arXiv subjects

Ping Xie

Publications and source records attributed to Ping Xie.

13 recordsLinked to original sources

arXiv2023

Testing for sufficient follow-up in censored survival data by using extremes

In survival analysis, it often happens that some individuals, referred to as cured individuals, never experience the event of interest. When analyzing time-to-event data with a cure fraction, it is crucial to check the assumption of `sufficient follow-up', which means that the right extreme of the censoring time distribution is larger than that of the survival time distribution for the non-cured individuals. However, the available methods to test this assumption are limited in the literature. In this article, we study the problem of testing whether follow-up is sufficient for light-tailed distributions and develop a simple novel test. The proposed test statistic compares an estimator of the non-cure proportion under sufficient follow-up to one without the assumption of sufficient follow-up. A bootstrap procedure is employed to approximate the critical values of the test. We also carry out extensive simulations to evaluate the finite sample performance of the test and illustrate the practical use with applications to leukemia and breast cancer datasets.

stat.ME↗

arXiv2021

Acceleration of DNA Replication of Klenow Fragment by Small Resisting Force

DNA polymerases are an essential class of enzymes or molecular motors that catalyze processive DNA syntheses during DNA replications. A critical issue for DNA polymerases is their molecular mechanism of processive DNA replication. We have previously proposed a model for chemomechanical coupling of DNA polymerases, based on which the predicted results have been provided about the dependence of DNA replication velocity upon the external force on Klenow fragment of DNA polymerase I. Here, we performed single molecule measurements of the replication velocity of Klenow fragment under the external force by using magnetic tweezers. The single molecule data verified quantitatively the previous theoretical predictions, which is critical to the chemomechanical coupling mechanism of DNA polymerases. A prominent characteristic for the Klenow fragment is that the replication velocity is independent of the assisting force whereas the velocity increases largely with the increase of the resisting force, attains the maximum velocity at about 3.8 pN and then decreases with the further increase of the resisting force.

cond-mat.soft↗

arXiv2007

Model for processive nucleotide and repeat additions by the telomerase

A model is presented to describe the nucleotide and repeat addition processivity by the telomerase. In the model, the processive nucleotide addition is implemented on the basis of two requirements: One is that stem IV loop stimulates the chemical reaction of nucleotide incorporation, and the other one is the existence of an ssRNA-binding site adjacent to the polymerase site that has a high affinity for the unpaired base of the template. The unpairing of DNA:RNA hybrid after the incorporation of the nucleotide paired with the last base on the template, which is the prerequisite for repeat addition processivity, is caused by a force acting on the primer. The force is resulted from the unfolding of stem III pseudoknot that is induced by the swinging of stem IV loop towards the nucleotide-bound polymerase site. Based on the model, the dynamics of processive nucleotide and repeat additions by Tetrahymena telomerase are quantitatively studied, which give good explanations to the previous experimental results. Moreover, some predictions are presented. In particular, it is predicted that the repeat addition processivity is mainly determined by the difference between the free energy required to disrupt the DNA:RNA hybrid and that required to unfold the stem III pseudoknot, with the large difference corresponding to a low repeat addition processivity while the small one corresponding to a high repeat addition processivity.

q-bio.BM↗

arXiv2006

Model for unidirectional movement of axonemal and cytoplasmic dynein molecules

A model for the unidirectional movement of dynein is presented based on structural observations and biochemical experimental results available. In this model, the binding affinity of dynein for microtubule is independent of its nucleotide state and the change between strong and weak microtubule-binding is determined naturally by the variation of relative orientation between the stalk and microtubule as the stalk rotates following nucleotide-state transition. Thus the enigmatic communication from the ATP binding site in the globular domain to the far MT-binding site in the tip of the stalk, which is prerequisite in conventional models, is not required. Using the present model, the previous experimental results such as the effect of ATP and ADP bindings on dissociation of dynein from microtubule, the processive movement of single-headed axonemal dyneins at saturating ATP concentration, the load dependence of step size for the processive movement of two-headed cytoplasmic dyneins and the dependence of stall force on ATP concentration can be well explained.

q-bio.BM↗

arXiv2005

On the Fibril Elongation Mechanism of the Prion Protein Fragment PrP106-126

Mouse prion protein PrP106-126 is a peptide corresponding to the residues 107-127 of human prion protein. It has been shown that PrP106-126 can reproduce the main neuropathological features of prionrelated transmissible spongiform encephalopathies and can form amyloid-like fibrils in vitro. The conformational characteristics of PrP106-126 fibril have been investigated by electron microscopy, CD spectroscopy, NMR and molecular dynamics simulations. Recent researches have found out that PrP106-126 in water assumes a stable structure consisting of two parallel beta-sheets that are tightly packed against each other. In this work we perform molecular dynamics simulation to reveal the elongation mechanism of PrP106-126 fibril. Influenced by the edge strands of the fibril which already adopt beta-sheets conformation, single PrP106-126 peptide forms beta-structure and becomes a new element of the fibril. Under acidic condition, single PrP106-126 peptide adopts a much larger variety of conformations than it does under neural condition, which makes a peptide easier to be influenced by the edge strands of the fibril. However, acidic condition dose not largely affect the stability of PrP106-126 peptide fibril. Thus, the speed of fibril elongation can be dramatically increased by lowering the pH value of the solution. The pH value was adjusted by either changing the protonation state of the residues or adding hydronium ions (acidic solution) or hydroxyl ions (alkaline solution). The differences between these two approaches are analyzed here.

q-bio.BM↗

arXiv2005

Study the effects of metallic ions on the combination of DNA and histones with molecular combing technique

The effects of monovalent (Na+, K+) and divalent (Mg2+, Ca2+, Mn2+) ions on the interaction between DNA and histone are studied using the molecular combing technique. Lamda-DNA molecules and DNA-histone complexes incubated with metal cations (Na+, K+, Mg2+, Ca2+, Mn2+) are stretched on hydrophobic surfaces, and directly observed by fluorescence microscopy. The results indicate that when these cations are added into the DNA solution, the fluorescence intensities of the stained DNA are reduced differently. The monovalent cations (Na+, K+) inhibit binding of histone to DNA. The divalent cations (Mg2+, Ca2+, Mn2+) enhance significantly the binding of histone to DNA and the binding of the DNA-histone complex to the hydrophobic surface. Mn2+ also induces condensation and aggregation of the DNA-histone complex.

q-bio.BM↗

arXiv2004

Model for processive movement of dynein

A model for the processive movement of dynein is presented based on experimental observations available. In the model, the change from strong microtubule-binding to weak binding of dynein is determined naturally by the variation of the relative orientation between the two interacting surfaces of the stalk tip and the microtubule as the stalk rotates from the ADP.Vi-state orientation to the apo-state orientation. This means that the puzzling communication from the ATP binding site in the globular head to the MT-binding site in the tip of the stalk, which is prerequisite in the conventional model, is not required. Using the present model, the previous experimental results, such as (i) the step size of a dynein being an integer times of the period of the MT lattice, (ii) the dependence of the step size on load, i.e., the step size decreasing with the increase of load, and (iii) the stall force being proportional to [ATP] at low [ATP] and becoming saturated at high [ATP], are well explained.

q-bio.BM↗

arXiv2004

Dynamics of heterodimeric kinesins and cooperation of kinesins

Using the model for the processive movement of a dimeric kinesin we proposed before, we study the dynamics of a number of mutant homodimeric and heterodimeric kinesins that were constructed by Kaseda et al. (Kaseda, K., Higuchi, H. and Hirose, K. PNAS 99, 16058 (2002)). The theoretical results of ATPase rate per head, moving velocity, and stall force of the motors show good agreement with the experimental results by Kaseda et al.: The puzzling dynamic behaviors of heterodimeric kinesin that consists of two distinct heads compared with its parent homodimers can be easily explained by using independent ATPase rates of the two heads in our model. We also study the collective kinetic behaviors of kinesins in MT-gliding motility. The results explains well that the average MT-gliding velocity is independent of the number of bound motors and is equal to the moving velocity of a single kinesin relative to MT.

q-bio.BM↗

arXiv2003

Mechanism of unidirectional movement of kinesin motors

Kinesin motors have been studied extensively both experimentally and theoretically. However, the microscopic mechanism of the processive movement of kinesin is still an open question. In this paper, we propose a hand-over-hand model for the processivity of kinesin, which is based on chemical, mechanical, and electrical couplings. In the model the processive movement does not need to rely on the two heads' coordination in their ATP hydrolysis and mechanical cycles. Rather, the ATP hydrolyses at the two heads are independent. The much higher ATPase rate at the trailing head than the leading head makes the motor walk processively in a natural way, with one ATP being hydrolyzed per step. The model is consistent with the structural study of kinesin and the measured pathway of the kinesin ATPase. Using the model the estimated driving force of ~ 5.8 pN is in agreements with the experimental results (5~7.5 pN). The prediction of the moving time in one step (~10 microseconds) is also consistent with the measured values of 0~50 microseconds. The previous observation of substeps within the 8-nm step is explained. The shapes of velocity-load (both positive and negative) curves show resemblance to previous experimental results.

q-bio.BM↗

arXiv2003

Model for processive movement of myosin V and myosin VI

Myosin V and myosin VI are two classes of two-headed molecular motors of the myosin superfamily that move processively along helical actin filaments in opposite directions. Here we present a hand-over-hand model for their processive movements. In the model, the moving direction of a dimeric molecular motor is automatically determined by the relative orientation between its two heads at free state and its head's binding orientation on track filament. This determines that myosin V moves toward the barbed end and myosin VI moves toward the pointed end of actin. During the moving period in one step, one head remains bound to actin for myosin V whereas two heads are detached for myosin VI: The moving manner is determined by the length of neck domain. This naturally explains the similar dynamic behaviors but opposite moving directions of myosin VI and mutant myosin V (the neck of which is truncated to only one-sixth of the native length). Because of different moving manners, myosin VI and mutant myosin V exhibit significantly broader step-size distribution than native myosin V. However, all three motors give the same mean step size of 36 nm (the pseudo-repeat of actin helix). Using the model we study the dynamics of myosin V quantitatively, with theoretical results in agreement with previous experimental ones.

q-bio.BM↗

arXiv2003

Control of spiral waves and turbulent states in a cardiac model by travelling-wave perturbations

We propose a travelling-wave perturbation method to control the spatiotemporal dynamics in a cardiac model. It is numerically demonstrated that the method can successfully suppress the wave instability (alternans in action potential duration) in the one-dimensional case and convert spiral waves and turbulent states to the normal travelling wave states in the two-dimensional case. An experimental scheme is suggested which may provide a new design for a cardiac defibrillator.

q-bio.TO↗

arXiv2003

A model for processivity of molecular motors

We propose a two-dimensional model for a complete description of the dynamics of molecular motors, including both the processive movement along track filaments and the dissociation from the filaments. The theoretical results on the distributions of the run length and dwell time at a given ATP concentration, the dependences of mean run length, mean dwell time and mean velocity on ATP concentration and load are in good agreement with the previous experimental results.

q-bio.BM↗

arXiv2003

Ionic effect on combing of single DNA molecules and observation of their force-induced melting by fluorescence microscopy

Molecular combing is a powerful and simple method for aligning DNA molecules onto a surface. Using this technique combined with fluorescence microscopy, we observed that the length of lambda-DNA molecules was extended to about 1.6 times their contour length (unextended length, 16.2 micrometers) by the combing method on hydrophobic polymethylmetacrylate (PMMA) coated surfaces. The effects of sodium and magnesium ions and pH of the DNA solution were investigated. Interestingly, we observed force-induced melting of single DNA molecules.

q-bio.BM↗