The Analysis of Adhesively Bonded Advance Composite Joints using Joint Finite Elements.

The design and sizing of adhesively bonded joints has always been a major bottleneck in the design of composite vehicles. Dense finite element (FE) meshes are required to capture the full behavior of a joint numerically, but these dense meshes are impractical in vehicle-scale models where a course mesh is more desirable to make quick assessments and comparisons of different joint geometries. Analytical models are often helpful in sizing, but difficulties arise in coupling these models with full-vehicle FE models. Therefore, a joint FE was created which can be used within structural FE models to make quick assessments of bonded composite joints. The shape functions of the joint FE were found by solving the governing equations for a structural model for a joint. By analytically determining the shape functions of the joint FE, the complex joint behavior can be captured with very few elements. This joint FE was modified and used to consider adhesives with functionally graded material properties to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. Furthermore, proof–of-concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint. Furthermore, the capability to model non-linear adhesive constitutive behavior with large rotations was developed, and progressive failure of the adhesive was modeled by re-meshing the joint as the adhesive fails. Results predicted using the joint FE was compared with experimental results for various joint configurations, including double cantilever beam and single lap joints.Ph.D.Aerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91417/1/sstaple_1.pd

The Analysis of Adhesively Bonded Advanced Composite Joints Using Joint Finite Elements

The design and sizing of adhesively bonded joints has always been a major bottleneck in the design of composite vehicles. Dense finite element (FE) meshes are required to capture the full behavior of a joint numerically, but these dense meshes are impractical in vehicle-scale models where a course mesh is more desirable to make quick assessments and comparisons of different joint geometries. Analytical models are often helpful in sizing, but difficulties arise in coupling these models with full-vehicle FE models. Therefore, a joint FE was created which can be used within structural FE models to make quick assessments of bonded composite joints. The shape functions of the joint FE were found by solving the governing equations for a structural model for a joint. By analytically determining the shape functions of the joint FE, the complex joint behavior can be captured with very few elements. This joint FE was modified and used to consider adhesives with functionally graded material properties to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. Furthermore, proof-of-concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint. Furthermore, the capability to model non-linear adhesive constitutive behavior with large rotations was developed, and progressive failure of the adhesive was modeled by re-meshing the joint as the adhesive fails. Results predicted using the joint FE was compared with experimental results for various joint configurations, including double cantilever beam and single lap joints

Functionally Graded Adhesives for Composite Joints

Adhesives with functionally graded material properties are being considered for use in adhesively bonded joints to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. An enhanced joint finite element, which uses an analytical formulation to obtain exact shape functions, is used to model the joint. Furthermore, proof of concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint

Corotational Formulation for Bonded Joint Finite Elements

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140672/1/1.j052422.pd

Influence of association state and DNA binding on the O2-reactivity of [4Fe-4S] fumarate and nitrate reduction (FNR) regulator

The fumarate and nitrate reduction (FNR) regulator is the master switch for the transition between anaerobic and aerobic respiration in Escherichia coli. Reaction of dimeric [4Fe-4S] FNR with O2 results in conversion of the cluster into a [2Fe-2S] form, via a [3Fe-4S] intermediate, leading to the loss of DNA binding through dissociation of the dimer into monomers. In the present paper, we report studies of two previously identified variants of FNR, D154A and I151A, in which the form of the cluster is decoupled from the association state. In vivo studies of permanently dimeric D154A FNR show that DNA binding does not affect the rate of cluster incorporation into the apoprotein or the rate of O2-mediated cluster loss. In vitro studies show that O2-mediated cluster conversion for D154A and the permanent monomer I151A FNR is the same as in wild-type FNR, but with altered kinetics. Decoupling leads to an increase in the rate of the [3Fe-4S]1+ into [2Fe-2S]2+ conversion step, consistent with the suggestion that this step drives association state changes in the wild-type protein. We have also shown that DNA-bound FNR reacts more rapidly with O2 than FNR free in solution, implying that transcriptionally active FNR is the preferred target for reaction with O2

Thienopyridone Drugs Are Selective Activators of AMP-Activated Protein Kinase β1-Containing Complexes

SummaryThe AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that plays a pivotal role in regulating cellular and whole-body metabolism. Activation of AMPK reverses many of the metabolic defects associated with obesity and type 2 diabetes, and therefore AMPK is considered a promising target for drugs to treat these diseases. Recently, the thienopyridone A769662 has been reported to directly activate AMPK by an unexpected mechanism. Here we show that A769662 activates AMPK by a mechanism involving the β subunit carbohydrate-binding module and residues from the γ subunit but not the AMP-binding sites. Furthermore, A769662 exclusively activates AMPK heterotrimers containing the β1 subunit. Our findings highlight the regulatory role played by the β subunit in modulating AMPK activity and the possibility of developing isoform specific therapeutic activators of this important metabolic regulator

Predicting phase equilibria in polydisperse systems

Many materials containing colloids or polymers are polydisperse: They comprise particles with properties (such as particle diameter, charge, or polymer chain length) that depend continuously on one or several parameters. This review focusses on the theoretical prediction of phase equilibria in polydisperse systems; the presence of an effectively infinite number of distinguishable particle species makes this a highly nontrivial task. I first describe qualitatively some of the novel features of polydisperse phase behaviour, and outline a theoretical framework within which they can be explored. Current techniques for predicting polydisperse phase equilibria are then reviewed. I also discuss applications to some simple model systems including homopolymers and random copolymers, spherical colloids and colloid-polymer mixtures, and liquid crystals formed from rod- and plate-like colloidal particles; the results surveyed give an idea of the rich phenomenology of polydisperse phase behaviour. Extensions to the study of polydispersity effects on interfacial behaviour and phase separation kinetics are outlined briefly.Comment: 48 pages, invited topical review for Journal of Physics: Condensed Matter; uses Institute of Physics style file iopart.cls (included

Differential regulation by AMP and ADP of AMPK complexes containing different γ subunit isoforms

The γ subunits of heterotrimeric AMPK complexes contain the binding sites for the regulatory adenine nucleotides AMP, ADP and ATP. We addressed whether complexes containing different γ isoforms display different responses to adenine nucleotides by generating cells stably expressing FLAG-tagged versions of the γ 1, γ 2 or γ 3 isoform. When assayed at a physiological ATP concentration (5 mM), γ 1- and γ 2-containing complexes were allosterically activated almost 10-fold by AMP, with EC50 values one to two orders of magnitude lower than the ATP concentration. By contrast, γ 3 complexes were barely activated by AMP under these conditions, although we did observe some activation at lower ATP concentrations. Despite this, all three complexes were activated, due to increased Thr172 phosphorylation, when cells were incubated with mitochondrial inhibitors that increase cellular AMP. With γ 1 complexes, activation and Thr172 phosphorylation induced by the upstream kinase LKB1 [liver kinase B1; but not calmodulin-dependent kinase kinase (CaMKKβ)] in cell-free assays was markedly promoted by AMP and, to a smaller extent and less potently, by ADP. However, effects of AMP or ADP on activation and phosphorylation of the γ 2 and γ 3 complexes were small or insignificant. Binding of AMP or ADP protected all three γ subunit complexes against inactivation by Thr172 dephosphorylation; with γ 2 complexes, ADP had similar potency to AMP, but with γ 1 and γ 3 complexes, ADP was less potent than AMP. Thus, AMPK complexes containing different γ subunit isoforms respond differently to changes in AMP, ADP or ATP. These differences may tune the responses of the isoforms to fit their differing physiological roles

Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. The VANISH Randomized Clinical Trial

IMPORTANCE: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN 20769191