888 research outputs found
Indirect Inference with Importance Sampling: An Application to Women’s Wage Growth
This paper has two main parts. In the first, we describe a method that smooths the objective function in a general class of indirect inference models. Our smoothing procedure makes use of importance sampling weights in estimation of the auxiliary model on simulated data. The importance sampling weights are constructed from likelihood contributions implied by the structural model. Since this approach does not require transformations of endogenous variables in the structural model, we avoid the potential approximation errors that may arise in other smoothing approaches for indirect inference. We show that our alternative smoothing method yields consistent estimates. The second part of the paper applies the method to estimating the effect of women's fertility on their human capital accumulation. We find that the curvature in the wage profile is determined primarily by curvature in the human capital accumulation function as a function of previous human capital, as opposed to being driven primarily by age. We also find a modest effect of fertility induced nonemployment spells on human capital accumulation. We estimate that the difference in wages among prime age women would be approximately 3% higher if the relationship between fertility and working were eliminated
An isogeometric finite element formulation for phase transitions on deforming surfaces
This paper presents a general theory and isogeometric finite element
implementation for studying mass conserving phase transitions on deforming
surfaces. The mathematical problem is governed by two coupled fourth-order
nonlinear partial differential equations (PDEs) that live on an evolving
two-dimensional manifold. For the phase transitions, the PDE is the
Cahn-Hilliard equation for curved surfaces, which can be derived from surface
mass balance in the framework of irreversible thermodynamics. For the surface
deformation, the PDE is the (vector-valued) Kirchhoff-Love thin shell equation.
Both PDEs can be efficiently discretized using -continuous interpolations
without derivative degrees-of-freedom (dofs). Structured NURBS and unstructured
spline spaces with pointwise -continuity are utilized for these
interpolations. The resulting finite element formulation is discretized in time
by the generalized- scheme with adaptive time-stepping, and it is fully
linearized within a monolithic Newton-Raphson approach. A curvilinear surface
parameterization is used throughout the formulation to admit general surface
shapes and deformations. The behavior of the coupled system is illustrated by
several numerical examples exhibiting phase transitions on deforming spheres,
tori and double-tori.Comment: fixed typos, extended literature review, added clarifying notes to
the text, added supplementary movie file
The Dynamics of Fit and the Fit of Dynamics: Aligning IT in a Dynamic Organization
Models of the fit of IT systems to their organization are predominantly static contingency models. A rational,top-downdynamicisassumed: fxstfromstrategytostructure,thentoIT,managementprocesses and work roles and skills. Recent research has presented “deviant” pathways to fit as a challenge to this rational view of dynamics. This paper extends our understanding of dynamics by exposing the hidden assumption that only a single change process, or Dynamic, is undertaken at one time. A case is used to illustrate multiple, concurrent Dynamics. Analysis reveals that concurrent Dynamics may have incompatible fit configurations and also that they may have competitive paths to fit as a result of temporal and interaction effects. An extended account of the dynamics of fit is summarized and areas for future theoretical development outlined
Aggressive shadowing of a low-dimensional model of atmospheric dynamics
Predictions of the future state of the Earth's atmosphere suffer from the
consequences of chaos: numerical weather forecast models quickly diverge from
observations as uncertainty in the initial state is amplified by nonlinearity.
One measure of the utility of a forecast is its shadowing time, informally
given by the period of time for which the forecast is a reasonable description
of reality. The present work uses the Lorenz 096 coupled system, a simplified
nonlinear model of atmospheric dynamics, to extend a recently developed
technique for lengthening the shadowing time of a dynamical system. Ensemble
forecasting is used to make forecasts with and without inflation, a method
whereby the ensemble is regularly expanded artificially along dimensions whose
uncertainty is contracting. The first goal of this work is to compare model
forecasts, with and without inflation, to a true trajectory created by
integrating a modified version of the same model. The second goal is to
establish whether inflation can increase the maximum shadowing time for a
single optimal member of the ensemble. In the second experiment the true
trajectory is known a priori, and only the closest ensemble members are
retained at each time step, a technique known as stalking. Finally, a targeted
inflation is introduced to both techniques to reduce the number of instances in
which inflation occurs in directions likely to be incommensurate with the true
trajectory. Results varied for inflation, with success dependent upon the
experimental design parameters (e.g. size of state space, inflation amount).
However, a more targeted inflation successfully reduced the number of forecast
degradations without significantly reducing the number of forecast
improvements. Utilized appropriately, inflation has the potential to improve
predictions of the future state of atmospheric phenomena, as well as other
physical systems.Comment: 14 pages, 16 figure
Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions
Purpose: Augmented reality (AR) and head-mounted displays (HMD) in medical practice are current research topics. A commonly proposed use case of AR-HMDs is to display data in image-guided interventions. Although technical feasibility has been thoroughly shown, effects of AR-HMDs on interventions are not yet well researched, hampering clinical applicability. Therefore, the goal of this study is to better understand the benefits and limitations of this technology in ultrasound-guided interventions.
Methods: We used an AR-HMD system (based on the first-generation Microsoft Hololens) which overlays live ultrasound images spatially correctly at the location of the ultrasound transducer. We chose ultrasound-guided needle placements as a representative task for image-guided interventions. To examine the effects of the AR-HMD, we used mixed methods and conducted two studies in a lab setting: (1) In a randomized crossover study, we asked participants to place needles into a training model and evaluated task duration and accuracy with the AR-HMD as compared to the standard procedure without visual overlay and (2) in a qualitative study, we analyzed the user experience with AR-HMD using think-aloud protocols during ultrasound examinations and semi-structured interviews after the task.
Results: Participants (n = 20) placed needles more accurately (mean error of 7.4 mm vs. 4.9 mm, p = 0.022) but not significantly faster (mean task duration of 74.4 s vs. 66.4 s, p = 0.211) with the AR-HMD. All participants in the qualitative study (n = 6) reported limitations of and unfamiliarity with the AR-HMD, yet all but one also clearly noted benefits and/or that they would like to test the technology in practice.
Conclusion: We present additional, though still preliminary, evidence that AR-HMDs provide benefits in image-guided procedures. Our data also contribute insights into potential causes underlying the benefits, such as improved spatial perception. Still, more comprehensive studies are needed to ascertain benefits for clinical applications and to clarify mechanisms underlying these benefits
An adaptive space-time phase field formulation for dynamic fracture of brittle shells based on LR NURBS
We present an adaptive space-time phase field formulation for dynamic
fracture of brittle shells. Their deformation is characterized by the
Kirchhoff-Love thin shell theory using a curvilinear surface description. All
kinematical objects are defined on the shell's mid-plane. The evolution
equation for the phase field is determined by the minimization of an energy
functional based on Griffith's theory of brittle fracture. Membrane and bending
contributions to the fracture process are modeled separately and a thickness
integration is established for the latter. The coupled system consists of two
nonlinear fourth-order PDEs and all quantities are defined on an evolving
two-dimensional manifold. Since the weak form requires -continuity,
isogeometric shape functions are used. The mesh is adaptively refined based on
the phase field using Locally Refinable (LR) NURBS. Time is discretized based
on a generalized- method using adaptive time-stepping, and the
discretized coupled system is solved with a monolithic Newton-Raphson scheme.
The interaction between surface deformation and crack evolution is demonstrated
by several numerical examples showing dynamic crack propagation and branching.Comment: In this version, typos were fixed, Fig. 16 is added, the literature
review is extended and clarifying explanations and remarks are added at
several places. Supplementary movies are available at
https://av.tib.eu/series/641/supplemental+videos+of+the+paper+an+adaptive+space+time+phase+field+formulation+for+dynamic+fracture+of+brittle+shells+based+on+lr+nurb
Phagocytes produce prostaglandin E2 in response to cytosolic Listeria monocytogenes
Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 (PGE2) downstream of cyclooxygenase-2 (COX-2) is essential for optimal L. monocytogenes T-cell priming. Here, we demonstrate that vacuole-constrained L. monocytogenes elicit reduced PGE2 production compared to wild-type strains in macrophages and dendritic cells ex vivo. In vivo, infection with wild-type L. monocytogenes leads to 10-fold increases in PGE2 production early during infection whereas vacuole-constrained strains fail to induce PGE2 over mock-immunized controls. Mice deficient in COX-2 specifically in Lyz2+ or CD11c+ cells produce less PGE2, suggesting these cell subsets contribute to PGE2 levels in vivo, while depletion of phagocytes with clodronate abolishes PGE2 production completely. Taken together, this work demonstrates that optimal PGE2 production by phagocytes depends on L. monocytogenes access to the cytosol, suggesting that one reason cytosolic access is required to prime CD8+ T-cell responses may be to facilitate production of PGE2
Intraovarian regulation of gonadotropin-dependent folliculogenesis depends on notch receptor signaling pathways not involving Delta-like ligand 4 (Dll4)
Background: In-situ hybridisation studies demonstrate that Notch receptors and ligands are expressed in granulosa cells (GCs) and in the theca layer vasculature of growing follicles. Notch signaling involves cell-to-cell interaction mediated by transmembrane receptors and ligands. This signaling pathway may represent a novel intraovarian regulator of gonadotropin-dependent follicular development to the preovulatory stage. We hypothesized that blocking Notch pathways would disrupt follicular maturation in the mouse ovary. Methods: Hypophysectomized CD21 female mice were administered pregnant mare serum gonadotropin (PMSG) for 3 days to stimulate follicular development. In one experiment, a pan-notch inhibitor, compound E, was initiated 2 days prior to and throughout stimulation (n = 10), while in a second experiment, a humanized phage Dll4 blocking antibody, YW152F, was used (n = 5). After sacrifice, ovarian histology, serum estradiol levels and uterine weights were compared to controls. The ovarian morphology was evaluated with hematoxylin/eosin staining and immunohistochemistry was performed for Notch1, Notch2, Notch3, Notch4, Jagged1, Dll4, platelet endothelial cell adhesion molecule (PECAM) and alpha-smooth muscle actin (α-SMA) detection. Results: We localized specific Notch ligands and receptors in the following structures: Dll4 is specific to theca layer endothelial cells (ECs); Notch1/Notch4 and Jagged1 are expressed in theca layer ECs and vascular smooth muscle cells (VSMCs), whereas Notch3 is restricted to VSMCs; Notch2 is expressed mostly on GCs of small follicles. Administration of a pan-Notch inhibitor, compound E, inhibits follicular development to the preovulatory stage (8.5 preovulatory follicles in treatment vs. 3.4 preovulatory follicles in control, p < 0.01; average number per ovary) with significant secondary effects on ovarian and uterine weight and estradiol secretion in a setting of uninhibited vascular proliferation, but disorganized appearance of ECs and VSMCs. Inhibition of endothelial Notch1 function through the inactivation of its ligand Dll4 with the blocking antibody YW152F induces mild disorganisation of follicular vasculature, but has no significant effect on gonadotropin-dependent folliculogenesis. Conclusions: Our experiments suggest that the complete blockage of the Notch signaling pathway with compound E impairs folliculogenesis and induces disruption of gonadotropin stimulated angiogenesis. It seems the mechanism involves Notch1 and Notch3, specifically, causing the improper assembly of ECs and VSMCs in the theca layer, although the potential role of non-angiogenic Notch signaling, such as Jagged2 to Notch2 in GCs, remains to be elucidated
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Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Functions to Promote Uterine Decidual Angiogenesis during Early Pregnancy in the Mouse
Implantation of an embryo induces rapid proliferation and differentiation of uterine stromal cells, forming a new structure, the decidua. One salient feature of decidua formation is a marked increase in maternal angiogenesis. Vascular endothelial growth factor (VEGF)-dependent pathways are active in the ovary, uterus, and embryo, and inactivation of VEGF function in any of these structures might prevent normal pregnancy development. We hypothesized that decidual angiogenesis is regulated by VEGF acting through specific VEGF receptors (VEGFRs). To test this hypothesis, we developed a murine pregnancy model in which systemic administration of a receptor-blocking antibody would act specifically on uterine angiogenesis and not on ovarian or embryonic angiogenesis. In our model, ovarian function was replaced with exogenous progesterone, and blocking antibodies were administered prior to embryonic expression of VEGFRs. After administration of a single dose of the anti-VEGFR-2 antibody during the peri-implantation period, no embryos were detected on embryonic d 10.5. The pregnancy was disrupted because of a significant reduction in decidual angiogenesis, which under physiological conditions peaks on embryonic d 5.5 and 6.5. Inactivation of VEGFR-3 reduced angiogenesis in the primary decidual zone, whereas administration of VEGFR-1 blocking antibodies had no effect. Pregnancy was not disrupted after administration of anti-VEGFR-3 or anti-VEGFR-1 antibodies. Thus, the VEGF/VEGFR-2 pathway plays a key role in the maintenance of early pregnancy through its regulation of peri-implantation angiogenesis in the uterine decidua. This newly formed decidual vasculature serves as the first exchange apparatus for the developing embryo until the placenta becomes functionally active
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