9,176 research outputs found
Double-stranded break can be repaired by single-stranded oligonucleotides via the ATM/ATR pathway in mammalian cells
Single-stranded oligonucleotide (SSO)-mediated gene modification is a newly developed tool for site-specific gene repair in mammalian cells; however, the corrected cells always show G2/M arrest and cannot divide to form colonies. This phenomenon and the unclear mechanism seriously challenge the future application of this technique. In this study, we developed an efficient SSO-mediated DNA repair system based on double-stranded break (DSB) induction. We generated a mutant EGFP gene with insertions of 24 bp to 1.6 kb in length as a reporter integrated in mammalian cell lines. SSOs were successfully used to delete the insertion fragments upon DSB induction at a site near the insertion. We demonstrated that this process is dependent on the ATM/ATR pathway. Importantly, repaired cell clones were viable. Effects of deletion length, SSO length, strand bias, and SSO modification on gene repair frequency were also investigated. © 2008 Mary Ann Liebert, Inc.published_or_final_versio
Cell death caused by single-stranded oligodeoxynucleotide-mediated targeted genomic sequence modification
Targeted gene repair directed by single-stranded oligodeoxynucleotides (ssODNs) offers a promising tool for biotechnology and gene therapy. However, the methodology is currently limited by its low frequency of repair events, variability, and low viability of "corrected" cells. In this study, we showed that during ssODN-mediated gene repair reaction, a significant population of corrected cells failed to divide, and were much more prone to undergo apoptosis, as marked by processing of caspases and PARP-1. In addition, we found that apoptotic cell death triggered by ssODN-mediated gene repair was largely independent of the ATM/ATR kinase. Furthermore, we examined the potential involvement of the mismatch repair (MMR) proteins in this "correction reaction-induced" cell death. Result showed that while defective MMR greatly enhanced the efficiency of gene correction, compromising the MMR system did not yield any viable corrected clone, indicating that the MMR machinery, although plays a critical role in determining ssODN-directed repair, was not involved in the observed cellular genotoxic responses. © 2009. Mary Ann Liebert, Inc.published_or_final_versio
Revisit Sparse Polynomial Interpolation based on Randomized Kronecker Substitution
In this paper, a new reduction based interpolation algorithm for black-box
multivariate polynomials over finite fields is given. The method is based on
two main ingredients. A new Monte Carlo method is given to reduce black-box
multivariate polynomial interpolation to black-box univariate polynomial
interpolation over any ring. The reduction algorithm leads to multivariate
interpolation algorithms with better or the same complexities most cases when
combining with various univariate interpolation algorithms. We also propose a
modified univariate Ben-or and Tiwarri algorithm over the finite field, which
has better total complexity than the Lagrange interpolation algorithm.
Combining our reduction method and the modified univariate Ben-or and Tiwarri
algorithm, we give a Monte Carlo multivariate interpolation algorithm, which
has better total complexity in most cases for sparse interpolation of black-box
polynomial over finite fields
Bioinformatics advances in saliva diagnostics
There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance
basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval,
integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart
Evidence for the classical integrability of the complete AdS(4) x CP(3) superstring
We construct a zero-curvature Lax connection in a sub-sector of the
superstring theory on AdS(4) x CP(3) which is not described by the
OSp(6|4)/U(3) x SO(1,3) supercoset sigma-model. In this sub-sector worldsheet
fermions associated to eight broken supersymmetries of the type IIA background
are physical fields. As such, the prescription for the construction of the Lax
connection based on the Z_4-automorphism of the isometry superalgebra OSp(6|4)
does not do the job. So, to construct the Lax connection we have used an
alternative method which nevertheless relies on the isometry of the target
superspace and kappa-symmetry of the Green-Schwarz superstring.Comment: 1+26 pages; v2: minor typos corrected, acknowledgements adde
Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and sometimes the only curative therapy for patients with certain hematological diseases. Allo-HSCT has been practiced in China for approximately 30 years, and great improvements have been made within the past decade, particularly in fields such as the haploidentical HSCT system, strategies to overcome relapse and GVHD, and modified HSCT for elderly patients. This review will describe the current situation and provide a prospective of these unique aspects of Allo-HSCT in China
IPod-based in-home system for monitoring gaze-stabilization exercise compliance of individuals with vestibular hypofunction
Background: In the physical therapy setting, physical therapists (PTs) often prescribe exercises for their clients to perform at home. However, it is difficult for PTs to obtain information about their clients' compliance with the prescribed exercises, the quality of performance and symptom magnitude. We present an iPod-based system for capturing this information from individuals with vestibular hypofunction while they perform gaze stabilization exercises at home. Method. The system's accuracy for measurement of rotational velocity against an independent motion tracker was validated. Then a seven day in-home trial was conducted with 10 individuals to assess the feasibility of implementing the system. Compliance was measured by comparing the recorded frequency and duration of the exercises with the exercise prescription. The velocity and range of motion of head movements was recorded in the pitch and yaw planes. The system also recorded dizziness severity before and after each exercise was performed. Each patient was interviewed briefly after the trial to ascertain ease of use. In addition, an interview was performed with PTs in order to assess how the information would be utilized. Results: The correlation of the velocity measurements between the iPod-based system and the motion tracker was 0.99. Half of the subjects were under-compliant with the prescribed exercises. The average head velocity during performance was 140 deg/s in the yaw plane and 101 deg/s in the pitch plane. Conclusions: The iPod-based system was able to be used in-home. Interviews with PTs suggest that the quantitative data from the system will be valuable for assisting PTs in understanding exercise performance of patients, documenting progress, making treatment decisions, and communicating patient status to other PTs. © 2014 Huang et al.; licensee BioMed Central Ltd
Mechanical Stress Inference for Two Dimensional Cell Arrays
Many morphogenetic processes involve mechanical rearrangement of epithelial
tissues that is driven by precisely regulated cytoskeletal forces and cell
adhesion. The mechanical state of the cell and intercellular adhesion are not
only the targets of regulation, but are themselves likely signals that
coordinate developmental process. Yet, because it is difficult to directly
measure mechanical stress {\it in vivo} on sub-cellular scale, little is
understood about the role of mechanics of development. Here we present an
alternative approach which takes advantage of the recent progress in live
imaging of morphogenetic processes and uses computational analysis of high
resolution images of epithelial tissues to infer relative magnitude of forces
acting within and between cells. We model intracellular stress in terms of bulk
pressure and interfacial tension, allowing these parameters to vary from cell
to cell and from interface to interface. Assuming that epithelial cell layers
are close to mechanical equilibrium, we use the observed geometry of the two
dimensional cell array to infer interfacial tensions and intracellular
pressures. Here we present the mathematical formulation of the proposed
Mechanical Inverse method and apply it to the analysis of epithelial cell
layers observed at the onset of ventral furrow formation in the {\it
Drosophila} embryo and in the process of hair-cell determination in the avian
cochlea. The analysis reveals mechanical anisotropy in the former process and
mechanical heterogeneity, correlated with cell differentiation, in the latter
process. The method opens a way for quantitative and detailed experimental
tests of models of cell and tissue mechanics
Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure
Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality
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