| 1. |
- Andersson, Mattias K., et al.
(författare)
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The extended substrate cleavage specificity of the human mast cell chymase reveals a serine protease with well-defined substrate recognition profile
- 2009
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Ingår i: International Immunology. - : Oxford University Press (OUP). - 0953-8178 .- 1460-2377. ; 21:1, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- The human chymase (HC) is a major granule constituent of mast cells (MCs) residing in the connective tissue and the sub-mucosa. Although many potential substrates have been described for this important MC enzyme, its full range of in vivo substrates has most likely not yet been identified. A major step toward a better understanding of the function of the HC is therefore to determine its extended cleavage specificity. Using a phage-displayed random nonapeptide library, we show that the HC has a rather stringent substrate recognition profile. Only aromatic amino acids (aa) are accepted in position P1, with a strong preference for Tyr and Phe over Trp. Aliphatic aa are preferred in positions P2 to P4 N-terminal of the cleaved bond. In the P1' position C-terminal of the cleaved bond, Ser is clearly over-represented and acidic aa Asp and Glu are strongly preferred in the P2' position. In P3', the small aliphatic aa Ala, Val and Gly were frequently observed. The consensus sequence, from P4 to P3': Gly/Leu/Val-Val/Ala/Leu-Ala/Val/Leu-Tyr/Phe-Ser-Asp/Glu-Ala/Val/Gly, provides an instrument for the identification of novel in vivo substrates for the HC. Interestingly, a very similar cleavage specificity was recently reported for the major chymase in mouse connective tissue mast cells (CTMCs), the beta-chymase mouse mast cell protease-4, suggesting functional homology between these two enzymes. This indicates that a rather stringent chymotryptic substrate recognition profile has been evolutionary conserved for the dominant CTMC chymase in mammals.
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| 2. |
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| 3. |
- Frank, Markus, 1970, et al.
(författare)
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Differential Impedance Measurement Method of RFID Transponder Chips at UHF
- 2013
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Ingår i: Proceedings of the 43rd European Microwave Conference. - 9782874870316 ; 2013, s. 68-71
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Konferensbidrag (refereegranskat)abstract
- A novel on-wafer measurement method of RFID transponder chips is presented. A comparison is made between single ended one-port, single ended two-port and differential two-port excitation. The two-port method is a flexible way of measuring chips consisting of both several individuals as well as chip types with different geometries with one and the same probe type. The theory of un-terminating and de-embedding is described and verified by measurements. A qualitative analysis is defined, which explains certain phenomena seen in communication tests performed on RFID protocol level. This is further supported by measurement results from the presented method.
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| 4. |
- Enoksson, Mattias, et al.
(författare)
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Intraperitoneal influx of neutrophils in response to IL-33 is mast cell-dependent
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:3, s. 530-536
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Tidskriftsartikel (refereegranskat)abstract
- IL-33 is a recently discovered cytokine involved in induction of Th2 responses and functions as an alarmin. Despite numerous recent studies targeting IL-33, its role in vivo is incompletely understood. Here we investigated inflammatory responses to intraperitoneal IL-33 injections in wild-type and mast cell–deficient mice. We found that wild-type mice, but not mast cell–deficient Wsh/Wsh mice, respond to IL-33 treatment with neutrophil infiltration to the peritoneum, whereas other investigated cell types remained unchanged. In Wsh/Wsh mice, the IL-33–induced innate neutrophil response could be rescued by local reconstitution with wild-type but not with T1/ST2−/− mast cells, demonstrating a mast cell–dependent mechanism. Furthermore, we found this mechanism to be partially dependent on mast cell–derived TNF, as we observed reduced neutrophil infiltration in Wsh/Wsh mice reconstituted with TNF−/− bone marrow–derived mast cells compared with those reconstituted with wild-type bone marrow–derived mast cells. In agreement with our in vivo findings, we demonstrate that humanneutrophils migrate toward the supernatant of IL-33–treated human mast cells. Taken together, our findings reveal that IL-33 activates mast cells in vivo to recruit neutrophils, a mechanism dependent on IL-33R expression on peritoneal mast cells. Mast cells activated in vivo by IL-33 probably play an important role in inflammatory reactions.
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| 5. |
- Enoksson, Mattias
(författare)
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Mast cell responses to danger signals
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Detecting and responding to danger is a paramount function of the immune system. Compounds heralding danger can be divided into two groups: exogenous and endogenous danger signals. The former group consists of conserved microbial structures such as lipopolysaccharide (LPS), while the latter consists of host compounds released or exposed by dead or dying cells as a consequence of trauma, stress or infection. Mast cells are long-lived immune cells present in almost all tissues, and are especially numerous at sites facing the external environment, making them ideal responders to danger signals. The aim of the work presented in this thesis was to investigate mast cell responses to danger signals of exogenous and endogenous origin. In Paper I, we investigated mast cell responses to the exogenous danger signal M-TriDAP, a bacterial peptidoglycan degradation product. We found that cord bloodderived mast cells (CBMCs) express NOD1, the receptor for M-TriDAP. Furthermore, M-TriDAP-treatment of CBMCs resulted in degranulation-independent release of cytokines and chemokines such as TNF, IL-8/CXCL8, MIP-1α/CCL3 and MIP-1β/CCL4. Importantly, we observed an augmented response when M-TriDAP was combined with the TLR4 agonist LPS, indicating cooperation between intracellular and extracellular pattern recognition receptors. In Paper II, we investigated mast cell responses to cell injury by subjecting murine mast cells to the supernatant of fibroblasts rendered necrotic by freeze-thawing. We found that mast cells respond to cell injury in this model by initiating a proinflammatory response, characterized by degranulation-independent release of cytokines and leukotrienes. By using genetically modified mice and molecular inhibitors, we found that the recognition of cell injury was MyD88-, T1/ST2- and p38- dependent. Finally, by using RNA-interference, we could pinpoint IL-33 as the necrotic cell compound that was responsible for the mast cell activation. In Paper III, we investigated responses to IL-33 administration in vivo. Here we found that wild-type C57BL/6 mice respond to intraperitoneal IL-33 administration with neutrophil infiltration. This response was not observed in mast cell-deficient mice but could be restored upon mast cell reconstitution, thus demonstrating a mast cell dependent mechanism. In Paper IV, we investigated the hypothesis that mast cells might function as sensors of damaged epithelia by responding to IL-33 during chronic inflammations of the airways, for instance in asthma. We found that IL-33 is released from necrotic airway epithelial cells and that CBMCs respond to the necrotic supernatant of these cells by secreting IL-5, IL-8/CXCL8, TNF and GM-CSF. However, no release of histamine, LTB4 or PGD2 could be detected. Interestingly, the exact same mediator release pattern was observed when CBMCs were treated with recombinant IL-33, suggesting that IL-33 might be an important factor released by injured airway epithelial cells that activates mast cells. In conclusion, the work presented in this thesis provides further evidence for important roles of mast cells in innate immune responses. The function of mast cells as sensors of cell injury is highlighted; a role that potentially can be either beneficial or detrimental. Finally, novel evidence is provided for the notion that IL-33 is an important danger signal capable of mast cell activation.
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| 6. |
- Frank, Markus, 1970, et al.
(författare)
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Design Equations for Lumped Element Balun With Inherent Complex Impedance Transformation
- 2017
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 65:12, s. 5162-5170
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates a novel lumped design approach for complex impedance transformation, based on symmetry relaxation in the out-of-phase-compensated-power-splitter. In the modified topology, a total of four component values are used, of which two values analytically depend upon the other two, keeping the balance parameter maximally flat and independent of the source and load impedance, as well as of the balun internal components. From the condition of zero input reflection loss, the two other component values are also determined analytically, hence specifying all component values uniquely. A Monte Carlo sensitivity analysis predicts an amplitude imbalance, which in practice defines the limit in balance operational bandwidth, of better than +/-1 dB, over a 20% bandwidth at 925 MHz operating frequency. Based on the design equations, demonstrators for four different design cases are fabricated, verifying the simulated performance.
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| 7. |
- Frank, Markus, 1970, et al.
(författare)
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Differential Transmission Line Loop for RFID Reactive Near-Field Coupling
- 2018
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 66:5, s. 2141-2153
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Tidskriftsartikel (refereegranskat)abstract
- The differential transmission line loop (DTLL) as an efficient reactive near-field coupling element for programming of radio frequency identification (RFID) inlays is proposed. It is validated, with simulations and measurements, that the differential excitation and the presence of a ground plane are fundamental properties for high performance in coupling while providing high electromagnetic isolation. As a proof of concept, super elliptical loop geometries as coupling elements are investigated for a number of commercially available inlay geometries. From simulations of the DTLL and inlay antenna, coupling efficiencies higher than 80% are predicted. Measurements of the \Delta \Gamma -value indicate a nonlinear input impedance with power, and verify the high values of simulated coupling efficiency. The threshold power levels read from interrogator are below 5 dBm, which are considered as very low in inlay encoding, and hence show that the DTLL is a promising candidate for efficient RFID programming in the reactive near field.
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| 8. |
- Frank, Markus, 1970, et al.
(författare)
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Lumped element balun with inherent complex impedance transformation
- 2017
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Ingår i: IEEE MTT-S International Microwave Symposium Digest. - 0149-645X. - 9781509063604 ; , s. 1285-1288
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Konferensbidrag (refereegranskat)abstract
- A novel lumped design approach for complex impedance transforming baluns is presented in this paper. It is shown that a relaxation of symmetry in the T-networks of the out-of-phase-compensated-power-splitter enables complex impedance transformation. Design equations are analytically derived for a total of 4 component values, of which 2 values depend upon the 2 other, which are free variables. The two free component values are used independently for adjustment of input reflection loss, further keeping the balance parameter maximally flat and independent of the load impedance. For Q-values of source and load, not being excessively high, the balun can be realized with only 8 components. A demonstrator is fabricated, transforming 26.9 + j11.1 Ω to 73.8 + j38.6 Ω. An amplitude balance of ±0.7 dB and phase balance better than ±5° is achieved over a 20 % bandwidth. The return loss is higher than 20 dB.
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| 9. |
- Frank, Markus, 1970, et al.
(författare)
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Shifted Source Impedance and Nonlinearity Impact on RFID Transponder Communication for Drive-Level Offsets
- 2016
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 64:1, s. 299 - 309
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Tidskriftsartikel (refereegranskat)abstract
- A measurement and analysis method to quantify the communication quality for ultrahigh-frequency radio frequency identification (RFID) transponder chips under a shifting source environment is presented. A detailed description of theory, setup, and procedure is provided. The differences in on/off impedance (|ΔΓ|-value) of the transponder chip are critical for backscatter modulation and, therefore, the overall communication and transponder response. In the present work, a new quantity which includes the difference in on/off impedance, as well as arbitrary source impedance, is defined as an overall figure of merit. A qualitative analysis, considered as novel in the RFID community, shows the impact a source impedance shift has on the communication quality. The bare chip measurement setup enables an ASK modulated wake up signal, realized as a pulse train. The chip response consisting of modulated impedance states are measured in a pulse profile setup. Results show that different degrees of non-linearity in a transponder chip, depending on vendor and type, will have impact on the communication performance.
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| 10. |
- Gallwitz, Maike, et al.
(författare)
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Expression profile of novel members of the rat mast cell protease (rMCP)-2 and (rMCP)-8 families, and functional analyses of mouse mast cell protease (mMCP)-8
- 2007
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Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 59:5, s. 391-405
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Tidskriftsartikel (refereegranskat)abstract
- Four hematopoietic serine proteases are common to the mast cell chymase locus of all analyzed mammals: α-chymase, cathepsin G, granzyme B, and granzyme C/H. Apart from these common genes, the mouse and rat loci hold additional granzyme-, β-chymase-, and Mcpt8-like genes. To better understand the functional consequences of these additional enzymes and to be able to compare human and rodent immune functions, we have analyzed the expression of novel β-chymase- and Mcpt8-like genes in the rat. Four novel genes, i.e., Mcpt2-rs2a, Mcpt2-rs2c, Mcpt8-rs1, and Mcpt8-rs4 were transcribed in tissues holding mucosal mast cells (MMC), where also the classical MMC protease Mcpt2 was expressed. We also found transcripts of rat vascular chymase (rVch) in some of these tissues. RVch is a β-chymase that converts angiotensin I, like the human chymase. Rat MMC may therefore have similar angiotensin-converting properties as chymase-positive human mast cells, although these are mostly regarded the counterpart of rat connective tissue mast cells. The human mast cells that are considered the counterpart of rat MMC express, however, only tryptase, whereas rat MMC express various proteases, but no tryptase. We further studied the proteolytic activity of mMCP-8 as a first representative for the Mcpt8-subfamily. Based on sequence comparison and molecular modeling, mMCP-8 may prefer aspartic acid in substrate P1 position. However, we could not detect hydrolysis of chromogenic substrates or phage-displayed random nonapeptides despite numerous trials. On the other hand, we have obtained evidence that the function of the Mcpt8-like proteases depends on proteolytic activity. Namely, the expression of the only Mcpt8-family member with a mutation in the catalytic triad, Mcpt8-rs3, was strongly reduced. Thus, the substrate specificity of mMCP-8 may be too narrow to be detected with the employed methods, or the enzyme may require a substrate conformation that is not provided by the analyzed peptides.
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