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A review of preserving privacy in data collected from buildings with differential privacy

Significant amounts of data are collected in buildings. While these data have great potential for maximizing the energy efficiency of buildings in general, only a small portion of the data are accessible to researchers, government, and industry for analyses. Concerns about privacy are one of the major barriers prohibiting access to these data. Privacy preservation techniques are generally applied to this problem not only to preserve underlying privacy but also to improve the usefulness of data. Among various privacy preserving techniques, differential privacy has become one of the more popular solutions since its introduction in 2006. Differential privacy is a mathematical measure for protecting privacy so that one's privacy cannot be incurred by participating in a database. Additionally, although significant research improvements have been made for more than a decade, applying differential privacy to data collected in buildings is still an immature field of study. Because implementing differential privacy on a certain use case is not straightforward and can be achieved with various configurations, it is important to understand variation of configurations with different use cases around data collected from buildings. This literature review aims to introduce what has been done to implement differential privacy in data collected in buildings, and to discuss associated challenges and potential future research opportunities.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Analysis of ionizing radiation induced DNA damage response in human adult stem cells and differentiated neurons

Findings of neurodegenerative features associated with human radiosensitive syndromes such as Ataxia telangiectasia suggest that DNA repair efficiency is crucial for maintaining the functional integrity of central nervous system. To gain a better understanding of ionizing radiation (IR) induced DNA damage response in undifferentiated and differentiated neural cell types and to evaluate the role of ATM in DNA double strand break (DSB) repair, an in vitro human neural cell differentiation model system was utilized in this study. As compared to adult stem cells, differentiated neurons displayed an attenuated DSB repair response (as judged by the persistence of 53BP1 foci) after IR exposure and the attenuation was even more pronounced in stem cells and neurons after suppression of ATM (Ataxia Telangiectasia Mutated) gene product suggesting the importance of ATM for an optimal DSB repair efficiency in human neural cell types. In corroboration with an attenuated DNA damage response, a sharp decline in the expression levels of several DSB repair genes was observed in neurons. Furthermore, our results suggest that cellular differentiation modulates the expression of several genes thereby compromising the DSB repair fidelity in post mitotic neurons. Further studies are required to verify whether or not ATM mediated exacerbation of DNA repair deficiency in differentiated neurons leads to neurodegeneration.

53 binding protein 1↗

Assessment of the hepatocytic differentiation ability of human skin-derived ABCB5+ stem cells

Highlights: • Stem cell-derived hepatocytes may be used for cell therapy of liver diseases. • ABCB5-positive stem cell feature characteristics of mesenchymal stromal cells. • Hepatocytic differentiation of ABCB5{sup +} stem cells is incomplete. • However, they secrete hepatotropic factors that may support liver regeneration. • Hepatic delivery of the cells does not cause obvious adverse effects in the mouse. The continuously decreasing willingness for liver donation aggravates treatment of end-stage liver diseases requiring organ transplantation as the only curative strategy. Cell therapy approaches using human hepatocytes or stem cell-derived hepatocyte-like cells may be a therapeutic option out of this dilemma. ABCB5-positive mesenchymal stromal cells from human skin featured promising potential to treat immune-mediated diseases. Since most of chronic liver diseases involve exaggerating immune mechanisms, it was the aim to demonstrate in this study, whether ABCB5{sup +} stem cells may serve as a resource to generate hepatocytic cells for application in liver cell transplantation. Using an established single-step protocol, which had been successfully applied to differentiate mesenchymal stromal cells into the hepatocytic lineage, ABCB5{sup +} skin-derived stem cells did not gain significant characteristics of hepatocytes. Yet, upon culture in hepatocytic differentiation medium, ABCB5{sup +} stem cells secreted immunomodulatory and anti-fibrotic factors as well as proteins, which may prompt hepatic morphogenesis besides others. Hepatic transplantation of ABCB5{sup +} stem cells, which had been prior cultured in hepatocytic differentiation medium, did not cause any obvious deterioration of liver architecture suggesting their safe application. Thus, human ABCB5{sup +} skin-derived stem cells secreted putative hepatotropic factors after culture in hepatocytic differentiation medium.

60 APPLIED LIFE SCIENCES↗

Down-regulation of A3AR signaling by IL-6-induced GRK2 activation contributes to Th17 cell differentiation

Highlights: • Cyclic AMP-PKA signaling is involved in Th17 cell differentiation. • IL-6 stimulation triggers the internalization of A{sub 3}AR and promotes cAMP production in T cells. • IL-6 induces A{sub 3}AR internalization in a GRK2 dependent manner. • GRK2 is a potential therapeutic target for treating Th17 driving immune diseases. IL-6-triggered Th17 cell expansion is responsible for the pathogenesis of many immune diseases including rheumatoid arthritis (RA). Traditionally, IL-6 induces Th17 cell differentiation through JAK-STAT3 signaling. In the present work, PKA inhibition reduces in vitro induction of Th17 cells, while IL-6 stimulation of T cells facilitates the internalization of A{sub 3}AR and increased cAMP production in a GRK2 dependent manner. Inhibition of GRK2 by paroxetine (PAR) or genetic depletion of GRK2 restored A{sub 3}AR distribution and prevented Th17 cell differentiation. Furthermore, in vivo PAR treatment effectively reduced the splenic Th17 cell proportion in a rat model of collagen-induced arthritis (CIA) which was accompanied by a significant improvement in clinical manifestations. These results indicate that IL-6-induced Th17 cell differentiation not only occurs through JAK-STAT3-RORγt but is also mediated through GRK2-A{sub 3}AR-cAMP-PKA-CREB/ICER-RORγt. This elucidates the significance of GRK2-controlled cAMP signaling in the differentiation of Th17 cells and its potential application in treating Th17-driven immune diseases such as RA.

60 APPLIED LIFE SCIENCES↗

Automatic Differentiation in MetaPhysicL and Its Applications in MOOSE

Efficient solution via Newton’s method of nonlinear systems of equations requires an accurate representation of the Jacobian, corresponding to the derivatives of the component residual equations with respect to the degrees of freedom. In practice these systems of equations often arise from spatial discretization of partial differential equations used to model physical phenomena. These equations may involve domain motion or material equations that are complex functions of the systems’ degrees of freedom. Computing the Jacobian by hand in these situations is arduous and prone to error. Finite difference approximations of the Jacobian or its action are prone to truncation error, especially in multiphysics settings. Symbolic differentiation packages may be used, but often result in an excessive number of terms in realistic model scenarios. An alternative to symbolic and numerical differentiation is automatic differentiation (AD), which propagates derivatives with every elementary operation of a computer program, corresponding to continual application of the chain rule. Automatic differentiation offers the guarantee of an exact Jacobian at a relatively small overhead cost. In this work, we outline the adoption of AD in the Multiphysics Object Oriented Simulation Environment (MOOSE) via the MetaPhysicL package. We describe the application of MOOSE’s AD capability to several sets of physics that were previously infeasible to model via hand-coded or Jacobian-free simulation techniques, including arbitrary Lagrangian-Eulerian and level-set simulations of laser melt pools, phase-field simulations with free energies provided through neural networks, and metallic nuclear fuel simulations that require inner Newton loop calculation of nonlinear material properties.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Differentiable Simulation of a Liquid Argon Time Projection Chamber

Liquid argon time projection chambers (LArTPCs) are widely used in particle detection for their tracking and calorimetric capabilities. The particle physics community actively builds and improves high-quality simulators for such detectors in order to develop physics analyses in a realistic setting. The ability of these simulators to mimic real, measured data is limited by the modeling of the physical detectors used for data collection. This modeling can be improved by performing dedicated calibration measurements. Conventional approaches calibrate individual detector parameters or processes one at a time. However, the impact of detector processes is entangled, making this a poor description of the underlying physics. We introduce a differentiable simulator that enables a gradient-based optimization, allowing for the first time a simultaneous calibration of all detector parameters. We describe the procedure of making a differentiable simulator, highlighting the challenges of retaining the physics quality of the standard, non-differentiable version while providing meaningful gradient information. We further discuss the advantages and drawbacks of using our differentiable simulator for calibration. Finally, we provide a starting point for extensions to our approach, including applications of the differentiable simulator to physics analysis pipelines.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Automatic Differentiation of C++ Codes on Emerging Manycore Architectures with Sacado

Automatic differentiation (AD) is a well-known technique for evaluating analytic derivatives of calculations implemented on a computer, with numerous software tools available for incorporating AD technology into complex applications. However, a growing challenge for AD is the efficient differentiation of parallel computations implemented on emerging manycore computing architectures such as multicore CPUs, GPUs, and accelerators as these devices become more pervasive. In this work, we explore forward mode, operator overloading-based differentiation of C++ codes on these architectures using the widely available Sacado AD software package. In particular, we leverage Kokkos, a C++ tool providing APIs for implementing parallel computations that is portable to a wide variety of emerging architectures. Here we describe the challenges that arise when differentiating code for these architectures using Kokkos, and two approaches for overcoming them that ensure optimal memory access patterns as well as expose additional dimensions of fine-grained parallelism in the derivative calculation. We describe the results of several computational experiments that demonstrate the performance of the approach on a few contemporary CPU and GPU architectures. We then conclude with applications of these techniques to the simulation of discretized systems of partial differential equations.

97 MATHEMATICS AND COMPUTING↗

Differentiation of mammalian skeletal muscle cells cultured on microcarrier beads in a rotating cell culture system

The growth and repair of adult skeletal muscle are due in part to activation of muscle precursor cells, commonly known as satellite cells or myoblasts. These cells are responsive to a variety of environmental cues, including mechanical stimuli. The overall goal of the research is to examine the role of mechanical signalling mechanisms in muscle growth and plasticity through utilisation of cell culture systems where other potential signalling pathways (i.e. chemical and electrical stimuli) are controlled. To explore the effects of decreased mechanical loading on muscle differentiation, mammalian myoblasts are cultured in a bioreactor (rotating cell culture system), a model that has been utilised to simulate microgravity. C2C12 murine myoblasts are cultured on microcarrier beads in a bioreactor and followed throughout differentiation as they form a network of multinucleated myotubes. In comparison with three-dimensional control cultures that consist of myoblasts cultured on microcarrier beads in teflon bags, myoblasts cultured in the bioreactor exhibit an attenuation in differentiation. This is demonstrated by reduced immunohistochemical staining for myogenin and alpha-actinin. Western analysis shows a decrease, in bioreactor cultures compared with control cultures, in levels of the contractile proteins myosin (47% decrease, p < 0.01) and tropomyosin (63% decrease, p < 0.01). Hydrodynamic measurements indicate that the decrease in differentiation may be due, at least in part, to fluid stresses acting on the myotubes. In addition, constraints on aggregate size imposed by the action of fluid forces in the bioreactor affect differentiation. These results may have implications for muscle growth and repair during spaceflight.

Non-NASA Center↗

Differential equations from unitarity cuts: nonplanar hexa-box integrals

We compute ϵ-factorized differential equations for all dimensionally-regularized integrals of the nonplanar hexa-box topology, which contribute for instance to 2-loop 5-point QCD amplitudes. A full set of pure integrals is presented. For 5-point planar topologies, Gram determinants which vanish in 4 dimensions are used to build compact expressions for pure integrals. Using unitarity cuts and computational algebraic geometry, we obtain a compact IBP system which can be solved in 8 hours on a single CPU core, overcoming a major bottleneck for deriving the differential equations. Alternatively, assuming prior knowledge of the alphabet of the nonplanar hexa-box, we reconstruct analytic differential equations from 30 numerical phase-space points, making the computation almost trivial with current techniques. We solve the differential equations to obtain the values of the master integrals at the symbol level. Full results for the differential equations and solutions are included as supplementary material.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

pyomo.dae: a modeling and automatic discretization framework for optimization with differential and algebraic equations

We describe pyomo.dae, an open source Python-based modeling framework that enables high-level abstract specification of optimization problems with differential and algebraic equations. The pyomo.dae framework is integrated with the Pyomo open source algebraic modeling language, and is available at http://www.pyomo.org. One key feature of pyomo.dae is that it does not restrict users to standard, predefined forms of differential equations, providing a high degree of modeling flexibility and the ability to express constraints that cannot be easily specified in other modeling frameworks. Other key features of pyomo.dae are the ability to specify optimization problems with high-order differential equations and partial differential equations, defined on restricted domain types, and the ability to automatically transform high-level abstract models into finite-dimensional algebraic problems that can be solved with off-the-shelf solvers. Moreover, pyomo.dae users can leverage existing capabilities of Pyomo to embed differential equation models within stochastic and integer programming models and mathematical programs with equilibrium constraint formulations. Collectively, these features enable the exploration of new modeling concepts, discretization schemes, and the benchmarking of state-of-the-art optimization solvers.

97 MATHEMATICS AND COMPUTING↗

Assessing I 2 S-LWR economic competitiveness using systematic differential capital cost evaluation methodology

One of the major factors impeding nuclear power plant (NPP) construction is their economics. In this study, a systematic differential economics evaluation approach was developed through the use of the Code of Accounts guidelines to assess the costs of nuclear power plants. The methodology, entirely based on publicly available data, may serve as a template to evaluate direct costs for reactors of any size and design at any stage of developments. In particular, this approach was used to assess the costs of the Integral Inherently Safe Light Water Reactor (I 2 S-LWR). The I 2 S-LWR is a design concept of a large (~1000 MWe) light water reactor. One of its key design features promoting inherent safety is implementation of an integral primary circuit configuration, which however necessitates a compact design of the core and primary circuit components. Through the methodology here presented, a representative loop PWR design was taken as a reference and the differential cost was estimated for each individual account based on the design difference, or similarity. Cost scaling techniques were applied to the accounts representing systems that differ from the ones of the reference PWR. Cost estimating techniques were used to evaluate cost of innovative components that are not part of standard PWR designs. By evaluating the cost difference of the I 2 S-LWR from the standard PWR, rather than the absolute cost, the uncertainty in the estimate is reduced. A similar approach was used by ORNL to estimate the cost of a Fluoride-salt High-temperature Reactor (FHR). A traditional four-loop PWR plant with a core thermal power of 3417 MWth (1144 MWe) was selected as the reference. Costs for that plant were prepared in 1978 by the Department of Energy (DOE) Energy Economics Data Base (EEDB), averaging actual cost incurred in the construction of several nuclear power plants (NPP), itemized with a great level of detail according to the Code of Accounts. This best estimate costs are denoted PWR12-BE. For each account, the cost of equipment, site labor and site material is provided. Industry experts at Westinghouse Electric Company performed a “sanity check” of the cost items, adjusting the cost of several items to match the current market and supply chain data. The detailed cost assessment of I 2 S-LWR was performed, systematically analyzing cost for each account, and applying the differential economics approach. First, Relative importance of each account, i.e., its contribution to the total cost was established, to help focus analysis on the most significant contributors. Moreover, the accounts describing components that are different than that of the PWR12-BE were identified. The integral configuration of the reactor has important implications on the cost of the reactor plant equipment (accounts 22x). Turbine generator equipment (Accounts 23x) is not believed to be much different than that of the reference design. I 2 S-LWR structures (Accounts 21x) mainly differ from that of a standard LWR as several buildings (containment building, shield building, annex building, waste processing building, fuel storage building) are integrated into a single building (nuclear island). Yardwork has a higher cost for the I 2 S-LWR, as the NI is partially below grade. On the other hand, due to its compact Nuclear Island footprint, I 2 S-LWR facilitates (and includes in its reference version) the use of seismic isolators, which contribute to reducing the direct cost. The total capital investment cost (TCIC), on the $/kW basis, of I 2 S-LWR is 5.84% lower than that of PWR12-BE, in spite of the lower power output of I 2 S-LWR. However, for the Western US (0.7 g), benefits of the seismic isolation are more pronounced, and the I 2 S-LWR total capital investment cost is 13.02% lower than that of PWR12-BE. If the I 2 S-LWR is compared to a PWR10-BE (traditional loop design, but scaled to the same power level as I 2 S-LWR), the savings are even higher, in the range 11.12%–17.89%. The analysis indicates that I 2 S-LWR has potential to offer an economically attractive design, with TCIC lower than that of a nuclear power plant based on a traditional loop PWR design. In other words, I 2 S-LWR design offers significantly enhanced safety, while at the same time improving economics. The differential economics approach developed in this paper can be used in identifying changes in cost of key components in order to improve the economics of a nuclear reactor design. The method can also help compare the economics of advanced Generation IV reactors and innovative water-cooled SMR (Small Modular Reactors) with respect to standard LWR technologies. In summary, the differential economics approach and can be used as a tool capable of helping stakeholder decisions.

Economic↗

Kruppel-like factor 4 (KLF-4) plays a crucial role in simvastatin (SVT)-induced differentiation of rabbit articular chondrocytes

Highlights: • SVT was shown to exhibit a protective effect on chondrocytes. • KLF-4 regulates the SVT-mediated differentiation of chondrocytes. • KLF-4 plays critical role in SVT-mediated chondrocyte differentiation. Simvastatin is a cholesterol-lowing reagent that is derived synthetically from the fermentation of Aspergillus terreus. Recently, SVT has been shown to possess a protective effect of chondrocytes. Kruppel-like factor 4 (KLF-4) is a zinc finger transcription factor that plays crucial roles during the development and maintenance of multiple organs. However, the roles of KLF-4 in chondrocytes have not been well unknown. Here, we investigated whether KLF-4 regulates SVT-caused differentiated phenotype of chondrocytes. A KLF-4 cDNA or KLF-4 siRNA was transfected into SVT-treated chondrocytes. Western blot analysis, RT-PCR and immunofluorescence staining analyzed expression of type II collagen and SOX-9, marker proteins of differentiation. The results showed overexpression of KLF-4 accelerates SVT-induced type II collagen expression, as determined by western blot analysis and causes sulfated-proteoglycan synthesis, as detected by Alcian blue staining. RT-PCR revealed that ectopic expression of KLF-4 induces SVT-caused SOX-9, a transcription factor of type II collagen, expression. Transfection of KLF-4 siRNA reversed SVT-caused type II collagen and SOX-9 expression and inhibited SVT-induced sulfated proteoglycan production. This study indicates that KLF-4 plays critical role in SVT-caused chondrocytes differentiation.

60 APPLIED LIFE SCIENCES↗

Fibromodulin modulates myoblast differentiation by controlling calcium channel

Fibromodulin (FMOD) is a proteoglycan present in extracellular matrix (ECM). Based on our previous findings that FMOD controls myoblast differentiation by regulating the gene expressions of collagen type I alpha 1 (COL1α1) and integral membrane protein 2 A (Itm2a), we undertook this study to investigate relationships between FMOD and calcium channels and to understand further the mechanism by which they control myoblast differentiation. Gene expression studies and luciferase reporter assays showed FMOD affected calcium channel gene expressions by regulating calcium channel gene promoter, and patch-clamp experiments showed both L- and T-type calcium channel currents were almost undetectable in FMOD knocked down cells. In addition, gene knock-down studies demonstrated the COL1α1 and Itm2a genes both regulate the expressions of calcium channel genes. Studies using a cardiotoxin-induced mouse muscle injury model demonstrated calcium channels play important roles in the regeneration of muscle tissue, possibly by promoting the differentiation of muscle stem cells (MSCs). Summarizing, the study demonstrates ECM components secreted by myoblasts during differentiation provide an essential environment for muscle differentiation and regeneration.

60 APPLIED LIFE SCIENCES↗

Leonurine hydrochloride promotes osteogenic differentiation and increases osteoblastic bone formation in ovariectomized mice by Wnt/β-catenin pathway

Highlights: • Leonurine hydrochloride promotes osteogenic differentiation of osteoblasts in vitro. • Wnt/β-catenin pathway acts as an important role in the osteogenic differentiation affected by Leonurine hydrochloride. • Leonurine hydrochloride alleviate the effect of osteoporosis by acclerating the bone formation. • Bone mineral density and micro-structures are improved by the treatment of Leonurine hydrochloride. Leonurine hydrochloride (LH) is a synthetic chemical compound derived from leonurine that can be extracted from Leonurus sibiricus and possesses antioxidant, anti-apoptosis, and neuroprotective activities. In previous studies, LH has been demonstrated to attenuate osteoclast activity and prevent bone loss. However, it is unknown whether LH accelerates bone formation and promotes osteogenic differentiation. We systematically examined the effects of LH on ovariectomized-induced osteoporotic mice and the MC3T3-E1 osteoblastic cell line. The results revealed that LH enhanced differentiation of MC3T3-E1 cells, with a dose-dependent increase in alkaline phosphatase (ALP) activity. Moreover, LH upregulated osteogenesis-related gene expression, including osterix, alpha 1 type 1 collagen, runt-related transcription factor 2 (Runx2) and ALP, as shown by quantitative reverse transcription-polymerase chain reaction analysis. At the same time, elevated expression of low-density lipoprotein receptor-related protein 5 and β-catenin mRNA was detected in the Wnt/β-catenin pathway. A western blot analysis revealed that LH dose-dependently increased the expression of Runx2 and β-catenin, and promoted phosphorylation of glycogen synthase kinase-3β in vitro. The in vivo results showed that administering LH (15 mg/kg/d) for 8 weeks alleviated destruction of the trabecular microstructure caused by osteoporosis. LH increased the bone mineral density and trabecular number, decreased trabecular separation according to a micro-computed tomography scan. In addition, LH enhanced the expression of β-catenin and Runx2 in vivo. In conclusion, LH promoted osteogenic differentiation and bone formation in vivo and in vitro, which alleviated osteoporosis through activation of the Wnt/β-catenin pathway.

60 APPLIED LIFE SCIENCES↗

Loss of trefoil factor 1 inhibits biliary regeneration but accelerates the hepatic differentiation of progenitor cells in mice

Highlights: • In models of hepatic injury, the effect of TFF1-deficiency is investigated. • The TFF1-deficiency result in the impaired regeneration of the bile duct. • On the other hand, the differentiation of HPCs into hepatocytes is accelerated. • Hepatic and biliary regeneration depends on the TFF1 protein in injured liver. Although the regeneration of the adult liver depends on hepatic progenitor cells (HPCs), many uncertainties regarding hepatic regeneration in the injured liver remain. Trefoil factor family 1 (TFF1), a secretory protein predominantly expressed in the gastrointestinal tract, is responsible for mucosal restitution. Here, we investigated the role of TFF1 in liver regeneration using a mouse model of hepatic injury (choline-deficient ethionine-supplemented diet and carbon tetrachloride administration) and genetically engineered mice (TFF1 knockout (TFF1−/−)). Immunohistochemistry analysis of human liver samples revealed TFF1 expression in the hepatocytes close to ductular reaction and the regenerating biliary epithelium in injured liver. The number of cytokeratin 19 (CK19)-positive bile ducts was significantly decreased in the TFF1−/− mice after liver injury. Notch pathway in the TFF1−/− mice was also downregulated. HPCs in the control mice differentiated into biliary cells (CK19{sup +}/SRY HMG box 9 (SOX9){sup +}) more frequently. In contrast, HPCs in the TFF1−/− mice more frequently differentiated into a hepatic lineage (alpha fetoprotein{sup +}/SOX9{sup +}) after acute liver damage. Hepatocyte proliferation was upregulated, and the liver weight was increased in TFF1−/− mice in response to chronic liver damage. Thus, TFF1 is responsible for liver regeneration after liver injury by promoting HPC differentiation into a biliary lineage and inhibiting HPC differentiation into a hepatic lineage.

60 APPLIED LIFE SCIENCES↗

Insulin-like growth factor binding Protein-3 suppresses osteoblast differentiation via bone morphogenetic protein-2

Highlights: • The maintenance of bone mass after induction of bone formation is difficult. • Insulin-like growth factor (IGF)-1 regulates bone mass including osteogenesis. • IGF-binding proteins (IGFBPs) are important for IGF-1 stability. • Bone morphogenetic protein-2 (BMP-2) induces osteoblast differentiation. • IGFBP-3 counteracts the effect of BMP-2 and suppresses bone formation. Bone augmentation therapy is used in dental implantation. While techniques to induce bone formation are generally successful, the maintenance of bone mass is more difficult. Therefore, it is important to understand the mechanisms that regulate this process. Insulin-like growth factor-1 (IGF-1) is one of the most abundant growth factors that regulate bone mass, promote osteoblast differentiation, and accelerate bone formation. The activity of IGF-1 is regulated by IGF-binding proteins (IGFBPs). IGFBP-3 forms a ternary complex with IGF-1, extending its half-life in the circulating system. Therefore, IGFBP-3 acts as a stabilizer and transporter of IGF-1. Recent studies reported new IGF-1-independent functions of IGFBP-3 related with bone metabolism. In this study, we investigated the function of IGFBP-3 in osteoblast differentiation. Our results showed that IGFBP-3 decreases the expression of osteoblast differentiation markers, whose expression is enhanced by bone morphogenetic protein-2 (BMP-2). IGFBP-3 also reduced BMP-2 effect on ALP activity and mineral nodule formation. In addition, IGFBP-3 suppresses the activity of the Smad Binding Element (SBE) reporter, induced by BMP-2 signaling. These results suggest that IGFBP-3 inhibits osteoblast differentiation through the BMP-2 signal pathway, and that IGFBP-3 might play a role in bone mass maintenance in an IGF-1-dependent and -independent manner.

60 APPLIED LIFE SCIENCES↗

Behavior of the Mo, Tl, and U isotope systems during differentiation in the Kilauea Iki lava lake

Stable molybdenum (Mo), thallium (Tl), and uranium (U) isotope ratios were determined in a suite of samples from the 1959 Kilauea eruption and from Kilauea Iki lava lake with the aim of understanding the effects of igneous differentiation on these isotope systems. The samples range from olivine cumulate with MgO up to 27% to internal differentiates with MgO less than 3%, representing a tholeiitic differentiation series. Molybdenum, Tl, and U behave incompatibly during differentiation, and Mo and U isotope ratios do not systematically vary amongst the different samples. δ 98 Mo values range from -0.17 to -0.31‰ and δ 238 U values range from -0.20 to -0.38‰. Most individual analyses for both isotope systems overlap within measurement uncertainty (± ~0.7 and ~ 0.6, respectively). Mean δ 98 Mo and δ238U values are -0.22 ± 0.08‰ (2σ) and - 0.29 ± 0.09‰ (2σ), respectively, which overlap with Pacific mid ocean ridge basalt (MORB). In contrast, Tl isotopes show small but resolvable variations, with ε 205 Tl ranging from +1.20 to -1.38. The most negative ε 205 Tl values are confined to some of the lowest [Tl] samples, but the ε 205 Tl values do not otherwise vary smoothly with MgO or [Tl]. Possible mechanisms for thallium isotope fractionation are considered (e.g., degassing, water leaching, sulfide fractionation) but none are found to be satisfactory. Overall, the lack of resolvable variation in the Mo and U isotope systems and the small magnitude of heterogeneity in the Tl isotope system indicate that differentiation in tholeiitic systems is unlikely to be a major contributor to global variation in these isotope systems.

58 GEOSCIENCES↗

On differentiable local bounds preserving stabilization for Euler equations

This work presents the design of nonlinear stabilization techniques for the finite element discretization of Euler equations in both steady and transient form. Implicit time integration is used in the case of the transient form. A differentiable local bounds preserving method has been developed, which combines a Rusanov artificial diffusion operator and a differentiable shock detector. Nonlinear stabilization schemes are usually stiff and highly nonlinear. This issue is mitigated by the differentiability properties of the proposed method. Moreover, in order to further improve the nonlinear convergence, we also propose a continuation method for a subset of the stabilization parameters. The resulting method has been successfully applied to steady and transient problems with complex shock patterns. Numerical experiments show that it is able to provide sharp and well resolved shocks. Furthermore, the importance of the differentiability is assessed by comparing the new scheme with its non-differentiable counterpart. Numerical experiments suggest that, for up to moderate nonlinear tolerances, the method exhibits improved robustness and nonlinear convergence behavior for steady problems. Additionally, in the case of transient problem, we also observe a reduction in the computational cost.

42 ENGINEERING↗