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1

Avdic, Selmir, Brian P. McSharry, Megan Steain, Emma Poole, John Sinclair, Allison Abendroth, and Barry Slobedman. "Human Cytomegalovirus-Encoded Human Interleukin-10 (IL-10) Homolog Amplifies Its Immunomodulatory Potential by Upregulating Human IL-10 in Monocytes." Journal of Virology 90, no. 8 (January 20, 2016): 3819–27. http://dx.doi.org/10.1128/jvi.03066-15.

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ABSTRACTThe human cytomegalovirus (HCMV) gene UL111A encodes cytomegalovirus-encoded human interleukin-10 (cmvIL-10), a homolog of the potent immunomodulatory cytokine human interleukin 10 (hIL-10). This viral homolog exhibits a range of immunomodulatory functions, including suppression of proinflammatory cytokine production and dendritic cell (DC) maturation, as well as inhibition of major histocompatibility complex (MHC) class I and class II. Here, we present data showing that cmvIL-10 upregulates hIL-10, and we identify CD14+monocytes and monocyte-derived macrophages and DCs as major sources of hIL-10 secretion in response to cmvIL-10. Monocyte activation was not a prerequisite for cmvIL-10-mediated upregulation of hIL-10, which was dose dependent and controlled at the transcriptional level. Furthermore, cmvIL-10 upregulated expression of tumor progression locus 2 (TPL2), which is a regulator of the positive hIL-10 feedback loop, whereas expression of a negative regulator of the hIL-10 feedback loop, dual-specificity phosphatase 1 (DUSP1), remained unchanged. Engagement of the hIL-10 receptor (hIL-10R) by cmvIL-10 led to upregulation of heme oxygenase 1 (HO-1), an enzyme linked with suppression of inflammatory responses, and this upregulation was required for cmvIL-10-mediated upregulation of hIL-10. We also demonstrate an important role for both phosphatidylinositol 3-kinase (PI3K) and STAT3 in the upregulation of HO-1 and hIL-10 by cmvIL-10. In addition to upregulating hIL-10, cmvIL-10 could exert a direct immunomodulatory function, as demonstrated by its capacity to upregulate expression of cell surface CD163 when hIL-10 was neutralized. This study identifies a mechanistic basis for cmvIL-10 function, including the capacity of this viral cytokine to potentially amplify its immunosuppressive impact by upregulating hIL-10 expression.IMPORTANCEHuman cytomegalovirus (HCMV) is a large, double-stranded DNA virus that causes significant human disease, particularly in the congenital setting and in solid-organ and hematopoietic stem cell transplant patients. A prominent feature of HCMV is the wide range of viral gene products that it encodes which function to modulate host defenses. One of these is cmvIL-10, which is a homolog of the potent immunomodulatory cytokine human interleukin 10 (hIL-10). In this study, we report that, in addition to exerting a direct biological impact, cmvIL-10 upregulates the expression of hIL-10 by primary blood-derived monocytes and that it does so by modulating existing cellular pathways. This capacity of cmvIL-10 to upregulate hIL-10 represents a mechanism by which HCMV may amplify its immunomodulatory impact during infection.
2

Insam, Christina, Lisa-Marie Ballat, Felix Lorenz, and Daniel Jean Rixen. "Hardware-in-the-Loop Test of a Prosthetic Foot." Applied Sciences 11, no. 20 (October 13, 2021): 9492. http://dx.doi.org/10.3390/app11209492.

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For a targeted development process of foot prostheses, a profound understanding of the dynamic interaction between humans and prostheses is necessary. In engineering, an often employed method to investigate the dynamics of mechanical systems is Hardware-in-the-Loop (HiL). This study conducted a fundamental investigation of whether HiL could be an applicable method to study the dynamics of an amputee wearing a prosthesis. For this purpose, a suitable HiL setup is presented and the first-ever HiL test of a prosthetic foot performed. In this setup, the prosthetic foot was tested on the test bench and coupled in real-time to a cosimulation of the amputee. The amputee was modeled based on the Virtual Pivot Point (VPP) model, and one stride was performed. The Center of Mass (CoM) trajectory, the Ground Reaction Forces (GRFs), and the hip torque were qualitatively analyzed. The results revealed that the basic gait characteristics of the VPP model can be replicated in the HiL test. Still, there were several limitations in the presented HiL setup, such as the limited actuator performance. The results implied that HiL may be a suitable method for testing foot prostheses. Future work will therefore investigate whether changes in the gait pattern can be observed by using different foot prostheses in the HiL test.
3

Damacharla, Praveen, Parashar Dhakal, Jyothi Priyanka Bandreddi, Ahmad Y. Javaid, Jennie J. Gallimore, Colin Elkin, and Vijay K. Devabhaktuni. "Novel Human-in-the-Loop (HIL) Simulation Method to Study Synthetic Agents and Standardize Human–Machine Teams (HMT)." Applied Sciences 10, no. 23 (November 25, 2020): 8390. http://dx.doi.org/10.3390/app10238390.

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This work presents a multi-year study conducted at the University of Toledo, aimed at improving human–machine teaming (HMT) methods and technologies. With the advent of artificial intelligence (AI) in 21st-century machines, collaboration between humans and machines has become highly complicated for real-time applications. The penetration of intelligent and synthetic assistants (IA/SA) in virtually every field has opened up a path to the area of HMT. When it comes to crucial tasks such as patient treatment/care, industrial production, and defense, the use of non-standardized HMT technologies may pose a risk to human lives and cost billions of taxpayer dollars. A thorough literature survey revealed that there are not many established standards or benchmarks for HMT. In this paper, we propose a method to design an HMT based on a generalized architecture. This design includes the development of an intelligent collaborative system and the human team. Followed by the identification of processes and metrics to test and validate the proposed model, we present a novel human-in-the-loop (HIL) simulation method. The effectiveness of this method is demonstrated using two controlled HMT scenarios: Emergency care provider (ECP) training and patient treatment by an experienced medic. Both scenarios include humans processing visual data and performing actions that represent real-world applications while responding to a Voice-Based Synthetic Assistant (VBSA) as a collaborator that keeps track of actions. The impact of various machines, humans, and HMT parameters is presented from the perspective of performance, rules, roles, and operational limitations. The proposed HIL method was found to assist in standardization studies in the pursuit of HMT benchmarking for critical applications. Finally, we present guidelines for designing and benchmarking HMTs based on the case studies’ results analysis.
4

Ferraresi, Carlo, Daniela Maffiodo, Walter Franco, Giovanni Gerardo Muscolo, Carlo De Benedictis, Maria Paterna, Oliviero Walter Pica, et al. "Hardware-In-the-Loop Equipment for the Development of an Automatic Perturbator for Clinical Evaluation of Human Balance Control." Applied Sciences 10, no. 24 (December 12, 2020): 8886. http://dx.doi.org/10.3390/app10248886.

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Nowadays, increasing attention is being paid to techniques aimed at assessing a subject’s ability to maintain or regain control of balance, thus reducing the risk of falls. To this end, posturographic analyses are performed in different clinical settings, both in unperturbed and perturbed conditions. This article presents a new Hardware-In-the-Loop (HIL) equipment designed for the development of an automatic perturbator for postural control analysis, capable of providing controlled mechanical stimulation by means of an impulsive force exerted on a given point of the body. The experimental equipment presented here includes the perturbator and emulates its interaction with both the subject’s body and the operator performing the test. The development of the perturbator and of the entire HIL equipment is described, including component selection, modeling of the entire system, and experimentally verified simulations used to study and define the most appropriate control laws.
5

Amit, Inbar, Itay Levin, Timothy Wyant, Natalie Levitin, Reut Barak, May Ben-Mayor, Olga Bluvshtein, et al. "704 The computationally designed human antibody, AU-007, mediates human immune activation by endogenous IL-2, while uniquely breaking the IL-2 auto-inhibitory loop and preventing Treg expansion." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A732—A734. http://dx.doi.org/10.1136/jitc-2021-sitc2021.704.

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BackgroundIL-2 binds two forms of IL-2 receptor: a high affinity trimeric receptor composed of CD25, CD122, and CD132, and a low affinity dimeric receptor composed of CD122 and CD132. Binding to the dimeric receptors, expressed on effector cells, causes expansion of the effector arm of the immune system including CD8 T-cells, NK-cells and NKT-cells. Binding to the trimeric receptor, expressed on Tregs as well as on pulmonary and vascular epithelium, results in expansion of Treg cells and Vascular Leak Syndrome, both are undesired outcomes of high-dose recombinant IL-2 (Aldesleukin), approved for treatment of Melanoma and Renal-Cell-Carcinoma.MethodsFlow-cytometry analysis of immune-cell populations of C57BL/6 mice and hPBMCs. Tumor-Growth-Index of murine cancer models.ResultsAU-007, is a computationally designed human antibody that bind the CD25-binding portion on IL-2, preventing binding of IL-2 to the trimeric receptor, but not the dimeric receptor. This leads to immune effector activation while also preventing the Treg expansion via the autoinhibitory loop caused by endogenous IL-2 secreted from activated T effector cells (figure 1). AU-007 binds human IL-2 with picomolar affinity and has excellent biophysical properties with low potential for anti-drug immunogenicity (figure 2). Administration of an AU-007/low dose hIL-2 complex to non-tumor bearing C57BL/6 mice promoted proliferation of effector cells with no effect on Tregs (figure 3). Additionally, an AU-007/low dose hIL-2 complex was highly effective in inhibiting tumor progression in a syngeneic B16F10 melanoma model (figure 4). pSTAT5 analysis of hPBMCs incubated with AU-007 and hIL-2 demonstrated activation of the effector cells and inhibition of Tregs expansion (figure 5). hPBMCs activated with anti-CD3/anti-CD28 and treated with either AU-007 or an isotype control antibody but without exogenous IL-2, showed expansion of effector cells. However, while the isotype control antibody expanded also Tregs , AU-007 inhibited Tregs proliferation, indicating that AU-007 captures endogenous IL-2 and prevents the Treg expansion autoinhibitory loop caused by endogenous IL-2 secreted from activated T effector cells (figure 6).Additionally, following establishment of the IL-2 auto-secretion feedback loop in mice genetically engineered to express hIL-2 instead of murine IL-2, AU-007 treatment significantly inhibited MC38 colorectal-tumor growth for twelve days, in a manner comparable to treatment with anti-PD1 (figure 7).ConclusionsAU-007 is a human antibody that blocks the CD25-binding epitope on IL-2. It redirects endogenous IL-2 to promote effector cell expansion while simultaneously blocking the Treg expansion autoinhibitory loop, indicating its unique therapeutic profile and high potential as a novel cancer treatment. AU-007 is expected to enter clinical testing in 2021.Abstract 704 Figure 1Schematic representation of IL-2 mechanism of action and its dual role in controlling immune response. IL-2 structure consists of three binding epitope sites that interact with different forms of IL-2-R complexes with different affinities (Left Panel). IL-2R complexes expressed on different cell populations and their different affinities to IL-2 allow immunosuppression under conditions of low local concentrations of IL-2 and immune stimulation when IL-2 local concentration rises (middle panel). Au-007 utilize autocrine human IL-2 MOA to promote immune stimulation. Targeting IL-2 to different cell populations can be used to modulate the immune response toward towards immune activation. An anti-human IL-2 antibody tumor clearance while reducing IL-2's undesired interactions with endothelial CD25 expressing cells preventing IL-2 induced pulmonary edema and vascular leaking.Abstract 704 Figure 2Au-007 bind human IL-2 with high affinity and inhibits the binding to CD25 while preserving the binding to CD122. Affinity and binding site are demonstrated using Surface Plasmon Resonance. Au-007 was captured on CM5 chip and soluble hIL-2 was injected, forming a complex. Subsequently, soluble CD25 was injected followed by injection of soluble CD122 (A). SPR trace of complex formation of Ab/IL-2/IL-2R arrows indicate where Au-007 (17.069), hIL-2, CD25 and CD122 were injected (B). SPR trace and calculated binding kinetics of chip bound Au-007 with hIL-2 serving as analyte (C). Biophysical profile of Au-007. Au-007 was subjected to five freeze thaw cycles, agitation for 3 days and incubation at 40°C for 1 week. Post treatment Au-007 integrity and indicated biophysical properties were measured (D).Abstract 704 Figure 3Au-007 demonstrated in-vivo potent immune stimulating effects in a dose depended manner, with no observed effect on Tregs. C57BL/6 healthy mice were administered daily with Au-007/hIL-2 complex for four days. On day five splenocytes were isolated and immune cells populations were analyzed using flow cytometry. (A) Dosing regimen outline. (B–E) Mean values of immune cells calculated as a percentage from parent population of each experimental group (n=6 per group)Abstract 704 Figure 4Au-007 inhibits tumor growth in an I/O resistant tumor model with a tolerable profile. C57BL/6 healthy mice were inoculated with B16F10 melanoma tumor cells (day 0), at day 5 mice were randomized to experimental groups (n=10 per group) and administered daily, with single injection per day of Ab/hIL-2 mix (20 ug/1 ug respectively) or with PBS for four days. From the end of schedule administration at day 8 until experiment endpoint, mice were monitored daily for tumor volume (A) and for mean percent of body weight change for each experimental group (B).Abstract 704 Figure 5AU-007 inhibits the effect of IL-2 on Tregs while preserving its effect on Teffs and NKs. (A and B) Phosphorylated STAT5 levels of human immune cell subsets responding to various concentrations of hIL-2 with and without 200 nM AU-007. Total naïve hPBMC culture were incubated with increasing doses of hIL-2 or with increasing doses of hIL-2 + 200nM AU-007 for 15 min. Immune cells subpopulations were analyzed by flow cytometry, gating was defined based on FMOs. (C–F) Phosphorylated STAT5 levels of human immune cell subsets responding to titrated AU-007 or isotype control. Total naïve hPBMC culture were incubated with hIL-2 and with increasing doses of indicated antibody for 15 min. Data presented is an average of 3 biological repeats from 3 human PBMC donors.Abstract 704 Figure 6Au-007 can rely on endogenous IL-2 to break auto-inhibitory loop in human PBMCs. Total hPBMCs were stimulated for 24h with anti-CD3/anti-CD28 (stimulation only, green) or stimulated with anti-CD3/anti-CD28 in the presence of: 200 nM of Au-007 mAb (red) or with 200 nM of isotype control mAb (blue). No exogenous IL-2 was added. Immune cells subpopulations were analyzed by flow cytometry. Percentage of immune cell sub-populations demonstrate exclusive inhibition of Tregs (A–E). Au-007 downregulate the suppressive markers of CD4+ regulatory Tregs from panel A, as defined by significant reduction in MFI of CD25 and FoxP3 (F and G). Gating was defined based on FMOs. Data presented is an average of 3 biological repeats from 3 human PBMC donors.Abstract 704 Figure 7Au-007 captures endogenous hIL-2 and inhibits tumor growth in colorectal cancer model (MC38). Genetically modified C57BL/6 mice, engineered to express human IL-2 in the background of complete knock-out of mouse IL-2, were inoculated with MC38 colorectal tumor cells. All animals treated with Au-007 showed significant inhibition in tumor growth with no observed significant adverse effects. (A) Administration outline: PBS (black), anti-mouse-PD-1 antibody (yellow), Au-007 pre-complexed with low dose IL-2 (blue) and Au-007 alone every three days followed with a single immune kick start with IL-2 (green, IL-2 single dose is marked in red). (B) Tumor growth progression of the four groups treated. (C) Percent of body weight changes per treatment.
6

Chen, Daming, and John Nicholas. "Structural Requirements for gp80 Independence of Human Herpesvirus 8 Interleukin-6 (vIL-6) and Evidence for gp80 Stabilization of gp130 Signaling Complexes Inducedby vIL-6." Journal of Virology 80, no. 19 (October 1, 2006): 9811–21. http://dx.doi.org/10.1128/jvi.00872-06.

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ABSTRACT Human herpesvirus 8 interleukin-6 (vIL-6) displays 25% amino acid identity with human IL-6 (hIL-6) and shares an overall four-helix-bundle structure and gp130-mediated STAT/mitogen-activated protein kinase signaling with its cellular counterpart. However, vIL-6 is distinct in that it can signal through gp130 alone, in the absence of the nonsignaling gp80 α-subunit of the IL-6 receptor. To investigate the structural requirements for gp80 independence of vIL-6, a series of expression vectors encoding vIL-6/hIL-6 chimeric and site-mutated IL-6 proteins was generated. The replacement of hIL-6 residues with three vIL-6-specific tryptophans implicated in gp80 independence from crystallographic studies or the A and C helices containing these residues did not confer gp80 independence to hIL-6. The N- and C-terminal regions of vIL-6 could be substituted with hIL-6 sequences with the retention of gp80-independent signaling, but substitutions of other regions of vIL-6 (helix A, A/B loop, helix B, helix C, and proximal half of helix D) with equivalent sequences of hIL-6 abolished gp80 independence. Interestingly, the B helix of vIL-6 was absolutely required for gp80 independence, despite the fact that this region contains no receptor-binding residues. Point mutational analysis of helix C, which contains residues involved in physical and functional interactions with gp130 domains 2 and 3 (cytokine-binding homology region), identified a variant, VI120EE, that was able to signal and dimerize gp130 only in the presence of gp80. gp80 was also found to stabilize gp130:g130 dimers induced by a distal D helix variant of vIL-6 that was nonetheless able to signal independently of gp80. Together, our data reveal the crucial importance of overall vIL-6 structure and conformation for gp80-independent signaling and provide functional and physical evidence of the stabilization of vIL-6-induced gp130 signaling complexes by gp80.
7

Li, Hong, та John Nicholas. "Identification of Amino Acid Residues of gp130 Signal Transducer and gp80 α Receptor Subunit That Are Involved in Ligand Binding and Signaling by Human Herpesvirus 8-Encoded Interleukin-6". Journal of Virology 76, № 11 (1 червня 2002): 5627–36. http://dx.doi.org/10.1128/jvi.76.11.5627-5636.2002.

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ABSTRACT Human herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the gp130 signal transducer but is not dependent on the IL-6 receptor α subunit (IL-6R, gp80) that is required for signaling by endogenous IL-6 proteins; however, IL-6R can enhance vIL-6 activity and can enable signaling through a gp130 variant, gp130.PM5, that is itself unable to support vIL-6 signaling. These findings suggest that the vIL-6-gp130 interactions are qualitatively different from those of human IL-6 (hIL-6) and that vIL-6 signaling may be more promiscuous than that of hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To examine the receptor binding requirements of vIL-6, we have undertaken mutational analyses of regions of gp130 and IL-6R potentially involved in interactions with ligand or in functional complex formation and used these variants in functional, ligand-binding, and receptor dimerization assays. The data presented identify positions within two interstrand loops of the gp130 cytokine-receptor homology domain that are important for vIL-6 signaling and vIL-6-induced receptor dimerization and show that vIL-6, like hIL-6, can form complexes with IL-6R and gp130 but that the roles of putative cytokine-binding residues of IL-6R in ligand-induced functional complex formation are qualitatively different in the case of vIL-6 and hIL-6.
8

Aoki, Yoshiyasu, Masashi Narazaki, Tadamitsu Kishimoto, and Giovanna Tosato. "Receptor engagement by viral interleukin-6 encoded by Kaposi sarcoma–associated herpesvirus." Blood 98, no. 10 (November 15, 2001): 3042–49. http://dx.doi.org/10.1182/blood.v98.10.3042.

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Abstract Receptor usage by viral interleukin-6 (vIL-6), a virokine encoded by Kaposi sarcoma– associated herpesvirus, is an issue of controversy. Recently, the crystal structure of vIL-6 identified vIL-6 sites II and III as directly binding to glycoprotein (gp)130, the common signal transducer for the IL-6 family of cytokines. Site I of vIL-6, however, comprising the outward helical face of vIL-6, where human IL-6 (hIL-6) would interact with the specific α-chain IL-6 receptor (IL-6R), is accessible and not occupied by gp130. This study examined whether this unused vIL-6 surface is available for IL-6R binding. By enzyme-linked immunosorbent assay, vIL-6 bound to soluble gp130 (sgp130) but not to soluble IL-6R (sIL-6R). Using plasmon surface resonance, vIL-6 bound to sgp130 with a dissociation constant of 2.5 μM, corresponding to 1000-fold lower affinity than that of hIL-6/sIL-6R complex for gp130. sIL-6R neither bound to vIL-6 nor affected vIL-6 binding to gp130. In bioassays, vIL-6 activity was neutralized by 4 monoclonal antibodies (mAbs) recognizing a domain within vIL-6 site I, mapped to the C-terminal part of the AB-loop and the beginning of helix B. The homologous region in hIL-6 participates in site I binding to IL-6R. In addition, binding of vIL-6 to sgp130 was interfered with specifically by the 4 neutralizing anti–vIL-6 mAbs. Based on the vIL-6 crystal structure, the vIL-6 neutralizing mAbs map outside the binding interface to gp130, suggesting that they either produce allosteric changes or block necessary conformational changes in vIL-6 preceding its binding to gp130. These results document that vIL-6 does not bind IL-6R and suggest that conformational change may be critical to vIL-6 function.
9

Ortiz, Jessica S., Guillermo Palacios-Navarro, Víctor H. Andaluz, and Bryan S. Guevara. "Virtual Reality-Based Framework to Simulate Control Algorithms for Robotic Assistance and Rehabilitation Tasks through a Standing Wheelchair." Sensors 21, no. 15 (July 27, 2021): 5083. http://dx.doi.org/10.3390/s21155083.

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The implementation of control algorithms oriented to robotic assistance and rehabilitation tasks for people with motor disabilities has been of increasing interest in recent years. However, practical implementation cannot be carried out unless one has the real robotic system availability. To overcome this drawback, this article presents the development of an interactive virtual reality (VR)-based framework that allows one to simulate the execution of rehabilitation tasks and robotic assistance through a robotic standing wheelchair. The virtual environment developed considers the kinematic and dynamic model of the standing human–wheelchair system with a displaced center of mass, since it can be displaced for different reasons, e.g.,: bad posture, limb amputations, obesity, etc. The standing wheelchair autonomous control scheme has been implemented through the Full Simulation (FS) and Hardware in the Loop (HIL) techniques. Finally, the performance of the virtual control schemes has been shown by means of several experiments based on robotic assistance and rehabilitation for people with motor disabilities.
10

Bodén, Anna C. S., Jesper Molin, Stina Garvin, Rebecca A. West, Claes Lundström, and Darren Treanor. "The human‐in‐the‐loop: an evaluation of pathologists’ interaction with artificial intelligence in clinical practice." Histopathology 79, no. 2 (May 30, 2021): 210–18. http://dx.doi.org/10.1111/his.14356.

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11

Yazar, Ozan, Serdar Coskun, Fengqi Zhang, and Lin Li. "A comparative study of energy management systems under connected driving: Cooperative car-following case." Complex Engineering Systems 2 (2022): 7. http://dx.doi.org/10.20517/ces.2022.06.

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In this work, we propose connected energy management systems for a cooperative hybrid electric vehicle (HEV) platoon. To this end, cooperative driving scenarios are established under different car-following behavior models using connected and automated vehicles technology, leading to a cooperative cruise control system (CACC) that explores the energy-saving potentials of HEVs. As a real-time energy management control, an equivalent consumption minimization strategy (ECMS) is utilized, wherein global energy-saving is achieved to promote environment-friendly mobility. The HEVs cooperatively communicate and exchange state information and control decisions with each other by sixth-generation vehicle-to-everything (6G-V2X) communications. In this study, three different car-following behavior models are used: intelligent driver model (IDM), Gazis–Herman–Rothery (GHR) model, and optimal velocity model (OVM). Adopting cooperative driving of six Toyota Prius HEV platoon scenarios, simulations under New European Driving Cycle (NEDC), Worldwide Harmonized Light Vehicle Test Procedure (WLTP), and Highway Fuel Economy Test (HWFET), as well as human-in-the-loop (HIL) experiments, are carried out via MATLAB/Simulink/dSPACE for cooperative HEV platooning control via different car-following-linked-vehicle scenarios. The CACC-ECMS scheme is assessed for HEV energy management via 6G-V2X broadcasting, and it is found that the proposed strategy exhibits improvements in vehicular driving performance. The IDM-based CACC-ECMS is an energy-efficient strategy for the platoon that saves: (i) 8.29% fuel compared to the GHR-based CACC-ECMS and 10.47% fuel compared to the OVM-based CACC-ECMS under NEDC; (ii) 7.47% fuel compared to the GHR-based CACC-ECMS and 11% fuel compared to the OVM-based CACC-ECMS under WLTP; (iii) 3.62% fuel compared to the GHR-based CACC-ECMS and 4.22% fuel compared to the OVM-based CACC-ECMS under HWFET; and (iv) 11.05% fuel compared to the GHR-based CACC-ECMS and 18.26% fuel compared to the OVM-based CACC-ECMS under HIL.
12

Calvani, Maura, Annamaria Rapisarda, Badarch Uranchimeg, Robert H. Shoemaker та Giovanni Melillo. "Hypoxic induction of an HIF-1α–dependent bFGF autocrine loop drives angiogenesis in human endothelial cells". Blood 107, № 7 (1 квітня 2006): 2705–12. http://dx.doi.org/10.1182/blood-2005-09-3541.

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AbstractHypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells, the transcriptional response to oxygen deprivation is largely mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1α and HIF-1β subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF-α subunits in this process are still poorly understood. We show that human umbilical vein endothelial cells (HUVECs) cultured in the absence of growth factors survive and form tubelike structures when cultured under hypoxic, but not normoxic, conditions. HUVECs expressed both HIF-1α and HIF-2α when cultured under hypoxic conditions. Transfection of HIF-1α, but not HIF-2α, siRNA to HUVECs completely abrogated hypoxic induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF, or PDGF-BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF-dependent induction of cord formation under normoxic conditions required HIF-1α activity, which was also essential for hypoxic induction of bFGF mRNA and protein expression. These results uncover the existence of an HIF-1α–bFGF amplification pathway that mediates survival and sprouting of endothelial cells under hypoxic conditions.
13

Neurath, A. R., N. Strick, K. Lin, A. K. Debnath, and S. Jiang. "Tin Protoporphyrin IX Used in Control of Heme Metabolism in Humans Effectively Inhibits HIV-1 Infection." Antiviral Chemistry and Chemotherapy 5, no. 5 (October 1994): 322–30. http://dx.doi.org/10.1177/095632029400500506.

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Recent observations indicated that several porphyrins bound to the V3 loop of the envelope glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) and inhibited infection of cells by HIV-1. The tin derivative of protoporphyrin IX (Sn-PTP-IX) has already been used clinically in humans to suppress hyperbilirubinemia. It was therefore of interest to determine whether Sn-PTP-IX has anti-HIV-1 activity. It is demonstrated here that Sn-PTP-IX effectively inhibited infection by several HIV-1 isolates (HIB, MN, RF, SF-2 and two isolates resistant to azidothymidine). This was surprising, since earlier studies indicated that incorporation of other metals into porphyrins markedly decreased their antiviral activity. Sn-PTP-IX blocked the binding to gp120 of anti-V3-loop-specific antibodies and of monoclonal antibodies specific for the CD4 binding site on gp120. The latter effect appeared to be allosteric and was not observed with a deletion mutant of gp 120 lacking the V3 loop sequence. This suggests that Sn-PTP-IX binds to the V3 loop and distorts the native conformation of the HIV-1 envelope, thereby preventing infection. These results merit the consideration of Sn-PTP-IX as a prophylactic and chemotherapeutic agent against HIV-1.
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Cui, Chun-Ping, Carmen Chak-Lui Wong, Alan Ka-Lun Kai, Daniel Wai-Hung Ho, Eunice Yuen-Ting Lau, Yu-Man Tsui, Lo-Kong Chan та ін. "SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop". Gut 66, № 12 (3 березня 2017): 2149–59. http://dx.doi.org/10.1136/gutjnl-2016-313264.

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ObjectiveWe investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness.DesignHCC cancer stemness was analysed by self-renewal ability, chemoresistance, expression of stemness-related genes and cancer stem cell (CSC) marker-positive cell population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level was examined with quantitative PCR in human paired HCCs. Immunoprecipitation was used to examine the binding of proteins and chromatin immunoprecipitation assay to detect the binding of HIFs with hypoxia response element sequence. In vivo characterisation was performed in immunocompromised mice and stem cell frequency was analysed.ResultsWe showed that hypoxia enhanced the stemness of HCC cells and hepatocarcinogenesis through enhancing HIF-1α deSUMOylation by SENP1 and increasing stabilisation and transcriptional activity of HIF-1α. Furthermore, we demonstrated that SENP1 is a direct target of HIF-1/2α and a previously unrecognised positive feedback loop exists between SENP1 and HIF-1α.ConclusionsTaken together, our findings suggest the significance of this positive feedback loop between HIF-1α and SENP1 in contributing to the increased cancer stemness in HCC and hepatocarcinogenesis under hypoxia. Drugs that specifically target SENP1 may offer a potential novel therapeutic approach for HCC.
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Sandino, Juan, Fernando Vanegas, Frederic Maire, Peter Caccetta, Conrad Sanderson, and Felipe Gonzalez. "UAV Framework for Autonomous Onboard Navigation and People/Object Detection in Cluttered Indoor Environments." Remote Sensing 12, no. 20 (October 16, 2020): 3386. http://dx.doi.org/10.3390/rs12203386.

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Response efforts in emergency applications such as border protection, humanitarian relief and disaster monitoring have improved with the use of Unmanned Aerial Vehicles (UAVs), which provide a flexibly deployed eye in the sky. These efforts have been further improved with advances in autonomous behaviours such as obstacle avoidance, take-off, landing, hovering and waypoint flight modes. However, most UAVs lack autonomous decision making for navigating in complex environments. This limitation creates a reliance on ground control stations to UAVs and, therefore, on their communication systems. The challenge is even more complex in indoor flight operations, where the strength of the Global Navigation Satellite System (GNSS) signals is absent or weak and compromises aircraft behaviour. This paper proposes a UAV framework for autonomous navigation to address uncertainty and partial observability from imperfect sensor readings in cluttered indoor scenarios. The framework design allocates the computing processes onboard the flight controller and companion computer of the UAV, allowing it to explore dangerous indoor areas without the supervision and physical presence of the human operator. The system is illustrated under a Search and Rescue (SAR) scenario to detect and locate victims inside a simulated office building. The navigation problem is modelled as a Partially Observable Markov Decision Process (POMDP) and solved in real time through the Augmented Belief Trees (ABT) algorithm. Data is collected using Hardware in the Loop (HIL) simulations and real flight tests. Experimental results show the robustness of the proposed framework to detect victims at various levels of location uncertainty. The proposed system ensures personal safety by letting the UAV to explore dangerous environments without the intervention of the human operator.
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Feng, Kang, and Kai Cheng Li. "A Hybrid Testing Method to the Application of Test Case Generation of the Simulation of CTCS-3 On-Board Subsystem." Applied Mechanics and Materials 341-342 (July 2013): 984–89. http://dx.doi.org/10.4028/www.scientific.net/amm.341-342.984.

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As an important part of the CTCS-3 train control system, the on-board subsystem is a safety critical system, and it plays an important role in assuring the safety of train. In this essay, we choose a hybrid testing method combined with the advantage of black-box and white-box testing method in the test of the Simulation of on-board subsystem of the CTCS-3 train control system. The main idea is to divide the tested system into several functional parts, and then test them step by step. At last, we use an example to show the advantage of this testing method in reducing the number of test cases. 1 Current situation in the testing of train control system at home and abroad Train control system plays an important role in ensuring the operational safety of the train, At home and abroad researchers attach great importance to the testing of the train control system, and also a lot of research has been done. The simulation test makes it easier for the testers to work in the lab instead of the field, so that it reduce the human and material costs, and the test environment can be controlled and repeatable easily. Besides, the special environment of the site can also be simulated. University of Florence in Italy has developed the loop of the ATP / ATC test system based on the simulation technology HIL (Hardware in Loop), it provides an effective solution to the test of ATP speed measurement device. CEDEX LIF laboratory in spain simulation has used the test method of simulation to establish the Eurocab test platform, and developed a number of testing tools, moreover, they have defined test sequence. Test sequence generation and viewing, test management and test result analysis and evaluation function have also achieved. Beijing Jiaotong University in China rail traffic control and security National Key Laboratory of CTCS-3 train Control System has also established simulation test platform, so that simulation test can be performed.
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Wang, Xiaowei, Xiaoju Liang, Huan Liang та Bing Wang. "SENP1/HIF‐1α feedback loop modulates hypoxia‐induced cell proliferation, invasion, and EMT in human osteosarcoma cells". Journal of Cellular Biochemistry 119, № 2 (27 вересня 2017): 1819–26. http://dx.doi.org/10.1002/jcb.26342.

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Zhao, Bin, Xiulong Niu, Suhui Huang, Jing Yang, Yiyi Wei, Xiujuan Wang, Junhong Wang, Yue Wang та Xiaoqin Guo. "TLR4 Agonist and Hypoxia Synergistically Promote the Formation of TLR4/NF-κB/HIF-1α Loop in Human Epithelial Ovarian Cancer". Analytical Cellular Pathology 2022 (14 квітня 2022): 1–19. http://dx.doi.org/10.1155/2022/4201262.

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Inflammation and hypoxia are involved in numerous cancer progressions. Reportedly, the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway and hypoxia-inducible factor-1α (HIF-1α) are activated and closely related to the chemoresistance and poor prognosis of epithelial ovarian cancer (EOC). However, the potential correlation between TLR4/NF-κB and HIF-1α remains largely unknown in EOC. In our study, the possible positive correlation among TLR4, NF-κB, and HIF-1α proteins was investigated in the EOC tissues. Our in vitro results demonstrated that LPS can induce and activate HIF-1α through the TLR4/NF-κB signaling in A2780 and SKOV3 cells. Moreover, hypoxia-induced TLR4 expression and the downstream transcriptional activity of NF-κB were HIF-1α-dependent. The cross talk between the TLR4/NF-κB signaling pathway and HIF-1α was also confirmed in the nude mice xenograft model. Therefore, we first proposed the formation of a TLR4/NF-κB/HIF-1α loop in EOC. The positive feedback loop enhanced the susceptibility and responsiveness to inflammation and hypoxia, which synergistically promote the initiation and progression of EOC. The novel mechanism may act as a future therapeutic candidate for the treatment of EOC.
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O’Connell, Emma J., Chloe-Anne Martinez, Yichuan G. Liang, Peter A. Cistulli, and Kristina M. Cook. "Out of breath, out of time: interactions between HIF and circadian rhythms." American Journal of Physiology-Cell Physiology 319, no. 3 (September 1, 2020): C533—C540. http://dx.doi.org/10.1152/ajpcell.00305.2020.

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Humans have internal circadian clocks that ensure that important physiological functions occur at specific times of the day. These molecular clocks are regulated at the genomic level and exist in most cells of the body. Multiple circadian resetting cues have been identified, including light, temperature, and food. Recently, oxygen has been identified as a resetting cue, and emerging science indicates that this occurs through interactions at the cellular level between the circadian transcription-translation feedback loop and the hypoxia-inducible pathway (hypoxia-inducible factor; subject of the 2019 Nobel Prize in Physiology or Medicine). This review will cover recently identified relationships between HIF and proteins of the circadian clock. Interactions between the circadian clock and hypoxia could have wide-reaching implications for human diseases, and understanding the molecular mechanisms regulating these overlapping pathways may open up new strategies for drug discovery.
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Scheifele, C., A. Lechler, and A. Prof Verl. "Materialflussmodelle für die HiL-Simulation*/Material Flow Models for HiL-Simulation – Simulating the material flow of machines in a Hardware-in-the-Loop simulation." wt Werkstattstechnik online 106, no. 03 (2016): 119–24. http://dx.doi.org/10.37544/1436-4980-2016-03-23.

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Bei einer Hardware-in-the-Loop (HiL)-Simulation wird die reale Steuerungstechnik mit einer experimentierfähigen Maschinensimulation verbunden. Soll das Bewegungsverhalten des Materialflusses in der Maschinensimulation zur Generierung von Steuerungssignalen berechnet werden, so müssen die harten Echtzeitanforderungen einer HiL-Simulation eingehalten werden. Dieser Beitrag betrachtet verschiedene Materialflussmodelle und gibt das Ziel eines mehrskaligen Simulationsmodells für die HiL-Simulation vor.   A Hardware-in-the-Loop (HiL) simulation couples real control technology with an experimental machine simulation. When computing the movement behavior of a material flow in the machine simulation to generate control signals, the hard real-time requirements of a HiL-simulation must be considered. This article checks different material flow models and defines the objective of a multi-scale material flow model for HiL-Simulation.
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Kiesbye, Jonis, David Messmann, Maximilian Preisinger, Gonzalo Reina, Daniel Nagy, Florian Schummer, Martin Mostad, Tejas Kale, and Martin Langer. "Hardware-In-The-Loop and Software-In-The-Loop Testing of the MOVE-II CubeSat." Aerospace 6, no. 12 (December 1, 2019): 130. http://dx.doi.org/10.3390/aerospace6120130.

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This article reports the ongoing work on an environment for hardware-in-the-loop (HIL) and software-in-the-loop (SIL) tests of CubeSats and the benefits gained from using such an environment for low-cost satellite development. The satellite tested for these reported efforts was the MOVE-II CubeSat, developed at the Technical University of Munich since April 2015. The HIL environment has supported the development and verification of MOVE-II’s flight software and continues to aid the MOVE-II mission after its launch on 3 December 2018. The HIL environment allows the satellite to interact with a simulated space environment in real-time during on-ground tests. Simulated models are used to replace the satellite’s sensors and actuators, providing the interaction between the satellite and the HIL simulation. This approach allows for high hardware coverage and requires relatively low development effort and equipment cost compared to other simulation approaches. One key distinction from other simulation environments is the inclusion of the electrical domain of the satellite, which enables accurate power budget verification. The presented results include the verification of MOVE-II’s attitude determination and control algorithms, the verification of the power budget, and the training of the operator team with realistic simulated failures prior to launch. This report additionally presents how the simulation environment was used to analyze issues detected after launch and to verify the performance of new software developed to address the in-flight anomalies prior to software deployment.
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Martella, Andrea, Cristoforo Silvestri, Francesca Maradonna, Giorgia Gioacchini, Marco Allarà, Giuseppe Radaelli, Darryl R. Overby, Vincenzo Di Marzo, and Oliana Carnevali. "Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop." Endocrinology 157, no. 5 (March 25, 2016): 1751–63. http://dx.doi.org/10.1210/en.2015-1384.

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Abstract The xenoestrogen bisphenol A (BPA) is a widespread plasticizer detectable within several ecosystems. BPA is considered a metabolic disruptor, affecting different organs; however, little is known about its mechanism of action in the liver, in which it triggers triglyceride accumulation. Adult zebrafish (Danio rerio) exposed to BPA developed hepatosteatosis, which was associated with an increase in the liver levels of the obesogenic endocannabinoids 2-arachidonoylglycerol and anandamide and a concomitant decrease in palmitoylethanolamide. These changes were associated with variations in the expression of key endocannabinoid catabolic and metabolic enzymes and an increase in the expression of the endocannabinoid receptor cnr1. Acute and chronic in vitro treatments with nano- and micromolar BPA doses showed increased anandamide levels in line with decreased activity of fatty acid amide hydrolase, the main anandamide hydrolytic enzyme, and induced triglyceride accumulation in HHL-5 cells in a CB1-dependent manner. We conclude that BPA is able to produce hepatosteatosis in zebrafish and human hepatocytes by up-regulating the endocannabinoid system.
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Xinyuan, Gao, Gu Kanru, and Zhou Qianru. "Hardware in the Loop Real-time Simulation of Doubly Fed Off-grid Wind Power System." Journal of Physics: Conference Series 2137, no. 1 (December 1, 2021): 012018. http://dx.doi.org/10.1088/1742-6596/2137/1/012018.

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Abstract Hardware in the Loop (HIL) semi-physical real-time simulation can shorten the research period and complete the harsh working condition test, which is difficult to be carried out on the physical platform. Taking the off-grid Doubly Fed Induction Generator (DFIG) wind power system as the research object, this paper proposes the bottom modelling method of HIL real-time simulation. Using the Hardware Description Language VERILOG, the bottom real-time models of DFIG, converter and load are designed on Field Programmable Gate Array (FPGA), connected with the real controller, and the HIL real-time simulation platform is constructed. The experiments of conventional working conditions and unbalance load are carried out on the HIL platform and the physical platform. The operation speed of the HIL platform reaches 0.48μs. Compared with the physical platform, the error of HIL platform is between 1.17 ~ 3.29% under various working conditions.
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Di Vito, Vittorio, and Giulia Torrano. "RPAS Automatic ADS-B Based Separation Assurance and Collision Avoidance System Real-Time Simulation Results." Drones 4, no. 4 (December 7, 2020): 73. http://dx.doi.org/10.3390/drones4040073.

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Remotely piloted aircraft systems (RPAS) are increasingly becoming relevant actors that are flying through the airspace and will gain much more importance in the future. In order to allow for their safe integration with manned conventional traffic in non-segregated airspaces, in accordance with the overall air traffic management (ATM) paradigm, specific enabling technologies are needed. As is well known, the detect and avoid (DAA) technology is fundamental among the enabling technologies identified as crucial for RPAS integration into the overall ATM system. In the meantime, to support extended surveillance, the universal introduction of cooperative automatic dependent surveillance-broadcast (ADS-B) on-board aircraft is being increasingly implemented because it has the potential to allow for the coverage of the entire airspaces in remote areas not usually covered by conventional radar surveillance. In this paper, experimental results that were obtained through the real-time validation, with hardware and human in the loop (RTS-HIL) simulations, of an automatic ADS-B based separation assurance and collision avoidance system aimed to support RPAS automatic operations (as well as remote pilot decision making) are presented and discussed. In the paper, after an introductory outline of the concept of operations (ConOps) of the system and its architectural organization, in addition to basic information about the main system functionalities, a description of the tests that were carried out is reported, and the obtained results are described and discussed in order to emphasize the performance and limitations of the proposed system. In particular, the obtained quantitative performances are reported and commented on, and the feedback presented by pilots in order to improve the system, e.g., in terms of preferred typology of conflict resolution maneuver elaborated by the system, is described.
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Difronzo, Michele, Md Multan Biswas, Matthew Milton, Herbert L. Ginn, and Andrea Benigni. "System Level Real-Time Simulation and Hardware-in-the-Loop Testing of MMCs." Energies 14, no. 11 (May 24, 2021): 3046. http://dx.doi.org/10.3390/en14113046.

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In this paper we present an approach for real-time simulation and Hardware-in-the-Loop (HIL) testing of Modular Multilevel Converters (MMCs) that rely on switching models while supporting system level analysis. Using the Latency Based Linear Multistep Compound (LB-LMC) approach, we achieved a 50 ns simulation time step for systems composed of several MMC converters and for converters of various complexity. To facilitate system level testing, we introduce the use of a serial communication-based (Aurora) interface for HIL testing of MMC converters and we analyzed the effect that communication latency has on the accuracy of the HIL test. The simulation and HIL results are validated against an MMC laboratory prototype.
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Wakitani, Shin, and Toru Yamamoto. "Design of an Educational Hardware in the Loop Simulator for Model-Based Development Education." Journal of Robotics and Mechatronics 31, no. 3 (June 20, 2019): 376–82. http://dx.doi.org/10.20965/jrm.2019.p0376.

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This study proposes a HIL simulator for model-based development (MBD) education and checks its behavior. In recent years, product structures have become diverse and complex; further, short-term development with limited resources is required to respond to consumers’ needs. MBD using computer simulation is effective for the efficient execution of such developments. An increasing number of companies have introduced MBD; however, engineers who are newly engaged in such development do not always have sufficient experience. Therefore, in this study, the authors have proposed an educational program to learn the basics of MBD in a short period of time. However, the introduction of industrial hardware in the loop (HIL) simulator, which plays an important role in MBD, is expensive. The present study proposes a method of designing an educational HIL simulator by using a microcomputer board. The proposed educational HIL simulator can reduce the production cost of industrial HIL simulators and can be provided to individual participants undergoing MBD training. Using numerical examples and experimental results, we show that the proposed HIL simulator can perform a simulation of experimental equipment used in actual MBD education.
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Yang, Qian Long. "Hardware-in-the-Loop Simulation of Missile Control System Based on Windows Operation System." Applied Mechanics and Materials 278-280 (January 2013): 1804–8. http://dx.doi.org/10.4028/www.scientific.net/amm.278-280.1804.

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A hardware-in-the-loop (HIL) simulation platform in use of windows operation system was successfully established based on general industrial PC combined with an external timer. The following HIL simulation process of missile control system indicated that the novel platform could not only satisfied the real-time requirement of HIL simulation, but also is low-cost and universal, which could provide a convenient new choice in the similar applications.
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Quantmeyer, Florian, and Xiao Bo Liu-Henke. "Hardware in the Loop Test Rig for Development of Control Algorithms for Electric Vehicles." Solid State Phenomena 198 (March 2013): 507–12. http://dx.doi.org/10.4028/www.scientific.net/ssp.198.507.

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Political pressure on the automotive industry will lead in future to an increasing electrification of the powertrain. The new components require the development of new vehicle control systems and control functions. Due to the high complexity of such systems the mechatronical development process including Model in the Loop (MIL), Software in the Loop (SIL) and Hardware in the Loop (HIL) simulation has been established. In this paper, a HiL test rig is presented, which has high flexibility and supports the model based development of control systems for battery electric vehicles at all levels.
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Sahoo, Saumya R., and Shital S. Chiddarwar. "Flatness-based control scheme for hardware-in-the-loop simulations of omnidirectional mobile robot." SIMULATION 96, no. 2 (June 26, 2019): 169–83. http://dx.doi.org/10.1177/0037549719859064.

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Omnidirectional robots offer better maneuverability and a greater degree of freedom over conventional wheel mobile robots. However, the design of their control system remains a challenge. In this study, a real-time simulation system is used to design and develop a hardware-in-the-loop (HIL) simulation platform for an omnidirectional mobile robot using bond graphs and a flatness-based controller. The control input from the simulation model is transferred to the robot hardware through an Arduino microcontroller input board. For feedback to the simulation model, a Kinect-based vision system is used. The developed controller, the Kinect-based vision system, and the HIL configuration are validated in the HIL simulation-based environment. The results confirm that the proposed HIL system can be an efficient tool for verifying the performance of the hardware and simulation designs of flatness-based control systems for omnidirectional mobile robots.
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Köhl, Susanne. "Hardware-in-the-Loop HiL Tools in Change." ATZautotechnology 11, no. 4 (August 2011): 54–57. http://dx.doi.org/10.1365/s35595-011-0054-z.

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Köhl, Susanne. "Hardware-in-the-loop HIL Tools in Change." ATZelektronik worldwide 6, no. 4 (August 2011): 48–51. http://dx.doi.org/10.1365/s38314-011-0042-5.

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Zamiri, Elyas, Alberto Sanchez, Marina Yushkova, Maria Sofia Martínez-García, and Angel de Castro. "Comparison of Different Design Alternatives for Hardware-in-the-Loop of Power Converters." Electronics 10, no. 8 (April 13, 2021): 926. http://dx.doi.org/10.3390/electronics10080926.

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This paper aims to compare different design alternatives of hardware-in-the-loop (HIL) for emulating power converters in Field Programmable Gate Arrays (FPGAs). It proposes various numerical formats (fixed and floating-point) and different approaches (pure VHSIC Hardware Description Language (VHDL), Intellectual Properties (IPs), automated MATLAB HDL code, and High-Level Synthesis (HLS)) to design power converters. Although the proposed models are simple power electronics HIL systems, the idea can be extended to any HIL system. This study compares the design effort of different coding methods and numerical formats considering possible synthesis tools (Precision and Vivado), and it comprises an analytical discussion in terms of area and speed. The different models are synthesized as ad-hoc modules in general-purpose FPGAs, but also using the NI myRIO device as an example of a commercial tool capable of implementing HIL models. The comparison confirms that the optimum design alternative must be chosen based on the application (complexity, frequency, etc.) and designers’ constraints, such as available area, coding expertise, and design effort.
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Lian, Jing, Ya Fu Zhou, Teng Ma, and Xiao Yong Shen. "Development of Automotive Electronics HIL Simulation Experimental Platform." Applied Mechanics and Materials 44-47 (December 2010): 1893–97. http://dx.doi.org/10.4028/www.scientific.net/amm.44-47.1893.

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This paper presents a low-cost, simple and reliable solution for automotive electronics Hardware-In-Loop (HIL) simulation, taking Jetta AT1.6 car as object, designs and develops automotive electronics HIL simulation platform. Firstly, the overall structure of the platform is designed; secondly, system hardware platform is developed and built using Protel DXP; then, HIL simulation models of ABS (Anti-lock Braking System), engine and automatic transmission are built using Matlab/Simulink and develop automotive electronics HIL simulation platform; finally, carry on the experiment and the results show that the designed HIL simulation experimental platform is good. The platform has widespread applicability in the teaching experiments and the aspects of developing, debugging and testing of automotive electronics control systems.
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Moretti, Giacomo, Andrea Scialò, Giovanni Malara, Giovanni Gerardo Muscolo, Felice Arena, Rocco Vertechy, and Marco Fontana. "Hardware-in-the-loop simulation of wave energy converters based on dielectric elastomer generators." Meccanica 56, no. 5 (February 26, 2021): 1223–37. http://dx.doi.org/10.1007/s11012-021-01320-8.

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AbstractDielectric elastomer generators (DEGs) are soft electrostatic generators based on low-cost electroactive polymer materials. These devices have attracted the attention of the marine energy community as a promising solution to implement economically viable wave energy converters (WECs). This paper introduces a hardware-in-the-loop (HIL) simulation framework for a class of WECs that combines the concept of the oscillating water columns (OWCs) with the DEGs. The proposed HIL system replicates in a laboratory environment the realistic operating conditions of an OWC/DEG plant, while drastically reducing the experimental burden compared to wave tank or sea tests. The HIL simulator is driven by a closed-loop real-time hydrodynamic model that is based on a novel coupling criterion which allows rendering a realistic dynamic response for a diversity of scenarios, including large scale DEG plants, whose dimensions and topologies are largely different from those available in the HIL setup. A case study is also introduced, which simulates the application of DEGs on an OWC plant installed in a mild real sea laboratory test-site. Comparisons with available real sea-test data demonstrated the ability of the HIL setup to effectively replicate a realistic operating scenario. The insights gathered on the promising performance of the analysed OWC/DEG systems pave the way to pursue further sea trials in the future.
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Alavanja, Darko, and Gordana Ostojić. "IMPLEMENTACIJA DNP3 PROTOKOLA ZA INDUSTRIJSKE UREĐAJE." Zbornik radova Fakulteta tehničkih nauka u Novom Sadu 35, no. 05 (April 30, 2020): 929–32. http://dx.doi.org/10.24867/07ih01alavanja.

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U radu je prikazan postupak razvijanja DNP3 udaljene stanice na HIL uređajima (eng. hardware-in-the-loop). Opisan je razvoj grafičkog interfejsa za konfi­guraciju DNP3 parametara, specifičnosti i karakteristike DNP3 protokola, funkcionalnosti koje su implementirane u Tajfun HIL softverskom okruženju, provera ispravnosti rada, rezultati testiranja i analiza DNP3 paketa.
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Rad, Ciprian, Vistrian Maties, Olimpiu Hancu, and Ciprian Lapusan. "Hardware-In-The-Loop (HIL) Simulation Used for Testing Actuation System of a 2-DOF Parallel Robot." Applied Mechanics and Materials 162 (March 2012): 334–43. http://dx.doi.org/10.4028/www.scientific.net/amm.162.334.

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This paper focuses on the subject of Hardware-in-the-Loop (HIL) simulations from mechatronic systems design perspective. HIL is a real-time simulation where real subsystem parts of a complex engineering system are coupled together with the numerical models of the remaining subsystems to form its complete representation. In a HIL simulation there are three main components: simulated components, dedicated hardware systems and real components. An impediment in using this method is the high cost of necessary hardware. The paper presents an economical alternative to existing dedicated hardware systems by using the development board FiO Std. Using this board, a HIL simulation aimed at analyzing the control and actuation system of a 2-DOF parallel robot is presented in this paper. The HIL simulation includes two models: a target model (running on FiO Std board) and a host model (running on MATLAB/Simulink). The dynamic model of the robot mechanical structure (simulated part) is implemented in host model and then coupled together with two servo-motors (real parts) through target model to form a complete representation of the studied system.
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Mystkowski, Arkadiusz, and Andrzej Kierdelewicz. "Fractional-Order Water Level Control Based on PLC: Hardware-In-The-Loop Simulation and Experimental Validation." Energies 11, no. 11 (October 26, 2018): 2928. http://dx.doi.org/10.3390/en11112928.

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An industrial-oriented water tank level control system with PLC- and Simulink-based fractional-order controller realizations is presented. The discrete fractional-order and integer-order PID implementations are realized via the PLC and Simulink simulator. The benefits of the fractional-order PID compared to the integer-order PID control are confirmed by the hardware-in-the-loop (HIL) simulations and experiments. HIL simulations are realized using real-time communication between PLC and Simulink. The fractional-order controller is obtained for a desired phase/gain margin and validated via HIL simulations and experimental measurements.
38

Bățăuș, Marius, Ionuț Stoica, and Mircea Oprean. "Cost effective teaching and research tools for automotive dynamics." Balkan Region Conference on Engineering and Business Education 2, no. 1 (December 20, 2017): 189–97. http://dx.doi.org/10.1515/cplbu-2017-0026.

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Abstract The paper examines the problem of developing cost effective teaching and research tools for automotive dynamics. Different available solutions are presented and the need of human feedback is emphasized. Based on the demands from industry and academia (benchmarking, virtual prototyping, comparative testing of alternative technologies, development and tuning of the automotive control etc.) a solution is proposed. At the core of the proposed tool is a H2iL (humanand- hardware-in-the-loop) simulator based on an electric vehicle. An architecture is elaborated for the simulator and the proof of concept is done in three steps.
39

Ju, Cunxiang, Mingkun Zhang, Dan Wu, Jing Tang, Shuai Li, Jing Zhao, Demin Wang, and Xiang Gao. "Human Interleukin 15 (IL15) Humanized NCG Mice Support the Human Natural Killer Cells Reconstitution and Development." Blood 134, Supplement_1 (November 13, 2019): 4871. http://dx.doi.org/10.1182/blood-2019-123661.

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NCG (GPT strain ID: T001475), one of the highly immune-deficient mouse models generated so far, is ideal for engraftment of human tissues and cells, such as patient derived tumors (PDX), human cancer cell lines (CDX), human peripheral blood mononuclear cells (PBMC) and human hematopoietic stem cells (HSCs). NK cells that are a critical component of the innate immune system have diverse biological functions, such as recognizing and killing viral-infected and neoplastic cells. Human HSCs (CD34+) could reconstitute human T but not NK cells in NCG mice. The cytokine Interleukin 15 (IL-15) plays a critical role in the generation of NK cells from HSCs. IL-15 is produced by non-lymphoid cells, including monocytes, dendritic and bone marrow stromal cells. Human and mouse IL-15 are only 70% identical to each other in primary amino acid sequence. Mouse IL-15 poorly supports the reconstitution of human NK cells. To overcome this problem, several lines of transgenic mice that express human IL-15 (hIL-15) have been established. However, the non-physiological levels of hIL-15 expression are detrimental to human immune system reconstitution.In the current study, we developed hIL-15 knock-in in NCG mice (NCG-hIL-15), in which the mouse IL-15 (mIL-15) gene was replaced by the hIL-15 gene. We quantified the mRNA expression of hIL-15 and found that the levels of hIL-15 expression in the BM, liver, lung, and small intestine of NCG-hIL-15 mice were similar to those of mIL-15 in NCG mice.Based on these data, we expect that NCG-hIL-15 mice can efficiently support the development, maturation and function of human NK cells. In the future, we will further study human NK cell engraftment and human NK cell-mediated cancer immunotherapy in NCG-hIL-15 mice. Taken together, our newly developed NCG-hIL-15 mice offer a novel mouse model for studying human NK cell biology and human NK-mediated cancer immunotherapy in vivo. Disclosures Ju: GemPharmatech Co., Ltd: Employment. Zhang:GemPharmatech Co., Ltd: Employment. Wu:GemPharmatech Co., Ltd: Employment. Tang:GemPharmatech Co., Ltd: Employment. Li:GemPharmatech Co., Ltd: Employment. Zhao:GemPharmatech Co., Ltd: Employment. Wang:GemPharmatech Co., Ltd: Employment. Gao:GemPharmatech Co., Ltd: Employment.
40

Kitamura, T., and A. Miyajima. "Functional reconstitution of the human interleukin-3 receptor." Blood 80, no. 1 (July 1, 1992): 84–90. http://dx.doi.org/10.1182/blood.v80.1.84.84.

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Abstract The high-affinity receptors for human interleukin-3 (IL-3), GM-CSF, and IL-5 are composed of alpha and beta subunits. The alpha subunits are primary ligand binding proteins specific for each ligand, whereas the three human receptors share a common beta subunit (beta c). In contrast to humans mice have two closely related genes, AIC2A and AIC2B, which are homologous to human beta c. The AIC2A gene encodes a low-affinity murine IL-3 binding protein, and the AIC2B protein is the beta subunit shared between murine GM-CSF receptors (mGMR) and IL-5 receptors (mIL- 5R). To examine the function of these receptor components, we established various stable transfectants of murine IL-2-dependent CTLL- 2 cells. CTLL-2 transfectants expressing both the alpha and beta subunits of the human IL-3 receptor (hIL-3R) proliferated in response to physiologic concentrations of hIL-3. Coexpression of hIL-3R alpha with AIC2B but not with AIC2A in CTLL-2 cells conferred a growth response to hIL-3. Although CTLL-2 transfectants expressing hIL-3R alpha alone did not proliferate in the presence of hIL-3, hIL-3- responsive sublines were repeatedly isolated. These sublines expressed endogenous AIC2B but not AIC2A. These results indicate that human beta c is essential for hIL-3 signaling and that AIC2B is a murine equivalent of human beta c. We also showed that hIL-3 and hGM-CSF induced tyrosine phosphorylation of several proteins in CTLL transfectants, similar to those observed in human factor-dependent TF-1 cells stimulated with hIL-3 and hGM-CSF.
41

Kitamura, T., and A. Miyajima. "Functional reconstitution of the human interleukin-3 receptor." Blood 80, no. 1 (July 1, 1992): 84–90. http://dx.doi.org/10.1182/blood.v80.1.84.bloodjournal80184.

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The high-affinity receptors for human interleukin-3 (IL-3), GM-CSF, and IL-5 are composed of alpha and beta subunits. The alpha subunits are primary ligand binding proteins specific for each ligand, whereas the three human receptors share a common beta subunit (beta c). In contrast to humans mice have two closely related genes, AIC2A and AIC2B, which are homologous to human beta c. The AIC2A gene encodes a low-affinity murine IL-3 binding protein, and the AIC2B protein is the beta subunit shared between murine GM-CSF receptors (mGMR) and IL-5 receptors (mIL- 5R). To examine the function of these receptor components, we established various stable transfectants of murine IL-2-dependent CTLL- 2 cells. CTLL-2 transfectants expressing both the alpha and beta subunits of the human IL-3 receptor (hIL-3R) proliferated in response to physiologic concentrations of hIL-3. Coexpression of hIL-3R alpha with AIC2B but not with AIC2A in CTLL-2 cells conferred a growth response to hIL-3. Although CTLL-2 transfectants expressing hIL-3R alpha alone did not proliferate in the presence of hIL-3, hIL-3- responsive sublines were repeatedly isolated. These sublines expressed endogenous AIC2B but not AIC2A. These results indicate that human beta c is essential for hIL-3 signaling and that AIC2B is a murine equivalent of human beta c. We also showed that hIL-3 and hGM-CSF induced tyrosine phosphorylation of several proteins in CTLL transfectants, similar to those observed in human factor-dependent TF-1 cells stimulated with hIL-3 and hGM-CSF.
42

Roskam, Rolf, and Elmar Engels. "A New Slip Algorithm for Use in Hardware-in-the-Loop Simulation to Evaluate Anti Slip Control of Vehicles." Applied Mechanics and Materials 490-491 (January 2014): 740–46. http://dx.doi.org/10.4028/www.scientific.net/amm.490-491.740.

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Hardware in the Loop (HIL) systems is widely used for testing vehicle controllers in automotive industry. But algorithms for simulation of the vehicle dynamics have to consider the special restrictions for HIL that is a fixed simulation time constant. Due to limitations of computing power the step size often is set to 1ms. Especially for calculation of the wheel slip this will cause a problem when speed starts from zero. Thats why a lot of authors propose a small vehicle speed at the beginning of the simulation. For evaluation of anti slip controllers in HIL systems this is not possible because stand still is the general starting point for the anti slip controller. Different ideas exist in literature to solve this problem but none of them consider the HIL restriction in an overall approach. In this paper a new algorithm for slip calculation is presented. Therefore two different approaches will be analyzed and combined to a new algorithm. Simulation results show the feasibility for HIL systems.
43

Romdlony, Muhammad Zakiyullah, and Fakih Irsyadi. "Hardware-in-the-loop simulation of DC motor as an instructional media for control system design and testing." Journal of Mechatronics, Electrical Power, and Vehicular Technology 12, no. 2 (December 31, 2021): 81–86. http://dx.doi.org/10.14203/j.mev.2021.v12.81-86.

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Instructional media in control systems typically requires a real plant as an element to be controlled. However, this real plant, which is costly to be implemented, can be replaced by a virtual plant implemented in a computer and modelled in such a way that it resembles the behavior of a real plant. This kind of set-up is widely termed as hardware-in-the-loop (HIL) simulation. HIL simulation is an alternative way to reduce the development cost. A virtual plant is easy to adjust to represent various plants or processes that are widely used in industry. This paper proposes a simple HIL simulation set-up designed as instructional media for design and testing a simple control system. The experimental result on DC motor control shows that HIL simulation dynamical response is similar to the real hardware response with a small average error on measured transient response, represented in 0.5 seconds difference in settling time and 7.43 % difference in overshoot. This result shows the efficacy of our HIL simulation set-up.
44

El-Baz, Wessam, Lukas Mayerhofer, Peter Tzscheutschler, and Ulrich Wagner. "Hardware in the Loop Real-Time Simulation for Heating Systems: Model Validation and Dynamics Analysis." Energies 11, no. 11 (November 14, 2018): 3159. http://dx.doi.org/10.3390/en11113159.

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Heating systems such as heat pumps and combined heat and power cycle systems (CHP) represent a key component in the future smart grid. Their capability to couple the electricity and heat sector promises a massive contribution to the energy transition. Hence, these systems are continuously studied numerically and experimentally to quantify their potential and develop optimal control methods. Although numerical simulations provide time and cost-effective solutions for system development and optimization, they are exposed to several uncertainties. Hardware in the loop (HiL) approaches enable system validation and evaluation under different real-life dynamic constraints and boundary conditions. In this paper, a HiL system of a heat pump testbed is presented. It is used to present two case studies. In the first case, the conventional heat pump testbed operation method is compared to the HiL operation method. Energetic and dynamic analyses are performed to quantify the added value of the HiL and its necessity for dynamics analysis. In the second case, the HiL testbed is used to validate a model of a single family house with a heat pump participating in a local energy market. The energetic analysis indicates a deviation of 2% and 5% for heat generation and electricity consumption of the heat pump model, respectively. The model dynamics emphasized its capability to present the dynamics of a real system with a temporal distortion of 3%.
45

Shchur, Ihor, Vsevolod Shchur, Ihor Bilyakovskyy, and Mykhailo Khai. "Hardware in the loop simulative setup for testing the combined heat power generating wind turbine." International Journal of Power Electronics and Drive Systems (IJPEDS) 12, no. 1 (March 1, 2021): 499. http://dx.doi.org/10.11591/ijpeds.v12.i1.pp499-510.

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This paper describes the design and implementation of hardware in the loop (HIL) system based on induction motor wind turbine emulator for the study of the operation of a combined heat-power (CHP) generating wind energy conversion system (WECS). The energy generation part of the WECS consists of two specially designed generators that are placed on a common vertical axis, which is connected to the induction motor through a gearbox. The first generator is an electric two-armature axial PMSG and the second one is a thermal electromagnetic retarder. The software part of the HIL setup simulates the interaction of the wind flow with a vertical axis wind turbine (VAWT) and is implemented in a programmable logic controller based on the model developed in the MATLAB/Simulink. The results of experimental studies of the CHP WECS with the created HIL simulative setup at both constant and turbulent wind speeds have shown good agreement with the corresponding results of computer simulation. The created HIL simulative setup will be used for the development of an energy management system for CHP WECS.
46

Wang, Yan, Long Han, Meng Ling Wu, and Zhuo Jun Luo. "A Hardware-in-the-Loop Simulation Test Bench for Subway Train Brake Systems." Advanced Materials Research 1064 (December 2014): 219–24. http://dx.doi.org/10.4028/www.scientific.net/amr.1064.219.

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A hardware-in-the-loop (HIL) simulation test bench for subway train brake systems is built in this paper to avoid the high costs of brake system field tests and maintain the reliability of test results. The HIL simulation test bench consists of a simulation part a hardware part. The simulation part includes a train model and a GUI. The hardware part mainly consists of six pneumatic brakes and a driver controller, which is used to generate brake commands. Signal transmissions between the simulation and hardware parts are realized using DAQ and signal transformation boards, as well as an MVB network. Test results suggest that the HIL test bench proposed is able to reproduce the braking behaviours of a train rather well, thus it can be used to carry out train braking tests in place of the costly field tests in some occasions.
47

Xiang, Yan, and Bernard Moss. "Correspondence of the Functional Epitopes of Poxvirus and Human Interleukin-18-Binding Proteins." Journal of Virology 75, no. 20 (October 15, 2001): 9947–54. http://dx.doi.org/10.1128/jvi.75.20.9947-9954.2001.

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ABSTRACT Molluscum contagiosum virus, a human poxvirus that causes persistent small benign skin tumors, encodes a variety of putative immune defense proteins. Three such proteins, MC51L, MC53L, and MC54L, have 20 to 35% amino acid sequence identities with human interleukin-18 (hIL-18)-binding protein (hIL-18BP), a naturally occurring antagonist of the proinflammatory cytokine IL-18. We previously demonstrated that seven amino acids within the immunoglobulin-like domain of hIL-18BP were important for high-affinity binding to hIL-18. Model building indicated that MC54L, which has been shown to bind hIL-18, contains five of the seven amino acids at corresponding positions in its immunoglobulin-like domain, the exceptions being the conservative substitution of isoleucine for a leucine and the nonconservative substitution of valine for a phenylalanine. We found that individual alanine substitutions for these six identical or highly conserved amino acids of MC54L caused changes in affinity and binding free energy for hIL-18 that were quantitatively similar to those produced by mutagenesis of hIL-18BP. Furthermore, when the nonconserved valine of MC54L was mutated to phenylalanine, making it more like hIL-18BP, its affinity for hIL-18 increased more than 10-fold. In addition, the carboxyl-terminal half of MC54L, which has no similarity with hIL-18BP, was dispensable for hIL-18 binding. Thus, despite their relatively low overall sequence identity, MC54L and hIL-18BP have similar hIL-18 binding sites and functional epitopes. On the other hand, MC51L and MC53L have nonconservative substitutions of three to six of the seven critical amino acids of hIL-18BP and neither protein bound hIL-18, suggesting that they may interact with unidentified ligands.
48

Kővári, Attila. "Real-Time HIL Closed Loop System of Rolling Mill’s Electro-Hydraulic Gap Adjustment." Materials Science Forum 659 (September 2010): 417–22. http://dx.doi.org/10.4028/www.scientific.net/msf.659.417.

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Hardware-in-the-loop (HIL) test is a good ground for examine the dynamic model of rolling to observe the movement of the mill and monitor dynamic behavior of the hydraulic system and the mill. Nowadays hydraulic actuators/capsules are used to control the gap in rolling mills which determines the strip thickness, profile and flatness. Using HIL simulation, dynamic parameters of rolling mill stand and hydraulic gap adjustment system can be tested together in realtime. It has possibility to examine the dynamic phenomena inside the mill stand and hydraulic system using trials to test how system dynamic behavior changes when system’s parameters are shifted. In this paper a HIL real-time model was developed and realized to test the dynamic behavior of the complete rolling mill system which enables us to observe the system’s parameter variations for example when seals are worn out in the hydraulic actuator.
49

Sun, Jian Xia, Da Qiang Bi, and Bao Ming Ge. "Research on the HIL Platform of Photovoltaic Grid Connected System." Applied Mechanics and Materials 654 (October 2014): 266–69. http://dx.doi.org/10.4028/www.scientific.net/amm.654.266.

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In order to analysis the characteristics of grid connected photovoltaic system, this paper proposes a Hardware-in-Loop (HIL) real time testing platform based on RT-LAB. The main circuit real time model is built in the RT-LAB, then connect the real time model with a DSP digital controller to achieve the double closed-loop control. And the HIL platform is used to analysis the low voltage ride through (LVRT) technology of grid connected photovoltaic under the of situation power grid fault. The experimental results validate the effectiveness and correctness of the model and the LVRT control strategy.
50

Xiao, Qing, Shuiqing Zeng, Mingliang Lv та Shiqi Ling. "Small hairpin loop RNA targeting HIF-1α down-regulates VEGF and up-regulates PEDF in human retinal pigment epithelial cells under hypoxic condition". Journal of Huazhong University of Science and Technology [Medical Sciences] 28, № 4 (серпень 2008): 460–64. http://dx.doi.org/10.1007/s11596-008-0419-8.

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