Sigmoidal Chemorheological Models of Chip-Underfill Materials Offer Alternative Predictions of Combined Cure and Flow

Prior rheology results on chip-underfill epoxy resins have been re-analyzed by a sigmoidal model that contains three variable physical parameters, including the terminal cured viscosity of the gel, an induction or dwell time and a time factor associated with the speed of conversion as viscosity undergoes large dynamic changes during rapid crosslinking. The analyses were conducted with resins that were originally cured between 150 and 180 °C and show obvious non-linearity, even on a semi-log plot of dynamic viscosity. The sigmoidal models more accurately represent a wider range of dynamic viscosity than power-law-based rheological models, which are both more common and more generally accepted for practical application. If total flow is the critical design parameter in terms of chip underfill, perhaps these alternative sigmoidal models need to be more thoroughly evaluated to gauge their practical use and validity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61221/1/832_ftp.pd

Lysophosphatidic Acid Induces Migration of Human Lung‐Resident Mesenchymal Stem Cells Through the β‐Catenin Pathway

Mesenchymal stem cells (MSCs) have been demonstrated to reside in human adult organs. However, mechanisms of migration of these endogenous MSCs within their tissue of origin are not well understood. Here, we investigate migration of human adult lung‐resident (LR) mesenchymal progenitor cells. We demonstrate that bioactive lipid lysophosphatidic acid (LPA) plays a principal role in the migration of human LR‐MSCs through a signaling pathway involving LPA1‐induced β‐catenin activation. LR‐MSCs isolated from human lung allografts and lungs of patients with scleroderma demonstrated a robust migratory response to LPA in vitro. Furthermore, LPA levels correlated with LR‐MSC numbers in bronchoalveolar lavage (BAL), providing demonstration of the in vivo activity of LPA in human adult lungs. Migration of LR‐MSCs was mediated via LPA1 receptor ligation and LPA1 silencing significantly abrogated the migratory response of LR‐MSCs to LPA as well as human BAL. LPA treatment of LR‐MSCs induced protein kinase C‐mediated glycogen synthase kinase‐3β phosphorylation, with resulting cytoplasmic accumulation and nuclear translocation of β‐catenin. TCF/LEF dual luciferase gene reporter assay demonstrated a significant increase in transcriptional activity after LPA treatment. LR‐MSC migration and increase in reporter gene activity in the presence of LPA were abolished by transfection with β‐catenin small interfering RNA demonstrating that β‐catenin is critical in mediating LPA‐induced LR‐MSC migration. These data delineate a novel signaling pathway through which ligation of a G protein‐coupled receptor by a biologically relevant lipid mediator induces migration of human tissue‐resident mesenchymal progenitors. S tem C ells 2012;30:2010–2019Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93548/1/1171_ftp.pd

Chemorheology of photopolymerizable acrylates using a modified Boltzmann sigmoidal model

Experiments were conducted to evaluate the influence of ambient photoconversion on rheology for a range of photopolymerizable urethane dimethacrylate (UDMA) resins containing varying amounts of three comonomers including 1,6 hexane diol-dimethacrylate (HDDMA), an alkoxylated cyclohexane dimethanol diacrylate monomer (CD-582), and hydroxyethyl methacrylate (HEMA). Experiments were performed both as a function of composition and time-dependent dose varying the intensity using a photorheometer. A semilog-based sigmoidal model allowed the determination of four physical model parameters to define the relationship between reaction kinetics and its dynamic influence on viscosity. We have observed induction times and viscosity changes associated with the model that shows a trend in reaction kinetics in the following order from most to least reactive: UDMA > CD582 > HDDMA > HEMA. With increasing amounts of reactive diluent included in the formulation, the kinetics of reaction was more sluggish. The value of this sigmoidal model is that it could help define formulation and process conditions most likely to control crosslinking to maximize dimensional stability or other thermophysical properties. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2319–2325, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61230/1/21563_ftp.pd

α-Catenin-Vinculin Interaction Functions to Organize the Apical Junctional Complex in Epithelial Cells

αE-catenin, a cadherin-associated protein, is required for tight junction (TJ) organization, but its role is poorly understood. We transfected an αE-catenin–deficient colon carcinoma line with a series of αE-catenin mutant constructs. The results showed that the amino acid 326–509 domain of this catenin was required to organize TJs, and its COOH-terminal domain was not essential for this process. The 326–509 internal domain was found to bind vinculin. When an NH2-terminal αE-catenin fragment, which is by itself unable to organize the TJ, was fused with the vinculin tail, this chimeric molecule could induce TJ assembly in the αE-catenin–deficient cells. In vinculin-null F9 cells, their apical junctional organization was impaired, and this phenotype was rescued by reexpression of vinculin. These results indicate that the αE-catenin-vinculin interaction plays a role in the assembly of the apical junctional complex in epithelia

E-Cadherin–dependent Growth Suppression is Mediated by the Cyclin-dependent Kinase Inhibitor p27KIP1

Recent studies have demonstrated the importance of E-cadherin, a homophilic cell–cell adhesion molecule, in contact inhibition of growth of normal epithelial cells. Many tumor cells also maintain strong intercellular adhesion, and are growth-inhibited by cell– cell contact, especially when grown in three-dimensional culture. To determine if E-cadherin could mediate contact-dependent growth inhibition of nonadherent EMT/6 mouse mammary carcinoma cells that lack E-cadherin, we transfected these cells with an exogenous E-cadherin expression vector. E-cadherin expression in EMT/6 cells resulted in tighter adhesion of multicellular spheroids and a reduced proliferative fraction in three-dimensional culture. In addition to increased cell–cell adhesion, E-cadherin expression also resulted in dephosphorylation of the retinoblastoma protein, an increase in the level of the cyclin-dependent kinase inhibitor p27kip1 and a late reduction in cyclin D1 protein. Tightly adherent spheroids also showed increased levels of p27 bound to the cyclin E-cdk2 complex, and a reduction in cyclin E-cdk2 activity. Exposure to E-cadherin–neutralizing antibodies in three-dimensional culture simultaneously prevented adhesion and stimulated proliferation of E-cadherin transfectants as well as a panel of human colon, breast, and lung carcinoma cell lines that express functional E-cadherin. To test the importance of p27 in E-cadherin–dependent growth inhibition, we engineered E-cadherin–positive cells to express inducible p27. By forcing expression of p27 levels similar to those observed in aggregated cells, the stimulatory effect of E-cadherin–neutralizing antibodies on proliferation could be inhibited. This study demonstrates that E-cadherin, classically described as an invasion suppressor, is also a major growth suppressor, and its ability to inhibit proliferation involves upregulation of the cyclin-dependent kinase inhibitor p27

Cadherin and catenin alterations in human cancer

Among the hallmarks of cancer are defective cell–cell and cell–matrix adhesion. Alterations in cadherin–catenin complexes likely have a major contributing role in cell-adhesion defects in carcinomas arising in many different tissues. E-cadherin, the prototypic member of the cadherin transmembrane protein family, regulates cell adhesion by interacting with E-cadherin molecules on opposing cell surfaces. E-cadherin's function in cell adhesion is also critically dependent on its ability to interact through its cytoplasmic domain with catenin proteins. A diverse collection of defects alter cadherin–catenin function in cancer cells, including loss-of-function mutations and defects in the expression of E-cadherin and certain catenins, such as Α-catenin. Although there is much evidence that Β-catenin is deregulated in cancer as a result of inactivating mutations in the APC and AXIN tumor-suppressor proteins and gain-of-function mutations in Β-catenin itself, the principal consequences of Β-catenin deregulation in cancer appear to be largely distinct from the effects attributable to inactivation of E-cadherin or Α-catenin. In this review, we highlight some of the specific genetic and epigenetic defects responsible for altered cadherin and catenin function in cancer, as well as potential contributions of cadherin–catenin alterations to the cancer process. © 2002 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35132/1/10083_ftp.pd