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Molecular mimicry between foreign and self Ags is a mechanism of TCR cross-reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign Ag Tax from the human T cell leukemia virus-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease human T cell leukemia virus-1–associated myelopathy/tropical spastic paraparesis, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found in our study that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics and that in contrast with other recent structures of TCRs with self Ags, A6 engages the HuD Ag with the same traditional binding mode used to engage Tax. Although peptide and MHC conformational changes are needed for recognition of HuD but not Tax and the difference of a single hydroxyl triggers an altered TCR loop conformation, TCR affinity toward HuD is still within the range believed to result in negative selection. Probing further, we found that the HuD–HLA-A2 complex is only weakly stable. Overall, these findings help clarify how molecular mimicry can drive self/nonself cross-reactivity and illustrate how low peptide-MHC stability can permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditional binding mode.
T cell receptor recognition of peptide Ags presented by class I or class II MHC proteins is a cornerstone of cellular immunity. Recognition of foreign Ags forms the basis for defense against viruses and other pathogens, yet recognition of self Ags can lead to autoimmunity. Although the central tolerance mechanism of negative selection plays a protective role against autoimmunity, the high level of cross-reactivity present within the T cell repertoire can promote autoimmunity if T cells are activated by foreign Ags that share key structural or chemical features with self Ags. This concept of molecular mimicry has been implicated in a number of autoimmune pathologies, including type 1 diabetes, lupus, and multiple sclerosis (1–3).
Previously determined structures of TCRs in complex with self Ags associated with autoimmunity have shown deviations from the binding mode traditionally seen in TCR recognition of foreign Ags. The traditional binding mode, typified by the structure of the αβ A6 TCR with the human T cell leukemia virus-1 (HTLV-1) Tax peptide presented by HLA-A2 (4), has the TCR centered diagonally over the peptide-MHC (pMHC), with the CDR3α and CDR3β loops positioned near the center of the peptide. Rather than adopting this configuration, the Ob.1A12 and 3A6 TCRs bind near the N terminus of the peptide, such that the focus of the TCRs is on the second and third positions of the peptide rather than the center residues (5, 6). In another case, recognition of the mylein basic protein Ac1-11 self Ag by three different TCRs proceeds with a more traditional binding mode (7, 8), but the Ac1-11 peptide only partially occupies the MHC peptide binding groove (9), resulting in atypical TCR–peptide interactions resembling those seen with the OB.1A12 and 3A6 TCRs. Although each of the examples above involves TCRs restricted to class II MHCs, there is evidence of similar behavior in class I systems (10). A hypothesis stemming from these observations is that deviations from the "traditional" binding mode used to engage foreign Ags are responsible for low-affinity TCR binding, allowing T cell escape from negative selection and contributing to the development of autoimmunity (11, 12).
However, the extent to which altered TCR binding would apply within the confines of molecular mimicry is unclear. Generally speaking, differential recognition of self and nonself by the same TCR would seem inconsistent with molecular mimicry as traditionally envisioned (i.e., the conservation of key features translating into a similar mode of recognition). Examinations of molecular mimicry in other systems, including TCR recognition of foreign mimics as well as other protein–protein interactions, have routinely shown a conservation of the overall binding mode (13–15). Indeed, although the two Ags were not classified beforehand as molecular mimics, the structure of the Ob.1A12 bound to a microbial Ag recapitulated the unusual binding mode seen with the mylein basic protein self Ag (16). In another demonstration, the murine TCR 2C cross-reacts with the foreign and self SIYR and dEV8 Ags via a common, traditional binding mode (17).
Yet differential docking of a single TCR on foreign and self pMHC ligands can occur, as demonstrated by the different orientation 2C adopts on the foreign QL9/H-2Ld ligand (18). Although this latter case is not one of molecular mimicry, unanticipated complexities observed in recent structural analyses of molecular mimics, including TCR, peptide, and MHC conformational changes and poor translation of sequence into structural mimicry (13, 14), warrants caution when presuming that foreign and self mimics will be recognized similarly.
In this study, we examined cross-recognition between self and nonself molecular mimics by the A6 TCR. As noted above, A6 recognizes the HTLV-1 Tax Ag presented by HLA-A2 (positions 11–19 of the Tax protein; sequence LLFGYPVYV). Although it is not highly promiscuous (19), A6 cross-reacts with a variety of modified Tax variants that share previously identified key residues, as well as microbial peptides, such as the yeast Tel1p peptide (13, 19–22). In a possible link with autoimmunity, A6 also recognizes a self Ag from an immunodominant region of the human neuronal protein HuD (positions 87–95; sequence LGYGFVNYI) (21, 23). T cell recognition of epitopes from HuD have been suggested to play a role in the neurologic disorder human T cell leukemia virus-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), a demyelinating autoimmune disease affecting a minority of HTLV-1–infected individuals (24, 25). Patients with HAM/TSP that are HLA-A2–positive have persistent, high levels of CD8+ T cells specific for the Tax epitope in their peripheral blood and cerebral spinal fluid (26, 27), and the A6 T cell clone was isolated from a HAM/TSP-affected individual (28). The Tax and HuD peptides have related sequences (Fig. 1A), sharing a key glycine at position 4 as well as aromatics at positions 5 and 8, which play predominant roles in the crystallographic structure of Tax–HLA-A2 bound to A6 (4).
To provide further insight into self/nonself recognition within the context of molecular mimicry and to help inform the possible link between TCR recognition of Tax and HuD in HAM/TSP, in this study we determined the structural basis for T cell cross-reactivity between the Tax and HuD epitopes. The structure of the HuD–HLA-A2 complex revealed it is a close but imperfect structural mimic of the Tax–HLA-A2 complex. Yet, the A6 TCR engaged the HuD ligand in the same "anti-foreign" manner as it engages the Tax ligand, with no unusual features in the TCR–pMHC interface. Notably though, recognition of HuD required peptide and MHC conformational adjustments not needed for recognition of Tax, and the difference of a single hydroxyl group between the peptides triggered a different conformation for the A6 CDR3β loop. The structural changes contributed to a large, 70-fold weaker affinity of A6 for the HuD ligand. However, TCR affinity toward HuD was still within the range shown to result in negative selection in other systems (29). Probing further, we found that the HuD–HLA-A2 complex is only weakly stable, explaining why HuD-reactive T cells can be found in the periphery despite the existence of T cells that engage them with the traditional anti-foreign binding mode.
Materials and Methods
Proteins and peptides
Soluble HLA-A2 and A6 TCR were refolded from bacterially expressed inclusion bodies as previously described (30). Peptides were synthesized locally or purchased from Genscript; peptide purity and identify were confirmed by liquid chromatography/mass spectrometry. Streptavidin was purchased from Rockland. The A6 TCR used included an engineered disulfide bond across the constant domains for improved heterodimer stability (31).
Crystallization and x-ray analysis
Peptide–HLA-A2 crystals were grown from 24% PEG 3350 in 25 mM MES, pH 6.5, 0.1 M NaF or 0.1 M NaCl. A6–HuD–HLA-A2 crystals were grown from 15% PEG 4000 in 0.1 M Tris, pH 8.5, 0.2 M MgCl2. Cryoprotection for all crystals consisted of 20–25% glycerol. Diffraction data were collected at Argonne National Laboratory at the indicated beamlines at 100 K using a wavelength of 0.979 Å. Data reduction, structure solution, refinement, and structure validation was performed as previously described (19). Coordinates for search models for the pMHC structures were from Brookhaven Protein Data Bank (PDB) entries 1TVB (32) for pMHC and 2GJ6 (19) for TCR–pMHC. Data collection and refinement statistics are presented in Table I. Surface area analysis was performed with the program Surface Racer using a probe radius of 1.4 Å (33). Shape complementarity (34) was calculated as implemented in CCP4 (35). Coordinates and structure factors are available from the PDB (www.rcsb.org). PDB accession numbers are 3PWL for HuD–HLA-A2, 3PWP for A6–HuD–HLA-A2, 3PWN for HuDG2L–HLA-A2, and 3PWJ for HuDG2L/I9V–HLA-A2.
Surface plasmon resonance
Surface plasmon resonance measurements were performed with a Biacore 3000 instrument as previously described (30). All data were collected at 25°C. Solution conditions were 10 mM HEPES, 3 mM EDTA, 150 mM NaCl, 0.005% surfactant P-20, pH 7.4. pMHC complexes were coupled to the sensor surface via a biotin–streptavidin linkage, with the streptavidin amine coupled to a CM5 sensor chip. Biotinylated HuD–HLA-A2, HuDG2L–HLA-A2, and HuDG2L/I9V–HLA-A2 were coupled to three of the flow cells, with the fourth serving as a reference. Soluble A6 TCR was then injected at 5 μl/min until steady state was reached. Each injection series was repeated twice and the data globally analyzed. Data were processed in BIAevaluation 4.1 and analyzed with Origin 7.5.
Thermal stability
Circular dichroism measurements of pMHC thermal stability were performed using a Jasco J-815 spectrometer monitoring 218 nm. Solution conditions were 20 mM phosphate and 75 mM NaCl (pH 7.4). Sample concentrations were 5 μM. A temperature increment of 1°C/min was used, maintaining the temperature within 0.1°C for 5 s before sampling. As peptide–HLA-A2 complexes do not show reversible unfolding, the data were fit to a nine-order polynomial and the apparent Tm taken from the maximum of the first derivative of the fitted curve.
The HuD–HLA-A2 self-complex is a close but imperfect mimic of the Tax–HLA-A2 nonself complex
We first determined the structure of the HuD–HLA-A2 complex at 1.65 Å resolution (Table I). The complex displayed the usual class I pMHC architecture with two molecules per asymmetric unit (Fig. 1A). There are no substantial differences between the two molecules in the unit cell (all atoms of the two peptides superimpose with an root mean square deviation (RMSD) of 0.1 Å; the backbones of the HLA-A2 peptide binding domains superimpose with an RMSD of 0.4 Å). Electron density images for the peptides in the HLA-A2 peptide binding grooves appear in Supplemental Fig. 1.
Comparison of the HuD–HLA-A2 complex with the Tax–HLA-A2 complex (36) revealed the HuD complex to be a close but imperfect mimic of the Tax complex. Other than a small region of the α2 helix discussed below, the HLA-A2 H chains are in full alignment (Fig. 1B). The peptide backbones adopt the same conformation, superimposing with an 0.4 Å RMSD (Fig. 1C). The majority of the peptide side chains overlay each other. However, the side chain of Tyr3 of HuD is rotated 110° compared with its analogue Phe3 in Tax, pointing the side chain toward the base of the peptide binding groove. Likewise, the side chain of Phe5 is rotated 120° compared with its analogue Tyr5 in Tax, also pointing the side chain toward the base of the binding groove. The concerted difference in the positions 3 and 5 side chains is attributable to differences in π-stacking between the two aromatic side chains: in HuD, Tyr3 and Phe5 are arranged in a classic parallel-displaced arrangement, whereas in Tax they are arranged in a T-shaped fashion (37). The differences reflect a common structural and energetic link between nonadjacent peptide side chains in pMHC complexes (38) and alter how an incoming TCR would see the peptide, particularly at the position 5 aa, which in the complex of the A6 TCR with the Tax peptide is accommodated in a central pocket formed by the CDR3α and CDR3β loops (4).
The small "linker region" connecting the short and long helical elements of the α2 helix in the HuD–HLA-A2 complex is slightly shifted relative to its position in Tax–HLA-A2 (highlighted in Fig. 1B; electron density images for this region are shown in Supplemental Fig. 3). Peptide-dependent shifts have been noted in this region previously (e.g., see Ref. 39), likely reflecting an influence of the peptide on HLA-A2 flexibility as recently described with the yeast Tel1p peptide (13). The shift is small, only 1.1 Å at the α carbon of Ala150. However, as discussed below, small changes in this region impact TCR recognition of the HuD–HLA-A2 complex.
The A6–HuD–HLA-A2 ternary complex is very similar to the A6–Tax–HLA-A2 complex
We next determined the structure of the ternary complex of the A6 TCR bound to HuD–HLA-A2 at a resolution of 2.7 Å (Table I; see Supplemental Fig. 2 for electron density images). The complex is very similar to the ternary complex of A6 with the Tax peptide, with the TCR positioning itself over HuD–HLA-A2 exactly as it does over Tax–HLA-A2, forming the same docking angle and tilt (Fig. 2A). With the exception of CDR3β, which is shifted toward the periphery of the interface as discussed later, the loops of A6 are in the same conformation in both complexes (Fig. 2B). A6 recognition of the Tax and HuD foreign and self Ags thus proceeds with the same traditional binding mode.
The difference in the TCR CDR3β loop between the HuD and Tax complexes is maximal at the α carbon of Gly101β, which in the HuD complex is moved toward the periphery of the interface by 3.3 Å (Fig. 2C). Further along the loop, Pro103β is displaced by 2.0 Å. Although the differences in the loop between the two structures are structurally significant, in context they are not unusual, as the maximal 3.3 Å shift is just below the average CDR3β movement tabulated in a recent comparison of free and bound TCRs (40). There is no obvious steric reason for the shift in CDR3β. However, CDR3β in A6 has been found to adopt a range of conformations in various structures with variants and mimics of the Tax peptide (13, 19, 20, 41). As discussed later, the loop shift reflects a need to optimize interface electrostatics, triggered by the loss of a hydrogen bond between position 5 of the peptide and the TCR.
The shift in the α2 helix linker region noted in the structure of the free HuD–HLA-A2 complex is more pronounced in the A6–HuD–HLA-A2 complex (Fig. 2D), with the region backing away from its position in the A6–Tax–HLA-A2 complex by 1.4 Å as measured at the α carbon of Ala150. Although smaller and less of a reorganization than that seen for CDR3β, movement of the α2 helix impacts the contacts made across the interface, likely contributing to the weaker affinity A6 maintains toward HuD–HLA-A2.
Although the TCR binds with the same mode, the amino acid differences between Tax and HuD, the different CDR3β conformation, and the small shift in the α2 helix linker region lead to a number of altered contacts within the TCR–pMHC interface. The majority of the differences are between CDR3β, the center of the peptide, and the shifted region of the HLA-A2 α2 helix. There is a net loss of six hydrogen bonds or salt-bridges in the HuD structure. Despite the changes, with few exceptions the pattern of amino acids used to form the complex is similar in Tax and HuD. The "hotspot" residue of Arg65 of the HLA-A2 α2 helix remains a major participant (42, 43), as do the other amino acids comprising the proposed class I MHC "restriction triad" (Arg65, Ala69, and Gln155 in HLA-A2) (44). A detailed comparison of the structural features of the HuD and Tax TCR–pMHC interfaces is provided in Supplemental Fig. 4.
Are there features in the A6–HuD–HLA-A2 interface easily identifiable as "suboptimal?" As noted above, the shift in CDR3β is within the range of those seen previously. The amount of buried solvent-accessible surface area in the HuD and Tax interfaces is nearly identical (2084 Å2 with Tax versus 2128 Å2 with HuD), as is the proportion of buried hydrophobic/hydrophilic surface (54% hydrophobic with Tax, 55% hydrophobic with HuD). The total number of interatomic contacts is also nearly identical (130 with Tax versus 126 with HuD). Although the number of hydrogen bonds and salt-bridges is reduced in the HuD complex compared with that of the Tax complex (15 with Tax, 9 with HuD), the number present is still within the range seen in other TCR–pMHC complexes with foreign Ags (45). Although the contacts are altered, the general pattern of amino acids contacted on both sides of the interface is similar with both the HuD and Tax peptides (see Supplemental Fig. 4). Lastly, the shape complementarity in the A6–HuD–HLA-A2 interface is actually improved compared with that in the A6–Tax–HLA-A2 interface (0.66 with HuD versus 0.63 with Tax). Thus, a priori, the complex of A6 with HuD–HLA–A2 does not show any easily identifiable "suboptimal" features.
The shift in CDR3β is attributable to imperfect chemical mimicry between HuD and Tax
Although the CDR3β loop is in a different conformation in the HuD structure than in the Tax structure, we noticed that the conformation of the loop is very similar to an alternate conformation observed previously with a variant of the Tax peptide. This peptide, referred to as TaxY5F(3,4FF), replaced Tyr5 of Tax with a doubly fluorinated phenylalanine derivative, with one of the two fluorines substituting for the tyrosine hydroxyl (41) (Fig. 3A). The fact that both structures showed nearly the same altered loop conformation suggested to us a mechanism in which the conformation of the CDR3β loop is dependent upon electrostatic interactions in the interface.
Notably, the HuD and the TaxY5F(3,4FF) peptides alter interface electrostatics similarly. In the structure with the native Tax peptide, the side chain of Arg95 of CDR3β, at the apex of the pocket formed by the CDR3α and CDR3β loops, hydrogen bonds to the Tax Tyr5 hydroxyl (Fig. 3B). Neither the HuD peptide nor the TaxY5F(3,4FF) peptide can form this hydrogen bond [fluorine is a poor hydrogen bond acceptor (46)], and in both cases Arg95β moves away from the side chain (Fig. 3C, 3D). The loss of this hydrogen bond in both structures is countered by the formation of a new salt-bridge between Arg102β seven residues down the loop and Glu154 of the HLA-A2 H chain. The difference in the position of the CDR3β loop in the HuD and TaxY5F(3,4FF) complexes thus results from the need to optimize electrostatics between the TCR and the pMHC, stemming from the loss of the hydrogen bond to the position 5 side chain. In other words, the difference of a single hydroxyl appears to trigger the altered positioning of the CDR3β loop.
Peptide conformational changes in HuD but not Tax upon A6 binding contribute to a weaker TCR affinity
In the complex with the TCR, the HuD peptide adopts the same conformation as the Tax peptide, as is clear in Fig. 2. As the side chains of Tyr3 and Phe5 of the HuD peptide are presented by HLA-A2 in conformations different from their counterparts in the Tax peptide, they must therefore rotate in order for the ternary complex to form (Fig. 4A, 4B). Similar conformational changes are not needed for A6 recognition of the Tax peptide, as the side chains of Phe3 and Tyr5 are presented in conformations compatible with TCR recognition (Fig. 4C, 4D).
With glycine at position 2 and isoleucine at position 9, the HuD peptide has poor anchor residues for HLA-A2 (47). We were initially concerned that reduced stability of the pMHC complex would impede crystallization and thus studied anchor-modified variants of the HuD peptide. In the first variant, glycine 2 was substituted with leucine (HuDG2L). The second variant included the Gly2→Leu modification but also substituted isoleucine 9 with valine (HuDG2L/I9V). Although as demonstrated earlier, reduced pMHC stability did not impact our studies with the native peptide, we did crystallize and determine the structures of the complexes of the two anchor-modified peptides with HLA-A2 (Table I; see Supplemental Fig. 3 for electron density images). Both complexes were identical to the complex with the native peptide except in the positioning of the side chains of Tyr3 and Phe5. Unlike the native peptide, in the HuDG2L–HLA-A2 complex, the peptide was presented with both side chains mimicking their conformations in the A6–HuD–HLA-A2 complex (this was true for both molecules in the asymmetric unit, for which all atoms of the peptide superimposed with an RMSD of 0.2 Å) (Fig. 5A). The positioning of the side chains in the HuDG2L/I9V–HLA-A2 structure was more complicated: the Tyr3 and Phe5 side chains in the first molecule in the asymmetric unit adopted their TCR-bound conformations, but the electron density in the second molecule in the asymmetric unit allowed the side chains to be modeled in both the TCR-bound and TCR-free conformations of the native peptide (Fig. 5B). Anchor modification thus perturbed the side-chain conformational equilibrium toward the TCR-bound state, with a greater perturbation in the singly modified HuDG2L peptide. The mechanism behind the perturbations is not clear, as there are no backbone or side-chain changes propagated from the anchor residues, and there are no crystallographic contacts in any of the structures that could influence side-chain position. However, anchor modification of class I MHC-presented peptides has previously been shown to affect the conformation of amino acids distant from the site of substitution (48–50).
A prediction from these structural results is that the affinity of A6 should be stronger for the anchor-modified HuD ligands than it is for the native ligand. To confirm this, we examined the affinity of the A6 TCR toward the native and the two anchor-modified HuD ligands in a Biacore binding assay. TCR affinity for the native ligand was weak at 140 μM, in good agreement with a previously reported measurement (23). Fully consistent with the structural data, the affinity for the doubly modified HuDG2L/I9V variant was 2-fold stronger at 70 μM, whereas affinity for the singly modified HuDG2L variant was stronger still at 48 μM (Fig. 5C). For comparison, the affinity for the Tax ligand is a much stronger 2 μM (30).
The results with the anchor-modified peptides can be extrapolated to help explain the difference in the A6 TCR's affinity toward the native HuD and Tax ligands. As A6 presents its central side chains in their TCR-bound conformation whereas HuD does not, we can conclude that one reason why A6 recognizes HuD more weakly than it does Tax is that, unlike Tax, the central aromatic side chains of the HuD peptide must shift into a binding-competent conformation in order for recognition to proceed.
The HuD–HLA-A2 complex is of low stability relative to the Tax–HLA-A2 complex
Although the A6 TCR recognized the HuD–HLA-A2 complex with a weaker affinity than that for the Tax–HLA-A2 complex, the affinity of 140 μM is still within a range believed to result in negative selection (29). As poor Ag presentation levels can also lead to escape from negative selection (51) and the HuD peptide has suboptimal anchors for HLA-A2, we examined the thermal stability of the HuD–HLA-A2 complex using circular dichroism spectroscopy. Circular dichroism has long been used to examine pMHC stability, and measurements of thermal stability correlate with pMHC binding affinity (52). The Tm of the native HuD–HLA-A2 complex was measured as 40°C (Fig. 6). As expected, anchor modification of the HuD peptide enhanced stability, with the Tm of the doubly modified HuDG2L/I9V complex measured as 59°C and the Tm of the singly modified HuDG2L complex measured as 63°C. For comparison, the Tm of the Tax–HLA-A2 complex was measured as 62°C, in close agreement with previous studies (13, 36). Thus, the native HuD–HLA-A2 complex has exceedingly low stability relative to the Tax–HLA-A2 complex.
T cell cross-reactivity between foreign and self Ags has been implicated in a number of autoimmune pathologies, and molecular mimicry between self and nonself is frequently discussed as an underlying component. Yet structures of TCRs bound to self Ags implicated in autoimmunity have shown unusual features that distinguish them from structures of TCRs bound to foreign Ags (5–8). These observations have led to hypotheses that relate unusual TCR binding to reduced TCR affinity and T cell escape from negative selection, permitting the development of autoimmunity (11, 12). The extent to which unusual binding would apply in the context of molecular mimicry however is unclear: unusual recognition of a self Ag together with more traditional recognition of a foreign Ag by the same TCR is inconsistent with molecular mimicry as traditionally envisioned (i.e., the conservation of key structural or chemical features translating into a similar mode of recognition). Although it is possible that conservation of "hotspots" could still permit differential TCR binding, resembling to some extent how the 2C TCR cross-reacts with the QL9/H-2Ld and dEV8/H-2Kb ligands (18), this still stretches the expectations of a molecular mimicry mechanism.
Cross-reactivity by the A6 TCR between the foreign Ag Tax and the self Ag HuD provided us with an opportunity to examine the structural basis for self/nonself cross-reactivity within the context of molecular mimicry. Consistent with a molecular mimicry mechanism, HLA-A2 presents the Tax and HuD peptides in very similar conformations, with differences in the positions of only two side chains. Also consistent with molecular mimicry, the A6 TCR engages HuD–HLA-A2 with the same center-focused, diagonal binding mode it uses to engage Tax–HLA-A2, with no differences in position or orientation. A traditional molecular mimicry mechanism in terms of both Ag presentation as well as receptor recognition can therefore account for TCR cross-reactivity between the Tax and HuD Ags.
Although the traditional anti-foreign TCR binding mode is conserved, there are differences in the interaction between A6 and the Tax and HuD complexes with HLA-A2. Unlike Tax, the central aromatic side chains of the HuD peptide must undergo conformational changes in order for the TCR to bind. There is a shift in the α2 helix that occurs upon recognition of HuD but not Tax. The inability of the central phenylalanine side chain of the HuD peptide to form a hydrogen bond within the CDR3α/CDR3β pocket results in a repositioning of the CDR3β loop. It is thus only due to the structural plasticity available to both the TCR and the pMHC that A6 is able to cross-react between the two ligands. This conformational "melding" of both receptor and ligand is not unique to this case: A6 cross-reacts between Tax and its foreign mimic from the yeast Tel1p protein via similar, albeit larger, conformational changes in the TCR, peptide, and the MHC (13). The LC13 TCR cross-reacts between foreign peptides with related sequences but divergent structures by forcing them to adopt similar conformations in the TCR-bound state (14), and the CDR3α and CDR3β loops of LC13 undergo significant changes from their unbound forms (53, 54). Recognition of the pBM8/H-2kbm8 ligand by the BM3.3 TCR occurs with changes in peptide and MHC, and although the structure of the free BM3.3 TCR is not available, the CDR3α and CDR3β loops adopt different conformations upon recognition of other ligands (55). To a lesser extent, conformational changes occur in foreign and self peptide/DR2b complexes upon recognition by the Ob.1A12, and again, there are differences in CDR loop positions in the foreign and self ternary complexes, and binding proceeds with kinetic and thermodynamic indicators of conformational changes (5, 16, 56). Thus, although previous work highlighted the need to focus on structural as opposed to just sequence similarities when considering molecular mimicry (2, 3, 57), it is becoming increasingly clear that both ligand and receptor adaptability or flexibility and the resultant conformational melding often needed for binding add an additional layer of complexity.
Although CD8+ T cell recognition of HuD Ags has been implicated in HAM/TSP, and although the A6 TCR was cloned from a HAM/TSP patient, whether T cell recognition of cells presenting the HuD peptide is a component of disease is controversial. Nonetheless, HuD-specific T cells, such as those expressing A6, must still escape the process of negative selection. If low affinity stemming from an altered TCR binding mode cannot explain this, what mechanisms can? The structural melding needed for A6 engagement of HuD weakens affinity 70-fold compared with that for the Tax ligand. However, the affinity of ∼140 μM may not be sufficiently weak to allow escape, as TCR–pMHC interactions with affinities in this range can still result in negative selection (29). A more likely explanation is found in the low stability of the HuD–HLA-A2 complex: in addition to weak TCR binding affinities, low levels of Ag presentation can also permit T cell escape from negative selection (51), and poorly stable pMHC complexes require correspondingly higher affinity TCR affinities for productive signaling (58). The HuD self Ag thus provides an example of how weak peptide binding to MHC can permit the survival of T cells with receptors capable of recognizing self Ags with a traditional anti-foreign binding mode. Similar observations have been made with the 2C TCR (17), suggesting such behavior may be common. Thus, cross-recognition of weakly stable self mimics of foreign Ags via conserved, traditional binding modes likely contribute to the development and progression of autoimmunity.
The authors have no financial conflicts of interest.
We thank Cynthia Piepenbrink for outstanding technical assistance.
This work was supported by the National Institute of General Medical Sciences, National Institutes of Health (GM067079); the Notre Dame Chemistry/Biochemistry/Biology Interface training program funded by the National Institute of General Medical Sciences, National Institutes of Health (GM075762 to K.H.P.); and by a fellowship from the Walther Cancer Foundation (to O.Y.B.). Results shown in this report are derived from work performed at the Structural Biology Center, Lilly Research Laboratories Collaborative Access Team, and Life Science Collaborative Access Team at the Advanced Photon Source, Argonne National Laboratory. Argonne is operated by UChicago Argonne for the U.S. Department of Energy under contract DE-AC02-06CH11357. Use of the Lilly Research Laboratories Collaborative Access Team facilities at Sector 31 of the Advanced Photon Source was provided by Eli Lilly & Company, which operates the facility.
The online version of this article contains supplemental material.
The coordinates and structures presented in this article have been submitted to the Brookhaven Protein Data Bank under accession numbers 3PWL, 3PWP, 3PWN, and 3PWJ.
Abbreviations used in this article:
- human T cell leukemia virus-1–associated myelopathy/tropical spastic paraparesis
- human T cell leukemia virus-1
- Brookhaven Protein Data Bank
- pMHC
- peptide-MHC
- root mean square deviation.
- Received September 21, 2010.
- Accepted December 5, 2010.
- Copyright © 2011 by The American Association of Immunologists, Inc.


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MOSCOW, March 18. /TASS/. The European Union believes that the recent protests against an unpopular labor law in Belarus indicate a need for democratization in that country, the European External Action Service (EEAS) said in a statement on Friday.
"The latest developments in Belarus highlight a clear need for a broader democratisation process in the country," the document says. "Freedom of association and of assembly needs to be ensured. Recently detained peaceful protesters, including journalists covering the events, must be immediately released."
"The European Union is committed to a stable, democratic and prosperous future for Belarus, for the benefit of its people, and will continue its work with all the stakeholders with this objective firmly in in mind," the EEAS said. "Steps taken by Belarus to respect universal fundamental freedoms, rule of law and human rights will remain key for the shaping of the European Union's relationship with the country."
Belarus' President Alexander Lukashenko signed a law, dubbed in the press as the "law against social parasites," in April 2015. The law requires all those who work less than 183 days a year to pay a levy of more than 200 U.S. dollars for "lost taxes" to help fund welfare policies.
The law sparked off mass protests across the country. More than 160 people have been detained since February 17. On March 12, several journalists were also detained in Orsha after a rally of "non-parasites.".


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Still smiling over the somewhat terrifying but wonderful news announced yesterday: my novel, And Me Among Them, has been nominated for the Trillium Book Award.
I'm in fine company, too. The other nominees in my category are Ken Babstock for Methodist Hatchet; David Bezmozgis for The Free World; Tony Burgess for Idaho Winter; David Gilmour for The Perfect Order of Things, and Phil Hall for Killdeer. May the best (woman?) win!
Here's what the jury wrote about And Me Among Them:
"Deceptively slim, And Me Among Them presents an uncanny world guided by a uniquely heightened perspective. As she grows up (and up, and up), the girl giant Ruth stretches everyone's consciousness, seeing into, above, and beyond the minds and dreams of her parents. Kristen den Hartog opens so many doors that every meaning is magnified, shifted, and understood anew — a magical, wonderful novel like no other."
Huge congratulations to the nominees in all the categories. I look forward to reading with them on June 19 at the Toronto Reference Library. The winners will be announced June 20.
Meanwhile, I remain Trillium Nervosa.


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AAfPE's History
Established in 1981, AAfPE's roots go back to the mid 1970s when the American Bar Association sponsored the first conferences for paralegal educators. While much has been accomplished in the field of paralegal education from this beginning, there is still much more to be done to fully develop the potential for both the paralegal field and education for the profession.
Position Statements | Strategic Plan
Mission Statement
Recognizing the need to increase and improve access to the legal system, the AAfPE promotes quality paralegal education, develops educational standards and encourages professional growth, in order to prepare graduates to perform a significant role in the delivery of legal services. - June 9, 2001
The goals that AAfPE strives to accomplish:
These goals are consistently met through the action of AAfPE's members and the organization's Board of Directors.
Establishing standards by which to measure paralegal education has been one of the central focus points of AAfPE. The Association recognizes the diverse nature of paralegal education and has developed a set of core competencies to complement this diversity. AAfPE also recognizes that a common core of legal knowledge must be coupled with critical thinking, as well as organizational, communication, and interpersonal skills in order for one to be a successful paralegal. Further, paralegal programs should provide an integrated set of core courses that develop these competencies. The development of Model Syllabi in courses typically taught in paralegal programs is an on-going project as well as the creation of Model Employer and Graduate Surveys. Through AAfPE's continued emphasis on high standards, rather than standardization, to shape paralegal education, excellent programs are available throughout the country that offer the diversity necessary to meet the specific needs of the legal community serviced by each program.
AAfPE has an impressive history. More important than what it has done, however, is what it is doing currently in this rapidly changing paralegal profession. AAfPE membership includes some of the most respected educators and leaders in the field of paralegal education. As such, AAfPE is the recognized source for standards in paralegal education and the continuing development of quality teaching.
AAfPE Strategic Plan
To provide greater access to legal services by promoting quality paralegal education.
Goal 1: Promote High Standards for Paralegal Education and the Paralegal Profession
Goal 2: Provide a Forum for Professional Development as Educators and Program Directors
Goal 3: Promote Member Participation and Leadership in AAfPE
Goal 4: Promote Research and Disseminate Information on the Paralegal Profession
Goal 5: Create Partnerships with National and International Paralegal Organizations
Position Statements
AAfPE Comment to the ABA Task Force on the Future of Legal Education
Download a printable version (PDF)
As directed by the membership during the 2013 Annual Business Meeting, the board drafted, approved, and disseminated a comment reflecting AAfPE's position on the education and training of paralegals as non-lawyer legal service providers and limited licensed legal technicians.
AAfPE Core Competencies for Paralegal Programs
Download a printable version (PDF)
In order to be a successful paralegal, an individual should possess not only a common core of legal knowledge, but also must have acquired vital critical thinking, organizational, research, writing, oral communication, and interpersonal skills. All paralegal education programs, regardless of the specialty areas they choose to emphasize, should provide an integrated set of core courses that develop the following competencies.
AAfPE Statement on Diversity and Inclusion
Download a printable version (PFD)
AAfPE respects and values the unique attributes, characteristics and perspectives of all persons. We believe that our strength lies in the diversity among our talented members. We consider diversity and inclusion essential to our ability to effectively accomplish our mission. Therefore, it is our aim that our members, partners, and key stakeholders reflect and embrace these core values.
Diversity embodies all those differences that make people unique and includes people of different race, ethnicities, culture, sexual orientation, gender, religion, age, personal style, appearance, and physical ability, as well as people of diverse opinions, perspectives, lifestyles, ideas, and thinking.
Inclusion fosters full participation and helps our organization leverage the diversity of our members, engaging them and encouraging collaboration. AAfPE promotes the open exchange of ideas and an organization that is free of cultural barriers.
AAfPE recognizes that organizations work best when people with different backgrounds and viewpoints are willing to work together toward a common goal. Therefore, AAfPE is committed to providing an environment of fairness and equitable treatment of everyone, regardless of gender, race, religion, creed, age, sexual orientation, national origin, disability, or class.
AAfPE will strive to effectively serve its members from all backgrounds, to encourage the professional growth of all members, and to embrace the diversity of our membership. To that end, AAfPE will continue to identify, and look for ways to reduce or eliminate, barriers to under-represented groups and will continue to look for ways to expand access to leadership opportunities within the organization in an effort to further strengthen our diversity. AAfPE, by and through its Officers, Directors, and Committee leaders, will encourage full and equal participation by qualified members of under-represented groups at all levels of the organization.
AAfPE Statement on Academic Quality
Download a printable version (PDF)
AAfPE, established in 1981, is an organization dedicated to promoting high standards for paralegal education. Educational institutions that are voting members of AAfPE have adopted this Statement of Academic Quality.
Paralegal education is a unique academic curriculum, composed of both substantive legal knowledge and professional skills that incorporates legal theory with an understanding of practical applications. This intellectually demanding course of study is derived from the responsibilities of paralegals as legal professionals. It is the philosophy of this organization that a person is qualified as a paralegal with (1) an associate or baccalaureate degree or equivalent course work; and (2) a credential in paralegal education completed in any of the following types of educational programs: associate degree, baccalaureate degree (major, minor or concentration), certificate, or master's degree. AAfPE recognizes these essential components of quality paralegal education programs:
Marketing and Promotion
Paralegal Instruction
Program Director
Quality paralegal education programs provide adequate release time, funding for professional development opportunities, and administrative support for the program director to develop, monitor, and accomplish the goals and objectives of the program, as well as assess the program's effectiveness in achieving these goals and objectives. The director is primarily responsible for the paralegal program. A program director is a legal professional or other similarly-qualified person appropriately credentialed and in good standing in his or her profession, with knowledge, involvement and understanding of the paralegal profession and paralegal education.
AAfPE Policy Statement Regarding Short-term Programs
Download a printable version (PDF)
AAfPE's membership includes hundreds of universities, colleges, and other institutions of higher learning throughout the United States and in Canada. Since 1981, AAfPE's member schools have trained thousands of paralegal students each year to help increase, improve, and support access to the legal system in their communities.
AAfPE Educational Standards for Paralegal Regulation Proposals
Download a printable version (PDF)
AAfPE's membership includes hundreds of universities, colleges, and other institutions of higher learning throughout the United States and in Canada. Since 1981, AAfPE's member schools have trained thousands of paralegal students each year to help increase, improve, and support access to the legal system in their communities. AAfPE acts as the national resource for paralegal education and has set minimum recommended educational standards for paralegal education programs to become institutional members. AAfPE believes that the paralegal profession requires training of sufficient length, sophistication, intensity, and quality to produce a functional entry-level paralegal.
Certain educational components should be required in any paralegal regulatory plan. AAfPE recommends that state legislatures, courts, and/or bar associations considering paralegal regulation should adopt or include the AAfPE educational minimum standards described below:
Formal Paralegal Education
It is the position of AAfPE that some form of formal paralegal education should be present as a meaningful requirement in any paralegal regulation plan. This formal paralegal education should be offered through a program specifically designed to provide paralegal education.
Minimum Length of Study
A person is qualified as a paralegal with (1) an associate or baccalaureate degree or equivalent course work and (2) a credential in paralegal education from a paralegal program associated with an educational institution accredited by a nationally recognized agency completed in any of the following types of educational programs: associate degree, baccalaureate degree (major or minor), certificate, or master's degree.
A paralegal's education shall include, either as separate courses or within the overall course of study, coursework in substantive and procedural law, the American legal system, law offices and related environments, the paralegal profession, legal research and writing, ethics, and areas of legal practice such as those described in AAfPE's Core Competencies for Paralegal Programs.
The paralegal's credential shall include no fewer than 18 semester credit hours of substantive paralegal classes and shall be from a paralegal education program that, at the time the paralegal credential is granted, is:
Other Educational Institution Requirements
The educational institution should be accredited by a nationally-recognized accrediting agency. Additionally, the institution should meet the educational standards described in the AAfPE Statement of Academic Quality.
Minimum Educational Requirements Are Essential in Any Paralegal Regulation Plan
Paralegal education is a unique academic curriculum, composed of both substantive legal knowledge and professional skills, which incorporates legal theory with practical application. Any proposal for regulation of paralegals should contain provisions incorporating the level of paralegal education necessary to enable graduates to meet the responsibilities of paralegals as legal professionals.
In recent years there has been a proliferation of short-term entry-level paralegal training programs of very limited duration, some with as few as 125 clock hours (which is less than nine semester credit hours). These programs do a fundamental disservice to the legal profession by creating unrealistic expectations in both employers and students that a quality paralegal education has been delivered, when such is not the case. State regulatory bodies are urged to adopt the educational minimums defined in this document as a requisite element of any paralegal regulation plan.
For further information on the American Association for Paralegal Education, please contact [email protected], or call our national headquarters at (407) 774-7880 .
The AAfPE Board of Directors adopted this Position Statement
on February 24, 2001, at San Antonio, Texas
Wed Nov 4, 2020AAfPE 39th National Conference ~ Nov 4-7 (Seattle, WA)
Category: Events
Wed Oct 6, 2021AAfPE 40th National Conference ~ Oct 6-9 (Orlando, FL)
Category: Events


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Scaled Agile Framework (SAFe)
The Scaled Agile Framework (abbreviated as SAFe), is a set of organization and workflow patterns intended to guide enterprises in scaling lean and agile practices.
Scrum Master
The primary role of a Scrum Master in the SAFe context is to help educate the team in Scrum, Extreme Programming (XP), Kanban, and SAFe, ensuring that the agreed upon Agile process is being followed.
The Scrum Master role is taken by a team member whose primary responsibility is assisting the self-organizing, self-managing team achieve its goals.
SAFe Advanced Scrum Master (SASM)
The SAFe Advanced Scrum Master (SASM) certification provides the skills that can be applied to lead high-performance Agile teams.
The SAFe Advanced Scrum Master (SASM) role has the knowledge to apply DevOps practices and Kanban techniques and manage the interactions between the teams, stakeholders, and Product Managers.
As an SASM certified professional, I am able to:
- Apply SAFe principles in a multi-team environment
- Build high-performing teams and enable continuous improvement
- Coach Agile and Scrum anti-patterns to less-experienced team members
- Facilitate program planning, implementation, and value delivery
- Support learning through participation in Communities of Practice and innovation cycles
In summary
In summary, the SAFe certification is considered as a standard for Lean-Agile practices.
Over 70% of US Fortune 100 companies are utilising SAFe and the call for the SAFe certified experts is increasing at an exponential rate.


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In Defense of Scott Shields
My name is Joseph Hudak. I am a FDNY Paramedic Instructor, forty-four years of age. For the last eight years, I was an instructor at the FDNY Academy training FDNY Paramedics and Firefighters. If you were in FDNY, you went through one of my courses.
I continue to teach at the Academy. I am also part of the FDNY competition team that represents both FDNY and the United States in both domestic and international EMS competitions.
No amount of money in the world could explain the gratification of saving a human life. Our profession is unique and for me to be a member of FDNY's paramedics has been an incredible experience.
As a rescue worker, an officer and a health care professional in FDNY is a reward in itself. Anyone in this field of rescuing others does not do it for the money. We do this because of the personal satisfaction and knowledge that your life has made a difference for other people. That your time spent on this small blue marble spinning in space we call home may have changed things.
If anyone ever fit this description, it is my good friend Scott Shields. Over the last eight years I have watched his sacrifice and good deeds do much for both this city and my country. I have also watched as he agreed to testify in Congress about the cover-up's of hazardous materials by high ranking NY politicians with Presidential ambitions. I have been with Scott in two of our nation's worst moments and watched his training, knowledge and skills make a difference that few are ever privileged to give. He has played a key role in two of our nation's darkest moments. For this reason I have decided to help in clearing his name which many who know the truth are scared to do after what happened to him.
On Sept 11, 2001 we witnessed the horrific explosion as the first plane hit the Towers. A short while later I was to witness the second strike.
I was to stay there working on the Pile the next three days.
I first saw Scott and his dog Bear on September 11th 2001 on the site of the World Trade Center collapse.
His Golden Retriever made an alert on a body under a fifty foot mound of rubble that turned out to be the decapitated remains of one of our own, Chief of Department Peter Ganci. Along with Firefighters TJ Mundy, Jean Paul Augier (who went on to make one of the few live rescues of the day) and later Firefighter Tommy Burke (from Squad 252) who was with Scott when Bear found FDNY Commissioner William Feehan. Hundreds of FDNY personnel watched Scott and Bear work for days.
For days firefighters relied on Bear and Scott. That first day they were the only K-9 team any of us saw on the site. I was to watch them work the next three days. The FEMA dogs were not trained to do 'cadaver work' and Bear was invaluable. He led the way!
I was to see this man Scott and his golden retriever make many more finds those days. In November, I attended a memorial service held at the Beacon theatre on the Westside. The thousands of Firefighters who were in the audience recognized him and his dog Bear. They had meant a lot to us and people had actually argued over getting their services on the site. Bear was lifted onto the stage to thundering applause and cheering of hundreds who had witnessed what this dog had done.
It was to be the beginning of a bond of friendship that only war or disaster can bring to life. Little did I realize then, that four years later I would be once again going to another hell much better equipped and able to make a huge difference both because of, and with Scott Shields.
After that night, I began both a friendship and a professional relationship with Scott. As time passed, I began to realize how special this man really was. He was responsible for safety for many of the events in New York harbor and slowly we began to both provide services and training for his Marine Safety Service (later part of the search and rescue foundation).
Scott was always eager to assist others and to tell the truth about what had happened at the WTC so it would not happen again (Katrina was a direct result of not telling the truth about WTC)! His real love was the Dogs and the water and somehow he combined them both into his 'career' as a rescuer.
Scott decided after the WTC to help other rescuers. People do not realize the sacrifices made by these mostly volunteer teams. Scott began to be fed up with a system that even after the WTC did not seem to prioritize rescue. Funding seemed to be going everywhere else but Search and Rescue. Almost a year to the date of the WTC Bear, his search dog, best friend and partner lost a battle with more than a dozen types of cancer that started in a wound he had got at the WTC. I decided to make sure that this dog who led us would be honored for what he had done at the WTC assisting FDNY. There is a memorial to Bear at the FDNY/EMS Academy at Ft. Totten that I helped authorize and build.
I guess Scott felt guilty for bringing what he loved most into that deadly place. A big part of Scott died that day. I think he swore to himself that this would not be one more death that went on to mean nothing. Scott, never had children and he treated and referred to his dog Bear as his 'son'. It may sound a little crazy, but there are no FDNY firefighters who would begrudge that relationship. They were always there for us on the pile and they were that close. Scott decided to dedicate his life to helping, not just the victims of disaster, but also those who would rescue them. He redoubled his efforts after Bear's death. He was angry at the cover-ups we all saw at the WTC. He decided to turn this tragedy into an opportunity to change things.
For us, the term brother is one whom you know with certainty will sacrifice his life for yours; I am proud to call Scott "Brother". There is no higher calling then to be a rescuer. Being a rescuer is the highest calling. I have watched Scott over the last nine years and know him to be in his heart of hearts one of our nation's most dedicated 'rescuers'.
I have participated in numerous rescues in New York harbor with Scott (on one occasion making 7 Kayaker rescues during one event, then responding to the Staten Island Ferry disaster after already putting in a twelve hour day). I read a story on the internet of that day by one of Scott's detractors, it was as far from the truth as reality could get.
In 2005 two months after assisting Scott in teaching (I taught the medical component) one of the nation's largest mass casualty water rescue trainings (that year's course organized by Scott was entitled "Responding to the Five Hundred Year Flood"). Scott arranged instructors to teach from a dozen Federal, State and City agencies in New York. He got Zodiac Boats to sponsor the event and sixty days later, they gave Scott more than 20 boats and five personnel to help maintain them in NOLA. Scott got other companies to loan or give equipment for the response to Katrina because of the training he has conducted through the years.
Scott got Sid Baumgarten head of Battery Park CERT (NYNG General, former NYC DA, and former deputy Mayor of New York to deploy his team through the foundation, and they, and other teams Scott led coxswain the inflatable boats (the same boats used for the training in NY two months earlier) for the 82nd Airborne's response in NOLA. Scott has been told this never happened! On the internet you can read how it never happened. I was there, it did! There are picture and national networks video coverage.
One of the companies Walker Bay Boats donated a hundred dinghies that Scott eventually donated to the USCGA and other charities. I have participated as lead medical officer in his marine safety training courses, multiple world-class kayak, boat, outrigger canoe and swim races he led for NYC Parks SAR Team in the waters surrounding NYC. At these courses, I have learned shipboard repelling, mass casualty rescue, knot tying and other marine oriented rescue techniques at these classes. I loved the training. It was out of the box and different then what we get in the Dept. It was very 'real world oriented' and not available from any organization I know of. Most fire department water rescue training is oriented towards rescue in swift water of a few people in a vehicle, Scott's courses where about what to do when the "Big One' strikes. Scott really pioneered mass casualty water rescue (for a Katrina like event). He had talked about it happening in the New York area for years and had prepared plans for a response in the City. He was always a critic of FEMA long before it became fashionable.
Scott's led five volunteer teams (associated with the Foundation) and helped deploy a dozen others in response to hurricane Katrina. They were authorized by Gov. Blanco otherwise we never could have gotten through the roadblock for only authorized teams. The FBI has also verified the deployment letter was sent from the Governor's office (despite what you read on the internet).The teams he led down to Louisiana were assigned to the 82nd Airborne's 3rd Brigade in New Orleans Louisiana. They (the Airborne) made just over a thousand actual rescues and 4000 transports of victims. Many of these carried out with our boat teams. We rescued over 1000 animals which Scott helped arrange transport to Battery Park City in New York through Gen. Sidney Baumgarten (his BPC CERT team had taken Scott's training and deployed with Scott through the Bear Search and Rescue Foundation to NOLA). Gen. Baumgarten arranged for their adoption from people who lived in the neighborhood of the WTC. He is also a former Deputy Mayor of New York and lawyer who could give you more illumination on the 'truth'. The amazing thing is no one ever checked up on those who created these web sites and contact e-mails to see who they where!
I was honored to respond to Hurricane Katrina through Scott's team. Almost thirty tri state agencies (including New Jersey Task Force 1 and the Jersey City FD) had taken Scott's mass casualty water training course ( entitled: 'Responding to the Five Hundred Year Flood') only sixty days earlier and most of them responded much better prepared and equipped to the Gulf Coast because of this. To all of us it seemed prophetic.
Many teams from around the country that had received grants or training from the Foundation and Scott responded to Hurricane Katrina under orders from Gov. Blanco authorizing Scott to deploy teams. those who say otherwise have not checked, just quoted from the web or those out to change our history.
I would like to make a very strong point. I have seen with my own eyes what Scott has accomplished. He has written about our emergency management system and spoken about what would happen at a Katrina like event years before it happened. He has testified in Congress and around the country. I have seen Scott in action for almost a decade. He has made the life safety of the American people his life's priority. His 'cause' was to be accomplished at any price, even at the expense of his family. He is a caring, giving human being who has always gone beyond the call of duty (I have seen him work injured himself). He is a rescue worker who has gone well beyond the call of duty and what most would do to help others.
I lost a lot of close personal friends on 9/11 (Tom Foley, Charlie Mone, George Cain, Carlos Cites, my ex-partner Kevin Peifer and more). Bear is included on that wall of heroes. It was to honor their memory and efforts that we built a wall at the Fire Academy. On Sept. 11th 2003 Scott was asked to be a guest speaker at the memorial ceremony at Fort Totten. He gave a beautiful reading of a poem he had written for Bear and all who serve so that others may live. There was not a dry eye or an untouched heart. His loss, was our loss and we all shared in that emptiness and pride in our work.
Scott has always been there for me. He constantly asks my opinions on how to better organize our rescue services and responses to disaster. He is a bottom up idea organizer. I have seen over and over the hard work and dedication (all the time through pain of his injuries from 9/11). He would do anything to keep people alive and safe. There are too many things he has done to even list and yet remain with a brief statement on my friend Scott. He has contributed more than most.
None of us are perfect. We all have weaknesses, or doubts. We contend with our faults and go on. I can honestly say I have never in my life met someone who has done so much for others. Not just civilians or the injured, but for assisting the so often overlooked rescue workers. No one could ever bring all he has done into context. In the world of rescue I deal in, I hear nothing but praise for Scott. Scott has been honored by having days in his name from the States of New York, New Jersey and Connecticut. Even Dr Jane Goodall did a show on Animal Planet about Scott and Bear. The history Channel has honored them and Channel Thirteen in New York did a few pieces on them.
On September 17, 2005 The Secretary of Transportation Norman Manetta, honored him with a medal for organizing the harbor shuttle into the WTC's North Cove. He arranged for units to be transported by water with the USCG and arrive whole and rested inside the WTC area instead of having to march down the gridlocked West Side Highway with all their heavy gear. Sometimes, it seemed as if Scott was everywhere. He had an amazing talent for organizing a disaster. Like many volunteer firefighters, he does not take money for arranging help for others.
The work he has done has made a difference. We are a better country for having had use of his services. I cannot count how many are alive today, and brought home to their loved ones because of him. Many of us want our lives to have made a difference. Scott has, over and over again. I stand beside him and all that he has done good for others. I look up to him as a professional, caring individual who does the job because he loves to.
I am well known in the field of EMS and in the New York City Fire Dept.; those who know me, know my reputation as one of the lead Medics in the Dept. and of honesty, fairness as a top ranked professional who takes my job and my honor seriously. I love my job and my profession. I love this man Scott Shields for all I have seen him do for others. I have been at his side in the two worst domestic disasters in modern history. I have watched as he has accomplished great things, only in the name of doing good and placing the life safety of people first and above everything. I can think of few whom I would want to go to hell with again. Scott is one of those.
I am happy to help tell the true story of Scott and Bear. It is an amazing story that I and many other firefighters have seen firsthand and have been honored to participate in.
In November of 2008 a man by the name of Phil Porteus (who owns the websites against Scott) was convicted of computer fraud, bank fraud and various other crimes against Scott in Federal Court in Newark N.J. Mr Porteus had also been removed from the USCGA for creating fraudulent documents. He had was also at the center of a similar campaign against the former head of the 'Childrens Protective Service' in New York Chief Burt Borkin.
Mr Porteus also had the highest number of pending charges against him of any firefighter from the FDNY Fire Marshalls office. He was known to have tortured "probies" (probationary firefighters) and to have poured gasoline on other firefighters bunker gear as well as stealing personal rescue gear from those he did not like.
What many do not understand is that Scott could not afford to defend himself and those appointed to do so did not give a damn about the truth. They were to lazy to even pick up a phone and call anyone who had ever worked with Scott
There is more to Porteus's background then the authorities are willing to admit. There is much more to Capt. Shields being charged with taking money for an apartment then anyone will ever know. He was an outspoken critic of FEMA (where the charges originate) long before Katrina and often lectured how FEMA covering up what happened at the WTC would lead to a Katrina like event. Porteus claims his actions against Scott was caused by PTSD; I would guess some other more nefarious motive. I have seen the name on his second mortgage, funny it is the same as whom Scott was asked totestify against in Congress. Porteus has a long history that goes far beyond his accusations against Scott and an ethical and moral problem that has ruined many who have come in contact with him.
Interestingly, Scott is not charged with any of the puff stories from Mr Porteus was able to get into the newspapers after three years, about Scott not being here or there, or his dog finding nothing (I witnessed quite the opposite with my own two eyes and so have hundreds of others). Anyone who claims otherwise is an outright liar!
That the Web could be used for so much evil is an unspeakable horror. That reporters would quote from it with so much zeal without fact checking speaks ill of their profession. At the time the Post was quoting from Mr Porteus as a "reliable source" he had pled in Federal court to computer fraud, bank fraud and various charges. Scott could not afford a lawyer to defend his good name (they wanted $50,000 just to start). That someone who has done so much good could be reduced to phony stories copied from one reporter to another, all starting with Mr. Porteus's website and his cronies (who often pretended to be other people) says nothing good about this new electronic society. Mr Porteus is now a convicted felon serving a three year sentence!
FEMA often in the past placed 'rescue & recovery' workers under 'refugee status' to pay for their housing (see Google "CNN No room at the INN"). Mr. Shields is a victim of being one of the very few good guys who will speak and write the truth at any price to his own personal safety or honor. Funny, the three pages that stated why he was given the 'housing allowance' are missing from Mr. Shields FEMA file. His prosecutor admitted there were three pages missing, just not what was in them. How could she know if they were removed on purpose!
Those who speak ill of Scott are just quoting from a very inaccurate websites and people who were hired to do so, sponsored by forces other then what they appear to be. Do you actually know whom any of these people are? Have you verified that they even knew Mr Shields? Or are they just words and letters on the internet claiming things you assume to be true? Those who quote from, or believe them are fools.
Prior to ever having been accused of anything Scott was in a Federal Victims of Crime program to protect him from Phil Porteus and his cohorts for three years. After having the government indict him on information supplied by Mr Porteus, Scott just gave up fighting for the truth. He was in shock and could get no assistance to continue the fight. Who could blame him. The real question is, who and what was behind this internet fraud and how did the FEMA IG's office get involved in forging our nation's history. They have said that Scott's teams did not coxswain the boats for the 82nd Airborne Division at Katrina; I was there, I coxswain one of those boats, we had national news crews with us, there were a hundred troopers who worked with us, yet, one bad FEMA IG made a claims and accusations that were taken as gospel (he was not even there) and a phony case against Scott.
Anyone doing the slightest real investigation of the FEMA agent's charges against Scott would find outright lies and creative interpretation of facts. Porteus is only a tool in some greater mechanism. Time and serious investigation will tell the truth about what really happened to Scott Shields.
Please feel free to contact me as someone must put an end to this conspiracy to destroy the credibility of a very, very good man.
For more FDNY personnel discussing the real truth about Scott & Bear go to:
Very truly yours,
Joseph Hudak FDNY
Paramedic Instructor
11/04/08 Greenwich Residents Scott And Patricia Shields Are Now Waiting To Report To Prison
New York Post
A self-proclaimed "9/11 hero" who concocted tales of rescuing victims with his golden retriever is being sued by the feds for more than $35,000 in relief funds he scammed from FEMA.
A lawsuit filed yesterday by the US Attorney's Office in Manhattan accuses Scott Shields and his sister, Patricia, of falsely claiming to need the money for rent on a Rector Street apartment while living in Greenwich, Conn.
The feds are asking for three times the stolen amount plus $11,000 for each of three bogus filings. Both siblings pleaded guilty to fraud, were sentenced to eight months behind bars, and are now waiting to report to prison.
Scott Shields, 57, won accolades after claiming he and his now-deceased dog, Bear, made "the only live finds" at Ground Zero. He repeated the lie in a self-published 2003 book titled "Bear, Heart of a Hero."
The Post exposed his lies in a 2006 exclusive that also revealed he filed for bankruptcy protection four months before 9/11
Please send your comments, news tips and press releases to email@example.com


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Blue Like Jazz
By Donald Miller
"I never liked jazz music because jazz music doesn't resolve. I used to not like God because God didn't resolve. But that was before any of this happened."
―Donald Miller
In Donald Miller's early years, he was vaguely familiar with a distant God. But when he came to know Jesus Christ, he pursued the Christian life with great zeal. Within a few years he had a successful ministry that ultimately left him feeling empty, burned out, and, once again, far away from God. In this intimate, soul-searching account, Miller describes his remarkable journey back to a culturally relevant, infinitely loving God.
For anyone wondering if the Christian faith is still relevant in a postmodern culture.
For anyone thirsting for a genuine encounter with a God who is real.
For anyone yearning for a renewed sense of passion in life.
Blue Like Jazz is a fresh and original perspective on life, love, and redemption.
Donald Miller grew up in Houston, Texas. Leaving home at the age of 21, he traveled across the country until he ran out of money in Portland, Oregon, where he lives today. Harvest House Publishers released his first book in 2000. Two years later, after having audited classes at Portland's Reed College, Don wrote BLUE LIKE JAZZ, which would slowly become a NEW YORK TIMES bestseller.
Don has teamed up with Steve Taylor and Ben Pearson to write the screenplay for BLUE LIKE JAZZ, which will be filmed in Portland and Nashville in 2009 and released thereafter. Don is the founder of The Belmont Foundation, a not-for-profit foundation which is working to recruit 10,000 mentors through 1,000 churches as an answer to the crisis of fatherlessness in America.
A sought-after speaker, Don has delivered lectures to a wide range of audiences, including the Women of Faith Conference, the Veritas Forum at Harvard University, and the Veritas Forum at Cal Poly. In 2008 Don was asked to deliver the closing prayer at the Democratic National Convention in Denver, Colorado.


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In addition to our branded gear, Fun Under Xtreme Konditions provides custom apparel design and fulfillment services.
We offer a full suite of services including logo design, product selection/fulfillment, and hosted online sales.
From edgy custom FuXk designs to more conservative Fun Under Xtreme Konditions, we have a solution for you! We like to include our logo on the gear but don't have to!\
Here are our current Custom products.
Contact email@example.com for more information.


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Posted: July 26, 2018
Skins Sexual Health is celebrating 10 years in business, and it has ambitious plans for its next decade. The brand first hit the market with Skins Condoms, and the intention was to 'change the perception of contraception' by producing a condom that people would be proud to buy, unashamed to carry, and ultimately enjoy wearing. A recent survey of over 400 students at Lincoln University, commissioned by the company, suggests it has gone a long way to succeeding in this aim as 82% of respondents agreed that the brand had strong appeal for them.
Milestones along its decade-long journey include partnerships with the NHS, American Pie Reunion, and cast members of Geordie Shore, endorsements from Dr Christian Jessen and Dr Pixie McKenna and sponsorship support for Eyes Open World Aids Day, National Federation of Young Farmers, and the University of Lincoln.
The brand now covers three key product areas: protection, performance, and pleasure. So in addition to Skins Condoms there are now Vibe Rings, Performance Rings, male sexual health food supplement pills Poweract, and Powerect – a 100% natural male enhancement cream. Skins see male performance as a key growth area and much of its product development is currently is in this field.
Skins co-founder Richie Bowles said: "We are passionate about sexual health. We hope to build on our success to date and enter new markets globally. As a brand we believe that a happy and healthy sex life should be available for all. Indeed, research is increasingly extolling the benefits of regular sex as a powerful force for many far-reaching health benefits. By aiming to introduce unique solutions at affordable prices we hope that Skins can continue to grow over the next ten years and play a small part in making people's lives happier and healthier."
Fellow co-founder Jane Bowles added: "Skins carries a simple naming policy. We wanted our brand to be as transparent as the product itself. Some people still find it embarrassing to buy condoms and therefore to make the process quick and easy, the options are clear, it is what it says on the tin, so there is no confusion or awkward conversations when purchasing our Skins. We believe this honest but funky approach to our packaging helps attract our customers – then once they've tried them they are hooked."
For more information visit www.skinssexualhealth.co.uk


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Please provide your question and email address in the fields below. Note, all fields are required.
Forgot Password? Please contact your school principal to have your password reset. Principal email addresses are located on the homepage of school websites.
If you are in eClass, please contact email@example.com.
This year's Holodomor Commemoration Assembly took place on Thursday November 22, 2018 in the gym. The assembly commenced with a Panachyda (memorial service) and then continued with a power point presentation.
One of or school traditions is the sharing of bread with JCS classmates. Bread (small bun) was shared with students to reflect on the tragedy of this event.
The other tradition is the preparation of the flower symbol of the Holodomor – the blue and yellow forget-me-not. All of the student flowers were used to create a large "wreath" commemorating the 85th anniversary of the Holodomor in Ukraine. The years of the worst of the famine were 1932 to 1933. The Holodmor was a result of ethnic cleansing – where millions of Ukrainians, including children, were starved to death on purpose.
Josyf Cardinal Slipyj students participated this week on this tragic event. We pray for all the victims of the Holodomor.
Have a question about TCDSB? Please send general inquiries to:
©2018 Toronto Catholic District School Board. All rights reserved.


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I came across this video last night - and immediately went mental over it. This little 'pop top' caravan is so cute. Tardis-like, it seems bigger on the inside and the girl and her friend did a spectacular job of decorating it. It just looks like summertime in a box! I want it - it would… Continue reading Camping, design and tiny houses
Tag: camping
WHW – day5
Buachaille Etive Mòr from White Corries A tough but enjoyable day on the Way today. Oddly, the worst section was the 4 or 5 mile valley walk along the bottom of Glen Coe. It felt like such a trauchle, somehow. My spirits lifted as I started the climb up the infamous Devil's Staircase, even though the rain… Continue reading WHW – day5
WHW – day4
Wild and atmospheric Rannoch Moor from the WayThe weather forecast for "light showers" all morning was fairly accurate. Happily, in practice this was far less miserable than I'd feared. The sky was generally overcast but the blustery breeze kept the rain clouds scudding along and allowed occasional patches of blue sky and sun to shine… Continue reading WHW – day4
WHW – day3
my peaceful campsite on the edge of Rannoch MoorHad an excellent walk today in gorgeous sunshine. I arrived at Inveroran in the early afternoon and set up camp. Performed my ablutions in the clear, bubbling burn then sat on a stone, midstream, while birds flitted round and little fish nibbled my toes. Later, on my way to… Continue reading WHW – day3
WHW – day2
Arrived at Tyndrum. Tent set up, midgie-net on, ready to explore Camping at Tyndrum tonight before heading off tomorrow to re-walk the last half of the West Highland Way. The forecast looks a bit miserable for the days ahead but I'll be walking in the mountains by day and cosy in my tent at night… Continue reading WHW – day2


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I recently did a major clean out of the house
and gave a lot away to good will.
This French Connection sweater below was from the 90's and just too short and fluffy to wear again.
It was packed up and ready to go to the Opp shop.
I had a read of my favourite magazine.
The black and white contrasting cover caught my eye
and I had an idea.
As usual when I read my favourite style & home magazines
I like to try one or two ideas I like
and apply them to my home to keep it feeling current.
after seeing this cover,
I decided I wanted some more contrast in my bedroom.
I wanted a black,
chunky knit cushion
for my bed.
I knew just how to get one
for $0!
Repurposing is one of my favourite things to do!!
And my Mother in Law, who loves to sew, is visiting!!
So I took that old French Connection sweater out
and asked her how we could turn it into a cushion.
I also happened to have an extra cushion insert
which was a perfect fit.
She is amazing.
She actually managed to stitch the sweater around the cushion
keeping the sweater completely intact!
Which means,
if I ever wanted to
I could unstitch it and wear it again?
Handy Hint: I used a razor and gently shaved off all the lint balls to make it look like new.
Now I have a
bedroom update for
I made this bedhead ages ago.
I originally picked up a large art work, from the side of the road, only for the amazing frame it had.
I nearly discarded the artwork inside but instead.....
I covered the large canvas with a layer of batting to add some cushioning.
Then I staple gunned some lovely thick linen upholstery fabric to it.
I thought it look a little bit plain,
so I stitched 3 subtle little grey x's in the middle.
Then I attached it to the wall with 3M velcro strips.
The other cushions are made out of linen tea towels to match.


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Easy Scallion Pancakes with Soy Dipping Sauce
All you need is a few basic pantry and fridge ingredients for the ultimate recipe for Easy Scallion Pancakes perfect for dunking in a sweet and spicy soy dipping sauce. Few…
Kelly Senyei
All you need is a few simple ingredients for fast and fresh 5-Ingredient Strawberry Breakfast Pastries.
Quick and easy breakfast pastries are a popular option around these parts. While we've mastered a blueberry-cream cheese version and aced a raspberry pinwheel variety, this time, simplicity shines with 5-Ingredient Strawberry Breakfast Pastries.
With just a handful of ingredients and 30 minutes (including the time it takes to eat
one all of them), you'll be ditching every last frozen, store-bought option and DIY'ing your way to the best way to start any day. Preheat your oven for breakfast pastry perfection then keep the strawberry party poppin' with recipes for strawberry hand pies, shortcake, stuffed French toast and more.
Craving more? Subscribe to Just a Taste to get new recipes and a weekly newsletter delivered straight to your inbox! And stay in touch on Facebook, Twitter, Pinterest and Instagram for all of the latest updates.
Preheat the oven to 400ºF. Line a baking sheet with parchment paper or a Silpat.
Cut the puff pastry into six rectangles by following the perforations in the dough to first cut the sheet into three long rectangles and then cut each rectangle in half to form two smaller rectangles. Transfer the pastries onto the baking sheet, arranging them at least 1 inch apart.
Lightly score the dough by cutting a border 1/2-inch from the edges (do not cut through the pastry). Prick the center of the pastry several times with a fork.
In a small bowl, stir together the cream cheese and strawberry jam. Place a dollop of the cream cheese mixture in the centers of each pastry and spread it within the scored area. Top the cream cheese with the sliced strawberries.
Whisk together the egg with 1 Tablespoon water. Brush the edges of the pastry with the eggwash then bake the pastries for 15 to 17 minutes until golden and puffed.
Remove the pastries from the oven oven, dust with powdered sugar (optional) and serve.
★ Did you make this recipe? Don't forget to give it a star rating below!
Recipe by Kelly Senyei of Just a Taste. Please do not reprint this recipe without my permission. If you'd like to feature this recipe on your site, please rewrite the method of preparation and link to this post as the original source.
Categories: Breakfast & Brunch, Recipes, Snacks, Video Tutorials
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There are gardening books for instruction, and gardening books to read for pleasure. The best of the latter is the late Christopher Lloyd's classic The Well-Tempered Garden (1970). Like all his books, this drew on his long experience in the garden at Great Dixter in East Sussex. He wrote well and his style, like his garden preferences, is personal and nicely opinionated.
At the other end of the scale is another oldie, The Reader's Digest Illustrated Guide to Gardening (1978), my bible when I first had a garden. I later discarded it – only to buy it again second-hand, unable to live without its stout hessian binding, its succinct descriptions and general understated excellence. Nor can I do without the Royal Horticultural Society's Illustrated Plants For Places (2001), a fat, squat little handbook telling you what is most likely to thrive in different soils and varieties of sites. This saves you from much heartbreak and failure.
Our copy of Jane Fearnley-Whittingstall's Peonies: the Imperial Flower (1999) is quite tatty from frequent reference. This is a book to read for pleasure as well as for information, and for the illustrations. But for a real feast for the eyes, combined with scrupulous scientific descriptions, I love best the two great volumes – one on herbaceous plants, one on trees and shrubs – of The Botanical Garden (2002) by Roger Phillips and Martyn Rix. Hugely expensive, worth every penny.
Victoria Glendinning's first book, 'A Suppressed Cry: the Short Life of a Victorian Daughter' (Virago, £9.99) has recently been republished; her latest book is 'Raffles and the Golden Opportunity' (Profile, £25)


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Monthly Archives: August 2007
Ipods and Sneakers: The Miseducation of Oprah Winfrey
By Patricia Wilson-Smith The last thing I wanted to do on a cozy Sunday evening here at home with my son staring over my shoulder is write an article that I'm certain some will view as a pot-shot at one … Continue reading
Posted in Commentary, Issues, Oprah Winfrey 3 Comments
Obama Video of the Day – 8/28/2007
Today's video of the day is extraordinary! Today's video comes from YouTube and features none other than Michelle Obama, speaking to an enthusiastic group of women in what appears to be a store-front church in Harlem: This video is FABULOUS, and … Continue reading
Posted in Did You Know?, Events, Michelle Obama, Speeches, The Campaign Trail Leave a comment
Camp Obama ATL, and the "Countdown to Change"
By Patricia Wilson-Smith There is nothing more gratifying than to come together with people of like minds for a common cause. This weekend in Atlanta, a large number of Barack Obama supporters have gathered to participate in "Camp Obama", a training initiative … Continue reading
Posted in Camp Obama, Did You Know?, Events, The Campaign Trail 1 Comment
Obama Video of the Day – 8/24/2007
Today's "Obama Video of the Day" was produced by none other than the ladies of Black Women for Obama Atlanta! To celebrate our first official meeting, we met at my house, strategized, organized, and engaged each other in a dialogue … Continue reading
Posted in Did You Know? Leave a comment
Obama Video of the Day – 8/18/2007
Today's video is as inspiring as it is entertaining! We found this video on YouTube as well. In this video, You Tube user Akinscribe5 has compiled footage of both ordinary citizens and elected officials, celebrating the candidacy of the Senator, and … Continue reading
Posted in Commentary, Did You Know?, The Campaign Trail Leave a comment
Obama Video of the Day – 8/15/2007
We've found another short but poignant video that celebrates the campaign of hope being waged by Senator Barack Obama! Today's video comes from mandorlapix, and was found on YouTube – America IS Ready!: If you watch very closely, you'll see … Continue reading
Posted in Uncategorized Leave a comment
Happy Birthday, Senator Obama!
By Patricia Wilson-Smith This Saturday, August 4th was Senator Barack Obama's 46th birthday. We at BlackWomenForObama.org would like to wish the next President of the United States a very happy birthday! And now, for a totally unrelated anecdote. I've just … Continue reading
Posted in Commentary, Did You Know? Leave a comment


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Dont Worry Im With You Now from Swan Dive Album
Dec 5th, 2016 by dannyhauger
From the new album "Swan Dive" coming to all digital stores this week! Enjoy track 3 for free! I love this song, its one of the proudest projects to come out of my studios. Its a comforting and reassuring look at the role of that special someone and the role you play in their life, comfort, and security. Please enjoy and share! Lots more free music at Danny Hauger free music podcasts on iTunes! Buy my music on Amazon to support my free podcast!
Stream the new Danny Hauger album "Swan Dive" now on Spotify!!
"Swan Dive" 3-song E.P. free! No sign-up needed, come grab my 3 favorite songs from the album and share it! It's a Bandcamp exclusive, check it out! Pay what you want or download it free!
thanks for listening and subscribing! Help me keep this podcast free for the world! - -> And check out my new Social Studies Class Podcast!
- My newest album, "Swan Dive" comes out this week to all digital stores!!
- Grab my "Together Now" or "If I Grow Up" album for just $1 on Bandcamp!! Pay what you want and help support my music!
- Follow me on Twitter @DHXmusic or @DannyHauger
- Subscribe to my podcast on iTunes and PlayerFM!
- Contact me for booking or interview requests dhxlive at gmail
- Watch some of my YouTube videos!
- Listen to me on Spotify for free or Soundcloud!
- Need voice overs, audio editing, or media production? find me on Fiverr!
- Tell a friend or send a link to Danny Hauger Podcasts! Its nice and you're nice, so be nice! Download this episode (right click and save)me get discovered by more fans : ) Download this episode (right clicack and save)I need your help, music lovers.


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We think that a coherent approach to embedded software achitecture is needed, and we believe that all necessary aspects are already recognized: We want systems that are truly event-driven (non-blocking), better structured with the modern hierarchical state machines and safer by design than the usual "shared-state concurrency and blocking" approach based on a traditional Real-Time Operating System (RTOS). This modern way of thinking is called reactive programming.
Quantum Leaps' QP™ real-time embedded frameworks (RTEFs) provide a modern, reusable, reactive software architecture based on event-driven active objects (actors) and hierarchical state machines, while our QM™ model-based design tool and other host-based tools support graphical modeling, automatic code generation, software tracing and unit testing for event-driven embedded software.
For over 15 years our modern embedded software and development tools have been delivering competitive advantage to hundreds of companies around the world in a wide variety of markets.
The following downloads provide all QP™ frameworks, QM™ modeling tool and the QTools™ collection bundled together in a single, streamlined "QP-bundle":
Official version: 6.8.1 (April 22, 2020)
Lightweight Real-Time Embedded Framework (RTEF) for embedded systems in C. Designed for 16- and 32-bit MCUs, such as ARM Cortex-M.
Lightweight Real-Time Embedded Framework (RTEF) for embedded systems in C++. Designed for 16- and 32-bit MCUs, such as ARM Cortex-M.
Ultra-lightweight Real-Time Embedded Framework (RTEF) for tiny embedded systems in C. Designed for low-end 8- and 16-bit MCUs with RAM < 1KB, such as MSP430, PIC24 and AVR.
The QP™ Real-Time Embedded Frameworks are highly portable and have been ported to many embedded processors in the past. In recent years, however, we focused on the incredibly popular ARM Cortex-M CPU family, whereas we support Cortex-M0/M0+, Cortex-M3, Cortex-M4 with FPU and Cortex-M7 with FPU. We also support PIC32, as well as PIC24 and MSP430 low-power MCUs. Please refer to the "Ports" sections in the QP/C Reference Manual, QP/C++ Reference Manual and QP-nano Reference Manual for the specific lists of currently supported CPUs, compilers and development boards, as well as 3rd-party RTOSes and operating systems (including embedded Linux and Windows embedded).
Free Model-Based Design (MBD) and automatic code generation tool for real-time embedded software in C or C++ based on hierarchical state machines and the QP™ Real-Time Embedded Frameworks (RTEFs).
Collection of various open source tools for QP, including:QP/Spy™ Software Tracing for QP/C or QP/C++ applications QUTest™ Unit Testing Harness for QP/C or QP/C++ applications QWin™ GUI for prototyping embedded devices on Windows
The QM™ Model-Based Design tool and the QTools™ collection run on all three host operating systems ( Windows, Linux and MacOS). However, we recommend Windows, because we use it as the main platform for development and testing of our host-based tools.
Our modern embedded software architecture addresses high-reliability applications across a wide variety of markets, such as IoT, medical, consumer, defense, industrial, communication, transportation, robotics and many others. In each of these application areas, our elegant software provides considerable competitive advantage and has been commercially licensed worldwide by hundreds of companies large and small.
Quantum Leaps' Miro Samek will present at the Embedded Online Conference. On May 21 (Thursday) at 9:AM-1:PM Eastern Time Miro will be available for life Q&A about the presentation. Make sure you register!
The QP-bundle release 6.8.1 now supports C++11 (QP/C++), and QM 5.0.1 improves support for high-resolution and high-DPI displays (e.g., 4K monitors).
QP-bundle brings simplified, one-stop download and installation of all QP frameworks, QM modelign tool and QTools in a single package. The release 6.7.0 improves compliance with MISRA-C:2012-Amendment-1 and brings support for PC-Lint-Plus static analysis tool. Also, the root cause of malware reported in the QTools/QP-bundle 6.6.0 for Windows has been identified and fixed in QP 6.7.0.
New video: Getting Started with QP/QM/QTools
The "Modern Embedded Systems Programming" video course now explains: Object-Oriented Programming
QP/C++ library for Arduino SAM-based boards (e.g., Arduino DUE, Arduino Zero) released
New video: QM Tutorial
New video: Debugging with QUTest
Please update your records to our new postal address
QTools and QP/C/C++ support debugging of unit test fixtures in QUTest.
New video: Modern Embedded Systems Programming Lesson 28: RTOS part-7
Low-Power Example demonstrates how to use multiple clock tick rates to reduce power.