The posterior margin of the dorsal lobe of the caudal fin is formed by a single line of scales, which continues and covers the base of the first principal caudal ray. Histological studies reveal a lepisosteoid-scale type with multiple ganoine layers, lack of dentine, and the presence of canaliculi of Williamson. The macro- and micromorphology of the scales shows features that are found in other teleosteomorphs, but also in other neopterygians

A Porolepiform Rhipidistian from the Lower Devonian of the Canadian Arctic

A holoptychiid fish is described from the Lower Devonian of Arctic Canada. The new form is distinct from other holoptychiids by the presence of a large supraorbital bone and a boomerang-shaped tabular. Nasogaluakus n. gen. is the oldest and most primitive holoptychiid based on a phylogenetic analysis of porolepiforms and their closest relatives. The sequence of the genera corresponds to their stratigraphic appearance. Ein Holoptychiide aus dem Unterdevon der kanadischen Arktis wird beschrieben. Er unterscheidet sich durch ein großes Supraorbitale und die Bumerang-Form des Tabulare von allen übrigen Holoptychiiden. Nasogaluakus n. gen. ist der älteste und primitivste Holoptychiide, was durch eine phylogenetische Analyse der Porolepiformes belegt wird. Die Abfolge der Gattungen in diesem Verwandtschaftsschema stimmt mit ihrem zeitlichen Auftreten überein. doi:10.1002/mmng.20000030106</a