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Eye formation in the absence of retina

Swindell, Eric C.; Liu, Chaomei; Shah, Rina; Smith, April N.; Lang, Richard A.; Jamrich, Milan
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
25.96%
Eye development is a complex process that involves the formation of the retina and the lens, collectively called the eyeball, as well as the formation of auxiliary eye structures such as the eyelid, lacrimal gland, cornea and conjunctiva. The developmental requirements for the formation of each individual structure are only partially understood. We have shown previously that the homeobox-containing gene Rx is a key component in eye formation, as retinal structures do not develop and retina-specific gene expression is not observed in Rx-deficient mice. In addition, Rx−/− embryos do not develop any lens structure, despite the fact that Rx is not expressed in the lens. This demonstrates that during normal mammalian development, retina-specific gene expression is necessary for lens formation. In this paper we show that lens formation can be restored in Rx-deficient embryos experimentally, by the elimination of β-catenin expression in the head surface ectoderm. This suggests that β-catenin is involved in lens specification either through Wnt signaling or through its function in cell adhesion. In contrast to lens formation, we demonstrate that the development of auxiliary eye structures does not depend on retina-specific gene expression or retinal morphogenesis. These results point to the existence of two separate developmental processes involved in the formation of the eye and its associated structures. One involved in the formation of the eyeball and the second involved in the formation of the auxiliary eye structures.

Recruitment of endogenous bone marrow mesenchymal stem cells towards injured liver

Chen, Ye; Xiang, Li-Xin; Shao, Jian-Zhong; Pan, Ruo-Lang; Wang, Yu-Xi; Dong, Xue-Jun; Zhang, Guo-Rong
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
25.96%
Recent studies suggest that mesenchymal stem cells (MSCs) possess a greater differentiation potential than once thought and that they have the capacity to regenerate damaged tissues/organs. However, the evidence is insufficient, and the mechanism governing the recruitment and homing of MSCs to these injured sites is not well understood. We first examined the MSCs circulating in peripheral blood and then performed chemotaxis, wound healing and tubule-formation assays to investigate the migration capability of mouse bone marrow MSCs (mBM-MSCs) in response to liver-injury signals. In addition, BM-MSCs from donor enhanced green fluorescent protein transgenic male mice were transplanted into liver-injured co-isogenic female recipients, either by intra-bone marrow injection or through the caudal vein, to allow in vivo tracking analysis of the cell fate after transplantation. Donor-derived cells were analysed by in vivo imaging analysis, PCR, flow cytometry and frozen sections. Microarray and real-time PCR were used for chemokine/cytokine and receptor analyses. We successfully isolated circulating MSCs in peripheral blood of liver-injured mice and provided direct evidence that mBM-MSCs could be mobilized into the circulation and recruited into the liver after stimulation of liver injury. CCR9...

Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes

Hoffmann, Stephanie A.; Hos, Deniz; Küspert, Melanie; Lang, Richard A.; Lovell-Badge, Robin; Wegner, Michael; Reiprich, Simone
Fonte: Company of Biologists Publicador: Company of Biologists
Tipo: Artigo de Revista Científica
Publicado em 01/01/2014 EN
Relevância na Pesquisa
25.96%
Neural precursor cells of the ventricular zone give rise to all neurons and glia of the central nervous system and rely for maintenance of their precursor characteristics on the closely related SoxB1 transcription factors Sox1, Sox2 and Sox3. We show in mouse spinal cord that, whereas SoxB1 proteins are usually downregulated upon neuronal specification, they continue to be expressed in glial precursors. In the oligodendrocyte lineage, Sox2 and Sox3 remain present into the early phases of terminal differentiation. Surprisingly, their deletion does not alter precursor characteristics but interferes with proper differentiation. Although a direct influence on myelin gene expression may be part of their function, we provide evidence for another mode of action. SoxB1 proteins promote oligodendrocyte differentiation in part by negatively controlling miR145 and thereby preventing this microRNA from inhibiting several pro-differentiation factors. This study presents one of the few cases in which SoxB1 proteins, including the stem cell factor Sox2, are associated with differentiation rather than precursor functions.

Distinct Requirements for Cranial Ectoderm and Mesenchyme-Derived Wnts in Specification and Differentiation of Osteoblast and Dermal Progenitors

Goodnough, L. Henry; DiNuoscio, Gregg J.; Ferguson, James W.; Williams, Trevor; Lang, Richard A.; Atit, Radhika P.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 20/02/2014 EN
Relevância na Pesquisa
36.14%
The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

HIPPO Pathway Members Restrict SOX2 to the Inner Cell Mass Where It Promotes ICM Fates in the Mouse Blastocyst

Wicklow, Eryn; Blij, Stephanie; Frum, Tristan; Hirate, Yoshikazu; Lang, Richard A.; Sasaki, Hiroshi; Ralston, Amy
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 23/10/2014 EN
Relevância na Pesquisa
25.96%
Pluripotent epiblast (EPI) cells, present in the inner cell mass (ICM) of the mouse blastocyst, are progenitors of both embryonic stem (ES) cells and the fetus. Discovering how pluripotency genes regulate cell fate decisions in the blastocyst provides a valuable way to understand how pluripotency is normally established. EPI cells are specified by two consecutive cell fate decisions. The first decision segregates ICM from trophectoderm (TE), an extraembryonic cell type. The second decision subdivides ICM into EPI and primitive endoderm (PE), another extraembryonic cell type. Here, we investigate the roles and regulation of the pluripotency gene Sox2 during blastocyst formation. First, we investigate the regulation of Sox2 patterning and show that SOX2 is restricted to ICM progenitors prior to blastocyst formation by members of the HIPPO pathway, independent of CDX2, the TE transcription factor that restricts Oct4 and Nanog to the ICM. Second, we investigate the requirement for Sox2 in cell fate specification during blastocyst formation. We show that neither maternal (M) nor zygotic (Z) Sox2 is required for blastocyst formation, nor for initial expression of the pluripotency genes Oct4 or Nanog in the ICM. Rather, Z Sox2 initially promotes development of the primitive endoderm (PE) non cell-autonomously via FGF4...

Toward a Security Domain Model for Static Analysis and Verification of Information Systems

Shaffer, Alan; Auguston, Mikhail; Irvine, Cynthia E.; Levin, Tim.
Fonte: OOPSLA Workshop on Domain-Specific Modelling (DSM '07). Montreal, Canada. Publicador: OOPSLA Workshop on Domain-Specific Modelling (DSM '07). Montreal, Canada.
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
36.14%
OOPSLA Workshop on Domain-Specific Modeling (DSM '07). Montreal, Canada.; Evaluation of high assurance secure computer systems requires that they be designed, developed, verified and tested using rigorous processes and formal methods. The evaluation process must include correspondence between security policy objectives, security specifications, and program implementation. This research presents an approach to the verification of programs represented in a specialized Implementation Modeling Language (IML) using a formal security Domain Model (DM). The DM is comprised of an invariant part, which defines the generic concepts of program state, information flow, and other security properties; and a variable part, specifying the behavior of the target program. The DM is written using the Alloy formal specification language, and its verification is accomplished using the Alloy Analyzer tool. It was found that, by separating the structural framework of the security policy from the semantics of the target program, efficiency of the Alloy Analyzer in detecting execution paths that violate the security properties specified in the DM is significantly improved.

Agnostic notes on regression adjustments to experimental data: Reexamining Freedman's critique

Lin, Winston
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
15.96%
Freedman [Adv. in Appl. Math. 40 (2008) 180-193; Ann. Appl. Stat. 2 (2008) 176-196] critiqued ordinary least squares regression adjustment of estimated treatment effects in randomized experiments, using Neyman's model for randomization inference. Contrary to conventional wisdom, he argued that adjustment can lead to worsened asymptotic precision, invalid measures of precision, and small-sample bias. This paper shows that in sufficiently large samples, those problems are either minor or easily fixed. OLS adjustment cannot hurt asymptotic precision when a full set of treatment-covariate interactions is included. Asymptotically valid confidence intervals can be constructed with the Huber-White sandwich standard error estimator. Checks on the asymptotic approximations are illustrated with data from Angrist, Lang, and Oreopoulos's [Am. Econ. J.: Appl. Econ. 1:1 (2009) 136--163] evaluation of strategies to improve college students' achievement. The strongest reasons to support Freedman's preference for unadjusted estimates are transparency and the dangers of specification search.; Comment: Published in at http://dx.doi.org/10.1214/12-AOAS583 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

A Programmer-Centric Approach to Program Verification in ATS

Ren, Zhiqiang; Xi, Hongwei
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 27/03/2012
Relevância na Pesquisa
16.33%
Formal specification is widely employed in the construction of high-quality software. However, there is often a huge gap between formal specification and actual implementation. While there is already a vast body of work on software testing and verification, the task to ensure that an implementation indeed meets its specification is still undeniably of great difficulty. ATS is a programming language equipped with a highly expressive type system that allows the programmer to specify and implement and then verify within the language itself that an implementation meets its specification. In this paper, we present largely through examples a programmer-centric style of program verification that puts emphasis on requesting the programmer to explain in a literate fashion why his or her code works. This is a solid step in the pursuit of software construction that is verifiably correct according to specification.; Comment: 15 pages, 11 figures. Examples available on-line http://www.ats-lang.org/EXAMPLE/PCPV

Finding a Collective Set of Items: From Proportional Multirepresentation to Group Recommendation

Skowron, Piotr; Faliszewski, Piotr; Lang, Jerome
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 13/02/2014
Relevância na Pesquisa
25.96%
We consider the following problem: There is a set of items (e.g., movies) and a group of agents (e.g., passengers on a plane); each agent has some intrinsic utility for each of the items. Our goal is to pick a set of $K$ items that maximize the total derived utility of all the agents (i.e., in our example we are to pick $K$ movies that we put on the plane's entertainment system). However, the actual utility that an agent derives from a given item is only a fraction of its intrinsic one, and this fraction depends on how the agent ranks the item among available ones (in the movie example, the perceived value of a movie depends on the values of the other ones available). Extreme examples of our model include the setting where each agent derives utility from his or her most preferred item only (e.g., an agent will watch his or her favorite movie only), from his or her least preferred item only (e.g., the agent worries that he or she will be somehow forced to watch the worst available movie), or derives $1/K$ of the utility from each of the available items (e.g., the agent will pick a movie at random). Formally, to model this process of adjusting the derived utility, we use the mechanism of ordered weighted average (OWA) operators. Our contribution is twofold: First...

Programming with models: writing statistical algorithms for general model structures with NIMBLE

de Valpine, Perry; Turek, Daniel; Paciorek, Christopher J.; Anderson-Bergman, Clifford; Lang, Duncan Temple; Bodik, Rastislav
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 19/05/2015
Relevância na Pesquisa
26.14%
We describe NIMBLE, a system for programming statistical algorithms within R for general model structures. NIMBLE is designed to meet three challenges: flexible model specification, a language for programming algorithms that can use different models, and a balance between high-level programmability and execution efficiency. For model specification, NIMBLE extends the BUGS language and creates model objects in R. Model objects can manipulate variables, calculate log probability values, generate simulations, and query the relationships among variables. For algorithm programming, NIMBLE provides functions that operate with models using two stages of evaluation. The first stage allows specialization of a function to a particular model and/or nodes, such as creating a Metropolis-Hastings sampler for a particular block of nodes. The second stage allows repeated execution of computations using the results of the first stage. To achieve efficient second-stage computation, NIMBLE compiles models and functions via C++, using the Eigen linear algebra library, and provides the user with an R interface to compiled objects. The NIMBLE language represents a compilable domain-specific language (DSL) embedded within R. This paper provides an overview of the design and rationale for NIMBLE along with illustrative examples including Markov chain Monte Carlo (MCMC) and Monte Carlo Expectation Maximization (MCEM).

Fine-Grained Authorization for Job and Resource Management Using Akenti and the Globus Toolkit

Thompson, M.; Essiari, A.; Keahey, K.; Welch, V.; Lang, S.; Liu, B.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
25.96%
As the Grid paradigm is adopted as a standard way of sharing remote resources across organizational domains, the need for fine-grained access control to these resources increases. This paper presents an authorization solution for job submission and control, developed as part of the National Fusion Collaboratory, that uses the Globus Toolkit 2 and the Akenti authorization service in order to perform fine-grained authorization of job and resource management requests in a Grid environment. At job startup, it allows the system to evaluate a user's Resource Specification Language request against authorization policies on resource usage (determining how many CPUs or memory a user can use on a given resource or which executables the user can run). Furthermore, based on authorization policies, it allows other virtual organization members to manage the user's job.; Comment: CHEP03, La Jolla, Mar 24-27, TUB2006, Grid Security, 7 pages, 5 figures

Hierarchical probabilistic inference of cosmic shear

Schneider, Michael D.; Hogg, David W.; Marshall, Philip J.; Dawson, William A.; Meyers, Joshua; Bard, Deborah J.; Lang, Dustin
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 10/11/2014
Relevância na Pesquisa
26.23%
Point estimators for the shearing of galaxy images induced by gravitational lensing involve a complex inverse problem in the presence of noise, pixelization, and model uncertainties. We present a probabilistic forward modeling approach to gravitational lensing inference that has the potential to mitigate the biased inferences in most common point estimators and is practical for upcoming lensing surveys. The first part of our statistical framework requires specification of a likelihood function for the pixel data in an imaging survey given parameterized models for the galaxies in the images. We derive the lensing shear posterior by marginalizing over all intrinsic galaxy properties that contribute to the pixel data (i.e., not limited to galaxy ellipticities) and learn the distributions for the intrinsic galaxy properties via hierarchical inference with a suitably flexible conditional probabilitiy distribution specification. We use importance sampling to separate the modeling of small imaging areas from the global shear inference, thereby rendering our algorithm computationally tractable for large surveys. With simple numerical examples we demonstrate the improvements in accuracy from our importance sampling approach, as well as the significance of the conditional distribution specification for the intrinsic galaxy properties when the data are generated from an unknown number of distinct galaxy populations with different morphological characteristics.; Comment: 23 pages...