Constitutive equations and failure criteria for amorphous polymeric solids

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2002.Includes bibliographical references (v. 2, p. 104-109).Anand & Gurtin (2002) have recently developed a continuum theory for the elastic-viscoplastic deformation of amorphous solids. Their theory is motivated by and builds on the work of Parks, Argon, Boyce, Arruda, and their co-workers (e.g. Boyce et al., 1988; Arruda & Boyce, 1993) on modeling the plastic deformation of amorphous polymers. The theory of Anand & Gurtin (2002) carefully accounts for restrictions placed on constitutive assumptions by frame-indifference and by a new mathematical definition of an amorphous material based on the notion that the constitutive relations for such materials should be invariant under all rotations of the reference configuration and, independently, all rotations of the relaxed configuration. Also, they explicitly account for the dependence of the Helmholtz free energy on the plastic deformation in a thermodynamically consistent manner, a dependence which leads directly to a backstress in the underlying flow rule. In addition to the standard kinematic and stress variables, their theory contains two internal variables: a variable s > 0 that represents an isotropic intermolecular resistance to plastic flow; and an unsigned variable 7 that represents the local free-volume. In this thesis, we extend the work of Anand & Gurtin (2002) to model the deformation and fracture response of amorphous glassy polymers which exhibit both a ductile mechanism of fracture associated with large plastic stretches and subsequent chain scission and a brittle mode of fracture.(cont.) For polymers such as polycarbonate (PC), the brittle fracture mode is characterized by a mechanism of elastic cavitational failure, which results in cleavage-type fracture similar to that observed in brittle fracture of metals. In contrast, polymers such as polymethylmethacrylate (PMMA) and polystyrene (PS) exhibit a brittle mode of fracture characterized by craze initiation, flow, and breakdown. To model crazing, we introduce a continuum constitutive relation which contains the three ingredients of crazing - initiation, widening, and breakdown - in a suitable statistically-averaged sense. We allow for local inelastic deformation due to shear yielding in possible concurrence with that due to crazing, and introduce a craze initiation criterion based on the local maximum principal tensile stress reaching a critical value which depends on the local mean normal stress. After crazing has initiated, our continuum model represents the transition from shear-flow to craze-flow by a change in the viscoplastic flow rule, in which the dilational inelastic deformation associated with craze-plasticity is taken to occur in the direction of the local maximum principal stress. Finally, for situations in which the local maximum tensile stress is positive, craze-breakdown and fracture is taken to occur when a local tensile plastic craze strain reaches a critical value. We apply our model to the techologically important polymer, polymethylmethacrylate ...by Brian Paul Gearing.Ph.D

A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain

BackgroundThere is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups.ResultsCBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006).ConclusionsThese pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0413-x) contains supplementary material, which is available to authorized users

The Flexure-based Microgap Rheometer (FMR)

Submitted to J. Rheol.We describe the design and construction of a new microrheometer designed to facilitate the viscometric study of complex fluids with very small sample volumes (1-10 μl)and gaps of micrometer dimensions. The Flexure-based Microgap Rheometer (FMR) is a shear-rate-controlled device capable of measuring the shear stress in a plane Couette configuration with directly-controlled gaps between 1 μm and 200 μm. White light interferometry and a three-point nanopositioning stage using piezo-stepping motors are used to control the parallelism of the upper and lower shearing surfaces which are constructed from glass optical flats. A compound flexure system is used to hold the fluid sample testing unit between a drive spring connected to an ‘inchworm’ motor and an independent sensor spring. Displacements in the sensing flexure are detected using an inductive proximity sensor. Ready optical access to the transparent shearing surfaces enables monitoring of the structural evolution in the gap with a long working-distance video-microscope. This configuration then allows us to determine the microgap-dependent flow behavior of complex fluids over 5 decades of shear rate. We demonstrate the capability of the FMR by characterizing the complex stress and gap dependent flow behavior of a typical microstructured food product (mayonnaise) over the range of gaps from 8 to 100 μm and stresses from 10 to 1500 Pa. We correlate the gap-dependent rheological response to the microstructure of the emulsion and changes induced in the material by prolonged shearing.Dupont MIT Allianc

A subset of HLA-I peptides are not genomically templated: evidence for cis- and trans-spliced peptide ligands

The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i.e., the fusion of peptide segments from distinct antigens) are also bound and presented by HLA molecules, and if so, in what proportion. Here, we have developed and applied a bioinformatic workflow and demonstrated that trans-spliced peptides are presented by HLA-I, and their abundance challenges current models of proteasomal splicing that predict cis-splicing as the most probable outcome. These trans-spliced peptides display canonical HLA-binding sequence features and are as frequently identified as cis-spliced peptides found bound to a number of different HLA-A and HLA-B allotypes. Structural analysis reveals that the junction between spliced peptides is highly solvent exposed and likely to participate in T cell receptor interactions. These results highlight the unanticipated diversity of the immunopeptidome and have important implications for autoimmunity, vaccine design, and immunotherapy

Gpr37 Modulates Progenitor Cell Dynamics in a Mouse Model of Ischemic Stroke

The generation of neural stem and progenitor cells following injury is critical for the function of the central nervous system, but the molecular mechanisms modulating this response remain largely unknown. We have previously identified the G protein-coupled receptor 37 (GPR37) as a modulator of ischemic damage in a mouse model of stroke. Here we demonstrate that GPR37 functions as a critical negative regulator of progenitor cell dynamics and gliosis following ischemic injury. In the central nervous system, GPR37 is enriched in mature oligodendrocytes, but following injury we have found that its expression is dramatically increased within a population of Sox2-positive progenitor cells. Moreover, the genetic deletion of GPR37 did not alter the number of mature oligodendrocytes following injury but did markedly increase the number of both progenitor cells and injury-induced Olig2-expressing glia. Alterations in the glial environment were further evidenced by the decreased activation of oligodendrocyte precursor cells. These data reveal that GPR37 regulates the response of progenitor cells to ischemic injury and provides new perspectives into the potential for manipulating endogenous progenitor cells following stroke

Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling

Introduction: It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes this effect remains unknown. Here we have tested the hypothesis that locally produced LIF can be responsible for Stat3 activation in mouse mammary tumors. Methods: The studies were performed in different tumorigenic and non-tumorigenic mammary cells. The expression of LIF and LIF receptor was tested by RT-PCR analysis. In tumors, LIF and Stat3 proteins were analyzed by immunohistochemistry, whereas Stat3 and extracellular signal-regulated kinase (ERK)1/2 expression and phosphorylation were studied by Western blot analysis. A LIF-specific blocking antibody was used to determine whether this cytokine was responsible for Stat3 phosphorylation induced by conditioned medium. Specific pharmacological inhibitors (PD98059 and Stat3ip) that affect ERK1/2 and Stat3 activation were used to study their involvement in LIF-induced effects. To analyze cell survival, assays with crystal violet were performed. Results: High levels of LIF expression and activated Stat3 were found in mammary tumors growing in vivo and in their primary cultures. We found a single mouse mammary tumor cell line, LM3, that showed low levels of activated Stat3. Incidentally, these cells also showed very little expression of LIF receptor. This suggested that autocrine/paracrine LIF would be responsible for Stat3 activation in mouse mammary tumors. This hypothesis was confirmed by the ability of conditioned medium of mammary tumor primary cultures to induce Stat3 phosphorylation, activity that was prevented by pretreatment with LIF-blocking antibody. Besides, we found that LIF increased tumor cell viability. Interestingly, blocking Stat3 activation enhanced this effect in mammary tumor cells. Conclusion: LIF is overexpressed in mouse mammary tumors, where it acts as the main Stat3 activator. Interestingly, the positive LIF effect on tumor cell viability is not dependent on Stat3 activation, which inhibits tumor cell survival as it does in normal mammary epithelium. © 2007 Quaglino et al.; licensee BioMed Central Ltd.Fil:Quaglino, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Schere-Levy, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Romorini, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Kordon, E.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina