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At least 631 records · Page 35Linked to original sources
PubMed1994

Acceleration perturbations of daily living. A comparison to 'whiplash'.

STUDY DESIGN: This study measured repeated human head accelerations (g) during daily activities. OBJECTIVES: Perturbations of daily living were compared to similar data from low velocity rear-end motor vehicle accidents. SUMMARY OF BACKGROUND DATA: Past assumptions suggest that motor vehicle accident severity does not correlate with the degree of sustained injury. Early engineering studies indicated that occupant disturbance in a low velocity motor vehicle accident is minor. METHODS: Eight volunteers were perturbed with 13 daily activities. Helmets on the heads of volunteers were instrumented with tri-planar accelerometers with output sampling of 500 Hz, sensitivity of 0.02 g, and a range of +/- 20 g. RESULTS: There was wide inter-subject response for various perturbations. Plopping backward into a chair caused maximum peak acceleration horizontally at 5.6 g and vertically at 8.5 g, with force vector of 10.1 g at 54.9 degrees. Mean impulse duration was 0.19 sec. There was no hint of injury in any subject. CONCLUSIONS: Perturbations of daily living compared similarly to the jostling expected in low velocity "whiplash"-type motor vehicle accidents.

Acceleration↗
PubMed1997

Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury.

Traumatic brain injury (TBI) is associated with primary and secondary injury. A thorough understanding of secondary injury will help to develop effective treatments and improve patient outcome. In this study, the GM model of controlled cortical impact injury (CCII) of Lighthall (1988) was used with modification to induce lateral TBI in rats. Forebrain mitochondria isolated from ipsilateral (IH) and contralateral (CH) hemispheres to impact showed a distinct difference. With glutamate + malate as substrates, mitochondria from the IH showed a significant decrease in State 3 respiratory rates, respiratory control indices (RCI), and P/O ratios. This decrease occurred as early as 1 h and persisted for at least 14 days following TBI. The State 3 respiratory rates, RCI, and P/O ratios could be restored to sham values by the addition of EGTA to the assay mixture. A significant amount of Ca2+ was found to be adsorbed to the mitochondria of both the IH and the CH with higher values seen in the IH. The rate of energy-linked Ca2+ transport in the IH was significantly decreased at 6 and 12 h. These data indicate that CCII-induced TBI perturbs cellular Ca2+ homeostasis and results in excessive Ca2+ adsorption to the mitochondrial membrane, which subsequently inhibits the respiratory chain-linked electron transfer and energy transduction.

Animals↗
PubMed2000

Acoustic modeling of American English /r/.

Recent advances in physiological data collection methods have made it possible to test the accuracy of predictions against speaker-specific vocal tracts and acoustic patterns. Vocal tract dimensions for /r/ derived via magnetic-resonance imaging (MRI) for two speakers of American English [Alwan, Narayanan, and Haker, J. Acoust. Soc. Am. 101, 1078-1089 (1997)] were used to construct models of the acoustics of /r/. Because previous models have not sufficiently accounted for the very low F3 characteristic of /r/, the aim was to match formant frequencies predicted by the models to the full range of formant frequency values produced by the speakers in recordings of real words containing /r/. In one set of experiments, area functions derived from MRI data were used to argue that the Perturbation Theory of tube acoustics cannot adequately account for /r/, primarily because predicted locations did not match speakers' actual constriction locations. Different models of the acoustics of /r/ were tested using the Maeda computer simulation program [Maeda, Speech Commun. 1, 199-299 (1982)]; the supralingual vocal-tract dimensions reported in Alwan et al. were found to be adequate at predicting only the highest of attested F3 values. By using (1) a recently developed adaptation of the Maeda model that incorporates the sublingual space as a side branch from the front cavity, and by including (2) the sublingual space as an increment to the dimensions of the front cavity, the mid-to-low values of the speakers' F3 range were matched. Finally, a simple tube model with dimensions derived from MRI data was developed to account for cavity affiliations. This confirmed F3 as a front cavity resonance, and variations in F1, F2, and F4 as arising from mid- and back-cavity geometries. Possible trading relations for F3 lowering based on different acoustic mechanisms for extending the front cavity are also proposed.

Humans↗
PubMed1987

Improved program for the analysis of DNA histograms.

We describe a computer program which will rapidly analyze a set of DNA histograms without further operator intervention after the initial input. The algorithm used was modified from that of Watson et al. (Cytometry 8:1-8, 1987). The program, coded in Pascal, has been implemented on two different systems. It has been tested by using simulated data and experimental data from cells labelled with bromodeoxyuridine. The program has been in use in this and other laboratories for over two years and has proved to be robust and fast and to give a reasonable approximation to the experimental data. It is particularly useful when dealing with badly perturbed DNA histograms.

Algorithms↗
PubMed1986

Substructure of skeletal myosin subfragment 1. Preferential destabilization of a domain by methanol and its effect on catalytic activity.

Evidence is presented that in increasing concentrations of methanol the structure of the subfragment 1 is perturbed in such a way that the Mr = 50,000 central portion of the associated heavy chain is preferentially unfolded. This unfolding is accompanied by the loss in ATPase function where the rate of inactivation can be correlated with the loss in the amount of the Mr = 50,000 fragment generated under standard tryptic digestion conditions. The residual protein appears to be a soluble aggregate of a complex of the Mr = 27,000, 21,000, and light chain with no intact Mr = 50,000 fragment. Tryptic digestions in the presence of MgATP are restricted to the usual linker regions and the Mr = 50,000 fragment is completely protected from attack. Binding of actin to subfragment 1 also results in the protection of the Mr = 50,000 segment and of the Mr = 50,000/21,000 junction from tryptic attack. The data suggest that, in terms of methanolic perturbation, the subfragment 1 appears to be comprised of two domains with differential stability. One domain appears to be the central Mr = 50,000 segment of the heavy chain which is preferentially unfolded by methanol and requires the presence of MgATP or of actin for stabilization. The other domain is more stable and appears to consist of the interacting Mr = 27,000, 21,000, and light chain. The results also suggest that the integrity of the Mr = 50,000 segment is essential for the ATPase function of the protein.

Animals↗
PubMedDate not supplied

Structural perturbation of proteins in low denaturant concentrations.

The presence of very low concentrations of the widely used chemical denaturants, guanidinium chloride and urea, induce changes in the tertiary structure of proteins. We have presented results on such changes in four structurally unrelated proteins to show that such structural perturbations are common irrespective of their origin. Data representative of such structural changes are shown for the monomeric globular proteins such as horseradish peroxidase (HRP) from a plant, human serum albumin (HSA) and prothrombin from ovine blood serum, and for the membrane-associated, worm-like elongated protein, spectrin, from ovine erythrocytes. Structural alterations in these proteins were reflected in quenching studies of tryptophan fluorescence using the widely used quencher acrylamide. Stern-Volmer quenching constants measured in presence of the denaturants, even at concentrations below 100 mM, were higher than those measured in absence of the denaturants. Both steady-state and time-resolved fluorescence emission properties of tryptophan and of the extrinsic probe PRODAN were used for monitoring conformational changes in the proteins in presence of different low concentrations of the denaturants. These results are consistent with earlier studies from our laboratory indicating structural perturbations in proteins at the tertiary level, keeping their native-like secondary structure and their biological activity more or less intact.

Acrylamide↗
PubMed1996

EEG spike and wave modelled by a stochastic limit cycle.

Many reports based upon correlation dimension studies have suggested the chaotic nature of electroencephalographic spike and wave activity (SW). Another study found no evidence for this, showing that surrogate stochastic data generated from SW have the same dynamical properties as the original data. The present paper explicitly models SW as the output of a non-linear stochastic system. Non-linear non-parametric kernel autoregression is used to show that the attractor of this system may be a limit cycle. The addition of system noise originates a simulated time series with the same interspike interval variability originally hypothesized as chaotic. Tests performed on the correlation dimension obtained from the original data as well as from both linear and non-linear surrogates show that the noise-perturbed limit cycle model achieves the best fit to the original data. We conclude that SW is likely to be a form of stochastic disturbed limit cycle behaviour rather than chaos.

Animals↗
PubMed1999

On the presence and absence of behavioural traits in sport: an example from championship squash match-play.

Here we report two experiments that analysed sport (squash) competition as a non-linear system that transits intermittently between different behavioural states. The first experiment involved a perceptual analysis of 60 rallies in which stable behaviour and unstable behaviour, delineated by behavioural transitions (i.e. shot perturbations), were reliably (kappa = 0.930) and validly (kappa = 0.844) identified by independent observers. In addition, experts were better than non-experts at identifying the type of system behaviour (P < 0.01). These results provide for three alternative descriptions: (a) the system is multi-stable and transits between states via the mechanism of instability; (b) the system is bi-stable and abruptly transits between two states, labelled stable and unstable; or (c) the system is mono-stable and displays variability, marked by transient instability, as a result of system perturbations. The second experiment analysed squash behaviour as expressed in the phase relation between the two players from time-motion analysis. The data, from four rallies, yielded evidence of a tight anti-phase coupling with transient phase shifts, or perturbations, that were quickly damped. These data suggest a mono-stable system with a single (anti-phase) attractor onto which system fluctuations are occasionally written. However, these fluctuations failed to correspond with the short perturbations that were identified from perceptual analysis. Together, these results affirm the presence of transient behaviours in squash match-play, although the information that forms these perceptual judgements has yet to be identified.

Competitive Behavior↗
PubMed2005

Morphological and biochemical perturbations in rat erythrocytes following in vitro exposure to Fenvalerate and its metabolite.

Erythrocytes are a convenient model to understand the membrane oxidative damage induced by various xenobiotic-prooxidants. In this investigation, we have examined the potency of Fenvalerate (FEN) and its metabolite, p-chlorophenyl isovaleric acid (p-CPIA) to induce oxidative stress response in rat erythrocytes in vitro in terms of lipid peroxidation and effects on selected antioxidant enzymes. Susceptibility of erythrocytes to FEN exposure was further investigated in terms of morphological alterations by scanning electron microscopy and protein damage by gel electrophoresis of erythrocyte ghosts. Following in vitro exposure, FEN caused a significant induction of oxidative damage in erythrocytes at concentrations beyond 0.1 mM as evidenced by increased thiobarbituric acid reactive substances (TBARS) levels. The response was both concentration and time dependent. At higher concentrations, significant decreases in the activities of vital antioxidant enzymes viz., catalase, superoxide dismutase, glutathione transferase and glutathione reductase were also discernible clearly suggesting the potency of both, parent compound and its metabolite to induce oxidative stress in erythrocytes. Scanning electron micrographs of erythrocytes following FEN exposure at higher concentrations revealed various degrees of distortion in shape and ruptured membranes. Furthermore, gel electrophoresis studies revealed consistent and significant aggregation of only band 3 protein in erythrocyte membranes exposed to either FEN or p-CPIA at higher concentrations. These in vitro findings show that FEN and its metabolite have the propensity to cause significant oxidative damage in rat erythrocytes, which is associated with marked damage to membrane proteins. These data suggest that both structural and functional perturbations may ensue in erythrocytes following exposure to FEN at higher concentrations under in vivo situations.

Animals↗
PubMed1997

A comparison of fertility control and lethal control of bovine tuberculosis in badgers: the impact of perturbation induced transmission.

In this paper we use mathematical modelling to consider the broad advantages and disadvantages of fertility control over lethal control for bovine tuberculosis in badger populations. We use a deliberately simple model, attempting to capture only the key transmission processes. The model is parametrized with reference to the long-term Woodchester Park study. Estimates of mortality rate from this study suggest no significant extra mortality risk for animals with evidence of infection as indicated by the presence of anti-Mycobacterium bovis antibodies or M. bovis isolation. We find that large reductions in prevalence are sometimes the consequence of only moderate reductions in population numbers. If we assume that the act of control does not in itself affect transmission rates, then as far as eradication is concerned, both fertility control and mortality control operate through the same epidemiological mechanism, the removal of susceptibles: if one is in principle capable of keeping a population low enough to be infection free then so is the other. It is necessary to continue either form of control at regular intervals to maintain a constant level of infection in the long term. If control were to be stopped, return to precontrol levels of badger population and infection prevalence would be expected within a few years. Fertility control is less effective in reducing population density than lethal control since it can only act, at maximum, to remove one age cohort per year. It is also less effective in reducing transmission as it can only ever remove susceptibles, while lethal control also removes infectious badgers. However, if the social disturbance caused by lethal control does in fact increase contact rates for the remaining infectious badgers, the relative efficacies of the two strategies become a great deal less clear. While we have no quantitative data on the extent to which social perturbation does act to promote transmission, model simulations show that it is possible to develop plausible scenarios in which the lethal control may actually act to increase the absolute numbers of animals infected, while reducing the number of uninfected animals to very low numbers.

Animals↗
PubMed2004

The effect of cane use on the compensatory step following posterior perturbations.

OBJECTIVE: The compensatory step is a critical component of the balance response and is impaired in older fallers. The purpose of this research was to examine whether utilization of a cane modified the compensatory step response following external posterior perturbations. DESIGN: Single subject withdrawal design was employed. Single subject statistical analysis--the standard deviation bandwidth-method--supplemented visual analysis of the data. METHODS: Four older adults (range: 73-83 years) with balance impairment who habitually use a cane completed this study. Subjects received a series of sudden backward pulls that were large enough to elicit compensatory stepping. We examined the following variables both with and without cane use: timing of cane loading relative to step initiation and center of mass acceleration, stability margin, center of mass excursion and velocity, step length and width. RESULTS: No participant loaded the cane prior to initiation of the first compensatory step. There was no effect of cane use on the stability margin, nor was there an effect of cane use on center of mass excursion or velocity, or step length or width. CONCLUSIONS: These data suggest that cane use does not necessarily improve balance recovery following an external posterior perturbation when the individual is forced to rely on compensatory stepping. Instead these data suggest that the strongest factor in modifying step characteristics is experience with the perturbation.

Accidental Falls↗
PubMed2001

Toward a biologically based dose-response model for developmental toxicity of 5-fluorouracil in the rat: a mathematical construct.

Biologically based dose-response (BBDR) models comprise one way to incorporate mechanistic information into a dose-response assessment to be used for risk assessments. The chemotherapeutic drug 5-fluorouracil (5-FU) has been used as a prototypic compound for the construction of a BBDR model for developmental toxicity. Previous work has provided data and a general mechanistic framework for the developmental toxicity of 5-FU when it was administered to pregnant rats subcutaneously on gestation day 14. In this paper, a mathematical model relating maternally administered treatment with 5-FU to embryonal thymidylate synthetase inhibition and thymidylate synthetase inhibition to various measures of deoxyribonucleotide triphosphate (dNTP) pool perturbation is developed, and parameters are estimated using the data collected. The strategy used was to develop semi-empirical submodels for each of the intervening steps, and to estimate model parameters from previously described data. The models developed predict that there is no practical threshold for dNTP pool perturbation; that is, even minimal doses of 5-FU should result in some perturbation of dNTP pools. In particular, the relationship between dNTP pool perturbation and fetal weight deficit suggests that if there is a biological threshold for the effect of 5-FU on fetal weight, the responsible repair or compensation mechanism must be downstream of dNTP pool perturbation, and saturable at 5-FU doses lower than 10 mg/kg (the lowest dose examined for developmental effects in these studies).

Abnormalities, Drug-Induced↗
PubMed2003

Role of the C-terminal extrinsic region of the alpha polypeptide of the light-harvesting 2 complex of Rhodobacter sphaeroides: a domain swap study.

The LH1 and LH2 complexes of Rhodobacter sphaeroides form ring structures of 16 and 9 protomers, respectively, comprising alpha and beta polypeptides, bacteriochlorophylls (Bchl), and carotenoids. Using the LH2 complex as a starting point, two chimeric LH complexes were constructed incorporating the alphaC-terminal domain of either the Rb. sphaeroides LH1 complex or the Rhodospirillum molischianum LH2 complex. The LH1 domain swap produced a new red-shifted component that comprised approximately 30% of the total absorbance. In the LH1alpha C-terminal mutant this new red-shifted species acts as the terminal emitter, with the new emission maximum located 10 nm further to the red than for the WT. Raman spectroscopy indicates that a fraction of the B850 Bchls is involved in relatively weak H-bonds, possibly involving the alphaTrp(+11) residue within the new alphaC-terminus, consistent with a more LH1-like character for one of the Bchls. The CD data indicate that the domain swaps have perturbed the native arrangement of the B850 Bchls, including the site energy difference between the alpha- and beta-bound Bchls. Thus, the normal energetic structure of the ring system has been disrupted, with one component blue shifted due to the presumed loss of an H-bond donor and the other red shifted by the influence of the new alphaC-terminal domain. The dichotomous response of the mutants to the carotenoids incorporated, spheroidenone or neurosporene, strongly suggests that the C-terminal region of the alpha polypeptide is involved in binding a carotenoid. The projection map of the LH1alpha C-terminal mutant complex was determined in negative stain at 25 A resolution, and it shows a diameter of 53 A, compared to 50 A for the WT. Hence these new spectral properties have not been accompanied by an alteration in ring size.

Amino Acid Sequence↗
PubMed2023

Active learning of enhancer and silencer regulatory grammar in photoreceptors.

Cis-regulatory elements (CREs) direct gene expression in health and disease, and models that can accurately predict their activities from DNA sequences are crucial for biomedicine. Deep learning represents one emerging strategy to model the regulatory grammar that relates CRE sequence to function. However, these models require training data on a scale that exceeds the number of CREs in the genome. We address this problem using active machine learning to iteratively train models on multiple rounds of synthetic DNA sequences assayed in live mammalian retinas. During each round of training the model actively selects sequence perturbations to assay, thereby efficiently generating informative training data. We iteratively trained a model that predicts the activities of sequences containing binding motifs for the photoreceptor transcription factor Cone-rod homeobox (CRX) using an order of magnitude less training data than current approaches. The model's internal confidence estimates of its predictions are reliable guides for designing sequences with high activity. The model correctly identified critical sequence differences between active and inactive sequences with nearly identical transcription factor binding sites, and revealed order and spacing preferences for combinations of motifs. Our results establish active learning as an effective method to train accurate deep learning models of cis-regulatory function after exhausting naturally occurring training examples in the genome.

Journal Article↗
PubMed2000

Resummation of QED perturbation series by sequence transformations and the prediction of perturbative coefficients

We propose a method for the resummation of divergent perturbative expansions in quantum electrodynamics and related field theories. The method is based on a nonlinear sequence transformation and uses as input data only the numerical values of a finite number of perturbative coefficients. The results obtained in this way are for alternating series superior to those obtained using Pade approximants. The nonlinear sequence transformation fulfills an accuracy-through-order relation and can be used to predict perturbative coefficients. In many cases, these predictions are closer to available analytic results than predictions obtained using the Pade method.

Journal Article↗
PubMed1969

Kinetic modeling in physiology.

The author discusses the construction of model biochemical/physiological systems to fit experimental data which is always incomplete. He suggests that the first experiments on any system should be first-order (usually tracer) perturbations of steady-state systems. The proposed model can then be given a preliminary fit to the data; criteria for best fit, consistency, and uniqueness of fit are suggested. More data may then be obtained by perturbations at another steady-state, and finally by studying transient situations.References are included to some of the author's own publications in which these matters are discussed in detail.

Journal Article↗
PubMed2025

UALCAN Mobile, an app for cancer proteogenomic data analysis.

Cancer is a complex disease affecting various organs and is a major cause of death worldwide. During cancer initiation, disease progression, and tumor metastasis, various genomic and proteomic alterations are observed. Recent technological advances have led to the generation of large amounts of molecular data, including genomics and transcriptomics. These large-scale datasets can be utilized to analyze and identify sub-class-specific cancer biomarkers and targets. However, there is a need for the development of user-friendly tools for large-scale data analysis, disseminating the analyzed data in a visualizable format to cancer researchers with no programming skills. We developed UALCAN, a comprehensive platform that allows users to integrate disparate data to better understand the genes, proteins, and pathways perturbed in cancer and make discoveries of potential biomarkers and targets. In the current study, we describe the development of the UALCAN Mobile application (app) that will provide cancer transcriptomic data obtained from The Cancer Genome Atlas (TCGA) project to evaluate protein-coding gene expression based on various stratifications, including stage, grade, race, gender, and molecular-subtypes across over 30 types of cancers. In addition, the UALCAN mobile provides data analysis options for epigenetic changes due to DNA promoter methylation and Clinical Proteomic Tumor Analysis Consortium (CPTAC) cancer proteomic data. The app provides access to large cancer molecular datasets on the go. To find changes in the expression of causative genes and proteins and to identify biomarkers and therapeutic targets, UALCAN mobile app will be extremely valuable. The "UALCAN Mobile" app is free to use and can be downloaded from both the iOS/Apple and the Android Play Store and has been downloaded over 100 times in each of iOS and android app stores.

app↗
PubMed1997

Perturbations in gastric physiology in Helicobacter pylori duodenal ulcer: are they all epiphenomena?

BACKGROUND: The Holy Grail of physiological studies in acid secretion has been to identify a specific abnormality in gastroduodenal physiology responsible for the development of duodenal ulcer disease. METHODS: We review the available data relating duodenal ulcer and Helicobacter pylori infection to perturbations in gastric physiology, especially acid secretion. RESULTS: It is known now that elevated serum pepsinogen levels, reduced inhibition of acid secretion with antral acidification or distention, exaggerated gastrin response to meals or infusion of bombesin or gastric-releasing peptide, exaggerated acid output in response to gastric-releasing peptide, and abnormalities in duodenal bicarbonate secretion in response to instillation of acid are reversible epiphenomena related to the H. pylori infection and are not in themselves responsible for duodenal ulcer disease. H. pylori is inhibited by bile, yet can thrive in the duodenal bulb of duodenal ulcer patients. Glycine-conjugated bile acids are precipitated by acid; thus, any mechanism that would increase the duodenal acid load may remove the inhibitory bile and allow unrestrained growth of H. pylori. CONCLUSION: These data and speculations offer one possible explanation for why duodenal ulcer occurs in only some people--those with high acid secretion--and suggest that the combination of high duodenal acid load and H. pylori infection is sufficient to result in duodenal ulcer disease.

Duodenal Ulcer↗