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Three Dimensional Finite Element Analysis of Layered Composite Plate with Elastic Pin under External Uniaxial Loading
No full textABSTRACT: Stress analysis plays important role in the structural integrity and optimization. Prior stress estimation helps in better design of the products. Composites find wide usage in the industrial and home applications due to its strength to weight ratio. Especially in the air craft industry, the usage of composites is more due to its advantages over the conventional materials. Composites are mainly made of orthotropic materials having unequal strength in the different directions. Composite materials has the drawback of delamination and debonding due to the weaker bond materials compared to the parent materials. So proper analysis should be done to the composite joints before using it in the practical conditions. In the present work, a composite plate with elastic pin is considered for analysis using finite element software Ansys. Initially the geometry is built using Ansys software using top down approach with different Boolean operations. The modeled object is meshed with 3 dimensional layered element solid46 for composite plate and structural three dimensional solid element Solid45 for pin material. Various combinations are considered to find the strength of the composite joint under uniaxial loading conditions. Due to symmetry of the problem, only quarter geometry is built and results are presented for full model using Ansys expansion options. The results show effect of pin diameter on the joint strength. Here the deflection and load sharing of the pin is increasing and other parameters like overall stress, pin stress and contact pressure is reducing due to lesser load on the plate material. Further material effect shows, higher young modulus material has little deflection, but other parameters are increasing. Interference analysis shows increasing of overall stress, pin stress, contact stress along with pin bearing load. This increase should be understood properly for increasing the load carrying capacity of the joint. Generally every structure is preloaded to increase the compressive stress in the joint to increase the load carrying capacity. But the stress increase should be properly analysed for composite due to its delamination and debonding effects due to failure of the bond materials. When results for an isotropic combination is compared with composite joint, isotropic joint shows uniformity of the results with lesser values for all parameters. This is mainly due to applied layer angle combinations. All the results are represented with necessasary pictorial plots.
Inner polar disks in early-type spiral galaxies
No full textAbstract. We measured a remarkable gas velocity gradient along the minor axis of a number of early-type spiral galaxies. This phenomenon suggests the presence of a kinematically-decoupled component in orthogonal rotation with respect to the galaxy disk which we named inner polar disk . If this is the case a second event has taken place in the history of the galaxy. Alternatively the gas velocity gradient is the result of non-circular motions induced by the potential of a triaxial bulge
Marine Sandwave and River Dune Dynamics -1 & 2
No full textAbstract We investigate analytically the linear stability of a planar sand bed sheared by a laminar boundary layer flow in a 2D and 3D configuration. The sand transport is described by a continuum phenomenological model taking into account the local bed shear stress (calculated from the resolution of the flow over a deformed sand bed), the grain inertia and the local bed slope. We find that the competition between the destabilizing effect of fluid inertia and the stabilizing ones of grain inertia and gravity leads to the selection of a single mode, that is longitudinal (i.e., parallel to the flow direction). The 3D calculation shows that there exists a band of unstable modes in the oblique direction, which can couple to the main longitudinal mode in the non-linear regime to give birth to a two-dimensional pattern no longer invariant in the transverse direction
Orexin A but Not Orexin B Rapidly Enters Brain from Blood by Simple Diffusion 1
No full textABSTRACT We determined the ability of orexin A and orexin B, recently discovered endogenous appetite enhancers, to cross the blood-brain barrier (BBB) of mice. Multiple time-regression analysis showed that an i.v. bolus of 125 I-orexin A rapidly entered the brain from the blood, with an influx rate (K i ϭ 2.5 Ϯ 0.3 ϫ 10 Ϫ4 ml/g⅐min) many times faster than that of the 99m Tcalbumin control. This relatively rapid rate of entry was not reduced by administration of excess orexin A (or leptin) or by fasting for 22 h, even when penetration into only the hypothalamus was measured. Lack of saturability also was shown by perfusion in blood-free buffer. HPLC revealed that most of the injected 125 I-orexin A reached the brain as intact peptide. Capillary depletion studies showed that the administered peptide did not remain bound to the endothelial cells comprising the BBB but reached the brain parenchyma. Efflux of 125 I-orexin A from the brain occurred at the same rate as 99m Tc-albumin. The octanol/buffer partition coefficient of 0.232 showed that orexin A was highly lipophilic, whereas the value for orexin B was only 0.030. Orexin B, moreover, was rapidly degraded in blood, so no 125 I-orexin B could be detected in intact form in brain when injected peripherally. Thus, although orexin B is rapidly metabolized in blood and has low lipophilicity, orexin A rapidly crosses the BBB from blood to reach brain tissue by the process of simple diffusion. The orexins were named for the Greek word for appetite The orexins were discovered during a search for peptides that activate orphan receptors whose amino acid sequences show the structural hallmarks of cell surface receptors for G proteins To assess the therapeutic potential of the orexins for the treatment of anorexia, it would be helpful to know their ability to cross the blood-brain barrier (BBB) from the periphery. Accordingly, the rate of entry into brain of i.v. 125 Ilabeled orexin A and orexin B was quantified by multiple time-regression analysis. HPLC was used to determine whether the 125 I-orexins penetrated the BBB in intact form. Capillary depletion was used to determine whether most of the 125 I-orexin reaching the brain was in the parenchyma or was bound to the endothelial cells comprising the BBB. 99m Tc-labeled albumin was injected together with the 125 Iorexin to reflect the vascular space and any disruption of the BBB. The octanol-to-buffer ratio was used to measure the lipophilicity of the orexins. Efflux from the brain and entry by a blood-free i.v. perfusion also were tested. Materials and Methods Multiple Time-Regression Analysis of Entry into Brain. Adult male albino ICR mice (Charles River, Wilmington, MA) (10 per group and weighing about 22 g) were anesthetized with urethane (4 g/kg i.p.). Orexin was radiolabeled with 125 I by the chloramine-T method and purified on a column of Sephadex G-10. Acid precipitation showed incorporation of 125 I into orexin of 95.7% to 99.6% for the iodinations used in this study. HPLC of the 125 I-orexin immediately before use showed more than 90% purity each time. The specific activity of 125 I-orexin A was 126 Ci/mmol, and that o
Marres & Lezaun_introduction _ final
No full textAbstract This introduction provides an overview of material-or device-centered approaches to the study of public participation, and articulates the theoretical contributions of the four articles that make up this special section. Set against the background of post-Foucaldian perspectives on the material dimensions of citizenship and engagement -perspectives that treat matter as a tacit, constituting force in the organization of collectives and are predominantly concerned with the fabrication of political subjects -we outline an approach that considers material engagement as a distinct mode of performing the public. The question, then, is how objects, devices, settings and materials acquire explicit political capacities, and how they serve to enact material participation as a specific public form. We discuss the connections between social studies of material participation and political theory, and define the contours of an empiricist approach to material publics, one that takes as its central cue that the values and criteria particular to these publics emerge as part of the process of their organization. Finally, we discuss four themes that connect the articles in this special section, namely their focus on 1) mundane technologies, 2) experimental devices and settings for material participation; 3) the dynamic of effort and comfort, and 4) the modes of containment and proliferation that characterize material publics
Microscopic Views of Drug Solubility
No full textAbstract The development of computational models for predicting drug solubility has increased drastically during the last decades. Nevertheless these models still have difficulties to estimate the aqueous solubility as accurate as desired. In this thesis different aspects that are known to have a large impact on the aqueous solubility of a molecule have been studied in detail using various theoretical methods with intension to provide microscopic view on drug solubility. The first aspect studied is the hydrogen bond energies. Eight drug molecules have been calculated using density functional theory and the validity of additive model that has often been used in solubility models is examined. The impact of hydrogen bonds in Infrared and Raman spectra of three commonly used drug molecules has also been demonstrated. The calculated spectra are found to be in good agreement with the experimental data. Another aspect that is important in solubility models is the volume that a molecule occupies when it is dissolved in water. The volume term and its impact on the solvation energy has therefore also been calculated using three different methods. It was shown that the calculated volume differed significantly dependent on which method that had been used, especially for larger molecules. Most of the solubility models assume the solute molecule to be in the bulk of the solvent. The molecular behavior at the water/gas interface has been investigated to see how it differs from bulk. It was seen that the concentration close to the interface was almost three times higher than in the bulk. The increase in concentration close to the surface depends on the larger gap between the interface energy and the gas phase energy than between the bulk energy and the gas phase energy. Preface The work presented in this thesis has been carried out at th
Rhamm-/-mice are defective in skin wound repair due to aberrant ERK1,2 signaling in fibroblast migration
No full textWe have considered the comments of the reviewers of our manuscript entitled "Rhamm -/-mice are defective in skin wound repair due to aberrant ERK1,2 signaling in fibroblast migration" and are resubmitting a revised manuscript that takes into consideration the helpful comments of reviewers. We have enclosed our responses to each of the reviewer's critique. Response: We have re-written most of the manuscript to present concepts and data in a more straightforward and simplified manner. In the text, we have replaced ambiguous descriptions or jargon (e.g."actin remodeling", "much more restricted") with what we hope is clearer language (e.g. "disassembly of actin stress fibers" and "reduced"). We have also quantified the disassembly of actin stress fibers using image analysis to reduce ambiguity about the changes that Rhamm loss has on the actin cytoskeleton organization. Comment: The authors comment on reduced clot formation (in the Abstract and Results on page 5) but do not indicate how it relates to their findings on cell migration. Also they claim reduced clot formation and show it nicely in the supplemental figure but in figure 1A clot formation looks increased in the KO cells. A more representative figure should be shown if this was their general finding. Unless they have more quantitative information and a proposed mechanism relative to their findings in this paper, they may want to omit this information. Response: We agree with Reviewer 1's comments that the data on clot formation shown in the original manuscript were not well documented and were peripheral to the main focus of the manuscript on cell migration. We have omitted these data and descriptions in the revised manuscript. Comment: The reviewers concerns also brought up an important point about the semiquantitative nature of the western blot assays previously shown in Comment: Response: We agree with the reviewer that this figure should be simplified. However, we feel strongly that the timelapsed images of the wounds provide data that is difficult to convey as a table. We have therefore removed Comment: Comment: Comment: Comment For example the higher magnification image of the Rh-/-mice in fig 2B (should be ?) seems to be of the lower part of the skin, where the fat pad is (as we can see a lot of vacuoles). Response: Rhamm-/-wounds aberrantly accumulate adipocytes within granulation tissue accounting for the large number of vacuolated cells depicted in the previous The authors state that the fibroblasts are less dense in the KO compared to the WT, but this is not reflected in the pictures shown, in fact, there are areas in the WT shaded area of the wound that look less dense (on the left hand side of the wound). Response: We agree with the reviewer that Rhamm-/-wounds exhibit areas of high fibroblast density as well as areas of lower fibroblast density, and this micrograph (now Comment 1b: The authors should show the resolution of the actual wound on the back of the animals, at different times to give a better picture of how these wounds heal. Response: We have repeated the wounding experiments and have taken photographs of wound sites on the animal's backs from day 0 to day 7. These photographs shown as Supplemental Comment 1d: What is the brown staining that is seen in the sections in figure 1? Response: Sections were stained for vimentin. Only the higher magnification micrographs have been retained in the present manuscript. Comment 2a: In figure 3 the section of wounded 3d Rh-/-animal again have a lot of vacuoles in them. Response: As noted above, these are adipocytes, which accumulate to a greater extent in Rh-/-vs. Wt wound sites. The 7d KO wound looks very washed out, and there seem to be fewer nuclei, which is at odds with the data that Rh-/-wounds have more cells per field compared to WT wounds both at 3d and 7d wounds. Response: Panel day 7 Rh-/-in Comment 2b: What is the correlation between the low levels of ERK expression and the miscuing of granulation tissue formation? Response: Both Wt and Rh-/-granulation tissue fibroblasts in vivo ("unpublished data") and Rh-/-and Rh FL -rescued fibroblasts in vitro express similar levels of ERK1,2 protein ( Also it does not seem surprising that the Rh-/-cells have a migration defect, given that it has been shown by these authors that "HA:Rhamm interactions promote cell locomotion via a protein tyrosine kinase signal transduction pathway that targets focal adhesions" and that "tyrosine kinase pp60c-src is associated with Rhamm in cells and is required for Rhamm mediated cell motility" (Hall and Turley 1995). Response: We agree that our results showing an effect of Rhamm loss on cell migration is predicted by previous data from cultured cells. However, in vitro analyses often do not predict in vivo functions and our previous studies also did not address whether other genes (e.g. CD44) can compensate for Rhamm in regulating migration and whether Rhamm-regulated migration is involved in a physiological process. We had expected CD44 to compensate for Rhamm loss since we have previously published that these receptors have overlapping functions and that Rhamm can compensate for CD44 to mediate migration and invasion during disease processes such as arthritis (Nedvetski et al., 2004, Proc. Natl. Acad. Sci. U.S.A.101:18081). Our results suggesting that Rhamm is involved in regulating fibroblast migration during the physiological process of wound repair is therefore noteworthy. These points of view are now emphasized in the Discussion section (page 13). There is no attempt to address the mechanism for changes in cell migration. What is the correlation between Rhamm and MAP Kinase signaling? We apologize for this omission. Response: Our results in the present manuscript showing an effect of Rhamm on MAP kinase signaling are consistent with our and other's previous data providing evidence that Rhamm can act at the level of receptor protein tyrosine kinases to activate upstream effectors of ERK1,2 including src, and Ras. We have now included these important points in the Discussion section of the revised manuscript (page 12). Comment 5: The authors' state in the text on page 9 that migration defect was displayed by primary dermal and "other" cells. What are the other "type of fibroblasts" that show the migration defect? Response: In this study, we used primary embryonic fibroblasts (MEF), immortalized embryonic fibroblasts (which were also transfected with full length Rhamm and/or mutant active Mek1), and primary dermal fibroblasts from littermatched Wt and Rh-/-mice. We apologize for the poor documentation of this in the previous manuscript. We have attempted to make the origin of the fibroblasts used for each experiment more clear 6 by presenting the data using immortalized Rh-/-and Rh Comment: Why was the rescue not done using the primary cells? Response: The transfection efficiency of primary fibroblasts is very low (<10%) and precluded their use in many analyses presented in this manuscript. We deliberately isolated immortalized Rh-/-and Rh FL -rescued fibroblast lines to circumvent this difficulty since these are much more easily transfect (transfection efficiency with lipofectamine Plus is 60-70%). Comment: Do the transformed KO and rescued cells have the same response in the migration and invasion assays as the primary WT and KO cells? Response: The cell lines we used are not transformed but rather immortalized (they do not grow in soft agar or form foci in focus forming assays that would indicate transformation). Both cell lines exhibit similar phenotypes although the rates of migration, for example, differ slightly. We have separated these data as noted above to prevent reader confusion. Comment For example, does Rhamm have effects on expression of p27 that regulates both migration and proliferation. Response: This is a very interesting suggestion that we will certainly consider for future experiments. However, we feel that this is beyond the scope of the present manuscript. Response: We agree with the reviewer. We have redone the wounding experiments and have restricted our analyses to the wound center, which is most easily identified. We also matched age (18 months), gender (male) and wound placement (left flank) to facilitate data interpretation. We also thank the reviewer for the excellent suggestion to use tenascin as a marker for granulation tissue. We have now used tenascin-staining to measure granulation tissue boundaries in Wt and Rh-/-wounds. These new data are presented in a new Comment: Do differences in migration of the fibroblasts that are described in the rest of the manuscript account for the differences in granulation tissue? Response: This is an important point that we have addressed indirectly in this manuscript in the sense that we did not observe differences in either proliferation or apoptosis in vivo leaving migration as a reasonable alternative. Defective migration is consistent with our in vitro data and with the differences in ERK1,2 activity observed both in vivo and in vitro. We are currently using knock-in approaches and ex vivo image analysis to directly address this point. Comment: Where does Rhamm localize in the granulation tissue of the WT? Response: We (Savani et al., 1995 Proc West Pharmacol Soc 38:131), and others (Lovoorn et al., 1998, J Pediatr Surg 33:1062, have previously published that Rhamm is expressed in granulation tissue fibroblasts as well as in white cells present in granulation tissue. Comment: Figure 3. It is not clear from Comment: Comment: Do differences in concentration of PDGF-BB compensate for the reported differences in ratios of P-ERK/total ERK ( Comment: Comment
A semiparametric mixture regression model for longitudinal data A semiparametric mixture regression model for longi- tudinal data
No full textLink to publication record in Manchester Research Explorer Citing this paper Please note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscript or Proof version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version. General rights Copyright and moral rights for the publications made accessible in the Research Explorer are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • A normal semiparametric mixture regression model is proposed for longitudinal data. Takedown policy The proposed model contains one smooth term and a set of possible linear predictors. Model terms are estimated using the penalized likelihood method with the EM-algorithm. A computationally feasible alternative method that provides an approximate solution is also introduced. Simulation experiments and real data example are used to illustrate the methods. Key-Words: • Curve Clustering; EM-algorithm; Finite Mixtures; Growth Curves. AMS Subject Classification: • 62G05, 62B99, 62J07. A semiparametric mixture regression model ... The focus in the present study is especially on modeling the mean within the mixture using semiparametric regression techniques DESCRIPTION OF THE PROBLE