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Biomedical subjects

Kun Hu

Publications and source records attributed to Kun Hu.

18 recordsLinked to original sources
PubMed2006

Spurious detection of phase synchronization in coupled nonlinear oscillators.

Coupled nonlinear systems under certain conditions exhibit phase synchronization, which may change for different frequency bands or with the presence of additive system noise. In both cases, Fourier filtering is traditionally used to preprocess data. We investigate to what extent the phase synchronization of two coupled Rössler oscillators depends on (1) the broadness of their power spectrum, (2) the width of the bandpass filter, and (3) the level of added noise. We find that for identical coupling strengths, oscillators with broader power spectra exhibit weaker synchronization. Further, we find that within a broad bandwidth range, bandpass filtering reduces the effect of noise but can lead to a spurious increase in the degree of phase synchronization with narrowing bandwidth, even when the coupling between the two oscillators remains the same.

Biophysics↗
PubMed2006

Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2.

Compelling evidence suggest that vascular endothelial growth factor (VEGF) and its receptors, especially receptor 2 (VEGFR2, or kinase insert domain-containing receptor, KDR), play a critical role in angiogenesis under both physiological and pathological conditions, including cancer and angiogenic retinopathies such as age-related macular degeneration (AMD). To this end, inhibition of angiogenesis with antagonists to either VEGF or KDR has yielded significant therapeutic efficacy both in preclinical studies in animal models and in clinical trials in patients with cancer and AMD. We previously reported the identification of a high affinity, fully human anti-KDR antibody fragment, 1121B Fab, through a highly stringent affinity maturation process with a Fab originally isolated from a naïve human antibody phage display library. In this study, we demonstrate that 1121B Fab is able to strongly block KDR/VEGF interaction, resulting in potent inhibition of an array of biological activities of VEGF, including activation of the receptor and its signaling pathway, intracellular calcium mobilization, and migration and proliferation of endothelial cells. Taken together, our data lend strong support to the further development of 1121B Fab fragment as an anti-angiogenesis agent in both cancer and angiogenic retinopathies.

Animals↗
PubMed2006

Cross-correlation of instantaneous phase increments in pressure-flow fluctuations: applications to cerebral autoregulation.

We investigate the relationship between the blood flow velocities (BFV) in the middle cerebral arteries and beat-to-beat blood pressure (BP) recorded from a finger in healthy and post-stroke subjects during the quasisteady state after perturbation for four different physiologic conditions: supine rest, head-up tilt, hyperventilation, and CO2 rebreathing in upright position. To evaluate whether instantaneous BP changes in the steady state are coupled with instantaneous changes in the BFV, we compare dynamical patterns in the instantaneous phases of these signals, obtained from the Hilbert transform, as a function of time. We find that in post-stroke subjects the instantaneous phase increments of BP and BFV exhibit well-pronounced patterns that remain stable in time for all four physiologic conditions, while in healthy subjects these patterns are different, less pronounced, and more variable. We propose an approach based on the cross-correlation of the instantaneous phase increments to quantify the coupling between BP and BFV signals. We find that the maximum correlation strength is different for the two groups and for the different conditions. For healthy subjects the amplitude of the cross-correlation between the instantaneous phase increments of BP and BFV is small and attenuates within 3-5 heartbeats. In contrast, for post-stroke subjects, this amplitude is significantly larger and cross-correlations persist up to 20 heartbeats. Further, we show that the instantaneous phase increments of BP and BFV are cross-correlated even within a single heartbeat cycle. We compare the results of our approach with three complementary methods: direct BP-BFV cross-correlation, transfer function analysis, and phase synchronization analysis. Our findings provide insight into the mechanism of cerebral vascular control in healthy subjects, suggesting that this control mechanism may involve rapid adjustments (within a heartbeat) of the cerebral vessels, so that BFV remains steady in response to changes in peripheral BP.

Blood Flow Velocity↗
PubMed2006

A convenient synthesis of an anti-Helicobacter pylori agent, dehydrodiconiferyl alcohol.

Potential anti-Helicobacter pylori agent dehydrodiconiferyl alcohol was synthesized in 44% overall yield, starting from vanillin which could be commercially available. Carbon extension of vanillin followed by the Horner-Wadsworth-Emmons reaction, a biomolecular radical coupling reaction and DIBAL-H reduction gave dehydrodiconiferyl alcohol.

Anti-Bacterial Agents↗
PubMed2006

Identification and characterization of a polysaccharide deacetylase gene from Bacillus thuringiensis.

One polysaccharide deacetylase gene was cloned from Bacillus thuringiensis and designated pdaA. Disruption of pdaA did not affect vegetative growth and sporulation but obviously affected spore germination. When L-alanine was added into the spore suspension, the spores of the pdaA disruption mutant showed a slow and partial reduction in absorbance at OD600 and became phase pale gray compared with phase dark of the wild-type strain. In contrast with the outgrowing of wild-type spores after germination, the pdaA mutant spores were blocked at the stage of spore germination. Transmission electron micrographs revealed a significant difference between the pdaA mutant and the wild-type strain in the spore cortex. Introduction of the pdaA gene into the pdaA disruption mutant complemented the germination-negative phenotype. Reverse transcription--polymerase chain reaction showed that pdaA was transcribed after incubation for 10 h in CCY medium.

Amidohydrolases↗
PubMed2006

Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes.

OBJECTIVE: Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs. RESEARCH DESIGN AND METHODS: We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 +/- 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO(2) rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI. RESULTS: The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P < 0.0001), and impaired CO(2) reactivity (P = 0.05). WMH volume was negatively correlated with baseline BFV (P < 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA(1c) (A1C), and inflammatory markers and positively associated with systolic blood pressure (R(2) = 0.86, P < 0.0001). CONCLUSIONS: Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes.

Aged↗
PubMed2005

Foot pressure distribution during walking in young and old adults.

BACKGROUND: Measurement of foot pressure distribution (FPD) is clinically useful for evaluation of foot and gait pathologies. The effects of healthy aging on FPD during walking are not well known. This study evaluated FPD during normal walking in healthy young and elderly subjects. METHODS: We studied 9 young (30 +/- 5.2 years), and 6 elderly subjects (68.7 +/- 4.8 years). FPD was measured during normal walking speed using shoe insoles with 99 capacitive sensors. Measured parameters included gait phase characteristics, mean and maximum pressure and force, and relative load.Time-series measurements of each variable for all sensors were grouped into 9 anatomical masks. RESULTS: Elderly subjects had lower normalized maximum pressure for the medial and lateral calcaneal masks, and for all medial masks combined. In the medial calcaneus mask, the elderly group also had a lower absolute maximum and lower mean and normalized mean pressures and forces, compared to young subjects. Elderly subjects had lower maximum force and normalized maximum force and lower mean force and normalized mean forces in the medial masks as well. CONCLUSION: FPD differences between the young and elderly groups were confined to the calcaneus and hallux regions and to the medial side of the foot. In elderly subjects, weight bearing on the lateral side of the foot during heel touch and toe-off phases may affect stability during walking.

Adult↗
PubMed2005

Quantifying signals with power-law correlations: a comparative study of detrended fluctuation analysis and detrended moving average techniques.

Detrended fluctuation analysis (DFA) and detrended moving average (DMA) are two scaling analysis methods designed to quantify correlations in noisy nonstationary signals. We systematically study the performance of different variants of the DMA method when applied to artificially generated long-range power-law correlated signals with an a priori known scaling exponent alpha(0) and compare them with the DFA method. We find that the scaling results obtained from different variants of the DMA method strongly depend on the type of the moving average filter. Further, we investigate the optimal scaling regime where the DFA and DMA methods accurately quantify the scaling exponent alpha(0) , and how this regime depends on the correlations in the signal. Finally, we develop a three-dimensional representation to determine how the stability of the scaling curves obtained from the DFA and DMA methods depends on the scale of analysis, the order of detrending, and the order of the moving average we use, as well as on the type of correlations in the signal.

Journal Article↗
PubMed2005

Effect of nonlinear filters on detrended fluctuation analysis.

When investigating the dynamical properties of complex multiple-component physical and physiological systems, it is often the case that the measurable system's output does not directly represent the quantity we want to probe in order to understand the underlying mechanisms. Instead, the output signal is often a linear or nonlinear function of the quantity of interest. Here, we investigate how various linear and nonlinear transformations affect the correlation and scaling properties of a signal, using the detrended fluctuation analysis (DFA) which has been shown to accurately quantify power-law correlations in nonstationary signals. Specifically, we study the effect of three types of transforms: (i) linear ( y(i) =a x(i) +b) , (ii) nonlinear polynomial ( y(i) =a x(k)(i) ) , and (iii) nonlinear logarithmic [ y(i) =log ( x(i) +Delta) ] filters. We compare the correlation and scaling properties of signals before and after the transform. We find that linear filters do not change the correlation properties, while the effect of nonlinear polynomial and logarithmic filters strongly depends on (a) the strength of correlations in the original signal, (b) the power k of the polynomial filter, and (c) the offset Delta in the logarithmic filter. We further apply the DFA method to investigate the "apparent" scaling of three analytic functions: (i) exponential [exp (+/-x+a) ] , (ii) logarithmic [log (x+a) ] , and (iii) power law [ (x+a)(lambda) ] , which are often encountered as trends in physical and biological processes. While these three functions have different characteristics, we find that there is a broad range of values for parameter a common for all three functions, where the slope of the DFA curves is identical. We further note that the DFA results obtained for a class of other analytic functions can be reduced to these three typical cases. We systematically test the performance of the DFA method when estimating long-range power-law correlations in the output signals for different parameter values in the three types of filters and the three analytic functions we consider.

Algorithms↗
PubMed2004

Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior.

There exists a robust day/night pattern in the incidence of adverse cardiac events with a peak at approximately 10 a.m. This peak traditionally has been attributed to day/night patterns in behaviors affecting cardiac function in vulnerable individuals. However, influences from the endogenous circadian pacemaker independent from behaviors may also affect cardiac control. Heartbeat dynamics under healthy conditions exhibit robust complex fluctuations characterized by self-similar temporal structures, which break down under pathologic conditions. We hypothesize that these dynamical features of the healthy human heartbeat have an endogenous circadian rhythm that brings the features closer to those observed under pathologic conditions at the endogenous circadian phase corresponding to approximately 10 a.m. We investigate heartbeat dynamics in healthy subjects recorded throughout a 10-day protocol wherein the sleep/wake and behavior cycles are desynchronized from the endogenous circadian cycle, enabling assessment of circadian factors while controlling for behavior-related factors. We demonstrate that the scaling exponent characterizing temporal correlations in heartbeat dynamics does exhibit a significant circadian rhythm (with a sharp peak at the circadian phase corresponding to approximately 10 a.m.), which is independent from scheduled behaviors and mean heart rate. Cardiac dynamics under pathologic conditions such as congestive heart failure also are associated with a larger value of the scaling exponent of the interbeat interval. Thus, the sharp peak in the scaling exponent at the circadian phase coinciding with the period of highest cardiac vulnerability observed in epidemiological studies suggests that endogenous circadian-mediated influences on cardiac control may be involved in the day/night pattern of adverse cardiac events in vulnerable individuals.

Adult↗
PubMed2004

Identification and characterization of a novel cytoplasm protein ICF45 that is involved in cell cycle regulation.

A novel cytoplasm protein, interphase cytoplasm foci protein 45 kDa (ICF45), was identified by screening the cDNA expression library for HeLa cells with serum from an autoimmune patient. The complete cDNA sequence of ICF45 was determined to be 1.32 kb and to encode 298 amino acids with an apparent molecular mass of 45 kDa. The ICF45 transcripts were detected in different tissues and were relatively rich in human liver and lung tissues but scarce in brain tissue. Immunofluorescence with anti-ICF45-specific antibodies demonstrated that ICF45 is strongly expressed in interphase and cannot be seen in mitosis. The subcellular localization of ICF45 and fusion proteins GFP-ICF45, ICF45-GFP, and HA-ICF45 showed ICF45 centralized into 1-2 dots in the cytoplasm and always near the nuclear membrane. The staining foci of ICF45 appeared to be slightly larger than centrosomes and in some cases were found to colocalize with centrosomes. After effectively silencing the ICF45 by RNAi, the growth and proliferation of the cells were significantly inhibited, and p53 was detected to be up-regulated. The silencing of ICF45 also resulted in an appearance of polycentrosome and multinuclear cells, which finally went to apoptosis. Our results suggest that ICF45 is a highly conserved novel protein, which is expressed in a cell cycle-dependent manner and seemed to be involved in cell cycle progression and cell proliferation.

Amino Acid Sequence↗
PubMed2004

Non-random fluctuations and multi-scale dynamics regulation of human activity.

We investigate if known extrinsic and intrinsic factors fully account for the complex features observed in recordings of human activity as measured from forearm motion in subjects undergoing their regular daily routine. We demonstrate that the apparently random forearm motion possesses dynamic patterns characterized by robust scale-invariant and nonlinear features. These patterns remain stable from one subject to another and are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, since they persist during daily routine and when the same subjects undergo time-isolation laboratory experiments designed to account for the circadian phase and to control the known extrinsic factors. Further, by modeling the scheduled events imposed throughout the laboratory protocols, we demonstrate that they cannot account for the observed scaling patterns in activity fluctuations. We attribute these patterns to a previously unrecognized intrinsic nonlinear multi-scale control mechanism of human activity that is independent of known extrinsic factors such as random and scheduled events, as well as the known intrinsic factors which possess a single characteristic time scale such as circadian and ultradian rhythms.

Adult↗
PubMed2004

Screening and identification of Shigella flexneri 2a virulence-related genes induced after invasion of epithelial cells.

An in vivo expression technology (IVET) was applied to screen S. flexneri 2a genes induced after invasion of epithelial cells, and virulence-related genes were further identified by mutational analysis. Thirteen intracellular induced genes were identified with a HeLa cell infection model. Of these, two were identified as alkylation-related genes; one was related to metabolism; one encoded a transcriptional regulator; three were identified as insertion elements; three appeared to be antisense to genes involved in the transmethylation, biosynthesis, and phosphotransferase system; and three were predicted to encode polypeptides with unknown functions. Intracellular survival assays showed that the mutants of alkA, citC and wcaJ genes had lower capability of intracellular replication or survival than the wild-type strain. The results indicated that alkA, citC and wcaJ genes could take part in the intracellular survival or replication of S. flexneri 2a and the capability of intracellular survival or replication could be one of the major virulence elements. However, the yaiC mutant was able to survive in the murine infection assay but almost not in HeLa cell infection assay. Very possibly, yaiC gene was involved in the other mechanism of S. flexneri virulence. This study might lead to a better understanding of the intracellular survival or proliferation process of S. flexneri 2a and perhaps provide insights into the pathogenicity of this pathogen.

Animals↗
PubMed2003

Identification of alkA gene related to virulence of Shigella flexneri 2a by mutational analysis.

AIM: In vivo induced genes are thought to play an important role during infection of host. AlkA was identified as an in vivo-induced gene by in vivo expression technology (IVET), but its virulence in Shigella flexneri was not reported. The purpose of this study was to identify the role of alkA gene in the pathogenesis of S. flexneri. METHODS: PCR was used to amplify alkA gene of S. flexneri 2a and fragment 028pKm. The fragment was then transformed into 2457T05 strain, a S flexneri 2a strain containing Red recombination system, which was constructed with a recombinant suicide plasmid pXLkd46. By in vivo homologous recombination, alkA mutants were obtained and verified by PCR and sequencing. Intracellular survival assay and virulence assay were used to test the intracellular survival ability in HeLa cell model and the virulence in mice lung infection model respectively. RESULTS: Deletion mutant of S. flexneri 2a alkA was successfully constructed by gamma Red recombination system. The mutant exhibited significant survival defects and much significant virulence defects in mice infection assay. CONCLUSION: AlkA gene plays an important role in the infection of epithelial cells and is a virulent gene of Shigella spp.

Animals↗
PubMed2003

[The red recombination system and its application to gene knock-out in microorganism].

Since many DNA-sequencing projects of varied microorganisms have been completed,studies on their functional genomics become more important. Inactivation of an interesting gene is a direct method to characterize its function. Though the Escherichia coli RecA recombination system can be used to produce gene mutants,it needs a complex manipulation process. Furthermore, its efficiency is very low. Recently a Red recombination system was developed. This recombination system consists of three proteins:alpha protein (gamma exonuclease), beta protein and Gam protein. In this system, the linear targeting DNA which contains a selectable marker flanked with a homologous region as short as only 35 approximately 60 bp can be directly targeted for gene knock-out with a higher efficiency.

English Abstract↗
PubMed2003

[Study on gene knockout using red system in Shigella flexneri].

The technology of gene knockout using lambda Red system in bacteria has been developed lately, but its application being limited to Esherichia coli. In order to get some experiences in other bacteria we select four genes, including alkA, wcaJ, yphF and dam, to test gene knockout using Red system in E. coli and Shigella. As a result, three genes were successfully knocked out in E. coli except dam while only alkA gene was knocked out in Shigella. It showed that the Red system should be improved if it was to be effectively used in Shigella and other bacteria.

Bacterial Proteins↗
PubMed2002

Effect of nonstationarities on detrended fluctuation analysis.

Detrended fluctuation analysis (DFA) is a scaling analysis method used to quantify long-range power-law correlations in signals. Many physical and biological signals are "noisy," heterogeneous, and exhibit different types of nonstationarities, which can affect the correlation properties of these signals. We systematically study the effects of three types of nonstationarities often encountered in real data. Specifically, we consider nonstationary sequences formed in three ways: (i) stitching together segments of data obtained from discontinuous experimental recordings, or removing some noisy and unreliable parts from continuous recordings and stitching together the remaining parts-a "cutting" procedure commonly used in preparing data prior to signal analysis; (ii) adding to a signal with known correlations a tunable concentration of random outliers or spikes with different amplitudes; and (iii) generating a signal comprised of segments with different properties-e.g., different standard deviations or different correlation exponents. We compare the difference between the scaling results obtained for stationary correlated signals and correlated signals with these three types of nonstationarities. We find that introducing nonstationarities to stationary correlated signals leads to the appearance of crossovers in the scaling behavior and we study how the characteristics of these crossovers depend on (a) the fraction and size of the parts cut out from the signal, (b) the concentration of spikes and their amplitudes (c) the proportion between segments with different standard deviations or different correlations and (d) the correlation properties of the stationary signal. We show how to develop strategies for preprocessing "raw" data prior to analysis, which will minimize the effects of nonstationarities on the scaling properties of the data, and how to interpret the results of DFA for complex signals with different local characteristics.

Computer Simulation↗