bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical round‐optimal blind signatures without random oracles or non‐interactive zero‐knowledge proofs
Authors: Yuan Zhou  , Haifeng Qian  
Published: September 2011

ABSTRACTBlind signatures are generated by means of a protocol between the signer and a user such that the signer can neither see the message being signed and nor learn any information on the signature being produced. Time/space complexity and security model (random oracle model versus standard model; sequential, parallel, or concurrent security) are commonly used to evaluate blind signature schemes. The paper presents the first round‐optimal blind signatures without random oracles or non‐interactive zero‐knowledge proofs. The proposed blind signature scheme achieves concurrent security and perfect blindness while preserving the efficiency of computation and communication. A novel class of computational problems, called one‐more‐output (OMO) problems, is introduced to prove the unforgeability of the scheme. The paper states the corresponding lower bound of the OMO problem in the generic group model. Such a computational problem might be of independent interests in designing other cryptographic protocol and primitives. Copyright © 2011 John Wiley & Sons, Ltd.
Application of Deadlock Risk Evaluation of Architectural Models
Authors: Monzón Antonio , Fernández José L. , de la Puente Juan A. 
Published: September 2011

SUMMARYSoftware architectural evaluation is a key discipline used to identify, at early stages of a real‐time system (RTS) development, the problems that may arise during its operation. Typical mechanisms supporting concurrency, such as semaphores, mutexes or monitors, usually lead to concurrency problems in execution time that are difficult to be identified, reproduced and solved. For this reason, it is crucial to understand the root causes of these problems and to provide support to identify and mitigate them at early stages of the system lifecycle. This paper aims to present the results of a research work oriented to the development of the tool called ‘Deadlock Risk Evaluation of Architectural Models’ (DREAM) to assess deadlock risk in architectural models of an RTS. A particular architectural style, Pipelines of Processes in Object‐Oriented Architectures–UML (PPOOA) was used to represent platform‐independent models of an RTS architecture supported by the PPOOA –Visio tool. We validated the technique presented here by using several case studies related to RTS development and comparing our results with those from other deadlock detection approaches, supported by different tools. Here we present two of these case studies, one related to avionics and the other to planetary exploration robotics. Copyright © 2011 John Wiley & Sons, Ltd.
Concise Review: Managing Genotoxicity in the Therapeutic Modification of Stem Cells
Authors: Baum Christopher , Modlich Ute , Göhring Gudrun , Schlegelberger Brigitte 
Published: September 2011

Abstract
The therapeutic use of procedures for genetic stem cell modification is limited by potential adverse events related to uncontrolled mutagenesis. Prominent findings have been made in hematopoietic gene therapy, demonstrating the risk of clonal, potentially malignant outgrowth on the basis of mutations acquired during or after therapeutic genome modification. The incidence and the growth rate of insertional mutants have been linked to the “stemness” of the target cells and vector-related features such as the integration pattern, the architecture, and the exact content of transgene cassettes. Milieu factors supporting the survival and expansion of mutants may eventually allow oncogenic progression. Similar concerns apply for medicinal products based on pluripotent stem cells. Focusing on the genetic stress induced by insertional mutagenesis and culture adaptation, we propose four conclusions. (a) Mutations occurring in the production of stem cell-based medicines may be unavoidable and need to be classified according to their risk to trigger the formation of clones that are sufficiently long-lived and mitotically active to acquire secondary transforming mutations. (b) The development of rational prevention strategies depends upon the identification of the specific mutations forming such “dominant clones” (which can also be addressed as cancer stem cell precursors) and a better knowledge of the mechanisms underlying their creation, expansion, and homeostatic control. (c) Quantitative assay systems are required to assess the practical value of preventive actions. (d) Improved approaches for the genetic modification of stem cells can address all critical steps in the origin and growth control of mutants.
Discovery of Nonsteroidal Anti-Inflammatory Drug and Anticancer Drug Enhancing Reprogramming and Induced Pluripotent Stem Cell Generation
Authors: Yang Chao-Shun , Lopez Claudia G. , Rana Tariq M. 
Published: September 2011

Abstract
Recent breakthroughs in creating induced pluripotent stem cells (iPSCs) provide alternative means to obtain embryonic stem-like cells without destroying embryos by introducing four reprogramming factors (Oct3/4, Sox2, and Klf4/c-Myc or Nanog/Lin28) into somatic cells. iPSCs are versatile tools for investigating early developmental processes and could become sources of tissues or cells for regenerative therapies. Here, for the first time, we describe a strategy to analyze genomics datasets of mouse embryonic fibroblasts (MEFs) and embryonic stem cells to identify genes constituting barriers to iPSC reprogramming. We further show that computational chemical biology combined with genomics analysis can be used to identify small molecules regulating reprogramming. Specific downregulation by small interfering RNAs (siRNAs) of several key MEF-specific genes encoding proteins with catalytic or regulatory functions, including WISP1, PRRX1, HMGA2, NFIX, PRKG2, COX2, and TGFβ3, greatly increased reprogramming efficiency. Based on this rationale, we screened only 17 small molecules in reprogramming assays and discovered that the nonsteroidal anti-inflammatory drug Nabumetone and the anticancer drug 4-hydroxytamoxifen can generate iPSCs without Sox2. Nabumetone could also produce iPSCs in the absence of c-Myc or Sox2 without compromising self-renewal and pluripotency of derived iPSCs. In summary, we report a new concept of combining genomics and computational chemical biology to identify new drugs useful for iPSC generation. This hypothesis-driven approach provides an alternative to shot-gun screening and accelerates understanding of molecular mechanisms underlying iPSC induction.
In Situ Genetic Correction of the Sickle Cell Anemia Mutation in Human Induced Pluripotent Stem Cells Using Engineered Zinc Finger Nucleases
Authors: Sebastiano Vittorio , Maeder Morgan L. , Angstman James F. , Haddad Bahareh , Khayter Cyd , Yeo Dana T. , Goodwin Mathew J. , Hawkins John S. , Ramirez Cherie L. , Batista Luis F. Z. , Artandi Steven E. , Wernig Marius , Joung J.Keith 
Published: September 2011

Abstract
The combination of induced pluripotent stem cell (iPSC) technology and targeted gene modification by homologous recombination (HR) represents a promising new approach to generate genetically corrected, patient-derived cells that could be used for autologous transplantation therapies. This strategy has several potential advantages over conventional gene therapy including eliminating the need for immunosuppression, avoiding the risk of insertional mutagenesis by therapeutic vectors, and maintaining expression of the corrected gene by endogenous control elements rather than a constitutive promoter. However, gene targeting in human pluripotent cells has remained challenging and inefficient. Recently, engineered zinc finger nucleases (ZFNs) have been shown to substantially increase HR frequencies in human iPSCs, raising the prospect of using this technology to correct disease causing mutations. Here, we describe the generation of iPSC lines from sickle cell anemia patients and in situ correction of the disease causing mutation using three ZFN pairs made by the publicly available oligomerized pool engineering method (OPEN). Gene-corrected cells retained full pluripotency and a normal karyotype following removal of reprogramming factor and drug-resistance genes. By testing various conditions, we also demonstrated that HR events in human iPSCs can occur as far as 82 bps from a ZFN-induced break. Our approach delineates a roadmap for using ZFNs made by an open-source method to achieve efficient, transgene-free correction of monogenic disease mutations in patient-derived iPSCs. Our results provide an important proof of principle that ZFNs can be used to produce gene-corrected human iPSCs that could be used for therapeutic applications.
Low Level of c-Kit Expression Marks Deeply Quiescent Murine Hematopoietic Stem Cells
Authors: Matsuoka Yoshikazu , Sasaki Yutaka , Nakatsuka Ryusuke , Takahashi Masaya , Iwaki Ryuji , Uemura Yasushi , Sonoda Yoshiaki 
Published: September 2011

Abstract
Although c-kit is expressed highly on murine hematopoietic stem cells (HSCs) and essential for bone marrow (BM) hematopoiesis, the significance of the high level of expression of c-kit on HSCs was not well determined. We show here that CD150+CD48−Lineage−Sca-1+c-kit+ HSCs in adult BM are distributed within the range of roughly a 20-fold difference in the expression level of c-kit, and that c-kit density correlates with the cycling status of the HSC population. This predisposition is more evident in the BM of mice older than 30 weeks. The HSCs in G0 phase express a lower level of c-kit both on the cell surface and inside the cells, which cannot be explained by ligand receptor binding and internalization. It is more likely that the low level of c-kit expression is a unique property of HSCs in G0. Despite functional differences in the c-kit gradient, the HSCs are uniformly hypoxic and accessible to blood perfusion. Therefore, our data indicate the possibility that the hypoxic state of the HSCs is actively regulated, rather than them being passively hypoxic through a simple anatomical isolation from the circulation.
Core Binding Factor Beta Functions in the Maintenance of Stem Cells and Orchestrates Continuous Proliferation and Differentiation in Mouse Incisors
Authors: Kurosaka Hiroshi , Islam Md. Nurul , Kuremoto Koh-ichi , Hayano Satoru , Nakamura Masahiro , Kawanabe Noriaki , Yanagita Takeshi , Rice David P.C. , Harada Hidemitsu , Taniuchi Ichiro , Yamashiro Takashi 
Published: September 2011

Abstract
Rodent incisors grow continuously throughout life, and epithelial progenitor cells are supplied from stem cells in the cervical loop. We report that epithelial Runx genes are involved in the maintenance of epithelial stem cells and their subsequent continuous differentiation and therefore growth of the incisors. Core binding factor β (Cbfb) acts as a binding partner for all Runx proteins, and targeted inactivation of this molecule abrogates the activity of all Runx complexes. Mice deficient in epithelial Cbfb produce short incisors and display marked underdevelopment of the cervical loop and suppressed epithelial Fgf9 expression and mesenchymal Fgf3 and Fgf10 expression in the cervical loop. In culture, FGF9 protein rescues these phenotypes. These findings indicate that epithelial Runx functions to maintain epithelial stem cells and that Fgf9 may be a target gene of Runx signaling. Cbfb mutants also lack enamel formation and display downregulated Shh mRNA expression in cells differentiating into ameloblasts. Furthermore, Fgf9 deficiency results in a proximal shift of the Shh expressing cell population and ectopic FGF9 protein suppresses Shh expression. These findings indicate that Shh as well as Fgf9 expression is maintained by Runx/Cbfb but that Fgf9 antagonizes Shh expression. The present results provide the first genetic evidence that Runx/Cbfb genes function in the maintenance of stem cells in developing incisors by activating Fgf signaling loops between the epithelium and mesenchyme. In addition, Runx genes also orchestrate continuous proliferation and differentiation by maintaining the expression of Fgf9 and Shh mRNA.
TAp63 Is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development
Authors: Rouleau Matthieu , Medawar Alain , Hamon Laurent , Shivtiel Shoham , Wolchinsky Zohar , Zhou Huiqing , De Rosa Laura , Candi Eleonora , de la Forest Divonne Stéphanie , Mikkola Marja L. , van Bokhoven Hans , Missero Caterina , Melino Gerry , Pucéat Michel , Aberdam Daniel 
Published: September 2011

Abstract
p63, a member of the p53 family, is essential for skin morphogenesis and epithelial stem cell maintenance. Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63-knockdown ESCs with wild-type ESCs, supplementation with Activin A, or overexpression of GATA-6 rescue cardiogenesis. Therefore, TAp63 acts in a non-cell-autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease.
Concise Review: Anemia Caused by Viruses
Authors: Morinet Frédéric , Leruez-Ville Marianne , Pillet Sylvie , Fichelson Serge 
Published: September 2011

Abstract
Most of the viruses known to be associated with anemia in human tend to persistently infect their host and are noncytopathic or poorly cytopathic for blood cell progenitors. Infections with Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human herpes virus 6 (HHV-6), B19 parvovirus, human immunodeficiency virus, hepatitis A and C viruses and the putative viral agent associated with non-A-G post-hepatitis aplastic anemia have been reported in association with anemia. Nevertheless, a direct cytotoxic effect on erythroid progenitors has been clearly demonstrated only for human parvovirus B19 and evocated for HHV-6. A major role for destructive immunity is strongly suspected in the pathogenesis of anemia associated with the other viral infections. Host genes play a role in the occurrence of virus-induced anemia in animal models, and there are some evidences that genetic background could also influence the occurrence of virus-associated anemia in human.
Mechanically Induced Focal Adhesion Assembly Amplifies Anti-Adipogenic Pathways in Mesenchymal Stem Cells
Authors: Sen Buer , Guilluy Christophe , Xie Zhihui , Case Natasha , Styner Maya , Thomas Jacob , Oguz Ipek , Rubin Clinton , Burridge Keith , Rubin Janet 
Published: September 2011

AbstractThe fate of pluripotent mesenchymal stem cells (MSC) is determined through integration of chemical, spatial, and physical signals. The suppression of MSC adipogenesis by mechanical stimuli, which requires Akt-induced inhibition of glycogen synthase kinase 3β (GSK3β) with β-catenin activation, can be enhanced by repetitive dosing within a single day. Here, we demonstrate that reapplication of cyclic strain within a 24-hour period leads to amplification of both Akt activation and its subsequent inhibition of GSK3β, such that total cycle number can be reduced while still inhibiting adipogenesis. Amplification of Akt signaling is facilitated by a dynamic restructuring of the cell in response to mechanical signals, as evidenced by a transient increase in focal adhesion (FA) number and increased RhoA activity. Preventing FA assembly or development of tension blocks activation of Akt by mechanical signals, but not by insulin. This indicates that the FA infrastructure is essential to the physical, but not necessarily the chemical, sensitivity, and responsiveness of the cell. Exploiting the transient nature of cytoskeletal remodeling may represent a process to enhance cell responsiveness to mechanical input and ultimately define the fate of MSCs with a minimal input.
Risk‐based optimal retrofit of a tall steel building by using friction dampers
Authors: Tafakori Ehsan , Banazadeh Mehdi , Jalali Seyed Alireza , Tehranizadeh Mohsen 
Published: September 2011

SUMMARYFriction dampers, whose configuration is optimized on the basis of the probabilistic seismic loss associated with a building's damage due to ground motion, were utilized in this study to optimally retrofit a 15‐story steel structure. In line with the concept of performance‐based earthquake engineering (PBEE), a decision‐making procedure based on the monetary seismic loss was incorporated for optimizing the dampers' configuration. A nonlinear numerical model was initially established for representing the structure. In this regard, a brace–damper system was modeled with the buckling of brace elements being addressed accurately and by representing the friction damper's load–displacement relationship on the basis of laboratory evidences. By monitoring the structural deformations in two different response levels, two patterns were established for the distribution of the dampers' strengths throughout the structure, and a number of retrofit alternatives were proposed subsequently. By using incremental dynamic analysis and following the PBEE methodology, the annualized loss (AL), which accounts for all potential damage states in the building and a broad range of seismic intensities, was calculated for each alternative frame. The AL is regarded as a decision variable upon which the best damper configuration is selected. Revealing conclusions were finally made regarding optimal configuration of the damper–brace system. Copyright © 2011 John Wiley & Sons, Ltd.
Evolution of SR protein and hnRNP splicing regulatory factors
Authors: Busch Anke , Hertel Klemens J. 
Published: September 2011

AbstractThe splicing of pre‐mRNAs is an essential step of gene expression in eukaryotes. Introns are removed from split genes through the activities of the spliceosome, a large ribonuclear machine that is conserved throughout the eukaryotic lineage. While unicellular eukaryotes are characterized by less complex splicing, pre‐mRNA splicing of multicellular organisms is often associated with extensive alternative splicing that significantly enriches their proteome. The alternative selection of splice sites and exons permits multicellular organisms to modulate gene expression patterns in a cell type‐specific fashion, thus contributing to their functional diversification. Alternative splicing is a regulated process that is mainly influenced by the activities of splicing regulators, such as SR proteins or hnRNPs. These modular factors have evolved from a common ancestor through gene duplication events to a diverse group of splicing regulators that mediate exon recognition through their sequence‐specific binding to pre‐mRNAs. Given the strong correlations between intron expansion, the complexity of pre‐mRNA splicing, and the emergence of splicing regulators, it is argued that the increased presence of SR and hnRNP proteins promoted the evolution of alternative splicing through relaxation of the sequence requirements of splice junctions. WIREs RNA 2012, 3:1–12. doi: 10.1002/wrna.100This article is categorized under:

RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution
RNA Processing > Splicing Regulation/Alternative Splicing
An improved method for whole protein extraction from yeast Saccharomyces cerevisiae
Authors: Zhang Tingting , Lei Jie , Yang Hanjiang , Xu Kun , Wang Rui , Zhang Zhiying 
Published: September 2011

AbstractA new method for protein extraction from yeast Saccharomyces cerevisiae cells is described. This method involves the use of LiAc and NaOH to enhance the permeability of yeast cell wall prior to protein extraction with SDS‐PAGE sample buffer. It was safe and efficient compared to other methods reported so far in the literature. The proteins extracted with this new method retained their immunoreactive properties and are suitable for most applications in molecular biology studies. Copyright © 2011 John Wiley & Sons, Ltd.
The effect of viscous relaxation on the spatiotemporal stability of capillary jets
Authors: Sevilla Alejandro 
Published: September 2011

AbstractThe linear spatiotemporal stability properties of axisymmetric laminar capillary jets with fully developed initial velocity profiles are studied for large values of both the Reynolds number, $\mathit{Re}= Q/ (\lrm{\pi} a\nu )$, and the Froude number, $\mathit{Fr}= {Q}^{2} / ({\lrm{\pi} }^{2} g{a}^{5} )$, where $a$ is the injector radius, $Q$ the volume flow rate, $\nu $ the kinematic viscosity and $g$ the gravitational acceleration. The downstream development of the basic flow and its stability are addressed with an approximate formulation that takes advantage of the jet slenderness. The base flow is seen to depend on two parameters, namely a Stokes number, $G= \mathit{Re}/ \mathit{Fr}$, and a Weber number, $\mathit{We}= \rho {Q}^{2} / ({\lrm{\pi} }^{2} \sigma {a}^{3} )$, where $\sigma $ is the surface tension coefficient, while its linear stability depends also on the Reynolds number. When non-parallel terms are retained in the local stability problem, the analysis predicts a critical value of the Weber number, ${\mathit{We}}_{c} (G, \mathit{Re})$, below which a pocket of local absolute instability exists within the near field of the jet. The function ${\mathit{We}}_{c} (\mathit{Re})$ is computed for the buoyancy-free jet, showing marked differences with the results previously obtained with uniform velocity profiles. It is seen that, in accounting for gravity effects, it is more convenient to express the parametric dependence of the critical Weber number with use made of the Morton and Bond numbers, $\mathit{Mo}= {\nu }^{4} {\rho }^{3} g/ {\sigma }^{3} $ and $\mathit{Bo}= \rho g{a}^{2} / \sigma $, as replacements for $G$ and $\mathit{Re}$. This alternative formulation is advantageous to describe jets of a given liquid for a known value of $g$, in that the resulting Morton number becomes constant, thereby leaving $\mathit{Bo}$ as the only relevant parameter. The computed function ${\mathit{We}}_{c} (\mathit{Bo})$ for a water jet under Earth gravity is shown to be consistent with the experimental results of Clanet and Lasheras for the transition from jetting to dripping of water jets discharging into air from long injection needles, which cannot be properly described with a uniform velocity profile assumed at the jet exit.