Ricardo A Medina - Profile on Academia.edu (original) (raw)

Papers by Ricardo A Medina

The abbreviated pluripotent cell cycle

Human embryonic stem cells (hESCs) and induced pluripotent stem cells proliferate rapidly and div... more Human embryonic stem cells (hESCs) and induced pluripotent stem cells proliferate rapidly and divide symmetrically producing equivalent progeny cells. In contrast, lineage committed cells acquire an extended symmetrical cell cycle. Self-renewal of tissue-specific stem cells is sustained by asymmetric cell division where one progeny cell remains a progenitor while the partner progeny cell exits the cell cycle and differentiates. There are three principal contexts for considering the operation and regulation of the pluripotent cell cycle: temporal, regulatory, and structural. The primary temporal context that the pluripotent self-renewal cell cycle of hESCs is a short G1 period without reducing periods of time allocated to S phase, G2, and mitosis. The rules that govern proliferation in hESCs remain to be comprehensively established. However, several lines of evidence suggest a key role for the naïve transcriptome of hESCs, which is competent to stringently regulate the embryonic stem cell (ESC) cell cycle. This supports the requirements of pluripotent cells to self-propagate while suppressing expression of genes that confer lineage commitment and/or tissue specificity. However, for the first time, we consider unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency. From both fundamental biological and clinical perspectives, understanding control of the abbreviated ESC cycle can provide options to coordinate control of proliferation versus differentiation. Wound healing, tissue engineering, and cell-based therapy to mitigate developmental aberrations illustrate applications that benefit from knowledge of the biology of the pluripotent cell cycle.

This study investigated the influence that angle of incidence of applied bi-directional ground mo... more This study investigated the influence that angle of incidence of applied bi-directional ground motions had on several engineering demand parameters (EDPs) for inelastic structures. The EDPs of interest in this study were peak drift, peak ductility, and peak slab rotation demands. The structural models had various degrees of inelasticity, plan irregularities, 5% damping ratios, and fundamental periods that ranged from 0.2 seconds to 2.0 seconds. This work utilized suites of ground motions recorded on stiff soils and on rock. The critical angle (the angle of incidence at which an EDP achieves a maximum) for a given EDP and bi-directional ground motion was found to occur at virtually any angle of incidence. For a given bi-directional ground motion and given fundamental period, the critical angle was found to vary unpredictably with increasing degree of inelasticity. The results also indicated that, on average, applying bi-directional ground motions only along the principal axes of an inelastic building underestimated the peak deformation demands when compared to those obtained at other ground motion angles of incidence. For a given degree of inelasticity, the average ratio of peak deformation responses based on all angles of incidence to the peak deformation response when the ground motion components were applied along the principal building orientations increased with fundamental period of vibration.

Paper: A PRACTICAL METHOD FOR PROPER MODELING OF STRUCTURAL DAMPING IN INELASTIC PLANE STRUCTURAL SYSTEMS

Seismic Demands for Performance-Based Design of Frame Structures

SEISMIC DEMANDS FOR PERFORMANCE-BASED DESIGN OF. FRAME STRUCTURES. Ricardo A. MEDINA 1 and Helmut... more SEISMIC DEMANDS FOR PERFORMANCE-BASED DESIGN OF. FRAME STRUCTURES. Ricardo A. MEDINA 1 and Helmut KRAWINKLER 2. ABSTRACT. This paper focuses on the presentation of results for engineering demand ...

Pacific Earthquake Engineering Research Center

... Jennifer N. Swift University of Southern California Sean Devlin US Geological Survey Yang Zhu... more ... Jennifer N. Swift University of Southern California Sean Devlin US Geological Survey Yang Zhu California Department of Transportation ... Jennifer N. Swift University of Southern California SeanDevlin US Geological Survey Yang Zhu California Department of Transportation ...

Component Acceleration Demands in Multistory Shear-Wall Structures

This paper deals with the statistical quantification of peak floor acceleration (PFA) demands and... more This paper deals with the statistical quantification of peak floor acceleration (PFA) demands and peak component acceleration (PCA) demands for acceleration‐sensitive nonstructural components attached to or suspended from shear‐wall structures with fundamental periods from 0.15 ...

Vertical Acceleration Demands on Nonstructural Components in Buildings

Cyclic Behavior of Deep Steel Columns Subjected to Large Drifts, Rotations, and Axial Loads

Proposed Method for Probabilistic Estimation of Peak Component Acceleration Demands

Seismic Collapse Assessment of a 20-Story Steel Moment-Resisting Frame Structure

Seismic demands for performance-based design

Collapse assessment of deteriorating SDOF systems

Implementation of performance-based earthquake engineering necessitates the probabilistic evaluat... more Implementation of performance-based earthquake engineering necessitates the probabilistic evaluation of engineering demand parameters that can be related to variables, such as monetary losses, on which quantitative seismic performance assessment can be based. The purpose of this paper is to identify relevant demand parameters, quantify these parameters for regular frame structures, and illustrate how statistically representative relationships between these parameters and ground motion intensity measures can be established. Emphasis is on the development of such relationships for ordinary ground motions, and on issues that have to be addressed in order to establish relationships between demand parameters and near-fault ground motions. 

Proceedings of The National Academy of Sciences, 2009

Competency for DNA replication is functionally coupled to the activation of histone gene expressi... more Competency for DNA replication is functionally coupled to the activation of histone gene expression at the onset of S phase to form chromatin. Human histone nuclear factor P (HiNF-P; gene symbol HINFP) bound to its cyclin E/cyclin-dependent kinase 2 (CDK2) responsive coactivator p220 NPAT is a key regulator of multiple human histone H4 genes that encode a major subunit of the nucleosome. Induction of the histone H4 transcription factor (HINFP)/p220 NPAT coactivation complex occurs in parallel with the CDK-dependent release of pRB from E2F at the restriction point. Here, we show that the downstream CDK-dependent cell cycle effector HINFP is genetically required and, in contrast to the CDK2/cyclin E complex, cannot be compensated. We constructed a mouse Hinfp-null mutation and found that heterozygous Hinfp mice survive, indicating that 1 allele suffices for embryogenesis. Homozygous loss-of-function causes embryonic lethality: No homozygous Hinfp-null mice are obtained at or beyond embryonic day (E) 6.5. In blastocyst cultures, Hinfp-null embryos exhibit a delay in hatching, abnormal growth, and loss of histone H4 gene expression. Our data indicate that the CDK2/cyclin E/p220 NPAT / HINFP/histone gene signaling pathway at the G1/S phase transition is an essential, nonredundant cell cycle regulatory mechanism that is established early in embryogenesis.

Control of the Human Pluripotent Cell Cycle

From Bench to Bedside, 2010

Human embryonic stem cells (hESCs) have the unique requirement to sustain plasticity through repe... more Human embryonic stem cells (hESCs) have the unique requirement to sustain plasticity through repeated cycles of cell division. While suppressing expression of genes for lineage commitment, these primitive cells retain competency for specialization in response to ...

In Situ Nuclear Organization of Regulatory Machinery

Methods In Molecular Biology™, 2008

Regulatory machinery for gene expression, replication, and repair are architecturally organized i... more Regulatory machinery for gene expression, replication, and repair are architecturally organized in nuclear microenvironments. This compartmentalization provides threshold concentrations of macromolecules for the organization and assembly of regulatory complexes for combinatorial control. A mechanistic under standing of biological control requires the combined application of molecular, cellular, biochemical, and in vivo genetic approaches. This chapter provides methodologies to characterize nuclear organization of regulatory machinery by in situ immunofluorescence microscopy.

Seismic Acceleration Demands on Nonstructural Components Attached to Elastic and Inelastic Structures

Improving the Seismic Performance of Existing Buildings and Other Structures, 2009

This paper addresses the quantification of peak component acceleration demands for acceleration‐s... more This paper addresses the quantification of peak component acceleration demands for acceleration‐sensitive nonstructural components attached to or suspended from inelastic structural wall and moment‐resisting frame structures. Under certain conditions, for a given ground ...

The EMBO Journal, 2004

Src/Yes tyrosine kinase signaling contributes to the regulation of bone homeostasis and inhibits ... more Src/Yes tyrosine kinase signaling contributes to the regulation of bone homeostasis and inhibits osteoblast activity. Here we show that the endogenous Yes-associated protein (YAP), a mediator of Src/Yes signaling, interacts with the native Runx2 protein, an osteoblast-related transcription factor, and suppresses Runx2 transcriptional activity in a dose-dependent manner. Runx2, through its PY motif, recruits YAP to subnuclear domains in situ and to the osteocalcin (OC) gene promoter in vivo. Inhibition of Src/Yes kinase blocks tyrosine phosphorylation of YAP and dissociates endogenous Runx2-YAP complexes. Consequently, recruitment of the YAP co-repressor to subnuclear domains is abrogated and expression of the endogenous OC gene is induced. Our results suggest that Src/Yes signals are integrated through organization of Runx2-YAP transcriptional complexes at subnuclear sites to attenuate skeletal gene expression.

Structural Safety, 2007

This study deals with the evaluation and formulation of methods to improve the probabilistic quan... more This study deals with the evaluation and formulation of methods to improve the probabilistic quantification of maximum story drift demands for structural systems exposed to severe ground motions. The focus is on flexible structures that are prone to dynamic instability. The quantification of drift demands is based on the probability distribution of the maximum story drift over the height, for a given ground motion hazard level, which in this study is represented by the spectral acceleration at the first mode period of the building. Improvements in the probabilistic estimation of maximum story drift demands are illustrated with a nine-story, moment-resisting frame building exposed to a set of 40 ground motions. It is concluded that (1) the three-parameter LN distribution more rationally describes maximum story drifts at higher values of spectral acceleration; (2) statistically adding values to replace truncated data points provides better goodness-of-fit in maximum drift demand prediction when the structure is close to the onset of dynamic instability, and (3) the least-squares fitting of the LN distribution yields parameters that provide an improved fit compared to that from maximum likelihood estimation and the method of moments.

Molecular and Cellular Biology, 2003

At the G 1 /S phase cell cycle transition, multiple histone genes are expressed to ensure that ne... more At the G 1 /S phase cell cycle transition, multiple histone genes are expressed to ensure that newly synthesized DNA is immediately packaged as chromatin. Here we have purified and functionally characterized the critical transcription factor HiNF-P, which is required for E2F-independent activation of the histone H4 multigene family. Using chromatin immunoprecipitation analysis and ligation-mediated PCR-assisted genomic sequencing, we show that HiNF-P interacts with conserved H4 cell cycle regulatory sequences in vivo. Antisense inhibition of HiNF-P reduces endogenous histone H4 gene expression. Furthermore, we find that HiNF-P utilizes NPAT/p220, a substrate of the cyclin E/cyclin-dependent kinase 2 (CDK2) kinase complex, as a key coactivator to enhance histone H4 gene transcription. The biological role of HiNF-P is reflected by impeded cell cycle progression into S phase upon antisense-mediated reduction of HiNF-P levels. Our results establish that HiNF-P is the ultimate link in a linear signaling pathway that is initiated