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Photon Kinetics is the leading supplier of test solutions for optical fiber, cable and component manufacturers. These solutions include fiber alignment tools, fiber … Consistent with their TCR expression, NKT cells develop in the thymus and, at least for the iNKT cell lineage, there is strong evidence that these cells undergo positive and negative selection (Godfrey et al. 2010 ). Interestingly, however, the positive selection of iNKT cells involves expression of CD1d on double-positive thymocytes, a phenomenon that appears to be common for T cell populations selected by non-classical MHC class I molecules, including Qa-1 and H2-M3 (Rodgers and Cook 2005 ). A key step in the development of iNKT cells is their acquisition of innate effector functions, which appears to be imparted by the transcription factor PLZF (promyelocytic leukemia zinc finger) (Kovalovsky et al. 2008 ; Savage et al. 2008 ). After their development in the thymus, a substantial proportion of iNKT cells remains in the thymus as a mature population and the remaining cells emigrate to the periphery, where they represent a substantial T cell subset in the spleen, blood, liver and bone marrow, but are more rare in lymph nodes and few of these cells are found in tissues. Curiously, humans have fewer iNKT cells in most organs than mice, and the prevalence of these cells varies dramatically among distinct human subjects, for reasons that are unclear. National Institute of Diabetes and Digestive and Kidney Diseases. NIDDK R01 DK081536 || DK. Cells of the immune system are typically grouped into cells that belong to the innate arm of the immune system and cells that belong to the adaptive arm of the immune system (Abbas et al. 2010 ; Murphy et al. 2007 ). Cells of the innate immune system express different receptors casino roulette tips, termed pattern-recognition receptors, which react with conserved molecular patterns in microorganisms. The innate immune receptors are encoded in the germline and are present in both invertebrate and vertebrate organisms. Cells of the adaptive immune system express diverse receptors with exquisite specificity for antigens derived from particular pathogens. The adaptive immune receptors are generated by somatic DNA rearrangement and are unique to vertebrates. Another important difference between cells of the innate and adaptive immune systems is that cells of the latter but not the former are capable of generating more robust and rapid responses upon repeated encounter with the same antigen, a property commonly referred to as immunological memory. The pro-inflammatory properties of iNKT cells, in particular, their capacity to produce IFN-γ and activate NK cells and CD8 T cells are critical for the anti-tumor activities of these cells (Terabe and Berzofsky 2008 ). These properties of iNKT cells have been demonstrated in models of tumorigenesis induced by the chemical carcinogen methylcholanthrene, transplantable tumors, and genetically engineered mice that develop oncogene-driven tumors. iNKT cell activation or inhibition can have varied effects on inflammatory diseases. In an allogeneic model of bone marrow transplantation where recipients were non-lethally irradiated, α-GalCer treatment of recipient mice protected against graft-versus-host disease in a manner that involved Th2 deviation in donor T cells (Haraguchi et al. 2005 ; Hashimoto et al. 2005 ). However, in a model where recipients were lethally irradiated and α-GalCer was administered at days 1 and 4 after transplantation, α-GalCer exacerbated disease (Kuns et al. 2009 ). Nevertheless, using the latter protocol, C20:2 potently inhibited graft-versus-host disease (Kuns et al. 2009 ). In models of allergic airway hyperresponsiveness, α-GalCer treatment during the sensitization phase exacerbated disease (Meyer et al. 2007 ). Consistent with this potentiating role of iNKT cells in airway hyperreactivity, blockade of iNKT cells with DPPE protected against allergen-induced airway hyperre-activity (Lombardi et al. 2010 ). In agreement with the pathogenic role of iNKT cells in atherosclerosis, α-GalCer exacerbated disease in apolipoprotein E-deficient mice (Major et al. 2006 ). In a model of contact hypersensitivity induced by the hapten oxazolone, the CD1d-dependent antagonists α-ManCer (α-mannosylceramide) and DPPE protected against disease (Nieuwenhuis et al. 2005 ). The pro-inflammatory functions of iNKT cells are critical for several inflammatory diseases (Van Kaer 2007 ). iNKT cells appear to be critical for the development of airway hyper-responsiveness, which is one of the cardinal features of asthma. This was demonstrated in experimental models that employed model allergens such as ovalbumin, the environmental pollutant ozone, and infection with respiratory viruses. iNKT cells were also shown to play a critical role in the development of liver disease induced by the mitogen concanavalin A, which is often used as a model for acute and chronic viral hepatitis. iNKT cells play a pathogenic role in the development of contact hypersensitivity induced by multiple contact antigens, in a manner that depended on interactions with B-1 cells. iNKT cells are crucial for the development of colitis induced by another contact antigen, the hapten oxazolone, and this depended on the capacity of iNKT cells to produce IL-13. iNKT cells are also required for acute tissue injury induced to liver or kidney in ischemia reperfusion models. Similar injury induced in blood vessels during sickle cell disease also required iNKT cells. In models of atherosclerosis roulette bonus yatzy, iNKT cells have been detected in atherosclerotic lesions, and these cells contributed to disease pathogenesis. In each of these examples, cytokines produced by iNKT cells likely play a key role in activating other cell types, resulting in disease pathogenesis. Although less well understood, studies with human subjects have suggested a similar response of human iNKT cells to α-GalCer stimulation in vivo. Treatment of human subjects with α-GalCer resulted in a transient “disappearance” of these cells due to TCR downregulation, followed by transient expansion and subsequent resistance to re-stimulation (Giaccone et al. 2002 ; Nieda et al. 2004 ). Consistent with the studies in mice, α-GalCer-loaded DCs were more effective than free α-GalCer in inducing iNKT cell responses and repeated injection with α-GalCer-loaded DCs resulted in profound iNKT cell expansion (Chang et al. 2005 ). iNKT cells can exhibit both pro- and anti-inflammatory properties, depending on their mode of activation (direct or indirect), the cytokine environment, the strength and duration of their activation, as well as many other parameters (Godfrey and Kronenberg 2004 ). Since iNKT cells in different organs appear to exhibit slightly different effector functions (Crowe et al. 2005 ), the location where iNKT cells are activated can influence their contribution to an immune response. Furthermore, iNKT cell subsets distinguished by CD4 and/or NK1.1 expression can exhibit distinct effector functions, and selective activation of these subsets might therefore also impact the outcome of an immune response (Coquet et al. 2008 ; Crowe et al. 2005 ). Considering these variables casino bonus norge fridge, it is not always possible to predict the impact of iNKT cells on an immune response or disease, as illustrated below. Funding The authors’ work was supported by grants from the National Institutes of Health (to L.V.K. and L.W.), a discovery grant from the Diabetes Research and Training Center at Vanderbilt University School of Medicine (to L.W.), and a postdoctoral fellowship from the National Multiple Sclerosis Society (to V.V.P.). Although iNKT cell activation holds substantial promise for developing immunotherapies and vaccine adjuvants, it should be noted that α-GalCer induces liver toxicity in mice (Osman et al. 2000 ). Nevertheless, no substantial adverse side effects of iNKT cell activation have been observed in clinical trials with human patients (Motohashi and Nakayama 2008 ). Cells of the innate immune system interact with pathogens via conserved pattern-recognition receptors, whereas cells of the adaptive immune system recognize pathogens through diverse, antigen-specific receptors that are generated by somatic DNA rearrangement. Invariant natural killer T (iNKT) cells are a subset of lymphocytes that bridge the innate and adaptive immune systems. Although iNKT cells express T cell receptors that are generated by somatic DNA rearrangement, these receptors are semi-invariant and interact with a limited set of lipid and glycolipid antigens, thus resembling the pattern-recognition receptors of the innate immune system. Functionally, iNKT cells most closely resemble cells of the innate immune system, as they rapidly elicit their effector functions following activation, and fail to develop immunological memory. iNKT cells can become activated in response to a variety of stimuli and participate in the regulation of various immune responses. Activated iNKT cells produce several cytokines with the capacity to jump-start and modulate an adaptive immune response. A variety of glycolipid antigens that can differentially elicit distinct effector functions in iNKT cells have been identified. These reagents have been employed to test the hypothesis that iNKT cells can be harnessed for therapeutic purposes in human diseases. Here, we review the innate-like properties and functions of iNKT cells and discuss their interactions with other cell types of the immune system. Pathways of iNKT cell activation. a Direct pathway of iNKT cell activation via lipid or glycolipid antigens that bind with CD1d and interact with the invariant T cell receptor (TCR ). b Indirect pathway of iNKT cell activation via toll-like receptor ( . Regulation of the mitochondrial response by Bcl-2 family proteins Recently, a third model of Bid-mediated perturbation of mitochondrial function has emerged. Several reports argue for an interaction between Bid and phospholipid metabolism. Following cleavage by caspase-8, the C-terminus of Bid translocates from the cytosol to the mitochondrial contact sites, the structures that form the contacts between the outer and inner mitochondrial membranes. This relocation occurs in a cardiolipin-dependent way. 29 ,30 Truncated Bid is far more potent in cardiolipin binding than Bid, explaining the requirement for proteolytic activation during apoptosis. 29 Very recently another connection was made with phospholipid metabolism. Bid possesses phospholipid transfer activity reflecting its role in dynamic remodelling of intracellular membrane. 57 Enhanced availability of phosphatidylglycerol, phosphatic acid and phosphatidylcholine, but not phosphatidylserine, induces relocation of Bid and tBid to the membranes. Other Bcl-2 family members such as Bcl-x L and Bak do not possess this lipid transfer activity. How can this be associated with the proapoptotic function of Bid and tBid? Death domain receptor and other proapoptotic stimuli often result in the activation of phospholipases 58 causing changes in phospholipid homeostasis, and resulting in enhanced lysolipids. These are preferentially transferred by tBid to the mitochondria and may contribute to the loss of membrane integrity. 57 ,59 Despite the overwhelming evidence for a central role for tBid, the phenotype of Bid-deficient mice is limited with respect to apoptosis induction. Bid-deficient mice are resistant to Fas- and TNF-induced hepatocyte apoptosis 39 but cells from these mice are still susceptible to granzyme B-induced death 36 and to drug and stress-induced apoptosis. 39 Furthermore nett sie kennenzulernen, Bid-deficient mice develop normally, in sharp contrast to the embryonic lethality caused by cytochrome c. caspase-9 or Apaf-1 deficiency, 40 suggesting that tBid generation is not required for programmed cell death in development and may be compensated for by downstream factors such as Bax and Bak. 41 Although the mitochondrial events in apoptosis have been documented for a wide variety of stimuli, the relative contribution of the different mitochondrial factors in the apoptotic process remains to be determined. It is still unclear whether the homeostatic functions of cytochrome c and AIF in oxidative phosphorylation are required for their proapoptotic activity after relocalization. A 'knockin' animal of cytochrome c or AIF only possessing their oxidative phosphorylation function will shed light on the precise contribution of these mitochondrial factors to the apoptotic process in the context of developmental cell death. Also for the other factors such as Smac/DIABLO and Omi/HtrA2 the contribution of the IAP binding motif to the propagation of apoptotic cell death will only become clear by 'knockin' studies with mutants that lack this motif. Moreover, their role as essential components in the apoptotic machinery will only be revealed by genetic deletion of the corresponding genes. Targeted disruption of Smac/DIABLO in vivo has no effect on apoptosis, possibly because Omi/HtrA2 is still fully active. 104 Double mutant mice, lacking both Smac/DIABLO and Omi/HtrA2, could hopefully clarify their physiological role in apoptotic cell death. Another important issue is the relative contribution of caspase-dependent and caspase-independent mechanisms in cytotoxicity. Do the caspase-independent pathways such as AIF, HtrA2/Omi and endonuclease G form a 'second line' of cytotoxic capability in cases where the enzymatic activity of caspases is compromised? If so, then it is important to identify these conditions of reduced or inappropriate caspase activity. It has been reported that viral infection, 127 ,128 nitrosylation 144 ,145 and ATP depletion 146 negatively influence caspase activity. Mitochondrial proteins released during SR>apoptotic cell death The precise molecular mechanism by which Bcl-2 family proteins protect from or induce mitochondrial damage is still controversial. Different models have been proposed to explain the permeabilisation of the mitochondrial membrane and the release of mitochondrial proteins (Figure 2 ). 45 The oldest model (Figure 2A ) argues that cytochrome c is released as a result of the opening of the permeability transition pore (PTP), a large, poorly characterised protein complex at contact sites between the outer and inner mitochondrial membranes. 46 The core components of these contact sites are the ANT protein (adenine nucleotide translocator), found in the inner membrane, and the VDAC protein (voltage-dependent anion channel), located in the outer membrane. The outer membrane is normally permeable for solutes up to 5 kDa, allowing the exchange of respiratory-chain substrates (ADP/ATP, NADH, FADH) between the intermembrane space and the cytosol. The inner membrane, however, is almost impermeable, a feature essential for maintaining an electrochemical potential across the inner membrane required for oxidative phosphorylation. 46 Opening of the PTP is postulated to result in the loss of mitochondrial membrane potential, swelling of the mitochondrial matrix and rupture of the outer membrane, allowing the release of proteins from the intermembrane space. An alternative model suggests that intermembrane space proteins would be released through the PTP itself. Pro- and anti-apoptotic Bcl-2 proteins were shown to interact with the PTP. 45 ,46 This PTP-Bcl-2 family member interaction has been reported to be either through ANT 47 or through VDAC. 48 Bax and Bak are believed to promote the opening of the PTP allowing cytochrome c to pass through it, while anti-apoptotic Bcl-2 and Bcl-x L would favour the closure of the PTP. 48 However, the exact mechanism whereby pro-apoptotic Bcl-2 proteins could modulate the opening of the PTP is still not clear. Moreover, how PTP, which are located at contact sites between outer and inner mitochondrial membrane, allow the passage of intermembrane space proteins is not yet explained in molecular terms. Concluding remarks and future perspectives Besides its IAP-interacting property, Omi/HtrA2 is also an inducer/accelerator of cell death through its serine protease catalytic domain. When the mature protein, without its mitochondrial presequence, is overexpressed in the cytoplasm, it induces cell death independent of caspase activation or IAP interaction. The catalytic domain is essential for this cytotoxic activity. 17 ,18 ,19 ,20 In addition to its amino-terminal mitochondrial presequence and its catalytic domain, Omi/HtrA2 also has a carboxyterminal PDZ domain. 105 PDZ domains, an acronym formed by the proteins in which they were first identified (postsynaptic density protein, disc large tumour suppressor and Zo-1 tight junction protein) have been found to be involved in a variety of protein - protein interactions including the assembly of multimeric complexes that can initiate signal transduction at specific subcellular locations, particularly at the cell surface. 108 ,109 One group of proteins that is characteristic for the presence of such PDZ modules are MAGUK (membrane-associated guanylate kinase) proteins, a class of proteins that are typically associated with cell junctions or other specialised sites on the plasma membrane. 110 In this context, the caspase recruitment domain proteins CARD11 and CARD14 were identified as MAGUK family members that interact with the B-cell lymphoma protein Bcl-10 and activate NF- B signalling pathways. 111 Via its PDZ domain, Omi/HtrA2 was shown to bind Mxi2, an alternatively spliced form of p38 stress-activated kinase, 112 but the function of this interaction is still elusive. Specific physiological substrates for Omi/HtrA2, in the context of cell death, are still unknown and require further investigation. Recently, the crystal structure of Omi/HtrA2 was revealed showing that the protein behaves as a homotrimer. 113 Trimerisation creates a pyramid-shaped structure, with the aminoterminal IAP-binding sequences on top and the PDZ domains at the bottom. Monomeric Omi/HtrA2 mutants are completely inactive showing that trimerisation is essential for protease activity and proper function. However, the IAP-binding motif was shown to be dispensable for its cell-killing activity, in contrast to the PDZ domain that seems to serve as a sensitive regulator of the protease activity in Omi/HtrA2. 113 Based on these structural and biochemical observations, it was proposed that the homotrimeric Omi/HtrA2 would most likely interact with its PDZ domains with a trimeric assembly. Omi/HtrA2 may so interact with trimeric death receptors, such as TNFR and Fas, or other components of the DISC, and by its proteolytic activity contribute to the activation of the apoptotic pathway. 113 Additional pathways for Bid activation have been proposed. Granzyme B, a cytotoxic T-cell specific serine protease, was shown to cleave Bid, activating the mitochondrial pathway. 32 ,33 ,34 On the other hand, granzyme B also affects mitochondria in a Bid-independent way resulting in mitochondrial depolarisation and cell death, even though these mitochondria fail to release cytochrome c. 35 ,36 Also lysosomal proteases and the calcium-dependent cysteine protease calpain were shown to cleave Bid in the protease-sensitive region preceding the BH3 domain, suggesting a role for Bid as a sensor for the integrity of lysosomes and the endoplasmic reticulum. 37 ,38 Several mitochondrial proteins have recently been shown to become toxic moieties when mitochondrial integrity is compromised. This is often the initiating event for caspase-dependent and caspase-independent mechanisms of cell death. Cytochrome c and Smac/DIABLO induce cellular damage by amplifying caspase-mediated proteolysis. Omi/HtrA2 may neutralise IAP proteins but also contributes as a caspase-independent proteolytic agent. AIF and endonuclease G are both involved in caspase-independent nuclear DNA disintegration. Under healthy conditions, each of these proteins seems to have a mundane, but essential, role in normal mitochondrial function and cell survival. Cytochrome c and AIF have an electron acceptor/donor (oxidoreductase) function in mitochondrial oxidative phosphorylation; endonuclease G was suggested to be involved in mitochondrial DNA replication (although this activity is controversial as it does not agree with an intermembrane localisation) and the serine protease Omi/HtrA2 is implicated in mitochondrial control of cell protein stability under osmotic, thermal and oxidative stress conditions. However, as yet, no mitochondrial function has been described for Smac/DIABLO. Following an apoptotic insult, each of these proteins is released into the cytosol where they become cytotoxic agents participating in the destruction of the cell. In this way, mitochondria possess an autonomic system, viz. an arsenal of innocent essential molecules required for mitochondrial (and cellular) homeostasis that, once released into the cytosol, become deadly weapons that push the balance towards cell death. Omi/HtrA2 represents an evolutionarily conserved protease whose bacterial orthologue, the E. coli DegP/HtrA endoprotease, is necessary for bacterial thermo-, oxidative and osmotic tolerance. 114 At high temperature, bacterial HtrA functions as a protease and at normal temperatures as a chaperone. 115 These prokaryotic functions could suggest that Omi/HtrA2 is a multi-functional protein with protective functions in mitochondria and cytotoxic functions once released into the cytosol. However, the precise function of Omi/HtrA2 in cell death, both caspase-dependent as well as caspase-independent, remains elusive and may only be revealed by 'knockin' transgenic studies using mutant forms of HtrA2/Omi that lack one of the functional domains. Although I have heard of some of the authors (and, heard one of the authors long back in Bangalore on some of these problems — Kaushik Bhattacharya), all these papers and the ideas presented in them are new to me. I am planning to read at least a couple of them and blog about them in these pages later. The light output from an individual VCSEL is a collimated beam with a dispersion of approximately 10°. This beam can be intercepted with low cost optical surfaces to redistribute the flux efficiently to wherever illumination is desired. In case where light spilling is unnecessary or undesirable, this feature translates into another 2x to 5x efficiency improvement when compared with isotropic high temperature conventional light sources. a power supply coupled to the chips for providing drive current to the elements. What is claimed is: Recent tests with the 980 nm VCSEL array fabricated by Sandia indicate that these arrays can be operated over a power range of from 0.5 to 5.0 mW at practically constant efficiency. Controller 35 can be used to effect this dimming by reducing the drive current to each of the VCSEL arrays equally and in parallel. The dimming range can be further extended if the VCSEL elements of each array have a single common cathode but multiple, independent anodes. This would allow parts of the VCSEL array to be turned on and off independently. Assuming that 10 separate anodes were fabricated for a single array, the dimming range of the array could be extended by an additional factor of 10, in combination with reducing the drive current. The cost of this extended dimming range is small, involving only small changes to the VCSEL fabrication process and controller design. Conventional light sources either cannot be dimmed, or, if they can be dimmed, they experience substantial losses in efficiency, and, in the case of halogen lamps, reduced operating life. Fluorescent lamps generate white light by stimulating a phosphor layer with UV light. The phosphor layer is a mixture of phosphors generating predominantly three nearly monochromatic lines of light (red, green and blue). The VCSEL light source would use six lines of light which improves the color rendering of the illumination source. Eventually it will be possible to build an illumination source with 12 half watt chips with 15 nm light steps instead of the previously described 6 one watt chips with 30 nm steps. Such a device will surpass the color rendering properties of practically any existing light source. As the VCSEL array operates at roughly room temperature, optical surfaces can be located safely in very close proximity. This permits the design and construction of very compact, flat lighting fixtures that are consistent with flush ceiling mounts in commercial or residential buildings. Global electricity consumption has an economic value of approximately 1.2 trillion dollars. Approximately 33-40% is used for lighting. Reducing the energy cost of lighting by a factor 5 to 10 has an economic impact of $300-400 billion a year. In its first embodiment, the present invention comprises a two dimensional array of 30 to 100 GaAlAs or GaInAs VCSELs, generating light at wavelengths of 850 nm and 980 nm, respectively. The individual VCSELs are driven in parallel from a single current source. To avoid possible eye damage, each laser is generating a relatively low amount of power; in this case, 3 mW. This array can be used for infra-red ("IR") wireless communication, such as the IrDA standard, but at higher speeds than can be obtained using LEDs. IR local area networks ("LAN"s) or interactive TV can also utilize this embodiment of the present invention. The described white light source has the inherent modulation speed of VCSELs, which can be turned off and on at gigahertz frequencies. This allows the illumination source to be used to distribute signals at gigabits per second rates. A low cost, highly asymmetric local area network where high speed signals such as video are broadcast via the light source and low speed signals use conventional telephone wiring can be readily constructed using the present invention. A unidirectional signal distribution system in a grocery store, wherein the VCSEL white light illumination source is used both for illumination and signal transmission would permit battery powered electronic shelf labels to be updated through the lighting system without the installation of an IR or RF broadcast system. In general, optical receivers are simpler than RF receivers. When using the present invention, the illumination power levels are very high, permitting the construction of a visible light receiver that would be even simpler than an IR receiver. By varying the drive current to the individual color VCSEL arrays in the white light source of FIG. 2 by using controller 35, the color temperature of the light can be changed from bluish cold white to a more yellow, warmer white or any variation or combination in between. Source 20 can thus operate over the entire chromaticity diagram. A single white light source can also be used as a monochromatic light source of at least six different colors with only a small additional expense. Combined with the dimming ability previously described, the ability to vary color and/or temperature makes the present invention a universal source for decorative or theatrical lighting. Table 1 shows the wavelength/flux relationship for a VCSEL illumination source having six VCSEL arrays and an input of 12 W. This light source with an input of 12 W will generate an optical flux of approximately 2400 lm. Its efficiency is roughly 200 lm/W. A comparison with conventional white light sources of comparable flux levels is shown in Table 2. The 2400 lm flux is equivalent to the flux of a 170 W incandescent light bulb. It is assumed that the same conversion efficiency that has been demonstrated for VCSELs operating at 980 nm will be available at any visible light wavelength from red to blue. The IR VCSEL chip described above can then be scaled to 1×1 mm with the same area density of lasers to provide a monochromatic visible light illumination VCSEL array chip. This chip, with approximately 500 lasers operating at 2 mA per laser, would have an optical flux of 1 W at 50% conversion efficiency. At 560 nm, such a chip would generate a luminous flux of 680 lm. At an input current of 1 A and an applied voltage of 2 V, the chip would have a luminous efficiency of 340 lm/W. Recently, Sandia National Laboratories demonstrated a VCSEL with a conversion efficiency from electrical power to optical flux of 50% (5 mW of optical power from a 5 mA current and 2 V voltage). The Sandia VCSEL used a GaInAs material system, generated light at a wavelength of 980 nm and was roughly 8-10 microns in diameter. 1. An infra-red illumination source comprising: Removing the heat is a straightforward task. If the lasers are fabricated on a GaAs substrate, the thermal resistance comprises a spreading term from the 10 μm circle to the substrate and a linear term of thermal resistance between the lasers and the back surface of the chip. With a heat flow of 0.25 W, the spreading resistance raises the temperature by 1.4° C. and the substrate adds another 2.9° C. for a total chip related temperature rise of 4.3° C. Mounting the chip on a heat spreading substrate, such as chemical vapor deposition ("CVD") grown diamond, AlN or plain copper controls the heat flux without a significant temperature rise. a plurality of vertical cavity surface emitting laser chips, each chip comprised of a plurality of vertical cavity surface emitting laser elements, the elements on each chip emitting infra-red light and being coupled together so that they can be driven at least in parallel, the chips being coupled together by a combination of series and parallel couplings; and Патентная формула (7) Here is a very simple roulette strategy but also a very effective one. It is considered that John Wayne has been using this roulette strategy and that it could be found in one of his biographical books. It's been a long time since John Wayne died but it is believed that he was a passionate roulette player. 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The measured position data ( ) was numerically differentiated (finite difference formula) for linear velocity ( ) which in turn was filtered using a first order Butterworth low pass filter with a normalized cutoff frequency of 10 Hz. The filtered velocity was then numerically differentiated for linear acceleration ( ). All postprocessing was completed in Matlab® 2015a. ) is measured between the shape radial and tangential vector. We only simulated the time periods when the KS wheel action was present norges com me forbund, not during the time the board was coasting with the smaller rollers. Measured kinetic board kinematics are generally in agreement with the expected simulation data (Figure 14 ). This completes the definition for the polar mass moment of inertia of a rolling shape. The kinematics are derived by summing moments with respect to the shape ground contact (Figure 4 ). This is achieved by combining (3 ) and (7 ) casino slots birthday cards, resulting in However, in this particular setup nett casino versus, if the KS mass is negligible compared to the dispensed platform and the KS definition reaction radial function ( ) and friction function ( ) is known, it is also possible to predict the linear kinematics of the dispensed platform by the following simplified equation: Kinetic shapes (KS) are smooth shapes that can produce a predicted reaction force parallel to the ground. Note that a KS may, but is not necessarily, defined as a spiral such as an Archimedean spiral. The two-dimensional KS equation (2 ) allows for a two dimensional shape ( A KS is useful in that it can be utilized to create a desired shape that will yield a predefined kinetic behavior of the shape. The KS concept can be used anywhere that exact position-dependent force redirection is needed, which includes the fields of musical acoustics [16 ], rehabilitation engineering [17 ], and prosthetic foot design [18 ]. The first KS rolled for 1.4 seconds to an angular position of radians (45°). This motion moved the dispensed platform a distance of 1.1 m (measured) compared to the modeled distance of 0.9 m. It stopped rolling as the end of the shape at radians hits the ground plane. The modeled displacement, velocity, and acceleration results were in close proximity and slightly lower to the recorded values. While not always aligned within one standard deviation of the recorded data, the simulated data always followed the same trend as the recorded data. Rehabilitation engineering, specifically gait rehabilitation and foot prosthetics, can greatly benefit from an expanded understanding of the dynamics of different types of shaped curves rolling over ground. A foot roll-over shape (ROS), shown in Figure 2(c). is the curve that the foot rolls over while pivoting over the ground during the stance phase in walking. The form of a ROS is considered a vital concept in foot prosthesis design and greatly affects the balance and dynamics of normal or pathological gait [18. 20 ]. The latest research on ROSs and prosthetic foot design lacks the ability to predict ROS behavior, while mentioning that an analytical solution to ROS rolling dynamics could be beneficial for improving the design of foot prostheses [21 ]. For instance, in prosthetic foot design, a properly adjusted ROS can moderate ground reaction forces channeled to a user’s stump [22 ]. Recent studies mention that ROSs can be improved and modified by utilizing customized KSs to manipulate ground reaction forces [1 ]. This section presents the derivation of a two-dimensional (2D) kinetic shape (KS) when it is not in static equilibrium. In particular spill casino del, we derive the equations of motion that can predict the kinematics of a KS. Further this dynamic analysis is not exclusive to KSs but can predict the motions of any smooth and continuous physical curve that is known, measured, or approximated and is rolling across flat ground as a force is applied to the axle point. A WBB is a plastic board (51 cm × 32 cm × 5.3 cm) that is primarily used in the gaming industry but has recently been utilized as a reliable force measurement device [31. 32 ] that is comparable to high end laboratory force analysis equipment [33 ]. The WBB is instrumented with four force sensors, one at each corner that allow for the measurement of a cumulative applied weight sampled at 50 Hz with a resolution of ±5 N. However, it is important to note that the WBB is only able to read forces that are orthogonal to the WBB stepping surface and not along the surface. The measured kinetics from the WBB were applied to the KS dynamics simulation model to predict the resulting kinematics. The second KS was recorded for 1.4 seconds, before the system came to a halt at an angular position of 0 radians (or radians). The linear position of the pushed platform oscillated around a specific position, which was when the KS rolled around its 0 radians (or rad) angular position. At this equilibrium point, the radial reaction force ( ) is a local minimum of the radial ground reaction force function (Figure 6 ). The platform at that equilibrium point was found to linearly move back and forth with a vibration amplitude of approximately 0.2 m. This zero-force oscillation point is found where zero-acceleration is measured, which is at 0.68 s for the measured data and 0.6 s for the model. Similar to the first KS, the predicted values are in close proximity to the recorded values. The measured experimental results and predicted simulation values for the linear displacement, velocity norsk casino bonus uten innskudd, and acceleration of the dispensed platform by both KSs are shown in Figure 8 . This KS definition begins with an initial shape radius of = 5.00 in (12.7 cm) and since the shape is defined by a sinusoidal function, it also ends with the same radius of = 5.00 in (12.7 cm). This continuity of the shape curve is due to its diminishing integral of its sinusoidal force definition and is explained further in [1 ]. The maximum physical dimension across this KS ( ) is 25.3 in (64.2 cm). Rolling of a KS occurs when the ground contact and applied vertical force ( ) are not aligned. Rolling KSs have been previously simulated in [1 ], presenting the kinematics of a plate being dispensed by a forced KS. However, this KS simulation was analyzed using a numerical approximation, while the exact solution to this KS dynamics problem was still unsolved. In this article, we will be solving and verifying this exact setup with two different KSs. term describes the exponential rate of the friction decay from static to kinematic. The horizontal friction force that the moving platform experiences due to friction is defined by Combining (17 ), (19 ), (20 ), and (21 ) defines the equation of motion of a platform ( ) moving linearly due to the forces exerted by a 2D KS: Note the term is multiplied to isolate the acceleration component in the direction of the dispensed platform. Also note that in our setup. Similar to the angular dynamics, linear velocity ( ) and linear position ( ) of the platform can be derived by time integration and applying initial conditions, and. These equations are used to predict the linear motion of the dispensed platform as a derived KS is pressed on the platform. ) linearly. (b) Representation of the modeled parameters based on the experimental setup. It is also possible to redefine the sum of moments in (3 ) in terms of the radial ground reaction force (parallel to the ground) ( ) instead of the applied vertical force ( ). Note that the cosine trigonometric function in the numerator turns into a sine function Future works include further modifying the KS equations of motion to be able to derive exact shapes that produce desirable motions for specific applications such as the kinetic board, Gait Enhancing Mobile Shoe (GEMS) for stroke rehabilitation [17. 34 ], or an enhanced walking crutch tip [28 ]. The GEMS wheels could be designed such that they produce overground foot motions that are customized to particular individuals, walking asymmetries, or gait cycle instances. A tailored walking crutch tip could allow for easier maneuvering, which can potentially diminish overall fatigue from daily use, and allow us to tailor the dynamics of different crutch gait styles and walking environments. One healthy individual (age 23, weight 180 lb (82 kg), height 70 in (178 cm)) was recorded using the kinetic board three times. For each trial, after rocking back and forth two times, the kinetic board’s position and user applied forces were recorded as the participant loaded the back KS wheel and then the front KS wheel. Figure 7: Actual setup used to measure the dynamics of the kinetic shape pushing a flat platform. A weight forces a defined kinetic shape onto a linearly moving platform, pushing the platform underneath itself. The constant offset between the simulated and measured data may be due to the user consistently pushing backward or forward with their legs instead of simply leaning directly on top of the KS wheels. Note that the WBB used to record the input forces was only able to record forces orthogonal to the WBB stepping surface. Notice that the linear acceleration of the pushed platform in the simulated model jumps to around 3 m/s 2. while the recorded data rises gradually to 2 m/s 2. This difference accounts for the overall shorter travel distance. This discrepancy can be explained by the friction model coefficients that were used. The friction model that was used assumes a high static friction (stiction) value after which it diminishes to an increasing viscous kinetic friction. Additionally, the exact and real frictional forces experienced during the short rolling period may be highly nonlinear and not easily modeled. The actual kinetic board used in this experiment is shown in Figure 12. The kinetic board is framed and held together by adjustable and rigid 1 in by 1 in (2.54 cm by 2.54 cm) 80/20® aluminum extrusion pieces. Two height-adjustable spring-loaded caster wheels with rubber rollers were used for the middle pivot. we define its horizontal KS push force ( ) to initially push with a higher force while gradually decreasing as the KS wheel rolls (Figure 11 ). The vertically applied force ( ) by the user was chosen to be the weight of the measured user of the board which was 180 lb (800 N) (31 ). The horizontal reaction force ( ) is described by (32 ). The resulting radial shape function ( ) is shown in (33 ). The initial radius. for the back KS wheel was chosen to be 3.0 in (0.077 m): The Archimedean spiral (similar to the involute of a circle) was first studied by Archimedes in 200 B.C. after being inspired by fellow mathematician Conon of Samos and his work on conic sections [2 ]. Conic sections are curves created by the intersection of cones, often producing interesting, smooth, and asymmetric curves (e.g. Archimedean spiral, logarithmic spiral, Cortes’ spiral norge casino watch, lituus, etc.). Although these curves have several variations norsk tipping casino 6 lug, the spirals, such as the Archimedes spiral, are particularly unique because they represent a curve of radius that increases with angle in polar coordinates. In a physical sense, this allows a spiral to roll on a flat surface much like a circular wheel rolls down an incline (Figure 1 ). A physical spiral is beneficial and is utilized in several applications including cam design [3 ], microbiology [4 ], and fluid dynamics [5 ] and can be a great tool in mechanical design situations where passive or forced rolling is desired. KSs could also benefit conventional crutches, which generally have a rubber point tip that the user swings/pivots over. Such a point tip mimics a constant radius (i.e. no radius change) when rolled over. Crutches do exist with a larger radial crutch tip; however these crutches have a large constant radius that does not change [27 ]. Point and constant radius tips cannot change the crutch walking dynamics. However, using a nonconstant crutch tip may alter crutch gait dynamics in a way that predictably assists or resists crutch movement during key positions and weight applications during the crutch gait cycle [28 ]. Such a nonconstant shape crutch tip can be customized to a variety of crutch walking styles, user disabilities, or energy expenditures. The exact motions of such a crutch tip shape can be predicted or customized with a greater understanding of KS rolling. Although we do have firm knowledge of how to exactly predict the behavior of a wheel rolling down a ramp as a force is applied to its axle (Lagrangian, Energy Method, etc.), the derivation of an arbitrary and asymmetric rolling curve in a similar situation has largely been ignored. Figure 14: Kinetic board measured and simulated dynamics. The overground displacement is measured and is integrated to determine the velocity and acceleration. The linear dynamics of the moving platform was recorded for three trials for each KS (six trials total). The shapes were released at different angles as denoted in Figure 6. The first KS was placed onto the platform at an orientation of 6.1 radians (345°) as the weight was applied, while the second KS was positioned at an initial contact point angle of 4.9 radians (280°). Throughout ancient and modern history, the mechanism of rolling has been both useful and fascinating. The dynamics of a circular object rolling down a slope is an elementary and age-old mechanics concept and is often taught in early mechanics courses. The equations of motion of a two dimensional circular object rolling down a slope is a common physics problem. However, a notion that has gained less attention is the forced rolling of irregular objects or curves. The equations of motion that exactly dictate the rolling of a shape as a known force input is applied to its rotational axle have not previously been developed. which is exerted by the KS onto the platform. It is also dependent on the velocity of the platform relative to the ground ( ). The friction model, which defines the coefficient of friction ( Note that solving (17 ) for the shape radius function ( ) would be very useful in that one could specify the vertically applied forces ( ), the radial ground reaction forces ( ), and a desired kinematics function over time ( ) that the resulting shape radius function ( ) will produce. However, if angular acceleration ( ) is considered to be a nonconstant, (10 ) yields a second order nonlinear partial differential equation dependent on angle and time. Additionally, if we consider angular acceleration to be a constant, we are confronted with the problem of isolating and solving for the shape radius ( ) that is embedded in the trigonometric functions. Both assumptions could not be solved analytically; however they could be solved using numerical methods to find the shape curve radius function ( ). As before, (20 ) was utilized to develop a friction model in order to more accurately represent the derived results in comparison to the experimental. This friction model ( ) aims to predict the total friction experienced by the kinetic board when moving forward. Therefore, as the user leans onto the back KS wheel with user weight ) and tangential vector ( ) in (11 ) and is shown in Figure 4(b). In (20 ), the Coulomb friction, or kinetic friction, is defined by. while the static friction is represented by. The viscous friction is the product of the Coulomb term and the linear velocity ( ). The friction is dependent on the signum function of the linear velocity, which has possible values of −1, 0, and 1. Finally, the In addition to the physical experiment, a Matlab script that simulated the physical experiment by applying our derived formulas was utilized to compare the modeled and measured results. The simulated results included linear acceleration, velocity, and displacement of the dispensed platform. The simulation was evaluated at a s time step and a rads angle step size around the KS definition. Figure 3: A physical kinetic shape curve ( ) in static equilibrium will react with a defined horizontal (parallel to the ground) force function ( ) when a known vertical (perpendicular to the ground) force function ( ) is applied to the curve’s origin. As the user shifts their weight onto the KS wheels, the force applied by the user onto the wheels is not perfectly perpendicular to the ground but also includes a force component that is slightly parallel to the ground. This horizontal push force is down and to the rear of the board as the user loads the back KS wheel, which slightly resists the forward motion. This impedance only seemed present at the beginning of the rolling motion. Once the equilibrium is unbalanced and the kinetic board’s inertia increased, the rear shape had no trouble rolling on and propelling the user forward. In mathematics, there have been articles centered on roulettes, which are curves traced by points on a two-dimensional circular or noncircular shape while rolling over flat or uneven surfaces. These provide insight to the kinematics of these shapes and the roulette curves that they produce but do not focus on any physical kinetics of these shapes when rolling over various surfaces [14 ]. ), while the same rolling motion is created for a rounded object by a decreasing shape radius around the object (relative to the axle point) (
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