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Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo
Communicated by Harvey Cantor, Harvard Medical School, Boston, MA, November 12, 2004 (received for review September 15, 2004)
Cancer patients can harbor significant numbers of CD8 and CD4 T cells with specificities to tumor antigens (Ags). Yet, in most cases, such T cells fail to eradicate the tumor in vivo. Here, we investigated the interference of Ag-specific CD4+CD25+ regulatory T cells (Treg) with the tumor-specific CD8 T cell immune response in vivo, by monitoring the homing, expansion, and effector function of both subsets in draining and nondraining lymph nodes. The results show that CD8 cells expand to the same extent and produce similar levels of IFN-γ in the presence or absence of Ag-specific Treg. Nevertheless, these Treg abrogate CD8 T cell-mediated tumor rejection by specifically suppressing the cytotoxicity of expanded CD8 cells. The molecular mechanism of suppression involves TGF-β because expression of a dominant-negative TGF-β receptor by tumor-specific CD8 cells renders them resistant to suppression and is associated with tumor rejection and unimpaired cytotoxicity.
CD4+CD25+ regulatory T cells (Treg) are negative regulators of T cell immune responses in vitro and in vivo (1, 2). Upon TCR ligation, Treg can suppress the proliferation of both CD4 and CD8 cells in coculture experiments (3). Recently, however, it has been shown that the regulation of CD4 T cell responses in vivo can have different kinetics (reviewed in ref. 4). When coinjected into normal mice, both Treg and naïve CD4 cells initially proliferate upon recognition of cognate antigen (Ag). Furthermore, Treg do not influence the commitment of Ag-experienced CD4 cells to produce IFN-γ and IL-2. However, Treg do suppress cytokine secretion and interfere with the proliferation and possibly survival of CD4 cells later during the immune response (5-7). Treg also can control the magnitude of recall CD8 T cell responses in different settings that include viral (8, 9) and bacterial (10) infections as well as allograft transplantation in vivo (11, 12). A role in Treg function has been attributed to IL-2, which stimulates Treg and in turn may inhibit division of memory CD8 T cells (13, 14). However, these studies did not trace Ag-specific Treg in draining lymph nodes (LN), and it is not clear to what extent the different outcomes reflect accumulation of Treg by specific homing and local expansion. In fact, most studies were conducted with polyclonal Treg of unknown specificity where such questions cannot be addressed, and, therefore, the mode of inhibition cannot be correlated with specific Treg accumulation. Analysis of tumor-bearing patients suggests that suppression of CD8 T cell cytotoxicity by Treg may be causally related to tumor progression, because tumor-specific CD8 cells and tumor-specific CD4 Treg frequently accumulate in tumors from melanoma patients, and tumor-specific CD8 cells fail to exert cytotoxic T lymphocyte effector function (15-17).
This study investigates how Treg suppress primary CD8 T cell immune responses directed against tumor cells expressing influenza hemagglutinin (HA) as a surrogate tumor-specific Ag. Naïve CD8 and regulatory CD4 T cells with transgenic receptors specific for distinct peptides of HA were used to allow us to follow the fate of these cells in tumor draining LN. The results show that Treg interfere with CD8 T cell-mediated tumor rejection relatively early during the immune response, and the mechanism by which Treg suppress naïve CD8 cells differs from the ones that have been reported for memory CD8 cells (10-12, 14). Treg influenced neither the kinetics of proliferation nor the commitment of recently activated CD8 cells to produce inflammatory cytokines. Nevertheless, CD8 cells failed to undergo normal functional maturation in the presence of Treg as evidenced by the fact that their cytotoxic potential to destroy specific targets in vivo was abolished. Thus, these experiments reveal a previously unreported fine-tuning by Treg on different effector functions of CD8 cells.
There is considerable controversy over a putative role of TGF-β in the Treg-dependent regulation of immune responses (18). Although two recent studies suggested that TGF-β has a crucial role in the suppression of CD8 T cell-mediated diabetes, perhaps by mechanisms that allow more potent expansion of Treg (19) and mechanisms that may affect unknown functions of CD8 cells (20), the essential role of TGF-β has been debated by others (18). Here, we show that Treg-dependent inhibition of tumor-specific CD8 T cell-mediated cytotoxicity requires expression of the TGF-β receptor by CD8 cells. These data suggest a specific role of TGF-β signaling in the inhibition of cytotoxicity independent of cellular proliferation.
Materials and Methods
Mice. T cell receptor (TCR)-HA recombination activating gene-deficient (RAG-/-) mice expressing a TCR specific for H2-IE d/HA107-119, TCR-CL4 RAG-/- mice expressing a TCR specific for H2-K d/HA512-520, and pgk-HA × TCR-HA mice were generated as described in refs. 21, 22, and 23, respectively. BALB/c mice were purchased from Taconic Farms. BALB/c Thy1.1 mice were obtained from Paul Allen (Washington University School of Medicine, St. Louis). Dominant-negative TGFβR type II (dnTGFβRII) B6 mice (24) were backcrossed to TCR-CL4 RAG -/- BALB/c mice for five or more generations.
T Cells. HA-specific CD8 cells from TCR-CL4 RAG-/- mice, HA-specific CD4 cells from TCR-HA RAG-/- mice, and HA-specific CD4 Treg from pgk-HA × TCR-HA mice were purified as described in ref. 23. Where indicated, cells were labeled with 10 μM carboxyfluorescein diacetate-succinimidyl ester (CFSE; Molecular Probes) prior to adoptive transfer. Dendritic cells (DCs) were magnetically purified (>98% CD11c+) from spleens of BALB/c mice that had been implanted with a Flt-3L secreting melanoma cell line (25).
Tumors. The CT26 tumor cell line was derived from a chemically induced murine colon carcinoma. The tumor cell line CT44 was generated by transfecting CT26 cells with a fusion protein of influenza HA and EGFP (23). We injected 106 CT44 and CT26 cells s.c. into the upper side of the left and right hind paws of anesthetized animals, respectively (23).
Flow Cytometry. All mAbs were obtained from Becton Dickinson, except anti-HA (clone 37.38), which was obtained from Southern Biotechnology Associates. Anti-TCR-HA (clone 6.5) was purified in our laboratory. Surface and intracellular staining and flow-cytometric analysis were performed as described in ref. 26.
In Vivo Cytotoxic T Lymphocyte Assays. Splenocytes from BALB/c mice were labeled with either 1 or 10 μM CFSE (namely, CFSE+ or CFSE2+), then incubated for 1 h at 37°C with either no peptide or 1 μg/ml HA107-119 peptide, respectively. Recipient mice were injected i.v. with a 1:1 ratio of the two populations (2 × 107 cells). Tumor-draining LN cells were obtained 16 h later and stained with appropriate mAbs, including anti-B220 mAb. Percentage specific lysis was calculated as follows: % specific lysis = [1 - (B220+ CFSE+ events/B220+ CFSE2+ events)] × 100.
Treg Abrogate CD8 Tumor Immunity. The specificity of CD8 T cell-mediated tumor responses was analyzed in normal healthy BALB/c mice that were injected s.c. with both 106 HA+ tumor cells (CT44, right foot) and 106 HA- tumor cells (CT26, left foot) on day 0. Both tumors grew equally well in the transplanted mice, indicating the lack of an efficient tumor-specific immune response in normal mice (Fig. 1a ). However, adoptive transfer of 105 naïve CD8 cells bearing a transgenic TCR specific for the K d-restricted HA512-520 peptide (hereafter termed HA-specific CD8 cells) 1 day before tumor challenge resulted in specific rejection of CT44 tumors (Fig. 1b ). CD8 T cell-mediated rejection of CT44 tumors was apparent between days 7 and 10 and was complete on day 14 (Fig. 1b ). In contrast, CT26 tumors within the same individuals were not rejected (Fig. 1b ).
We then investigated whether CD4 Treg with specificity for a class II-restricted HA epitope may influence primary CD8 T cell immune responses directed against the class I restricted HA peptide (bystander suppression). HA-specific CD4 Treg were obtained from mice expressing influenza-HA under the control of the ubiquitous pgk promoter (pgk-HA) and a transgenic TCR (TCR-HA) specific for the I-E d-restricted HA107-119 peptide (26). BALB/c mice were adoptively transferred with a mixture of 105 naïve HA-specific CD8 cells and 105 HA-specific CD4 Treg and subsequently challenged with CT26 and CT44 tumors. The results showed that Treg completely abrogated CD8 T cell-mediated rejection of CT44 tumors (Fig. 1c ), in that the kinetic of CT44 tumor growth was as fast as that displayed by the CT26 tumor within the same individual (Fig. 1c ), and comparable with the kinetic of CT44 or CT26 tumor growth in mice that did not receive HA-specific CD8 cells (Fig. 1a ).
In contrast to the Treg-dependent abrogation of CD8 T cell-mediated tumor rejection, the cotransfer of 105 nonregulatory CD4 cells with the same specificity as the Treg did not abrogate but rather enhanced tumor rejection by CD8 cells (Fig. 1d ), in line with the reported role of CD4 cells in augmenting immune responses by CD8 cells (21, 27). As reported in ref. 23, adoptive transfer of naïve HA-specific CD4 cells alone did not mediate rejection of CT44 tumors. The steady-state levels of adoptively transferred T cells in these experiments in the absence of Ag challenge were comparable for both CD4 and CD8 cells, in the range of 0.01% Ag-specific T cells among total CD8 or CD4 cells, respectively. These experiments, therefore, indicate that Treg were able to interfere effectively at early stages with the CD8 immune response.
CD8 T Cell Homing and Expansion. Because CD4 Treg were reported to impair CD8 T cell proliferation in vitro (28), we investigated whether a similar mechanism contributed to the Treg-dependent impairment of the CD8 immune response in vivo. In initial experiments, CFSE-labeled HA-specific Thy1.2 CD8 cells were adoptively transferred into Thy1.1 BALB/c mice that subsequently were challenged with CT44 and CT26 tumors simultaneously. The number of HA-specific CD8 cells (defined as Thy1.2+ CD8+) rapidly increased 200-fold in CT44 draining LN (Fig. 2 a and b ), whereas HA-specific CD8 cells did not accumulate in CT26 draining LN (Fig. 2c ). As shown in Fig. 2b , the accumulation of CD8 cells in CT44 draining LN was accompanied by extensive cell division. Similar accumulation and expansion of HA-specific CD8 cells was observed when cotransferred with HA-specific naïve CD4 cells (Fig. 2b ). The CD4 T cell population (defined as Thy1.2+ CD4+) also rapidly expanded in CT44 draining LN, reaching 2.9 ± 0.4% of CD4 cells on day 7, which is equivalent to 3.3 ± 2.0 HA-specific CD4 cells per HA-specific CD8 cell. The Ag-specific proliferation of both HA-specific CD8 and CD4 cells in CT44 draining LN indicated that HA512-520 and HA107-119 peptides were effectively presented in this environment. Because CT44 tumor cells do not express class II MHC molecules, the results indicate that HA Ags were released from tumor cells and presented by class II MHC positive cells, most likely DCs, in the draining LN.
In further experiments, the fate of HA-specific CD8 cells that were cotransferred with HA-specific CD4 Treg was studied. The presence of Treg did not alter the expansion of HA-specific CD8 cells because the kinetic of expansion of CD8 cells in the CT44 draining LN remained unchanged or only slightly reduced after cotransfer with Treg. This notion was further supported by the observation that the dilution of CFSE label was not significantly different in CD8 cells expanding in the absence or presence of Treg (Fig. 2b ). HA-specific CD4 Treg also accumulated within the same LN, starting from ≈0.01% of CD4 cells immediately after adoptive transfer (data not shown) and reaching 3.4 ± 0.8% of all LN CD4 cells on day 7 (Fig. 2b ). HA-specific CD4 Treg accumulated slightly faster than HA-specific CD8 cells in CT44 draining LNs, because we found 2.8 ± 1.2 HA-specific Treg per HA-specific CD8 cell on day 7. Neither CD8 cells nor Treg accumulated in the LN draining the HA-negative CT26 tumor (Fig. 2c ). HA-specific CD4 Treg did not accelerate apoptosis of HA-specific CD8 cells, because the vast majority of cells remained annexin V-negative in the presence or absence of Treg (Fig. 2b ). Collectively, these data indicate that Treg did not interfere with the accumulation and division of tumor-specific CD8 cells in CT44 draining LN.
CD8 T Cell Differentiation Markers. In additional assays it was analyzed whether Treg interfered with the expression of differentiation cell surface molecules on HA-specific CD8 cells. To this end naïve HA-specific CD8 cells were adoptively transferred into BALB/c mice subsequently challenged with CT44. A significant fraction of Ag-primed HA-specific CD8 cells acquired an activated CD25+CD127-CD69+CD44highCD62Llow phenotype, as demonstrated on day 7 in CT44 draining LN (see Fig. 6, which is published as supporting information on the PNAS web site). Similar phenotypic changes were observed when HA-specific CD8 cells were cotransferred with either naïve HA-specific CD4 cells or HA-specific CD4 Treg (Fig. 6). Because HA-specific CD8 cells acquired an activated phenotype irrespective of the absence or presence of Treg, expression of these markers could not be used as a diagnostic tool to predict survival of tumors.
CD8 T Cell Cytokines. Ag-primed effector CD8 cells release cytokines and lytic molecules that mediate a local inflammatory response and effect target cell apoptosis (29, 30). The influence of HA-specific Treg on the functional activity of CD8 cells was investigated by analyzing cytokine production in HA-specific CD8 cells on d 7 after tumor challenge. The majority of HA-specific CD8 cells produced IFN-γ and TNF-α upon restimulation with exogenous K d-restricted HA512-520 peptide or phorbol 12-myristate 13-acetate (PMA)/ionomycin (Fig. 3 a-c and Fig. 7, which is published as supporting information on the PNAS web site). Cotransfer of HA-specific CD4 Treg with HA-specific CD8 cells did not inhibit cytokine production. This result occurred whether the cells were restimulated only with class I MHC-restricted peptide, with both class I and class II MHC-restricted peptides, or with PMA and ionomycin, indicating that the reactivation of Treg in vitro did not suppress cytokine production by activated CD8 cells (Fig. 3 a and b ).
We further investigated whether peptide presentation by K d + I-E d + antigen-presenting cells only (i.e., favoring close proximity of Treg and CD8 cells) could selectively impair CD8 T cell activity. To this end, purified splenic DCs (>97% CD11c+ K d + I-E d +) were pulsed with only the class I MHC-restricted peptide or with both class I and class II MHC-restricted peptides and used as antigen-presenting cells. Stimulation by PMA/ionomycin was used in controls. In the absence of HA-specific CD4 Treg, a significant fraction of HA-specific CD8 cells produced IFN-γ upon restimulation with peptide-pulsed DCs (Fig. 3c ). This fraction was lower than the number of IFN-γ-producing HA-specific CD8 cells upon restimulation with PMA/ionomycin or with exogenously added HA peptide(s) (Fig. 3a ). The difference is likely due to reduced Ag presentation when peptide-pulsed DCs were used (Fig. 3c ) instead of supplying cultures with peptides without subsequent removal of nonbound peptide (Fig. 3 a and b ). Importantly, the presence of HA-specific CD4 Treg did not interfere with cytokine production by CD8 cells even when the CD4 cells were restimulated with the class II MHC-restricted HA peptide (Fig. 3c ). Collectively these experiments indicate that the Treg did not interfere with the ability of CD8 cells to produce IFN-γ at early stages of the immune response.
Suppression of CD8 T Cell Cytotoxicity. The cytotoxicity of HA-specific CD8 cells was addressed by in vivo readouts on day 6 after tumor challenge. In the absence of HA-specific CD4 Treg, HA-specific CD8 T cells specifically killed HA512-520 peptide-pulsed targets in CT44 draining LNs but not in CT26 draining LNs. The presence of HA-specific CD4 Treg abolished the specific cytotoxic activity of HA-specific CD8 cells (P < 0.0001; Fig. 4). No in vivo killing of HA+ targets was observed in popliteal LNs of nonchallenged mice or in CT44 draining LNs from CT44-bearing mice that did not receive HA-specific CD8 cells (data not shown). Importantly, because Treg did not interfere with the proliferation of naïve CD8 cells, the observed reduced cytotoxic activity in the presence of Treg in CT44 draining LNs indicates direct suppression of cytolytic activity rather than indirect suppression through impairment of proliferation.
TGF-β-Dependent Suppression. A potential role of TGF-β in the suppression of tumor rejection by CD8 cells was analyzed by introducing a dominant-negative TGF-β receptor into the tumor-specific CD8 cells, by crossing mice with the transgenic TCR specific for K d/HA512-520 with mice harboring a dnTGFβR (24). Expression of dnTGFβR by HA-specific CD8 cells did not alter their naïve phenotypic status at least in 4- to 6-wk-old animals, because the vast majority of both dnTGFβR and WT HA-specific CD8 cells were CD25-CD127+CD45RBhighCD69-CD44lowCD62Lhigh (see Fig. 8, which is published as supporting information on the PNAS web site), whereas some dnTGFβR HA-specific CD8 cells in older animals (12-16 wk old) did exhibit the CD44 activation marker (data not shown). Therefore, CD8 cells used in further experiments were from 4- to 6-wk-old mice. When 105 naïve dnTGFβR or WT HA-specific CD8 cells were transferred into BALB/c mice, both populations of cells displayed similar kinetics of expansion in response to challenge with CT44 tumors (Fig. 5a ) and rejected CT44 tumors (Fig. 5c ). Thus, expression of the dnTGFβR in CD8 cells did not alter their expansion and the kinetic of tumor rejection. When coinjected with Treg, dnTGFβR and WT HA-specific CD8 cells also similarly expanded in response to challenge with CT44 tumors (Fig. 5a ). However, expression of dnTGFβR by HA-specific CD8 cells interfered with the suppression of tumor immunity by Treg because the kinetic of tumor rejection mediated by dnTGFβR HA-specific CD8 cells was comparable with the one mediated by WT HA-specific CD8 cells in the absence of Treg (Fig. 5c ). To address whether this reaction resulted from a failure of Treg to suppress cytotoxicity, the effector function of dnTGFβR and WT CD8 cells in CT44 draining LN on day 7 was compared. Whereas the HA-specific CD8 cells efficiently lysed HA-peptide pulsed syngeneic target cells in vivo only in the absence of Treg, the cytotoxicity displayed by dnTGFβR HA-specific CD8 cells in the presence or absence of Treg was indistinguishable (Fig. 5b ). Thus, expression of dnTGFβR by HA-specific CD8 cells was sufficient to render CD8 cells resistant to regulation by Treg and allowed efficient tumor rejection by cytolytic activity.
This report describes the influence of HA-specific CD4+CD25+ Treg on the primary response of naïve HA-specific CD8 cells against HA-expressing tumors in vivo. The results show the following: (i) HA-specific CD8 cells were capable of rejecting HA-expressing tumors, whereas HA-negative tumors were not affected; (ii) HA-specific Treg effectively interfered with tumor rejection; (iii) suppression affected neither proliferation of CD8 cells during the first 10 days of the response nor the acquisition of a fully activated surface phenotype; (iv) suppression affected only the cytolytic activity of CD8 cells and had no impact on IFN-γ or TNF-α secretion; and (v) the molecular mechanism of CD8 suppression essentially involved TGF-β signaling because CD8 cells incapable of TGF-β signaling were resistant to suppression. Thus, Treg can effectively suppress the early tumor-specific immune response by CD8 cells by inhibiting their cytolytic activity in a TGF-β-dependent manner.
It has been shown that Treg can suppress the proliferation of CD4 and CD8 cells in vitro (3, 28, 31) and that in vivo Treg are capable of interfering with the proliferation of as well as production of IFN-γ by CD8 cells (8, 10, 12, 14). Indeed, secretion of IFN-γ by CD8 cells has been suggested to play a critical role in tumor rejection (32, 33). However, most of these studies have used polyclonal Treg where specific homing and expansion cannot be studied and no correlation between Ag-specific Treg and inhibition of CD8 cells can be made. Here, we have analyzed the impact of Treg on a primary CD8 immune response under conditions where CD8 cells and Treg have specificity for different peptides of the same protein expressed by tumor cells and where initially both naïve CD8 cells and Treg are present at a low frequency, as might be expected under physiological conditions. This procedure permits one to follow the Ag-specific responses of both cell types in the tumor draining LN and to correlate the mode of inhibition with local expansion. The data show that during the first week both the Ag-specific CD8 cells as well as the Ag-specific Treg home to and expand in the tumor draining LN and that the expanding Treg do not affect the proliferation of CD8 cells. Of interest is the observation that despite this finding, Treg interfere with tumor rejection by CD8 cells, which otherwise is complete by day 10 or shortly thereafter. Because suppression of proliferation could not explain these results, we analyzed whether Treg interfered with the effector functions of CD8 cells. Although no significant impairment of IFN-γ production was observed by day 7, there was an almost complete suppression of CD8-mediated cytolytic activity at this point in time. This suppression was essentially dependent on TGF-β signaling because CD8 cells with a dominant negative TGF-β receptor were resistant to suppression. This study also illustrates the importance of the Ag specificity of Treg on the control of CD8 cells, a feature of the immune system that is still poorly defined in vivo. It is noteworthy that the HA-specific CD8 cells were not controlled by the abundant CD4+CD25+ T cell repertoire endogenously present in the recipient mice, but were impaired selectively by lower numbers of HA-specific Treg, at least upon extensive Ag-specific proliferation.
We show that suppression of immune responses in vivo can occur by affecting distinct effector mechanisms at different stages of an immune response. In interpreting the results, one can envisage a scenario in which Treg and CD8 cells initially do not effectively interact with each other because of the low frequency of each population in the draining LN and, hence, physical separation of the two subsets. Thus, both populations expand significantly and thereby reach a frequency allowing a more effective interaction either directly or through Ag-presenting cell intermediates. It appears that at this stage, the suppression of cytolytic activity is more effective than the suppression of cytokine production or proliferation, i.e., cytotoxicity appears most sensitive to suppression, a notion consistent with observations by others that these effector functions can be regulated independently (27, 34-37), perhaps because they require different intensity of TCR signaling (38). Also, the cytokine requirement for proliferation of primary and memory CD8 cells may differ, and, hence, Treg may be more efficient in suppressing the proliferation of memory than of primary CD8 T cells. It is tempting to speculate that in vivo Treg-mediated suppression inhibits TCR signaling, the intensity of which controls different effector functions. This hypothesis could explain the reported suppression of CD8 T cell proliferation (8, 10) and/or IFN-γ secretion (9) in cases of viral or bacterial infection, under conditions in which the ratio of Ag-specific Treg and CD8 cells is unknown. Our results also show that in this model of tumor rejection, loss of cytolytic activity is sufficient to allow tumor outgrowth even when tumor-specific T cells still produce high levels of IFN-γ.
Independent evidence suggests that the suppression of CD8 T cell cytotoxicity by Treg may be common in cancer. It is of interest that tumor-specific CD8 cells frequently accumulate in tumors of melanoma patients but fail to exert cytolytic effector function (15), especially under conditions where tumor-specific CD4 Treg also could be identified within the tumor stroma (16, 17). These observations are consistent with results described in this study showing that tumor-specific CD4 Treg did not perturb the proliferation of HA-specific CD8 cells but suppressed their cytolytic activity in vivo. Such suppression may not only occur in draining LN but also among extravasated CD4 and CD8 cells within the tumor. In this context, it is of considerable interest that the pathway of immune suppression of cytolytic activity essentially depends on signaling by the TGF-β receptor on CD8 cells. Although previous studies on TGF-β-mediated inhibition have not addressed specific effector functions (20), our observations provide a rational explanation for earlier findings indicating that T-cell-specific blockade of TGF-β signaling renders mice resistant to tumors that otherwise would have been lethal (39). TGF-β-mediated suppression of CD8 T cell cytolytic activity in vitro has been studied by several investigators, and it has been reported by some that TGF-β interferes at early phases of the cytotoxic response but is rather ineffective once cells have developed cytolytic activity (40). However, there are also studies describing a more direct inhibition of cytolytic activity by TGF-β by interfering with the production of pore-forming protein independently of proliferation (41) that are consistent with our observations. Our results, thus, show that under conditions where the homing and accumulation of Ag-specific T cells and their CD8 targets can be tightly monitored, it is possible to identify a specific effector CD8 T cell function, namely cytolytic activity, that is most susceptible to TGF-β-mediated inhibition of regulatory T cells.
We thank Ludger Klein for critical suggestions, Silke Paust for discussions, Thorsten Mempel (CBR Institute, Harvard Medical School) and Glenn Dranoff (Dana-Farber Cancer Institute, Harvard Medical School) for providing us Flt3L-expressing tumor cells and advice, and Dina Lazik for excellent technical assistance. M.L.C. was supported bya Cancer Research Institute Investigator Award in Cancer Immunology; M.P. was supported by Swiss National Foundation Grant PBLAB-100856 and Human Frontier Science Program Organization Grant LT00369/2003; and K.K. was supported by Ruth L. Kirschstein National Research Service Award R33 CA97728-02 and Idea Award DAMD17-02-1-0361.
↵ ** To whom correspondence may be addressed at: Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Smith 736, Boston, MA 02115. E-mail: khashayarsha_khazaie{at}dfci.harvard.edu or harald_von_boehmer{at}dfci.harvard.edu.
↵ † M.-L.C. and M.J.P. contributed equally to this work.
↵ ¶ Present address: Biogen Idec, Cambridge, MA 02142.
Author contributions: H.v.B. and K.K. designed research; M.-L.C., M.J.P., and K.K. performed research; M.-L.C., M.J.P., and K.K. analyzed data; L.G., R.A.F., and R.W. contributed new reagents/analytic tools; and K.K. and M.J.P. wrote the paper.
Abbreviations: Ag, antigen; CFSE, carboxyfluorescein diacetate-succinimidyl ester; DC, dendritic cell; dnTGFβR, dominant-negative TGFβR type II; HA, influenza hemagglutinin; LN, lymph node; PMA, phorbol 12-myristate 13-acetate; RAG-/-, recombination activating gene-deficient; TCR, T cell receptor; Treg, CD4+CD25+ regulatory T cells.
- Copyright © 2005, The National Academy of Sciences
- ↵
- ↵
Suri-Payer, E., Amar, A. Z., Thornton, A. M. & Shevach, E. M. (1998) J. Immunol. 160 , 1212-1218. pmid:9570536
von Boehmer, H. (2003) J. Exp. Med. 198 , 845-849. pmid:12975452
Walker, L. S., Chodos, A., Eggena, M., Dooms, H. & Abbas, A. K. (2003) J. Exp. Med. 198 , 249-258. pmid:12874258
Fisson, S., Darrasse-Jeze, G., Litvinova, E., Septier, F., Klatzmann, D., Liblau, R. & Salomon, B. L. (2003) J. Exp. Med. 198 , 737-746. pmid:12939344
Yamazaki, S., Iyoda, T., Tarbell, K., Olson, K., Velinzon, K., Inaba, K. & Steinman, R. M. (2003) J. Exp. Med. 198 , 235-247. pmid:12874257
Suvas, S., Kumaraguru, U., Pack, C. D., Lee, S. & Rouse, B. T. (2003) J. Exp. Med. 198 , 889-901. pmid:12975455
- ↵
Kursar, M., Bonhagen, K., Fensterle, J., Kohler, A., Hurwitz, R., Kamradt, T., Kaufmann, S. H. & Mittrucker, H. W. (2002) J. Exp. Med. 196 , 1585-1592. pmid:12486101
- ↵
- ↵
- ↵
Murakami, M., Sakamoto, A., Bender, J., Kappler, J. & Marrack, P. (2002) Proc. Natl. Acad. Sci. USA 99 , 8832-8837. pmid:12084927
Zippelius, A., Batard, P., Rubio-Godoy, V., Bioley, G., Lienard, D., Lejeune, F., Rimoldi, D., Guillaume, P., Meidenbauer, N., Mackensen, A., et al. (2004) Cancer Res. 64 , 2865-2873. pmid:15087405
- ↵
- ↵
Piccirillo, C. A., Letterio, J. J., Thornton, A. M., McHugh, R. S., Mamura, M., Mizuhara, H. & Shevach, E. M. (2002) J. Exp. Med. 196 , 237-246. pmid:12119348
Peng, Y., Laouar, Y., Li, M. O., Green, E. A. & Flavell, R. A. (2004) Proc. Natl. Acad. Sci. USA 101 , 4572-4577. pmid:15070759
Green, E. A., Gorelik, L., McGregor, C. M., Tran, E. H. & Flavell, R. A. (2003) Proc. Natl. Acad. Sci. USA 100 , 10878-10883. pmid:12949259
Kirberg, J., Baron, A., Jakob, S., Rolink, A., Karjalainen, K. & von Boehmer, H. (1994) J. Exp. Med. 180 , 25-34. pmid:8006585
- ↵
- ↵
- ↵
- ↵
Klein, L., Khazaie, K. & von Boehmer, H. (2003) Proc. Natl. Acad. Sci. USA 100 , 8886-8891. pmid:12857946
Lyman, M. A., Aung, S., Biggs, J. A. & Sherman, L. A. (2004) J. Immunol. 172 , 6558-6567. pmid:15153470
Piccirillo, C. A. & Shevach, E. M. (2001) J. Immunol. 167 , 1137-1140. pmid:11466326
- ↵
- ↵
Somasundaram, R., Jacob, L., Swoboda, R., Caputo, L., Song, H., Basak, S., Monos, D., Peritt, D., Marincola, F., Cai, D., et al. (2002) Cancer Res. 62 , 5267-5272. pmid:12234995
Qin, Z., Schwartzkopff, J., Pradera, F., Kammertoens, T., Seliger, B., Pircher, H. & Blankenstein, T. (2003) Cancer Res. 63 , 4095-4100. pmid:12874012
- ↵
- ↵
Hernandez, J., Aung, S., Marquardt, K. & Sherman, L. A. (2002) J. Exp. Med. 196 , 323-333. pmid:12163561
- ↵
Valitutti, S., Muller, S., Dessing, M. & Lanzavecchia, A. (1996) J. Exp. Med. 183 , 1917-1921. pmid:8666949
- ↵
Erard, F., Garcia-Sanz, J. A., Moriggl, R. & Wild, M. T. (1999) J. Immunol. 162 , 209-214. pmid:9886388
Smyth, M. J., Strobl, S. L., Young, H. A., Ortaldo, J. R. & Ochoa, A. C. (1991) J. Immunol. 146 , 3289-3297. pmid:1827481


text:
By Father Cleopa
"…For God resisteth the proud,
and giveth grace to the humble."
(1 Peter, 5:5)
Since in my previous sermons I talked about the kinds of temptations and the reasons for which God allows us to be tempted – to our benefit and for the salvation of our souls –, this time, I have thought about talking about the temptations that present themselves to the humble as well as those that befall the proud. In what follows, it will become evident that Our Good Lord does not allow for all people to be tempted in the same way; but rather, there are many different types of temptations, according to His indescribable and unfathomable wisdom. We will see that in the case of the humble and gentle persons, who realize their powerlessness and unworthiness well, Our Good and All-wise God does not release temptations and problems that are too big. In the case of proud and haughty people, God allows for great and heavy temptations and problems to come upon them, which, many times, surpass their limits of patience. He does this will great wisdom and economy, in order to bring such people back to humility and humbleness, to make them acknowledge their powerlessness and unworthiness here on earth, and make them all come to the holy path of salvation.

subset: commoncrawl


text:
Bouli Bar
Bouli Bar, situated next door to Boulettes Larder, is a more casual offering than its forebear, serving casual wood-fired cuisine, cocktails, and desserts. Selections include wood fired pizzas, meats, and fish as well as mezze plates, salads, and soups. The food is created with the careful and sophisticated array of spices, salts, oils, and culinary products that Chef Schwertner stocks in her Larder. Craft cocktails, wine list, and selections of beer are served alongside the thoughtful daily menu. An expansive wooden bar allows diners to nest up and watch as bartenders concoct a delicious mélange of choice spirits for your enjoyment.
Tuesday through Saturday, Boulibar is a destination stop for shoppers and commuters and can be yours as well, for a late afternoon business conversation or rendezvous with friends and colleagues.


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Matthew Modine
Matthew Avery Modine (born March 22, 1959) is an American actor, activist and filmmaker, who rose to prominence through his role as United States Marine Corps Private Joker in Full Metal Jacket. His other film roles include the title character in Birdy, the high school wrestler Louden Swain in Vision Quest, Drake Goodman in Pacific Heights and Dr. Ralph Wyman in Short Cuts. On television, Modine portrayed Dr. Martin Brenner in Stranger Things, the oversexed Sullivan Groff on Weeds, Dr. Don Francis in And the Band Played On and Ivan Turing in Proof. Modine has been nominated twice for a Golden Globe Award for Best Actor in a Miniseries or Motion Picture Made for Television for his work in And the Band Played On and What the Deaf Man Heard and won a Special Golden Globe for him and the rest of the ensemble in Short Cuts. He was also nominated for a Primetime Emmy Award for Outstanding Lead Actor in a Miniseries or a Special for And the Band Played On.WIKIPEDIA


text:
Dear XML Security WG, Following the PAG's report [1] concerning RIM/Certicom's IP on related XML Security specification(s), we would like to share RIM's official response (please see attached) to a wider audience that may have an interest in this topic. [1] http://lists.w3.org/Archives/Public/public-xmlsec/2012Oct/0005.html Regards, Suresh Chitturi Research In Motion Corporation --------------------------------------------------------------------- This transmission (including any attachments) may contain confidential information, privileged material (including material protected by the solicitor-client or other applicable privileges), or constitute non-public information. Any use of this information by anyone other than the intended recipient is prohibited. If you have received this transmission in error, please immediately reply to the sender and delete this information from your system. Use, dissemination, distribution, or reproduction of this transmission by unintended recipients is not authorized and may be unlawful.
This archive was generated by hypermail 2.4.0 : Friday, 17 January 2020 19:42:30 UTC


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(Halifax, NS) – The Dalhousie Tigers were shutout by the U SPORTS ranked No. 4 StFX X-Men at the Halifax Forum Wednesday night. The Tigers got plenty of opportunities, but strong power play unit, and a stellar performance by their goaltender saw StFX take the win.
The X-Men struck early with a power play opportunity. With a textbook breakout from their own zone, the visitors caught a Tigers defender out of position and came in on a 2-on-1. Michael Clarke (London, ON) carried the puck in wide and attracted the defender, sending a great pass across the slot to Holden Cook (Oshawa, ON) who had plenty of time to pick his spot and burry the shot.
The best chance for the Tigers in the period came off a solid neutral-zone pass from Jackson Playfair (Fort St.-James, BC) to Kelly Bent (Halifax, NS) who got behind the StFX defenders. Bent walked in and made a move followed by a low shot, but X-Men netminder Brandon Hope (Canton, MI) was able to get the pads down fast enough to keep it out.
The X-Men had another great chance late in the period when Brent Turnbull (Stellarton, NS) intercepted a clearing attempt at the point and fired a hard pass in front that was redirected by Matt Needham (Penticton, BC), but Corbin Boes (Saskatoon, SK) slid across the crease to make the stop.
The first period came to end an with the lone goal giving StFX the 1-0 lead.
The X-Men began the period on the power play, but the Tigers showed strong positioning and were able to kill it off with no threatening chances allowed.
There was a lot of back-and-forth action early in the second period with neither team able to establish control of the puck for extended periods of play.
The Tigers put a long stretch of pressure on the X-Men midway through the period, holding the puck in the attacking end. Only one real chance was generated, however, coming off of a scramble in front with Chandler Yakimowicz (Kingston, ON) jamming it at the goal, but Hope held his ground and kept the X-Men ahead.
The Tigers ended the period on a strong possession deep in the attacking zone. After forcing a turnover at the blue line they had three attackers in the slot with plenty of ice. The pass came across the slot to Andrew Shewfelt (Dartmouth, NS), but his quick one-timer sailed just high, over the net.
Surviving that final scare, StFX held onto their 1-0 lead heading into the third period.
The X-Men found themselves on the power play again early in the final period, and it took them just 15 seconds to find the back of the net. A pass from the point found Santino Centorame (Mississauga, ON) along the half boards, and he fired a bullet over the blocker-side shoulder of Boes to pop the water bottle and put StFX up 2-0.
The X-Men were threatening for another one a few minutes later when a scramble in front had bodies on the ice in front of the crease. The puck squeaked out to Matt Needham, but he was robbed by the blocker of Boes, sliding back across the crease.
The Tigers had a good chance with time ticking away on them as Alex Pawelczyk (Detroit, MI) threaded a pass across the crease to Playfair, but his shot was stopped by a sliding Hope.
With just over two minutes to go, the Tigers elected to empty their net for the extra attacker. They controlled the puck well, but the X-Men put heavy traffic in front of the net and made it difficult to get a shot through.
Time ran out on the Tigers, as they were unable to solve Brandon Hope, who came away with 39 saves, the shutout, and the Subway Player of the Game award.
Both the Tigers and X-Men have one game remaining prior to the Christmas break. Dalhousie will play at Moncton on Friday night followed by the X-Men at Moncton to face the same Aigles Bleus squad on Saturday night.
Courtesy Kirk Jessome, Dalhousie Sports Information


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AHMEDABAD — Gujarat governor OP Kohli has sent the controversial Gujarat Control of Terrorism and Organised Crime Bill, 2015 to the President for his assent, state home minister Rajnikant Patel said here today.
"I have learned today that Governor has sent the bill to the President for his approval, as some of the provisions require presidential assent," said Patel.
The GCTOC bill was passed by the state Assembly for the fourth time on March 31 this year.
Some of its provisions, such as the admissibility of evidence collected through telephonic interception and confession made before a police officer, have become controversial.
Also, it provides that a charge-sheet can be filed within six months of arrest (against a shorter period in ordinary cases) and no bail can be obtained on a personal bond.
The bill had been sent back by President APJ Abdul Kalam in 2004 and his successor Pratibha Patil in 2008 when Narendra Modi was the Chief Minister.
The Assembly passed it again in 2009, but it remained pending with the President. This year it was renamed and passed yet again.
The bill is modelled on the stringent Maharashtra Control of Organised Crime Act (MCOCA).
Gujarat unit of Congress said it would request President Pranab Mukherjee not to sign the bill.
"Earlier when this bill was sent to the Governor by the BJP-led state government for approval, we had met him and requested him not to sign the bill, as the earlier version had been rejected twice by former presidents and once by governor owing to controversial provisions," said senior Congress MLA Shailesh Parmar.
"Now, as the bill has been sent to the President, senior Congress leaders will meet him (Mukherjee) to make an appeal that he should not sign this bill which contains provisions which are politically-driven and in contravention of the current law system," said Parmar.
Contact HuffPost India


text: I've been reading in the book in Job. And wow, Job used the word "trouble" frequently! He definitely had reason to do so, as he lost everything he had and his wife wanted him to curse God and die. Things had gotten that bad! While Job is well-known for his trust in God, for a few chapters, he boldly asks the big question to God that we all ask when we just don't understand. Why? I've … [Read more...] about 15 Bible Verses For Trusting God in Tough Times


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Cosmetic Dental Care
A healthy and natural smile can make a person feel more confident. Lifestyle and bad oral hygiene affect how our teeth look. But damage or trauma can affect teeth and gums too. We can repair your smile to give you a more natural aesthetic smile.
A natural and youthful smile can make a person beam with confidence. We provide full range of cosmetic dentistry to give you an aesthetic, natural and healthy smile.


text:
A five-minute taxi ride from Cefalu station will bring you to the car park of an ugly football stadium from where you can get a fairly close-up view of the former Abbey of Thelema, notorious as the home of Aleister Crowley and a small group of disciples in the early 1920s. A number of videos can be found of the interior in various states of distress, such as this one when Kenneth Anger made one of his visits. Apparently the house has been on the market for a while but it would appear that there have been no takers so far. These photos were taken by me on Thursday 21st February.
Eartheater Details New LP For PAN
41 minutes ago


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Saturday, July 30, 2005
SPACE CENTER, Houston — Two astronauts floated out of shuttle Discovery for the mission's first spacewalk Saturday and tested repair techniques developed after the Columbia tragedy more than two years ago.
"What a view," said Soichi Noguchi as he emerged from the linked shuttle and international space station about 222 miles over central Asia. It took about an hour for Noguchi and Stephen Robinson to "gain their space legs" and begin working.
"There are just no words to describe how cool this is," Robinson said while riding the space station's robotic arm to connect a device needed for the installation of a storage platform next week.
The astronauts worked side-by-side in Discovery's open cargo bay during a portion of the planned 6 1/2-hour spacewalk. They used a variety of damaged tile and carbon samples brought to space to test the repair methods.
Robinson and Noguchi, a Japanese astronaut, worked with tools similar to an oversized caulk gun and large putty knives to apply an experimental material to the sample tiles that NASA hopes can be used in future missions to repair cracks in the delicate carbon panels lining the shuttle's wings.
The astronauts rearranged their schedule to perform the repairs while temperatures outside the shuttle were ideal for the experiment. Temperatures change very quickly; if they are in the sun, it can be up to 250 degrees Fahrenheit. When it's dark, it can be 250 degrees below.
"No bubbling at all. It's behaving very nicely," Robinson said of the experimental material as he applied it with the specialized gun.
During another application, Robinson did note a little bubbling. "It's gluey stuff so it's a little hard to get off."
The experimental material can be used to repair cracks or coating loss up to four inches long, but won't work on holes such as the one blown into Columbia's left wing by a 1.67 pound chunk of foam in 2003. All seven astronauts aboard that shuttle died.
In certain areas of the wing, NASA says cracks or coating damage measuring 2 inches long and .02 of an inch wide could doom the spacecraft.
NASA has developed a repair technique for holes in its carbon paneling, but that technique — which involves installing a patch over the hole and then bolting it inside the wing — will be tested inside Discovery later in the flight.
During the spacewalk, the pair also coated thermal tile samples with a caulk-like material in hopes of restoring the tiles' heat-rejecting ability — necessary for the shuttle to safely re-enter the Earth's atmosphere.
The sample tiles won't be tested for heat resistance until the astronauts return to Earth, but researchers want to see how well the mixture adheres in space and if there are any problems applying it in zero-gravity.
"That works pretty well," Robinson said as Noguchi used a foam brush applicator on one of the sample tiles.
Astronaut Andrew Thomas directed the experiments from inside the shuttle and noted the material became stringy as Noguchi applied it.
Once the repair testing was complete, Robinson shifted his focus to preparing tools and other equipment for two spacewalks scheduled next week. Noguchi, meanwhile, replaced a broken global positioning antenna on the space station.
NASA grounded future missions earlier this week after learning Discovery's external tank lost four sizable pieces of foam during Tuesday's liftoff. The foam pieces were bigger than the space agency wanted to see shed and officials said despite 2 1/2 years of tank redesign and the hundreds of millions of dollars spent, more work is needed.
NASA officials have said Discovery appears to have sustained no major damage during launch and is scheduled to return to Earth on Aug. 7.
That date, however, could be pushed back a day so the shuttle's astronauts can spend another day working aboard the station and leaving its crew with additional supplies — such as surplus food, water and laptop computers.
The station relies on the shuttle to ferry large cargo and additions needed for the station's completion.
NASA Administrator Michael Griffin said Friday that the agency may be able to launch another shuttle by year's end, but wants to do what it can for the station in case its fleet is grounded longer.


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Phoenix, Arizona – Integral to its reputation, Metro Lock and Safe Inc. makes sure that it finds the solution to any lock problem that a client has with a rated BBB A+ business rating and its licensed technicians to give a helping hand. As a testimonial to their services, Brian Fisher, one of their clients, mentions his positive experience. "Called to schedule and they were here in about 30 minutes. Job was done in about 30 and works great. Called around to several places before I asked them to come out for free quote and their price was also reasonable, right in the middle of all the calls I made. Very happy customer. Highly recommend and will use them again if I need a locksmith." Majority of customer reviews have praised the company's troubleshooting, saying that it saves time and money.
The company caters to commercial and residential locksmith needs as well as the use of electronics in locks. All of them cover standard locksmith services like lockouts, lock repairs, lock replacement, and key duplication. Security is also considered a compulsory protocol that is mostly overlooked by some clients; Metro Lock and Safe Inc. gives them less to worry about with their Security Consulting and Assessment. They provide the works: access control, master key, alarm system, locking gates, and high security in general.
As an additional feature, the company also answers to safes and lockable compartments for the safekeeping of valuables. The quality lock of a safe is just as important as one put on their door or gate. Metro Lock and Safe Inc. uses the best lock brands on the market. Apart from Phoenix, Metro Lock and Safe Inc. serves locations such as East Valley, Scottsdale, Mesa, Arizona, Chandler, Tempe, Gilbert, West Valley, Goodyear, Glendale, and its surrounding areas.
If the lack of technician qualification is something that one would be reaching out for or needing a variety of safe and lock types to choose from, do not hesitate to check out Metro Lock and Safe Inc. for more information.
Arrange for an appointment through the official website, http://www.metrolockandsafe.com/, by visiting the Phoenix office at 10209 North 35th Avenue #127 Phoenix AZ 85051, by contacting them via phone at (602) 663-9828, or via email at [email protected]
Media Contact
Company Name: Metro Lock & Safe Inc.
Contact Person: Michael Meehl
Email: [email protected]
Phone: (602) 663-9828
Address:10209 North 35th Avenue #127
City: Phoenix
State: Arizona
Country: United States
Website: www.metrolockandsafe.com/
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text:
5.0 out of 5.0 based on 15 Positive Review(s)
Feel free to Watch our videos on "How To Buy and Sell" lots in Cape Coral, Florida.
Our videos cover every aspect of buying or selling lots and are short, concise and to the point on every topic you'll need to be successful in buying or selling a lot in Cape Coral, Fl.
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text:
Freshman Ann-Marie Herod's interview with junior Tim Abram for PBS NewsHour Extra's "Listen to Me" series focuses on the most important issues in the election year, whether or not political system is broken. This is her first national story and part of a series of videos being produced in Dr. Mark K. Dolan's media history class on alternative campus voices.
Watch the interview on YouTube.


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Author: Max Hudson
Release Date: 20 March 2018 Price: $0.99
Reviewed by Sophie
Cover Art: This cover art is boring. I don't like it at all. There is a white player center stage with the ghosting image of a black player in the background. It's not creative at all in my mind. The men are both holding basketballs. There is no sexual tension in this art. It turns me off as a reader.
Main Characters: The main characters are Milo and Taylor. They are college basketball players who are at odds with each other. They both feel trapped in their lives, forced to live what others expect. Their animosity towards each other gradually turned to "passion". Personally, Milo and Taylor are not likable characters for me in the first part of the story. By the second half, they have matured greatly and have become somewhat likable but still I think that there was really nothing to bring them together for a happily ever after.
Secondary Characters: I hated them. They were horrible to Milo. They were shallow and stuck in their own world. There was nothing redeemable about them.
Plot: This a straightforward story. It is in the sports romance genre with an I hate you theme. It has been done so many times before.
Writing Style: The author is very wordy. It makes the narrative boring. Every other chapter is narrated by either Milo or Taylor. The only negative I could find about it was the fact that the story dragged on and it took so long to get to any form of sex. In the first part of the book, the sex was okay but not the best from this author. It felt like it was placed there to fill a hole. Basically, one sex act and the mention of heterosexual sex. The second half of the story's sex is rushed and not meaningful. The story in my opinion is not a romance because the only romance in the book is a hook up.
I loved the author's dialogue. I like how it flowed out of the characters. It was real. It was the only positive aspect of this story. The author knows how to craft the conversation.
Conflict/Climax: Milo and Taylor face many issues throughout the story. The main one and the most important is about their sexuality. The society that they are a part of forces them to be in the closet when they know they want their own sex. I think that the author did an excellent job of expressing this conflict within the men. It made me feel bad for them.
Conclusion: I am disappointed in this story. Sports romances are not usually my thing, but I am openminded, so I gave it a try. I did not like how the author made Bloomington, Indiana out to be backwards, when it is a rather progressive place. If the author had done any sort of research, he would have found that out.
I found the characters rather unlikeable and it is rather unbelievable that they could fall in love with each other. The author started the story off decently and then he moved it drastically in a direction that made the romance flat and unreal.
For all these reasons, I give this a 4* out of ten.


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Table of Contents
Latest Posts
Tag: java long string
long to String Conversion Example Java
April 26, 2011
1 min read
###### We know earlier, [parsing](http://way2java.com/java-lang/wrapper-classes/) is the operation on strings to convert into data types. This parsing, we used in command-line arguments and User Password validation. Now we think the other way. Sometimes, it is required to convert data types to string; exactly opposite of parsing. For this purpose, the String class comes with valueOf() static method. valueOf() is overloaded many times to take any data type as parameter and converts into string; it converts even objects into strings. Now we study long to String.
Read More


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I mentioned this to Nate a while back, but I figured I'd put it on here, too, just so that I'd maybe actually follow through with it.
I'm going to be 30 next year, which is…weird.* But anyway, I thought it would be kind of a cool thing to take Billy Joel's We Didn't Start the Fire and re-write it so that it covers the events of the last 30 years. Partially because the original song covers about 40 years and I don't want to wait another decade, and partially because I'd like the challenge of rhyming "fuck, we elected Trump" with something.
So yeah, I'm going to try to do that by this time next year! Hopefully we won't get Trump'd in the meantime.
*It's not bad, just weird. I don't mind the idea of aging, I just don't feel like I've lived for almost 3 decades. I feel like I'm still 19 or something.


text:
Philly Tech People News 10/3/2010
Adam Miller Joins Comcast Corporation (Business Wire)
A somewhat mysterious announcement. More of an explanation here:
Deal P.R. Adviser Joins Comcast (New York Times: DealBook)
Rodale Inc. Promotes Mary Murcko to EVP, Group Publisher (Business Wire)
Integromics Appoints Dr. Michael J. McManus as President & CEO (PharmaLive)
Project Management Institute Names Executive Vice President and COO Mark A. Langley as New President and CEO
(PR Newswire)
Oxford Communications adds Bob Quintana as director of interactive services (Philly Ad Club News)


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Take me straight to the recipe
If you've been to Hoi An, you've heard of Ms. Vy and her famous menagerie of restaurants–the most well known of which is Morning Glory. I included all of Ms. Vy's amazing restaurants on my Hoi An travel guide here.
While Peter and I didn't make it down to Hoi An on our recent visit to Vietnam, our trip to Northern Vietnam had me salivating as I reminisced about all the other delicious Vietnamese meals we'd had before (because obviously there's nothing better than eating awesome food while simultaneously thinking about more awesome food you want to eat later).
Ms. Vy's Barbecue Chicken and Lime Leaf is a recipe I've been wanting to make at home for months. It was my favorite dish when we were in Hoi An and one of Ms. Vy's specialty dishes. While Barbecue Chicken and Lime Leaf may not be a dish you typically think of when cooking Vietnamese cuisine, chicken is often paired with lime leaf in Southeast Asian cooking to complement its flavor.
I used boneless and skinless chicken thighs rather than chicken breasts which often end up dry after grilling. For the marinade I mixed a combination of dried spices, sauces, shallots, garlic, lemongrass and lime leaves which all smelled absolutely heavenly.
As you know, Peter and I love spicy foods, so I didn't skimp on the chili flakes with this dish. They added enough kick without over powering the bold flavors of the marinade. However if you're wary of spice, I'd skip the chili flakes.
After marinating, thread your chicken pieces on to pre-soaked skewers (an important step, that I nearly forgot, to avoid the skewers from burning on the grill). For more flavor you can also thread extra lime leaves on your skewers before tossing the skewers on your hot barbecue grill.
These were so aromatic while cooking that I had to fight Peter off to snag these photos before we could eat. Since we used chicken thighs rather than breasts, the meat is juicy and succulent and richly flavored.
Ms. Vy's Barbecue Chicken and Lime Leaf is definitely a new staple on our barbecue and party menu and I'm sure it will be one of yours too.
The Recipe
- 1.5 lbs boneless, skinless chicken thighs
- 1 tsp salt
- 1 tbsp palm sugar (sub brown sugar)
- ½ tsp ground black pepper
- ½ tsp five spice
- 1 tbsp ground turmeric
- 2 tbsp garlic, minced
- 2 tbsp shallots, minced
- ? cup lemongrass, thinly sliced
- 1 tsp dried chilli flakes (optional)
- 4 kaffir lime leaves, thinly sliced
- 1 tsp sesame oil
- 1 tbsp fish sauce
- 8-10 wooden skewers, pre-soaked in water for 1 hour
- extra kaffir lime leaves, optional
- Cut chicken thighs in to 1 inch strips and add to a large resealable plastic bag
- In large bowl, mix salt, palm sugar, black pepper, five spice, and turmeric
- Add garlic, shallots, lemongrass, chili flakes, and thinly sliced lime leaves
- Stir in sesame oil and fish sauce
- Mix well
- Pour mixture in to resealable plastic bag over the chicken
- Ensure chicken is well coated with marinade
- Seal plastic bag and refrigerate to marinate for minimum 1 hour
- Soak skewers for minimum 1 hr just before chicken is to be cooked
- Thread marinated chicken pieces on to pre-soaked skewers
- Option to skewer extra lime leaves in between chicken pieces
- Heat grill to medium heat
- Place chicken skewers on grill and cook for 4-5 minutes on each side
adapated from 'Taste Vietnam: The Morning Glory Cookbook' © Trinh Diem Vy


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TRENTON — In a trip billed as a "Jersey to Jerusalem Trade Mission", Gov. Chris Christie will travel to Israel during Holy Week to expand business opportunities, experience the culture and meet with world leaders. He will also spend time in Jordan with King Abdullah II.
A delegation of business and religious leaders will join Christie, his family and staff, the administration announced this afternoon. The Republican governor will be in Israel from Sunday through Thursday and Jordan until Easter Sunday.
"I think it's important for me to continue to get a greater awareness of the world around me as a leader and someone who now has a bit of a national voice," Christie said in an interview in Washington in late February. "I think it's important for me to continue to open up my mind and my experience to things that are outside of the state of New Jersey."
While travel to Israel has been a tradition for New Jersey governors since Gov. Tom Kean, Christie's growing national profile makes a trip to the Middle East all the more significant. He first announced plans to visit Israel back in October.
The Republican Jewish Coalition is co-sponsoring the trip, along with Choose New Jersey, a nonprofit formed by business executives in 2010 to expand the state's economy. The RJC has also sponsored similar trips for former Mississippi Gov. Haley Barbour, Massachusetts Gov. Mitt Romney and former President George W. Bush when he was governor of Texas.
The RJC will pay for the Christies' flight, other transportation and lodging. Members of the traveling delegation will pay for their own travel and hotel costs, but Choose NJ and the RJC will cover the cost of on-site activities, transportation and meals in Israel. Taxpayers will pick up the tab for Christie's security detail.
Lt. Kim Guadagno will serve as acting governor while Christie is out of the country.


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Johnson Creek, WI
Sponsored Topics
Johnson Creek is a village in Jefferson County, Wisconsin, United States. The population was 1,581 at the 2000 census. The village is located approximately halfway between Milwaukee and Madison, at the intersection of Wisconsin Highway 26 and Interstate 94.
The first two settlers were Charles Goodhue and Timothy Johnson, the latter of whom also founded nearby Watertown. While sometimes called Belleville, this caused it to be confused with another Belleville, Wisconsin, and the post office has always been named Johnson Creek.


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An Endowed Valentine
- $1.59
- Published By: eXtasy Books
- Author: Tianna Xander
- Page: 31
- Word Count: 5965
- Publication Date: February 11, 2014
- Heat Level:
- Available Formats: Adobe Acrobat, Epub, Mobipocket, Mobipocket (.mobi)
- Categories: Erotic Romance , Menage, Paranormal, Vampire
Qty + -
Find love where you least expect it this Valentine's Day.
Valentine's Day sucks. At least that's what Mia thinks when her two lovers disappear and never arrive at their Valentine's Day ceremony. Now her boss wants her to attend this year's mass wedding. It's that or lose her job. What will she do when she finds that her two missing grooms are in attendance as well?
To read excerpts, you need to have an account with us. Please log in first.


text:
No executive wants to deal with "Vic the Victim" or "Negative Ned". And no employee really wants to be the permanent bearer of bad tidings. But the truth, although often inconvenient, is actually a crucial business tool.
Some executives just can't bear to hear bad news, especially when they don't see how they can fix the problem situation. And many executives' aversion to whining is so strong that they explicitly discourage employees from telling a sob story more than once, even when that story is real and true.
But such explicit discouragement can drive critical business problems underground, ensuring that no one can see them well enough to disentangle them. Weird behavior patterns and resentments can result unless thoughtful diagnostics and appropriate pressure are applied to the individuals or departments in need of improvement.
When Management Stalls, Problems Complexify
In a real-life example, Company A experienced drastic inventory shortfalls during a time of sales growth. Sales reps complained vociferously to their management that their accounts weren't receiving the committed merchandise. When management's promises to look into the situation and improve it didn't pan out, a couple of sales reps started "stealing" product from the warehouse and hid it elsewhere on premises so they could take care of their own customers.
This unofficial allocation meant that the actual amount of merchandise in stock was overstated, which triggered a cycle of production slowdowns and eventually even greater shortfalls. True allocation wasn't being tracked and no one's needs were being met except those of the most entrepreneurial sales reps, who appeared, for a while, to be the most successful. As a result, even more reps started stashing merchandise. Not only were important customers disappointed, but it took a long time to learn how bad the shortfalls really were and where production levels really needed to be set.
Most employees don't want to whine. The good ones try hard to work with the problematic structure, department, or person before giving up or looking for workarounds. And since most good employees don't want to trash their colleagues, even unsuccessful ones, they may purposely avoid necessary conflict or not escalate the problem quickly enough. (Here are some suggestions for coping with colleagues who aren't playing well together.)
But it's downright painful and confusing when a senior exec tells a junior: "We know it's a problem, but we have other things we need to focus on right now." Or worse: "Yes, we've told that department they need to do better." What's implied, of course, is, "Keep your nose clean and your head down. Do your own work and stop bellyaching."
Don't Silence the Messenger
This kind of silencing can trigger unnecessary heroics at best, and at worst, the turnover of your strongest players. The most common outcome, though, is ongoing rework, delays, and barely adequate performance, when what's desperately needed is clear thinking, inspired implementation, and innovation.
Junior execs, who may not have the know-how or the clout to make "the other department" do better, nonetheless need to know how to raise the issue again. It's worth going back on record periodically, and at the beginning of every new initiative, to say: "Here's how I'm going to handle this project. I want to remind you that conditions are not optimal because of the XYZ problem, and here's how we'll mitigate that as much as possible. Let me emphasize that if you can see some way to fix XYZ, here are the improvements we'd be able to make in this new initiative."
Senior execs who might seem to tolerate the unsatisfactory situation must differentiate between whiny employees who play the victim and dedicated, forward-looking team players who are reporting hard truths. Senior execs also need to recognize that going on record — effectively, handicapping the situation — should be taken into account in actual planning.
That's true whether the goal is to continue at the current level of mediocre results or to seek real advances; it's also the case whether improved performance comes through the work of cross-functional task forces, individual coaching and training, or drastic organizational changes. It's very seldom that persistent problems are due to lack of effort, so avoiding complaints is like telling someone who smells a gas leak that they don't smell anything, or that it's a normal smell — and then waiting for the explosion.Business & Finance Articles on Business 2 Community


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Ball & Chain Golf Tournament Registration form Details
02/24/2017 - 05/09/2017
Harbor Oaks Country Club, Pine Bluff, Ark. To print out a registration form, click here.
Four-man scramble. ADC employees may begin registering for the tournament. An open invitation to the publc begins April 15, 2017 thru May 9, 2017.


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Social Work Scotland are hosting a number of engagement sessions around Scotland for those working in children and families services. You do not need to be a member to attend these sessions and they are for staff at all levels.
The sessions are about Social Work Scotland, as a membership and leadership body hearing from members and potential members about the things that they are challenged with and what they'd like to see Social Work Scotland doing to tackle them. They also want to hear from people about how they might like to be involved and answer any questions they might have.
The sessions take place in Edinburgh, Aberdeen and Glasgow and the links to them are below. These sessions are free to attend.
West- https://www.eventbrite.co.uk/e/west-engagement-session-tickets-28524522615
East- https://www.eventbrite.co.uk/e/east-engagement-session-tickets-28524573768
North- https://www.eventbrite.co.uk/e/north-engagement-session-tickets-28524590819


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We've stockpiled candles, rooted out the torches and charged our devices. Ophelia is hurtling her way nearer. We've filled the cupboards with non-perishables. We're ready. The last job before the expected power outages is to download some essentials from Netflix to save everyone's sanity. Here are some of our faves from the 'available for download' options on Netflix. They'll come in handy later when the power is out! There's still time. Go!
Treated cruelly by her parents, clever Matilda Wormwood finds joy in reading and uses telekinetic powers to teach lessons to some of the awful adults in her life. Danny De Vito and Rhea Pearlman play her thick-witted parents perfectly and Pam Ferris as The Trunchbull will have your kids' eyes as wide as the students she hammer throws. Roald Dahl at his best.
Orphan Annie and her buddies are holed up in a 1930s orphanage with the reprehensible, bathtub gin-swilling Miss Hannigan. There's some 'goddamning' and Miss Hannigan's sexual frustration is palpable but the kids will love the all-singing, all-dancing cast of youngsters and, in the heel of the hunt, Annie is rescued by a parent who loves her, so it's all good. Grown ups will enjoy the chuckles and nostalgia. Worth watching for Carol Burnett's performance alone.
Hotel Transylvania
Adam Sandler and Steve Buschemi are among the stars voicing this fun seasonal caper. When ghouls and monsters want to get away from it all they visit Dracula's lavish hotel for refuge. Complications unfold when an unsuspecting human is thrown into the mix and falls in love with Dracula's teenaged daughter. Expect gags for both adults and kids. And if you like it, Hotel Transylvania 2 is available for download too!
This prequel to the Despicable Me series is voiced by Sandra Bullock, Jon Hamm and Michael Keaton and sees the familiar babbling, yellow creatures attempt to foil the attempts at world domination of supervillain Scarlet Overkill. You'll miss Steve Carell's felonious Gru and the Minionese will drive you to distraction but the kids will howl with laughter.
Gnomeo & Juliet
This re-imagining of Shakespeare's classic (without the tragic ending) sees two feuding families of garden gnomes struggle to overcome the romance of their kids, star-crossed lovers voiced by Emily Blunt and James McEvoy. Much like Toy Story, the gnomes come to life in neighbouring gardens resulting in fun, colourful visuals and unexpected action. All this, combined with some choice gags and an Elton John soundtrack makes for fun family viewing on a stormy afternoon.
Disclosure: I'm a member of the Netflix Stream Team. I receive a Netflix subscription in return for Stream Team contributions.


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Wrap Up From The LMA Annual Conference: 2014 Your Honor Awards
As part of its 2014 Annual Conference, the Legal Marketing Association (LMA) gives out its "Your Honor Awards". We are pleased that the LMA has a separate award category that relates to mobile: Online Interactive Marketing Tools.
The First Place entry was the Constangy Employment Law Resource mobile app from Constangy, Brooks & Smith, LLP. LFM conducted its review of this app here. The firm's app can be found here. The LMA award noted a number of interesting aspects of how the firm promoted its app (often an important element missing from the roll-out of other law firms' apps), including:
- An informal client focus group
- A webinar to attorneys and staff educating them about the app
- External promotional campaign with a slogan, "Work. Learn. Play."
- Sent out postcards with the app's QR code
- E-mail promoting a drawing to win an "App-e-tizer" party
- Auto-detection of mobile visitors to the firm website inviting the user to download the app
- Added a link to attorney email signatures
- Print advertising in the magazine for the Association of Corporate Counsel
- Advertising in a national HR association's workplace law e-newsletter
- Use of social media promotion through Twitter, Facebook and LinkedIn
- A conference booth giveaway: app-branded screen cleaners that stick to backs of smartphones
The Third Place entry was Bracewell & Giuliani LLP's ShalePlay Mobile App. The firm's app can be found here.


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text: "Occupy DC" protesters comprise various groups and have split up to protest and meet later in the square [Reuters] Protesters have scuffled with security guards at a Washington museum and marched through New York City in the latest popular demonstrations in the US inspired by the Occupy Wall Street movement. Al Jazeera's Monica Villamizar, reporting from Washington, said Saturday's protests were organised to oppose the use of drones by the US military. "Protesters walked to the Smithsonian National Air and Space Museum and tried to go in with a banner against the use of drones," our correspondent said. Hundreds of people and groups, including anti-war activists, joined the Occupy DC protests in opposition to the use of unmanned aircraft by the US military, she said. The protest coincided with the 10th anniversary of the start of the Afghanistan war, where drones have frequently been used. A museum spokesperson said one person was arrested as up to 200 protesters attempted to enter the museum, blocked by six guards. "There was a lot of shoving going on," Isabel Lara said, adding that one of the guards was surrounded and used pepper spray before the demonstrators were moved outside. The shoving match broke out in the entrance after guards told the protesters they could not enter with signs, Lara said. She said she was not aware of any injuries. Elsewhere in the US, protests were ongoing. 'Occupying' America Several thousand Occupy Wall Street protesters marched to New York City's Washington Square Park for a meeting which they described as a "general assembly", on Saturday. Demonstrators peacefully marched from Manhattan's Zuccotti Park, the group's unofficial headquarters dubbed "Liberty Plaza" by the group, where protesters have been camping for more than three weeks. They met to discuss expanding their protest to other sites. Lucas Vasquez, a student leading the march, said protesters were looking at setting up camp in Washington Square and Battery Parks. In Alabama, meanwhile, Kristin Thompson, a 22-year-old teacher and one of hundreds of protesters inthe town of Mobile said, "We're tired of other people controlling, or thinking they control, our lives and our livelihoods." In Santa Fe, New Mexico, about 250 protesters lined the streets outside a Bank of America branch, waving signs at passing vehicles. "We are all in this together," said Ramona Beene, 45, who owns a cake company. She said her two college-age children were "spending thousands of dollars and won't have jobs after they graduate". The Occupy Wall Street movement started in New York on September 17, spreading to over cities, including San Francisco and Los Angeles, California; Chicago, Illinois; Austin and Houston, Texas; Atlanta, Georgia; and Washington DC. Dozens of protesters were arrested in New York on Wednesday when thousands marched on Wall Street in their biggest show of support yet. The same day, 25 people who were part of the Seattle, Washington's 'Occupy' protest were arrested and police confiscated demonstrators' tents and other belongings. Seven hundred people were also arrested in New York the previous Saturday after spilling onto the roadway while crossing the Brooklyn Bridge. Protesters say they are speaking out against corporate greed and the gap between the rich and poor. They say they have no leaders and are making decisions by consensus. SOURCE: Al Jazeera and agencies Politics US & Canada United States


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After Charity Hospital's doors were shuttered following Hurricane Katrina, the poor and uninsured who had depended on the public hospital for everything from emergency treatment to help with routine maladies were left without ready access to health care. But in that vacuum, something new, at least in the New Orleans area, took root.
Community health centers sprouted up to fill the need, with existing centers expanding into other neighborhoods and new clinics growing out of makeshift outfits that opened their doors in the chaotic days after the storm.
The clinics received a $100 million injection of federal money in 2007, but when that grant ran out, Gov. Bobby Jindal's administration and the federal government agreed to continue providing help through a Medicaid waiver only applicable in Orleans, Jefferson, St. Bernard and Plaquemines parishes. This waiver allows adults who make too much money to qualify for Medicaid to receive primary care and mental health treatment through the nonprofit clinics, although any hospital stays aren't covered.
The effort, championed by Dr. Karen DeSalvo, who is now New Orleans' health commissioner, has been heralded by a diverse collection of supporters, from Jindal's health leaders to the Obama administration's secretary of the U.S. Department of Health and Human Services. Instead of relying solely on the sometimes-cumbersome and centralized Charity system, the new system allowed people to regularly see doctors or physician assistants close to home, managing diseases like hypertension or diabetes before complications developed.
The non-profit clinics have been banking on the state expanding the Medicaid program in January 2014, when the current waiver expires. The expected expansion -– a key feature of Obama's health overhaul -– would have continued the insurance benefits to the patients now on the wavier, as well as covering hundreds of thousands of additional people across the state.
But Jindal has said he won't expand the Medicaid waiver, arguing that, while the costs are covered by the federal government in the program's initial years, the state will eventually have to pick up part of the tab, to the tune of $3.7 billion over 10 years. Jindal also objects philosophically to expanding the program, saying it is too costly for taxpayers at a time when the federal government should be cutting back.
Clinics, meanwhile, are starting to fret about their long-term financial stability: If the waiver isn't extended or Medicaid isn't expanded, they'll lose part of their paying patient base.
The success of the primary care clinics in New Orleans also begs a question: If providing coverage -– albeit in a limited form -– has made sense for the uninsured in this region, why not expand it to the entire state?
"It (the waiver program) is a nice example of an effort to put people who were previously without primary care in a primary care network," said Mark Keiser, executive director of Access Health Louisiana, a network of health centers in this region. The Medicaid expansion, he said, would give more low-income people ready access to primary care doctors at a time when the charity hospital system run by LSU -– the sole available venue for many uninsured people throughout Louisiana -– is cutting back on inpatient beds and clinic hours.
Bruce Greenstein, secretary of the Louisiana Department of Health and Hospitals, called the network of clinics "a great, great model" in a recent interview. The clinics, he said, will be there to provide care for patients as the Interim LSU Public Hospital, which eventually replaced Charity after the storm, ratchets down services because of budget cuts.
But Greenstein said the inflexibility of the federal Medicaid program, created during the 1960s "Great Society," is one reason the Jindal administration rejects the expansion. As an example, he noted the federal government has always rejected implementing a co-pay to help offset the costs.
"If we had much more flexibility in our Medicaid program and could arrange it a certain way, it would make total sense," he said.
Whether or not expanding Medicaid is even an option may depend on the outcome of next week's election. While the Obama administration would obviously push forward with implementing the Affordable Care Act, Republican challenger Mitt Romney has vowed to repeal as much of the law as possible.
Romney says he will turn the Medicaid program into a block grant, which he emphasizes would give states greater flexibility in how they spend the money. Many experts, however, believe the changes will also mean a cut to the overall program, and how much states like Louisiana receive.
When the Louisiana Department of Health and Hospitals originally conceived of the Medicaid waiver, it was thought of as a "bridge to national health care reform implementation," according to a May 2010 white paper. That paper was written before the U.S. Supreme Court decision this summer upholding the health care law. While the decision upheld Obamacare, as the law is often called, it made the Medicaid expansion optional for states.
In a statement in response to questions, state Department of Health and Hospitals officials said the waiver "was never intended as a state guarantee of what would occur with federal health care reform" and noted that the health care market is changing nationwide.
"The providers who treat recipients need to use this time-limited waiver program to develop systems that allow them to become competitive in this marketplace," the statement said.
The program that was approved in September 2010 is called the Greater New Orleans Community Health Connection. It allows adults in families with incomes up to 200 percent of the federal poverty limit – or about $38,184 for a family of three – to qualify.
In contrast, the Medicaid program for the rest of the state is much more restrictive: It has an annual income cap of $2,860 for a family of three, according to the Louisiana Budget Project. By comparison, a person working a full-time minimum wage job would make about five times that much. Adults who don't have children and aren't disabled simply aren't eligible. Under the federal law's Medicaid expansion, a family of three with incomes up to $25,390 would qualify for coverage.
While Louisiana has some of the toughest restrictions for covering adults with Medicaid, the state's program provides generous benefits for children, resulting in a 97 percent child coverage rate in Louisiana.
Clinic leaders said they considered the local program, which covers about 53,000 people, as an intermediate step before Medicaid expansion. Without something in place, clinics will be left with a much larger chunk of uninsured patients, and will thus have to scramble for ways to cover the cost of the care they provide.
Michael Griffin, president and CEO at the Daughters of Charity clinics, which have grown from one clinic before Katrina to four now, was stoic about the prospect of the waiver's expiration. But he noted that the waiver had reduced the "uninsured" portion of his patient load by half, from 70 percent to 35 percent.
"That is a considerable amount of resources that you would have to find money for," he said.
Keiser, whose clinic network operates three centers in the region covered by the waiver, said without the Medicaid expansion, people who now have coverage through the waiver will again become uninsured. Eventually that will force clinics to cut back, he said.
"Those people become uninsured, low-income folks without access to primary care. The clinics will have no source of funding to provide those services," he said. "Consequently, the clinics will shrink."
Bethany Bultman with the New Orleans Musicians' Clinic has had a less positive experience with the waiver than some other providers; she found that only 400 of her 2,400 patients qualified. The clinic recently undertook austerity measures, including cutting back some services and implementing a $10 co-pay.
Still, Bultman said she believed the Medicaid expansion was on the horizon. "Our long-term strategy was that in 2014 that it would mean that we would by that point be a medical home and 80 percent of our care would be covered by the Affordable Care Act," she said. "Our patients would be covered."
If Jindal continues on his current course, DeSalvo said New Orleans officials are looking at asking the federal government to allow the city to apply directly for a local Medicaid expansion. In an August interview, she also raised the possibility of simply asking for a renewal of the waiver.
Greenstein said there isn't funding to extend the waiver, adding that it was intended to "build sustainability" for the clinics. Under the waiver, they are getting paid more than typical Medicaid providers would for similar patients. That's something that the clinics will have to improve upon, he said.
See related story: Health care waiver covers fewer uninsured patients than earlier federal grant.


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Sameera Reddy
Wallpapers & Mini Biography
Part : 2
Read More ...>>>
The stunning Sameera Reddy is a Bollywood actress who was first seen in the music video 'Ahista'. From a marketing executive to an actress, it's been quite a journey.
Sameera Reddy was born on 17th December 1982 in Hyderabad, Andhra Pradesh, India. She has two sisters Sushma Reddy and Meghna Reddy who were a big part of the glamour industry working as models and video jockeys.
Sameera Reddy studied at the Sydenham College and is involved with Crayons and Dreamz Homes. While in college, she appeared in the music video for Pankaj Udhas' Ahista. However she opted to work as a marketing executive before she moved into movies. Read More ...>>>
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These guys are an independedent Canadian rock band. I've tried, but I seriously haven't managed to find a hint of irony yet in this video. In the song, as well, I've listened a bunch of times, and I haven't found any irony in there, either -- just a song about being joyful (the song's titled "Be Joyful")
If it's true, well, I can't think of a time I've seen a video match a song more perfectly.
And it makes me happy. It's like they were actually listening to the song when they planned the video, and made a list of all the cool stuff that makes people happy and put it in a video together. With puppets!


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Search Result for travel jokes:
Free-Extras.com is the greatest site that offers free travel jokes pictures, and free travel jokes images for you to use on Pinterest or facebook. We have hundreds of travel jokes images. We are always adding new pictures that you can use. So make sure to check back and find new travel jokes pictures and images right here at free-extras.com


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Abundance is the one thing in the world able to create prosperity. That seems to be the reason why people strive for more. How to get a better home, a faster car, a lovelier spouse, new clothes, healthier relationships, a trip around the world, and so on?
Although life's unlimited resources are at our disposal we constantly feel lacking and, what's worse, a sense of competitiveness in order to conquer the last piece of pie on the table. Constant negative news about the world's energy resources coming to an end are very distracting and we seem to forget that not everybody is after the same things. We all have different wants and needs and nobody is taking the other person's place.
Nevertheless, abundance is what we aim. And that is a good thing; we just need to understand what it really stands for and how it works. Shall we?
"Abundance is not something we acquire, it is something we tune into"
(Dr Wayne Dyer)
Abundance means "To Flow". Nowadays, this concept is deeply rooted into money for the simple fact that the word "Currency" means to run or to flow. So, the only way we can generate abundance in life is to let it flow THROUGH us.
Letting Go seems to be the foundation for life's stability, well-being, peace of mind and also… Abundance. Let go of your thoughts, they are creating your suffering. Let go of your need to control, it is creating your stress. Let go the need of attract savings, it is causing you to lose money.
Everything that stops moving dies. Simple as that! Everything that stops circulating gets stagnant, stops growing and ends its evolution process. Our blood is constantly circulating in our veins. A river never stops running towards the ocean. The cosmos is in a perpetual and endless motion. So should we.
Start moving. Give and take! Let go and start again. The more you give, the more you take. You can't pour more tea into a full cup; you need to empty it first. Likewise, how are you supposed to learn something new if your mind is filled with concepts, prejudices and preconceived ideas?
The more you give, the more the universe will flood you with renewed energy, goods and opportunities. If you want to take more knowledge or expertise, give it more time and focused practice. If you want to take deeper relationships for yourself, give it more care. If you want to take more income from your current job give it more vital energy.
This doesn't mean you should sell all your belongings, start mindlessly donating your money and adopt a life in the woods! When one door closes another opens, right? Isn't it funny, when you lose a client, another one suddenly surprises you?
Got it: Give and take, so… no catch? Yes, there is a catch.
Scan your intentions, why are you giving? Is it heart-felt or are you hiding something? Be true to yourself. Unwilling gifts or sense of losing something can reveal your deepest motifs. Why are you so eager for knowledge or expertise? Is it to surpass everyone around or is it to feed your hungry soul? Why are you digging in relationships? Is it rooted into loneliness or into love? Why do you want the promotion so much? Is it fear of inferiority or is it pride on giving your absolute best?
THINK about your joyful gestures:
T – Is it True?
H – is it Helpful?
I – is it Inspiring?
N – is it Necessary?
K – is it Kind?
Learn how to give what you want to receive. Scan your intentions and act based on joy. Give what you can give. Give your attention to people, give love and affection, and show appreciation or gratitude. Offer a gift, write a letter and compliment a lot.
"Purify your heart before you let love into it, for even the sweetest honey sour in a dirty container."


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August 21, 2009 – TeraRecon Inc. will showcase its Aquarius iNtuition at the Transcatheter Cardiovascular Therapeutics (TCT) symposium Sept. 21-25, 2009 in San Francisco.
The company said iNtuition provides comprehensive cardiovascular decision support and advanced visualization to interventional cardiologists, radiologists, clinical cardiologists, vascular medicine specialists and other health care professionals with a special interest in the field of interventional and vascular medicine. For cardiovascular professionals involved in imaging, TeraRecon's advanced cardiovascular visualization tools provide decision support with robust innovative automated technologies that preprocess the image data without user intervention, to deliver valuable decision support, such as centerlines of coronary vessels, segmentation of cardiac chambers, and various other automatic analysis tasks to make interpretation faster and more efficient. If required, the automated processing can be edited by a specialist and saved for physician access or collaborative review.
With increasing emphasis on the limitation of dose in CT imaging, TeraRecon said its analysis algorithms in its software enables use of lower dose strategies. The software is designed to be more tolerant to the noise associated with lower-dose acquisitions. Standardization in cardiac reporting is also key to successful patient outcomes and TeraRecon recently incorporated the Society of Cardiovascular Computed Tomography (SCCT) reporting guidelines* into its structured reporting model for coronary CTA.
TeraRecon said iNtuition also offers best-in-class aortic intervention planning. This endograft planning tool delivers a seamless workflow that culminates in automatic completion of endograft sizing worksheet from a wide variety of manufacturers including Cook, Medtronic, Gore, Bolton and Endologix. Post-operative evaluation can easily be achieved with customized 3D templates that can help identify endoleaks, aneurysm growth and the integrity of implanted devices.
iNtuition delivers these capabilities via a client/server solution. The final results can be distributed by sending a URL link to referring clinicians, which enables them to launch AquariusWEB, an interactive zero-download 3D viewer, within their own Web browser.
For more information: www.terarecon.com
*Raff GL, Abidov A, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. Journal of Cardiovascular Computed Tomography. 2009;3:122-136.


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Portland plans legal actions against landlord
One part of property passes while other has violations
The deadline has passed for the owner of a Portland building to make repairs and he is facing future legal action.
The city of Portland plans to take legal action against Gregory Nesbit over code violations at his property at 186 through 192 Dartmouth Street. Nesbit is also the owner of the property on Noyes Street in which six people died from a fire in 2014.
City inspectors checked the Dartmouth Street building on Monday. Monday was also the deadline for Nisbet to make repairs in a number of areas, including installing a fire alarm, providing a secondary escape route and locked doors at escape routes when the building is occupied.
Repairs were made to the 186 side of the building, but the 188 side was not up to code during the inspection. The city plans to file paperwork on Wednesday that would hold Nisbet legally responsible to fix the violations.
"It's a civil case, we'd be seeking possible civil penalties. And asking that the landlord not be able to -- possibly not be able to rent if he does not come into compliance and correct the violations," said Jessica Grondin, director of communications for the city of Portland.
Tenants in the 186 side of the building, which had completed repairs, will be able to stay. The tenants in the 188 unit remain under eviction, an order unrelated to the inspection.


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If you believe the reports, it is notoriously difficult to keep New Year's resolutions. Here are 8 New Year's Resolutions that are easy to keep.
Happy New Year! We may be a couple of weeks into the New Year, but it's not too late to adopt some easy New Year's Resolutions.
Here are 8 New Year's Resolutions that are easy to keep
- I will talk to God more this year.
- I will pause for at least one minute between each activity in my day.
- I will do some form of exercise or physical activity every day. Top tip: Get a dog!
- I will open my Bible every day.
- I will smile more.
- I will tidy my desk (or, if you are blessed enough not to have one, perhaps a drawer or wardrobe).
- I will pay sole attention to the person who is talking to me.
- I will remind myself of three things I am grateful for every day.
Not Life Changing
I appreciate this list isn't life changing. Though since reports tell us we find it difficult to keep New Year's resolutions, perhaps this list of New Year's resolutions that are easy to keep might just change our lives if we could keep them! So what do you think? Don't worry about keeping all of them. Just choose two or three. Or use the list to come up with your own.
Form a Habit
The key is to stick with a few New Year's resolutions that are easy to keep until they become a habit. Research suggests this will take at least sixty-six days. It's then that positive change actually begins to stick.
It's never too late to make a fresh start. Why not start today?
Your Response
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Why not check out these posts from around the blog?
- How to Evaluate Church Leadership
- Prioritising Before God
- Busy Pastor, Pace Yourself
- Evangelism: Speak Up!
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- Leave a comment below.
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Our latest prom dress collection is now in-store for you to see & try on! Be the belle of the ball in one of our gorgeous new styles. Whether you want figure hugging & fitted, or a blingy ball-gown. Low backed, high fronted, floaty or fishtail, make sure a visit to Platinum Brides is at the top of your list!
We only sell one of each style per school, so the sooner you visit, the more choice you'll have to stake your claim!! We can do appointments at weekends of weekdays, after school time. It's definitely best to book!
The most beautiful prom dress collection in Solihull (well, we think so anyways)!
Price range: Sale gowns from £99. New Collection from £199. Photographs of our latest prom dress collection can be seen on our Facebook page www.facebook.com/platprom1