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PubMed1987

A possible biochemical missing link among archaebacteria.

Until recently all archaebacteria isolated conformed to one of three basic phenotypes: they were either methanogens, extreme halophiles, or ('sulphur-dependent') extreme thermophiles. However, a novel phenotype, that fits none of these categories, has recently been described. The organism, strain VC-16 (tentatively called "Archaeoglobus fulgidus") reduces sulphate--the only archaebacterium so far known to do so--and makes very small quantities of methane, although it lacks some of the cofactors normally associated with methanogenesis. These characteristics suggest that strain VC-16 might represent a transition form between an anaerobic thermophilic sulfur-based type of metabolism (which seems to be the ancestral metabolism for archaebacteria and methanogenesis (which somehow then derives from it). We here show that the lineage represented by strain VC-16 arises from the archaebacterial tree precisely where such an interpretation would predict that it would, between the Methanococcus lineage (which is the deepest of the methanogen branchings) and that of Thermococcus (the deepest of all branchings on the methanogen side of the tree).

Archaea↗
PubMed2001

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy.

Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.

Amino Acid Sequence↗
PubMed2004

Comparison of mathematical model predictions to experimental data of fatigue and performance.

As part of the "Fatigue and Performance Modeling Workshop," six modeling teams made predictions for temporal profiles of fatigue and performance in five different scenarios. One scenario was based on a laboratory study of fatigue and performance during 88 h of extended wakefulness with or without nap opportunities. Another scenario was based on a field study of alertness in freight locomotive engineers. Two scenarios were based on laboratory studies with various conditions of chronic sleep restriction and recovery. There was a theoretical scenario for future ultra-long-range flight operations as well. Experimental data were available for all scenarios except the latter. The model predictions were compared with the experimental data; after linear scaling using mixed-effects regression, mean square errors were computed to quantify goodness-of-fit. The six models were also compared among each other on the basis of these mean square errors. The present paper provides detailed information about the results of these comparisons. The models were capable of predicting the data for some scenarios fairly well. However, predicting the data for the two scenarios involving chronic sleep restriction was more problematic. Differences among the predictions from the six models were relatively small, suggesting that these models have a broad common basis. More experimental research is needed to yield new insights for the further development of fatigue and performance models.

Adult↗
PubMed1995

Statistical and linguistic features of DNA sequences.

We present evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationary" feature of the sequence of base pairs by applying a new algorithm called Detrended Fluctuation Analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and noncoding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to all eukaryotic DNA sequences (33 301 coding and 29 453 noncoding) in the entire GenBank database. We describe a simple model to account for the presence of long-range power-law correlations which is based upon a generalization of the classic Levy walk. Finally, we describe briefly some recent work showing that the noncoding sequences have certain statistical features in common with natural languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function. We suggest that noncoding regions in plants and invertebrates may display a smaller entropy and larger redundancy than coding regions, further supporting the possibility that noncoding regions of DNA may carry biological information.

Algorithms↗
PubMed1994

Evolution of heliobacteria: implications for photosynthetic reaction center complexes.

The evolutionary position of the heliobacteria, a group of green photosynthetic bacteria with a photosynthetic apparatus functionally resembling Photosystem I of plants and cyanobacteria, has been investigated with respect to the evolutionary relationship to Gram-positive bacteria and cyanobacteria. On the basis of 16S rRNA sequence analysis, the heliobacteria appear to be most closely related to Gram-positive bacteria, but also an evolutionary link to cyanobacteria is evident. Interestingly, a 46-residue domain including the putative sixth membrane-spanning region of the heliobacterial reaction center protein show rather strong similarity (33% identity and 72% similarity) to a region including the sixth membrane-spanning region of the CP47 protein, a chlorophyll-binding core antenna polypeptide of Photosystem II. The N-terminal half of the heliobacterial reaction center polypeptide shows a moderate sequence similarity (22% identity over 232 residues) with the CP47 protein, which is significantly more than the similarity with the Photosystem I core polypeptides in this region. An evolutionary model for photosynthetic reaction center complexes is discussed, in which an ancestral homodimeric reaction center protein (possibly resembling the heliobacterial reaction center protein) with 11 membrane-spanning regions per polypeptide has diverged to give rise to the core of Photosystem I, Photosystem II, and of the photosynthetic apparatus in green, purple, and heliobacteria.

Bacteria, Anaerobic↗
PubMed1999

Statistical model building and model criticism for human circadian data.

Mathematical models have played an important role in the analysis of circadian systems. The models include simulation of differential equation systems to assess the dynamic properties of a circadian system and the use of statistical models, primarily harmonic regression methods, to assess the static properties of the system. The dynamical behaviors characterized by the simulation studies are the response of the circadian pacemaker to light, its rate of decay to its limit cycle, and its response to the rest-activity cycle. The static properties are phase, amplitude, and period of the intrinsic oscillator. Formal statistical methods are not routinely employed in simulation studies, and therefore the uncertainty in inferences based on the differential equation models and their sensitivity to model specification and parameter estimation error cannot be evaluated. The harmonic regression models allow formal statistical analysis of static but not dynamical features of the circadian pacemaker. The authors present a paradigm for analyzing circadian data based on the Box iterative scheme for statistical model building. The paradigm unifies the differential equation-based simulations (direct problem) and the model fitting approach using harmonic regression techniques (inverse problem) under a single schema. The framework is illustrated with the analysis of a core-temperature data series collected under a forced desynchrony protocol. The Box iterative paradigm provides a framework for systematically constructing and analyzing models of circadian data.

Adult↗
PubMed2002

Perceived orientation in physical and virtual environments: changes in perceived orientation as a function of idiothetic information available.

Two experiments examined perceived spatial orientation in a small environment as a function of experiencing that environment under three conditions: real-world, desktop-display (DD), and head-mounted display (HMD). Across the three conditions, participants acquired two targets located on a perimeter surrounding them, and attempted to remember the relative locations of the targets. Subsequently, participants were tested on how accurately and consistently they could point in the remembered direction of a previously seen target. Results showed that participants were significantly more consistent in the real-world and HMD conditions than in the DD condition. Further, it is shown that the advantages observed in the HMD and real-world conditions were not simply due to nonspatial response strategies. These results suggest that the additional idiothetic information afforded in the real-world and HMD conditions is useful for orientation purposes in our presented task domain. Our results are relevant to interface design issues concerning tasks that require spatial search, navigation, and visualization.

Adolescent↗
PubMed1987

A new technique to determine the correlation between the QT interval and heart-rate for control and SIDS babies.

The ability of the autonomic nervous system to alter the QT interval in response to heart rate changes is essential to cardiovascular control. An accurate way to determine the relation between QT intervals and their corresponding RR intervals is described. A computer algorithm measures the RR intervals using digital filtering and cross-correlating the QRS sections of consecutive waveforms. The QT intervals is calculated by choosing a section of, the ECG that includes the T wave and cross-correlating it with all the consecutive T waves. At least 4000 pairs of QT-RR intervals are computed for each subject and a best fit correlation function determines the relations between the QT and RR intervals. This technique enables to establish a precise correlation between RR and QT in order to distinguish between control and SIDS babies.

Algorithms↗
PubMed1992

The statistical analysis of circadian phase and amplitude in constant-routine core-temperature data.

Accurate estimation of the phases and amplitude of the endogenous circadian pacemaker from constant-routine core-temperature series is crucial for making inferences about the properties of the human biological clock from data collected under this protocol. This paper presents a set of statistical methods based on a harmonic-regression-plus-correlated-noise model for estimating the phases and the amplitude of the endogenous circadian pacemaker from constant-routine core-temperature data. The methods include a Bayesian Monte Carlo procedure for computing the uncertainty in these circadian functions. We illustrate the techniques with a detailed study of a single subject's core-temperature series and describe their relationship to other statistical methods for circadian data analysis. In our laboratory, these methods have been successfully used to analyze more than 300 constant routines and provide a highly reliable means of extracting phase and amplitude information from core-temperature data.

Adult↗
PubMed1996

Sequence, overproduction and purification of Vibrio proteolyticus ribosomal protein L18 for in vitro and in vivo studies.

A strategy suggested by comparative genomic studies was used to amplify the entire Vibrio proteolyticus (Vp) gene for ribosomal protein L18. Vp L18 and its flanking regions were sequenced and compared with the deduced amino acid (aa) sequences of other known L18 proteins. A 26-aa residue segment at the carboxy terminus contains many strongly conserved residues and may be critical for the L18 interaction with 5S rRNA. This approach should allow rapid characterization of L18 from large numbers of bacteria. Both Vp L18 and Escherichia coli (Ec) L18 were overproduced and purified using a T7 expression vector which fuses an N-terminal peptide segment (His-tag) containing 6 histidine residues to the recombinant protein. The purified fusion proteins, Vp His::L18 and Ec His::L18, were both found to bind to either the Vp 5S or Ec 5S rRNAs in vitro. Vp His::L18 protein was also shown to incorporate into Ec ribosomes in vivo. This His-tag strategy likely will have general applicability for the study of ribosomal proteins in vitro and in vivo.

Amino Acid Sequence↗
PubMed2001

Efficiency of parallel direct optimization.

Tremendous progress has been made at the level of sequential computation in phylogenetics. However, little attention has been paid to parallel computation. Parallel computing is particularly suited to phylogenetics because of the many ways large computational problems can be broken into parts that can be analyzed concurrently. In this paper, we investigate the scaling factors and efficiency of random addition and tree refinement strategies using the direct optimization software, POY, on a small (10 slave processors) and a large (256 slave processors) cluster of networked PCs running LINUX. These algorithms were tested on several data sets composed of DNA and morphology ranging from 40 to 500 taxa. Various algorithms in POY show fundamentally different properties within and between clusters. All algorithms are efficient on the small cluster for the 40-taxon data set. On the large cluster, multibuilding exhibits excellent parallel efficiency, whereas parallel building is inefficient. These results are independent of data set size. Branch swapping in parallel shows excellent speed-up for 16 slave processors on the large cluster. However, there is no appreciable speed-up for branch swapping with the further addition of slave processors (>16). This result is independent of data set size. Ratcheting in parallel is efficient with the addition of up to 32 processors in the large cluster. This result is independent of data set size.

Algorithms↗
PubMed1997

Judgments of the distance to nearby virtual objects: interaction of viewing conditions and accommodative demand.

Ten subjects adjusted a real-object probe to match the distance of nearby virtual objects optically presented via a see-through, helmet-mounted display. Monocular, binocular, and stereoscopic viewing conditions were used with two levels of required focus. Observed errors may be related to changes in the subjects' binocular convergence. The results suggest ways in which virtual objects may be presented with improved spatial fidelity.

Computer Graphics↗
PubMed2004

Species differentiation of a diverse suite of Bacillus spores by mass spectrometry-based protein profiling.

In this study, we demonstrate the versatility of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOFMS) protein profiling for the species differentiation of a diverse suite of Bacillus spores. MALDI-TOFMS protein profiles of 11 different strains of Bacillus spores, encompassing nine different species, were evaluated. Bacillus species selected for MALDI-TOFMS analysis represented the spore-forming bacterial diversity of typical class 100K clean room spacecraft assembly facilities. A one-step sample treatment and MALDI-TOFMS preparation were used to minimize the sample preparation time. A library of MALDI-TOFMS spectra was created from these nine Bacillus species, the most diverse protein profiling study of the genus reported to date. Linear correlation analysis was used to successfully differentiate the MALDI-TOFMS protein profiles from all strains evaluated in this study. The MALDI-TOFMS protein profiles were compared with 16S rDNA sequences for their bacterial systematics and molecular phylogenetic affiliations. The MALDI-TOFMS profiles were found to be complementary to the 16S rDNA analysis. Proteomic studies of Bacillus subtilis 168 were pursued to identify proteins represented by the biomarker peaks in the MALDI-TOFMS spectrum. Four small, acid-soluble proteins (A, B, C, and D), one DNA binding protein, hypothetical protein ymf J, and four proteins associated with the spore coat and spore coat formation (coat JB, coat F, coat T, and spoIVA) were identified. The ability to visualize higher-molecular-mass coat proteins (10 to 25 kDa) as well as smaller proteins (<10 kDa) with MALDI-TOFMS profiling is critical for the complete and effective species differentiation of the Bacillus genus.

Bacillus↗
PubMed1998

Deterioration of cerebral autoregulation during orthostatic stress: insights from the frequency domain.

To determine whether dynamic cerebral autoregulation is impaired during orthostatic stress, cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler) and mean arterial pressure (MAP; Finapres) were measured continuously in 12 healthy subjects during ramped maximal lower body negative pressure (LBNP) to presyncope. Velocity and pressure were averaged over 6-min periods of stable data at rest and during LBNP to examine steady-state cerebral hemodynamics. Beat-to-beat variability of velocity and pressure were quantified by a "variation index" (oscillatory amplitude/steady-state mean value) and by power spectral analysis. The dynamic relationship between changes in pressure and velocity was evaluated by the estimates of transfer and coherence function. The results of the study were as follows. Steady-state MAP remained relatively constant during LBNP, whereas CBF velocity decreased progressively by 6, 15, and 21% at -30, -40, and -50 mmHg LBNP, respectively (P < 0.05 compared with baseline). At the maximal level of LBNP (30 s before presyncope) MAP decreased by 9.4% in association with a prominent reduction in velocity by 24% (P < 0.05 compared with baseline). The variation index of pressure increased significantly from 3.8 +/- 0.3% at baseline to 4.5 +/- 0. 6% at -50 mmHg LBNP in association with an increase in the variation index of velocity from 6.0 +/- 0.6 to 8.4 +/- 0.7% (P < 0.05). Consistently, the low- (0.07-0.20 Hz) and high-frequency (0.20-0.30 Hz) power of variations in pressure and velocity increased significantly at high levels of LBNP (P < 0.05) in association with an increase in transfer function gain (24% at -50 mmHg, P < 0.05). We conclude that the damping effects of autoregulation on variations in CBF velocity are diminished during orthostatic stress in association with substantial falls in steady-state CBF velocity. We suggest that these changes may contribute in part to the development of presyncope.

Adult↗
PubMed1992

How should Fitts' Law be applied to human-computer interaction?

The paper challenges the notion that any Fitts' Law model can be applied generally to human-computer interaction, and proposes instead that applying Fitts' Law requires knowledge of the users' sequence of movements, direction of movement, and typical movement amplitudes as well as target sizes. Two experiments examined a text selection task with sequences of controlled movements (point-click and point-drag). For the point-click sequence, a Fitts' Law model that used the diagonal across the text object in the direction of pointing (rather than the horizontal extent of the text object) as the target size provided the best fit for the pointing time data, whereas for the point-drag sequence, a Fitts' Law model that used the vertical size of the text object as the target size gave the best fit. Dragging times were fitted well by Fitts' Law models that used either the vertical or horizontal size of the terminal character in the text object. Additional results of note were that pointing in the point-click sequence was consistently faster than in the point-drag sequence, and that pointing in either sequence was consistently faster than dragging. The discussion centres around the need to define task characteristics before applying Fitts' Law to an interface design or analysis, analyses of pointing and of dragging, and implications for interface design.

Data Display↗
PubMed1993

Ten years in the library: new data confirm paleontological patterns.

A comparison is made between compilations of times of origination and extinction of fossil marine animal families published in 1982 and 1992. As a result of ten years of library research, half of the information in the compendia has changed: families have been added and deleted, low-resolution stratigraphic data been improved, and intervals of origination and extinction have been altered. Despite these changes, apparent macroevolutionary patterns for the entire marine fauna have remained constant. Diversity curves compiled from the two data bases are very similar, with a goodness-of-fit of 99%; the principal difference is that the 1992 curve averages 13% higher than the older curve. Both numbers and percentages of origination and extinction also match well, with fits ranging from 83% to 95%. All major events of radiation and extinction are identical. Therefore, errors in large paleontological data bases and arbitrariness of included taxa are not necessarily impediments to the analysis of pattern in the fossil record, so long as the data are sufficiently numerous.

Animals↗