text:
Report Inaccurate Claims
Has Iran Threatened to Use Nuclear Weapons against Israel and the U.S.?
by Iran Fact Check on Aug 30, 2012 • 1:11 am No Comments
Fact: Iran has never threatened to use nuclear weapons.
Iranian officials deny they are seeking nuclear weapons. Iran's top decision-maker, Supreme Leader Ali Khamenei, issued a fatwa against nuclear weapons and has publicly expressed categorical opposition to the existence of nuclear weapons, stating, "Islam is opposed to nuclear weapons" and "the Islamic religion forbids the use of nuclear weapons.
Iranian officials have never threatened to use weapons that they deny they seek and that the Supreme Leader has condemned.
Some commentators have claimed that the anti-Israel rhetoric espoused by current Iranian President Mahmoud Ahmadinejad constitutes a threat to use nuclear weapons. However, experts disagree.
Politifact determined that a claim by Michelle Bachmann that Iran threatened to use nuclear weapons based on Ahmadinejad's rhetoric was false:
"Ahmadinejad has said some tough things about the United States and Israel, but we find no evidence that he has said he would use a nuclear weapon against either country. In fact, he has maintained Iran has no interest in building one." (Politifact)
Israel's Minister of Intelligence and Atomic Energy, Dan Meridor, agrees:
"This idea that Iran wants to wipe Israel out, now that's a common trope that is put about by a lot of people in Israel, a lot of people in the United States, but as we know Ahmadinejad didn't say that he plans to exterminate Israel, nor did he say that Iran's policy is to exterminate Israel." (New York Times, "Israeli Minister Agrees Ahmadinejad Never Said Israel 'Must Be Wiped Off the Map'"; April 17, 2012)
Iranian officials who have commented directly on Ahmadinejad's comments have stated that they are not intended in a military sense:
CNN: Larijani sought to downplay the significance of comments attributed to President Mahmoud Ahmadinejad a few years ago suggesting that Israel should be wiped off the map. He said the comments were 'definitely not" meant in a military sense and that such an approach was not "a policy of Iran.'" (CNN; March 15, 2012)
Previous postDid the IAEA Say Iran is Building Nuclear Weapons? Next postDo Israel and the U.S. Consider Iran Irrational?
© 2012 Iran Media Fact Check. All Rights Reserved.
Follow Iran Media Fact Check
Fact: Iran has never threatened to use nuclear weapons. Iranian officials deny they are seeking nuclear weapons. Iran's top decision-maker, Supreme Leader Ali Khamenei, issued a fatwa aga


Browsing Jambar Newspaper Archives by Author "Turner, Beth Anne"
Abstract: As part of an administrative shake-up, President Leslie Cochran appointed Judy Gaines the executive director of the Office of Student Life. Bassam Deeb, who held the post since it was created in 1995, became the executive director of Enrollment Management.
Abstract: Former YSU political science professor Larry E. Esterly has been named to the YSU Board of Trustees by Ohio governor George Voinovich. Esterly retired from teaching five years ago and is an alumnus of the university.


Objectives: To test the reliability and validity of the Students' Attitudes Towards Addressing Sexual Health questionnaire (SA-SH), measuring students' attitudes towards addressing sexual health in their future professions.
Method: A cross-sectional online survey (22 items) were distributed to 186 nursing, occupational therapy and physiotherapy students in Sweden, April 2015. Validity and reliability were tested.
Results: The construct validity analysis led to three major factors: present feelings of comfortableness, future working environment and fear of negative influence on future patient relations. The construct validity, internal consistency reliability and intrarater reliability showed good results.Conclusion: The SA-SH is valid and reliable.


text:
PNAS Staff
Recommend PNAS to Your Librarian
PNAS Classics
Highlights from Latest Articles
PNAS in the News
Purpose and Scope
Editorial and Journal Policies
Submission Procedures
New Research In
Applied Physical Sciences
Earth, Atmospheric, and Planetary Sciences
Economic Sciences
Psychological and Cognitive Sciences
Applied Biological Sciences
Biophysics and Computational Biology
Immunology and Inflammation
Population Biology
MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus
Vijay G. Bhoj, Qinmiao Sun, Elizabeth J. Bhoj, Cynthia Somers, Xiang Chen, Juan-Pablo Torres, Asuncion Mejias, Ana M. Gomez, Hasan Jafri, Octavio Ramilo, and Zhijian J. Chen
PNAS September 16, 2008 105 (37) 14046-14051; https://doi.org/10.1073/pnas.0804717105
Vijay G. Bhoj
Qinmiao Sun
Elizabeth J. Bhoj
Cynthia Somers
Xiang Chen
Juan-Pablo Torres
Asuncion Mejias
Ana M. Gomez
Hasan Jafri
Octavio Ramilo
Zhijian J. Chen
For correspondence: zhijian.chen@utsouthwestern.edu
Edited by Thomas Maniatis, Harvard University, Cambridge, MA, and approved July 8, 2008 (received for review May 15, 2008)
Figures & SI
Infection by RNA viruses is detected by the host through Toll-like receptors or RIG-I-like receptors. Toll-like receptors and RIG-I-like receptors signal through the adaptors MyD88 and MAVS, respectively, to induce type I IFNs (IFN-I) and other antiviral molecules, which are thought to be essential for activating the adaptive immune system. We investigated the role of these adaptors in innate and adaptive immune responses against respiratory syncytial virus (RSV), a common human pathogen. Deletion of Mavs abolished the induction of IFN-I and other proinflammatory cytokines by RSV. Genome-wide expression profiling in the lung showed that the vast majority of RSV-induced genes depended on MAVS. Although Myd88 deficiency did not affect most RSV-induced genes, mice lacking both adaptors harbored a higher and more prolonged viral load and exhibited more severe pulmonary disease than those lacking either adaptor alone. Surprisingly, Myd88−/−Mavs−/− mice were able to activate a subset of pulmonary dendritic cells that traffic to the draining lymph node in response to RSV. These mice subsequently mounted a normal cytotoxic T-lymphocyte response and demonstrated delayed but effective viral clearance. These results provide an example of a normal and effective adaptive immune response in the absence of innate immunity mediated by MAVS and MyD88.
Immune detection of pathogens is mediated by pathogen recognition receptors (PRRs), which, in the case of RNA viruses, involve a subset of Toll-like receptors (TLRs 3, 7, and 8) and the cytoplasmic RIG-I-like receptors (RLRs) (1–3). TLR 7/8 binds viral single-stranded RNA in endosomes and engages the cytosolic adaptor MyD88 to activate downstream signaling pathways leading to the activation of NF-κB and interferon regulatory factors (i.e., IRF3, IRF7). The RLRs, including RIG-I and MDA5, bind viral double-stranded RNA or 5′-triphosphorylated uncapped viral RNA in the cytosol (4, 5). Through their common adaptor, MAVS (also known as IPS-1, VISA, or CARDIF), RLRs also activate NF-κB and IRFs (6–9). Together with activated AP-1, NF-κB and IRFs subsequently induce transcription of antiviral genes, including type 1 IFNs (e.g., IFN-α and IFN-β, herein referred to as IFN-I). In addition to IFN-I, proinflammatory cytokines and chemokines are induced downstream of TLR and RLR signaling. It is thought that these innate responses serve to limit the extent of infection until the adaptive immune response is able to clear the virus.
Activation of adaptive B and T cell responses is driven by dendritic cells (DCs) (10). Upon detection of viral infection through PRRs, DCs become activated and traffic to lymph nodes, where they present viral antigens and provide additional signals to activate CD4+ and CD8+ T cells. Activated CD4+ T cells can, in turn, activate virus-specific B cells, resulting in antibody production.
Respiratory syncytial virus (RSV) belongs to the Paramyxovirus family of negative-sense single-stranded RNA viruses. RSV infection is currently recognized as the leading cause of respiratory disease in infants and young children, and it can also be life threatening in elderly and immune-compromised adults (11–13). There is currently no vaccine available against RSV. A previous failed vaccine attempt underscores the importance of a better understanding of the host response to the virus for the design of safe and effective treatment and prophylaxis (14, 15). In this report, we generated mice lacking Mavs, Myd88, or both (double knockout, DKO) to investigate the roles of RLR and TLR signaling in the innate and adaptive immune responses to RSV.
Innate Cytokine Induction Depends on MAVS-Mediated Signaling.
In the first series of experiments, we studied the cell-specific IFN-I response to RSV. Lung fibroblasts, bone marrow-derived macrophages, and conventional DCs (cDCs) were isolated and infected with RSV. Measurement of IFN-α and -β production by ELISA, shown in Fig. 1 A–E, revealed that IFN-I induction by RSV in all these cell types completely depended on MAVS. Previous studies have suggested that plasmacytoid DCs (pDCs) rely on TLR7 and MyD88 to induce IFN-I in response to RNA viruses, whereas other cell types use the RLR-MAVS pathway (16, 17). Although Sendai virus (SeV) infection triggered IFN-I production in purified pDCs, we were unable to detect any IFN-α or -β in these cells after RSV infection [supporting information (SI) Fig. S1A]. Consistent with this result, the induction of IFN-α and -β by RSV depended on MAVS in bone marrow cells treated with the Flt3 ligand, which leads to the generation of pDCs and cDCs (Fig. S1 B and C). In contrast, infection of Flt3L-DCs with SeV triggered IFN-I production in a manner that was independent of MAVS. This is consistent with our previous finding that MAVS is dispensable for IFN-I induction by SeV in pDC, which is the major source of IFN-I in SeV-infected Flt3L-DCs (16).
In vitro and in vivo cytokine responses to RSV infection are lost in the absence of MAVS. Adult lung fibroblasts (A), bone marrow-derived macrophages (BMDM; B and C), and cDCs (D and E) from WT+/+ and Mavs−/− mice were infected with SeV or RSV for 24 h before culture supernatants were analyzed for IFN-β or -α by ELISA. Data are represented as mean ± SD. (F) Mice of the indicated genotypes were intranasally infected with RSV (107 pfu) for 24 h, and then BALF was harvested for cytokine measurements by ELISA (for IFN-α, IFN-β, and IL-1β) or Cytometric Bead Array (for IL-6, TNF-α, and MCP-1) (*, P < 0.001; **, P < 0.01; ***, P < 0.05; ANOVA, Tukey's test) (n = 4 per group). n.d., not detected. Data are represented as mean ± SEM.
To examine the role of MAVS and MyD88 in RSV infection in vivo, we infected Mavs−/−, Myd88−/−, and DKO mice with RSV via the intranasal route (Fig. 1F). Consistent with the in vitro results, 1 day after infection, WT mice secreted a large amount of IFN-I, which was detected in bronchoalveolar lavage fluid (BALF). This response was normal in MyD88-null mice but abolished in mice lacking MAVS. Consistently, MAVS-deficient mice failed to induce and activate STAT1 in the lung after RSV infection, whereas this IFN signaling response was normal when these mice were infected with vesicular stomatitis virus, an RNA virus known to induce IFN-I independent of MAVS (Fig. S2; ref. 16). Other proinflammatory cytokines, including IL-6, TNF-α, monocyte chemoattractant protein (MCP)-1, and IL-1β, also depended on MAVS for their expression. Interestingly, maximal production of TNF-α, MCP-1, and IL-1β also required MyD88. At the same time point, day 1, we were unable to detect significant levels of IFN-γ, IL-12, or IL-10 in the BALF (data not shown). Neither IFN-α nor -β was detectable in sera and mediastinal lymph nodes by ELISA or quantitative PCR in mice of any genotype (data not shown). Recently, it has been shown that in response to intranasal Newcastle disease virus infection, IFN-α–producing alveolar macrophages and cDCs could be detected after 24 h in WT mice (18). In MAVS-deficient animals, however, this response was abolished and a compensatory IFN-α response was detected in pDCs at 48 h. However, we found no evidence of IFN-I production 2, 5, 9, or 14 days after RSV infection in Mavs−/− mice (Fig. S3, data not shown), consistent with our in vitro observation that RSV does not induce IFN-I in pDCs.
To evaluate the roles of MyD88- and MAVS-mediated signaling in the global pulmonary innate immune response to RSV, we analyzed lung RNA by microarray 24 h after infection (Fig. 2). Of the 659 genes induced by ≥2-fold in WT mice, 440 (≈66.8%) depended on MAVS but not on MyD88, 12 (≈1.8%) depended on MyD88 but not on MAVS, and 90 (13.7%) depended on both (Fig. S4). The induction of most IFN-related genes was MAVS-dependent and MyD88-independent (Fig. 2A). A similar pattern of dependence was seen for most of the cytokine-, chemokine-, and PRR-related genes (Fig. 2 B–D, Fig. S5). In contrast, optimal expression of TNF-α and IL-1β depended on both adaptors (Fig. 2E). Interestingly, both IL-24 and Cxcl-16 were induced in all RSV-infected groups compared with mock-treated groups. With the exception of these chemokines, innate immune responses were largely absent in Mavs−/− and DKO mice.
Global gene expression analysis of lung RNA after infection with RSV reveals profound defects in mice lacking MAVS. For each genotype, two mice were mock treated and three were inoculated with RSV (107 pfu) for 24 hours before lungs were harvested for total RNA extraction, which was analyzed by microarray. (A–D) Mean relative expression of genes known to be involved in immune responses, including interferon-related (A), chemokine or cytokine receptors (B), cytokines (C), and chemokines (D). (E) Induction of selected genes was confirmed by qPCR. Data are represented as mean ± SEM.
Viral Clearance in the Absence of MAVS and MyD88.
Next, we evaluated viral clearance in these mice by measuring viral loads in the BALF at various times after infection. In WT mice, viral loads peaked on day 5 after infection and reached undetectable levels by day 9 as previously observed in this model (Fig. 3A) (19). Consistent with a previous study, MyD88-deficient mice showed no significant differences in viral clearance compared with WT mice (20). In contrast, viral loads in Mavs−/− mice were ≈100 times higher than those in the WT mice on days 1 and 5 after infection. Surprisingly, despite the absence of IFN-I and other antiviral molecules, these mice were able to clear the virus to undetectable levels by day 9. The DKO mice showed no significant difference in viral loads compared with the Mavs−/− group 1 day after infection, suggesting the importance of MAVS- but not MyD88-mediated viral clearance in the early phase of infection. This is consistent with the lack of a pDC response, which would otherwise be the major source of early TLR-dependent antiviral interferons. As the infection progressed, however, DKO mice harbored significantly higher viral loads compared with all other genotypes. Remarkably, DKO mice were also able to clear the infection by day 28 (Fig. 3B).
Mavs−/− and DKO mice are able to clear RSV and resolve pulmonary disease. (A and B) WT, Myd88−/−, Mavs−/−, and Myd88−/−Mavs−/− (DKO) mice were infected with RSV (107 pfu) and BALF was harvested at the indicated times to measure viral loads by plaque assay. (A: *, mavs−/− vs. myd88−/−, P < 0.001; **, mavs−/− vs. DKO and mavs−/− vs. myd88−/−, P < 0.001; B: *, mavs−/− vs. DKO and mavs−/− vs. myd88−/−, P < 0.01; ANOVA) (n = 3–5). (C) Lungs from infected mice and mock controls were analyzed by immunohistochemistry using a polyclonal anti-RSV antibody. (D) Mice infected with RSV were assessed by whole-body plethysmography to measure airway obstruction (*, P < 0.0001; **, P < 0.03; ***, P < 0.04; ANOVA). n.d., not detected; Penh, enhanced pause. Data are represented as mean ± SEM.
Consistent with unrestricted viral replication in Mavs−/− and DKO mice in the early phase of RSV infection, immunohistochemical staining with RSV antibodies in the lungs of these mice showed evidence of infection of ciliated respiratory epithelium lining the bronchioles and bronchi on days 1 and 5 after infection (Fig. 3C). This staining was undetectable by day 14. Histological examination of lungs of infected mice revealed no striking differences on day 1 (Fig. S6A). On day 5, the inflammation seen in DKO mice appeared in patches compared with the diffuse inflammation in the other three genotypes. At this time point, there was no gross difference in the composition of the cellular infiltrate among all groups. However, few multinucleated syncytial cells were observed in the bronchioles of DKO mice (Fig. S6B). On day 14, inflammation had largely subsided in WT and Myd88−/− mice but remained in the other two groups. Although Mavs−/− mice had some chronic inflammation at this stage, DKO mice exhibited patchy acute pneumonia, numerous syncytial cells, and reactive bronchial epithelium (Fig. S6C). By day 28, inflammation was significantly reduced and comparable in all genotypes (Fig. S6D).
MAVS or MyD88 Deficiency Alleviates only the Initial Phase of Pulmonary Disease, and All Mice Eventually Recover.
Next, we evaluated the roles of MAVS and MyD88 signaling in the pulmonary function of mice by plethysmography (Fig. 3D). One day after infection, only WT mice exhibited pulmonary dysfunction, possibly attributable to inflammatory cytokine responses that cause airway obstruction (P < 0.0001). We also consistently noted that only WT mice had ruffled hair and were less active than other genotypes on day 1. This is consistent with cytokine measurements, which showed that mice lacking MAVS, MyD88, or both had markedly reduced levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1β (Figs. 1 and 2). Between days 2 and 10, all groups developed increased airway obstruction compared with their baseline function. Whereas the WT, Mavs−/−, and Myd88−/− mice returned to normal function around day 10, the DKO mice experienced slightly prolonged pulmonary dysfunction but eventually also returned to normal lung function (Fig. 3D; day 12, P = 0.03; day 14, P = 0.04).
Antibody Production Is Defective in the Absence of MAVS or MyD88.
The surprising ability of Mavs−/− and DKO mice to clear RSV led us to examine anti-RSV adaptive immune responses in these mice. Serum anti-RSV antibody responses, including the production of both IgG1 and IgG2a, were significantly attenuated in mice lacking either MAVS or MyD88 and were reduced even further in the DKO mice (Fig. 4A). These results suggest that both MAVS and MyD88 play an important role in the generation of anti-RSV antibodies in the adaptive phase of the antiviral response. This is in contrast to antibody production in response to influenza, which is MyD88 dependent and MAVS independent (21). However, depletion of B cells, followed by RSV infection, has suggested that the antibody response is unlikely to be a major mediator of primary RSV clearance (22).
Adaptive immune responses in mice lacking Mavs and Myd88. (A) RSV-specific antibody subtypes, IgG, IgG1, and IgG2a, were measured by ELISA using sera taken on the indicated day after RSV infection (IgG; *, WT vs. Myd88−/−; P < 0.01, Myd88−/− vs. DKO, P < 0.05; ** and ***, WT vs. Myd88−/−, P < 0.001) (IgG1; *, Mavs−/− vs. DKO, P < 0.01; ** and ***, WT vs. Myd88−/− and Myd88−/− vs. DKO, P < 0.05) (IgG2a; *, WT vs. Myd88−/− and Mavs−/− vs. DKO, P < 0.01; **, WT vs. Mavs−/−, P < 0.001; ***, WT vs. Myd88−/−, P < 0.001) (ANOVA, Tukey's test) (n = 7–10 per group). (B) Mice were mock-infected or infected with RSV for 8 days before lung cells were harvested for stimulation with an RSV- or SeV (control)-derived peptide. Six hours after stimulation, intracellular IFN-γ levels in CD3+CD8+ cells were measured by FACS. The percentage of IFN-γ+CD3+CD8+ cells in RSV-peptide treated cultures minus that from SeV-peptide cultures is plotted for each genotype (P = 0.35; ANOVA) (n = 5 per group). (C) Bronchoalveolar lavage fluid IFN-γ was measured in WT and DKO mice at the indicated times after RSV infection (n = 3 per group). (D) Lung cells (effectors) from day 8 RSV- or mock-infected mice were incubated with EL4 target cells loaded with a peptide (RSV peptide or SeV control peptide). The target cells were differentially labeled with CFSE and incubated with the effector cells at the indicated effector:target (E:T) ratios for 4 hours. Cells were then analyzed by flow- cytometry and the specific killing of RSV peptide-loaded targets was calculated (n = 3 per group). (E) Mice were either depleted of CD8+ T cells (with antibody 2.43) or mock depleted (IgG) and infected with RSV. BALF was extracted on day 8 and IFN-γ was measured by ELISA (n = 3 per group). (F) BALF viral titers were measured for mice described in E. Data are represented as mean ± SEM.
Normal CD8+ T Cell Response in the Absence of MAVS and MyD88.
Next, we examined the activation of the CD8+ cytotoxic T-lymphocyte (CTL) response in the lungs of mice after intranasal infection of RSV. Eight days after infection, lung cells were stimulated in vitro with an RSV-derived peptide previously identified as a CD8+ T cell stimulating epitope or with a control SeV-derived peptide, both of which bind H2-Db (23). The percentage of IFN-γ– producing CD8+ pulmonary T cells was quantified by FACS (Fig. 4B and Fig. S7). Unexpectedly, RSV-specific CD8+ T cell activation was similar in Myd88−/− and Mavs−/− mice compared with WT counterparts. Even the DKO mice were clearly able to activate CD8+ T cells in response to RSV, although the responses were slightly but not significantly lower (P = 0.35). In fact, measurement of IFN-γ in the BALF of WT and DKO mice at various times after infection revealed that DKO mice produced this cytokine more robustly than WT counterparts (Fig. 4C). In WT mice, IFN-γ peaked on day 6 after RSV infection and was undetectable by day 10. In DKO mice, however, IFN-γ peaked on day 8 at a higher level than in WT mice, suggesting that the higher viral load in DKO mice led to a corresponding increase in IFN-γ production. Additionally, analysis of CD8+ T cell cytolytic activity showed that, compared with cells from mock-treated animals, lung cells from RSV-infected mice of all genotypes demonstrated increased ability to specifically kill target cells loaded with the MHC-I–binding RSV epitope (Fig. 4D). Furthermore, depletion of CD8+ T cells in conjunction with RSV infection firmly established a role for these cells. Analysis of BALF 8 days after infection revealed that production of IFN-γ was intact in all mice treated with control IgG but absent in mice depleted of CD8+ T cells, pointing to these cells as the likely source of the cytokine (Fig. 4E). Finally, measurement of viral titers in Mavs−/− and DKO mice showed much higher levels of virus when CD8+ T cells were depleted (Fig. 4F). In contrast, depletion of CD8 T cells did not increase the viral titers in WT and Myd88−/− mice, presumably because these mice still had an intact MAVS pathway to clear the virus. Together, these data clearly show that CTL activation was intact and effective in DKO mice.
Subset of Pulmonary DCs Is Activated in Mavs−/− and DKO Mice.
To investigate how Mavs−/− and DKO mice mount a largely normal CTL response in the absence of innate IFNs and cytokines known to be important for activating adaptive immunity, we examined the activation of DCs. We first measured up-regulation of CD86 in CD11c+ GM-CSF-derived bone marrow-derived DCs (BMDCs) in response to RSV and SeV infection in vitro. CD86 up-regulation was observed in WT and Myd88−/− DCs but not in Mavs−/− and DKO DCs (Fig. S8), suggesting a complete dependence on MAVS-mediated signaling. As a control, LPS-induced CD86 surface expression was observed in DCs of all genotypes.
Because the RSV-induced response in these cultured DCs did not explain intact CD8+ T cell activation in mice lacking MAVS, we examined in vivo activation of pulmonary cDCs, which were identified as CD11c+, CD2−, and F4/80− cells (18). Both WT and MyD88-deficient CD11c+ DCs up-regulated surface levels of CD86 (Fig. 5A) and CD80 (data not shown) after RSV infection compared with mock-infected mice. In both MAVS-deficient and DKO mice, up-regulation of these molecules was drastically reduced. However, a small percentage of the pulmonary DCs in these mice consistently up-regulated these molecules, indicating their activation. In contrast, CD86 up-regulation was completely MAVS-dependent in CD11c+CD2+F4/80+ alveolar macrophages of the same mice (Fig. 5A).
A subset of pulmonary DCs is activated by RSV in mice lacking Mavs. (A) Mice of the indicated genotypes were infected with RSV or mock treated for 24 hours before CD86 levels were assessed on pulmonary DCs and alveolar macrophages by flow cytometry. Shaded histograms represent isotype-control antibody staining, blue histograms represent DCs from mock-infected mice and red histograms represent RSV infected mice. (B) Mediastinal lymph nodes (MLNs) were taken from mice described in A and surface expression of CD86 was assessed on dendritic cells by flow cytometry. Representative mice are shown for each genotype (n = 3 per group).
After activation, antigen-loaded DCs traffic from their peripheral tissue location to draining lymph nodes, where they activate T cells. Therefore, we examined the phenotype of DCs in the mediastinal lymph nodes draining the lung (Fig. 5B). Upon RSV infection, the majority of lymph node DCs in WT and Myd88−/− mice were CD86high compared with DCs in mock-treated mice. Consistent with the notion that the subset of pulmonary DCs activated in the absence of MAVS may subsequently traffic to the lymph node, we found a significant percentage of CD86high DCs in the lymph nodes of Mavs−/− and DKO mice. This subset of DCs may be responsible for the effective activation of RSV-specific CTLs in the absence of innate immunity mediated by MAVS and MyD88.
We have provided both in vivo and in vitro evidence that MAVS is essential for the production of IFN-I and inflammatory cytokines in response to RSV infection. Global gene expression profiling further demonstrated that MAVS is required for RSV-induced production of the vast majority of antiviral molecules. In contrast to MAVS, MyD88 is dispensable for the induction of IFN-I and the majority of antiviral cytokines, with a few exceptions such as TNF-α, IL-1β, and MCP-1. The defective production of these molecules in all of the mutant mice may reflect the complex regulation unique to these potent inflammatory mediators. Notably, Il-24 and cxcl-16 were induced independently of MAVS and MyD88. Whether these cytokines play any role in the immune response to RSV requires further study.
It has recently been shown that systemic infection with the RNA virus, LCMV, results in IFN-I, inflammatory cytokine and chemokine production in a MyD88-dependent but largely MAVS-independent manner (24). Using an intranasal mode of infection, the same group found that influenza virus-induced IFN-I is defective only in mice lacking both MAVS and MyD88 (21). Further, pulmonary NDV infection indicated that mice lacking either MAVS or MyD88 are still capable of producing IFN-α (18). These results indicate that the requirement of MAVS and MyD88 for innate cytokine responses depends on the pathogen and on the route of infection. Our data suggest that RSV solely relies on the RLR-MAVS pathway for IFN-I induction in vivo. Further, we find no evidence of compensatory MyD88-mediated IFN-I production, which is consistent with recent data on the lack of IFN production by pDCs in response to RSV infection (25) but inconsistent with other reports suggesting IFN-I induction in these cells by RSV (26, 27). Our observation that RSV-infected Myd88−/− mice induce normal levels of IFN-I suggests that in this model, pDCs do not produce these cytokines because they are expected to use TLR7, which requires MyD88 for signaling. The reason for these seemingly conflicting results is unclear but may be partially explained by differences in virus strain or cell depletion methods.
Despite such a drastically defective cytokine response and the fact that Mavs−/− mice harbored higher viral loads shortly after RSV infection, these mice still cleared the virus effectively by activating a normal CTL response. Antibody-mediated depletion of CD8+ T cells significantly prolonged RSV replication, confirming their appropriate activation and demonstrating the important role of these cells in controlling the virus. Although deletion of Myd88 alone had no effect on RSV loads, mice lacking both adaptors had higher and more prolonged viral loads than those lacking either one alone, suggesting that in the absence of MAVS, MyD88 signaling contributed to antiviral immunity through a mechanism independent of IFN-I induction. Remarkably, even the DKO mice were able to activate CD8+ T cells and clear the virus effectively.
It is surprising that CD8+ T cell activation is normal in the absence of MAVS, because it is widely believed that IFNs and cytokines produced during innate antiviral responses are required for activating adaptive immunity, including cross-priming (28, 29). A possible answer to this conundrum is our finding that a subset of pulmonary DCs is activated by RSV in the lung and then migrates to the mediastinal lymph nodes in the absence of MAVS and MyD88. It is possible that this subset of DCs may be responsible for the cross-priming of CD8+ T cells in a manner that depends on TLR3 and Trif (30). We have assessed the expression of several surface markers, including CD8α, CD4, CD11b, B220, mPDCA1, and GR-1, on the pulmonary DCs and found that none are specifically enriched or lower in the activated subset in the WT mice or in those lacking MAVS or MyD88. Therefore, it is still not clear what makes this subset of DCs unique in getting activated by RSV in the absence of MAVS and MyD88. Further characterization of this DC subset should provide important insights into the regulation of T cell responses to RSV and possibly other pathogens.
Our results highlight the sophistication of the host's antiviral defense mechanisms and provide an example of an effective adaptive immune response in the absence of known innate immune mediators. Our results also have important implications for the development of RSV therapeutics and vaccines, as a significant contributor of RSV disease is an inappropriate CD8+ T cell response. Indeed, antibody-mediated depletion of CD8+ T cells alleviates disease progression in RSV-infected mice (22, 31). Because MAVS is required for optimal anti-RSV antibody production but not for a CD8+ T cell response, agents that activate the RLR-MAVS pathway may serve as important adjuvants in future RSV vaccines and therapeutics.
The generation of Mavs−/− mice has been described in ref. 16. Briefly, Mavs−/− mice were made by homologous recombination with a targeting vector in 129/Sv ES cells, which were then injected into C57BL/6 blastocysts to create chimeric mice. Myd88+/− mice, which had been back-crossed to the C57BL/6 background, were kindly provided by Shizuo Akira (Osaka University). To obtain mice lacking mavs, myd88, or both (DKO), mavs+/− and myd88+/− mice were bred with each other, and the resulting progeny with appropriate genotypes were used in the experiments. All mice described in this report were engineered and housed in animal facilities at the University of Texas Southwestern Medical Center, and the experimental protocols were approved by the Institutional Animal Care and Use Committee.
In Vivo Infection.
Mice were anesthetized with inhaled isoflurane before intranasal inoculation with 107 pfu of live RSV in 100 μl of Eagle Minimal Essential Medium supplemented with l-glutamine, Hepes, penicillin, streptomycin, and 10% FBS. Control animals were sham-inoculated with 100 μl of cell-culture media (19).
CD8+ T Cell Analyses.
For IFN-γ production, lung cells were incubated in complete media with either an SeV-derived peptide (FAPGNYPAL) or an RSV-derived peptide (NAITNAKII) (23) (10 μg/ml) and brefeldin A (10 μg/ml; Sigma) for 6 h. Cells were then incubated with antibodies against CD3 and CD8, followed by fixation, permeabilization, and staining for IFN-γ using the Becton Dickinson fix/perm reagent according to the manufacturer's instructions. Samples were run on a Becton Dickinson FACSCalibur and analyzed using FlowJo 8.3 (Tree Star, Inc.). Cytotoxicity assays were performed as described (23). EL4 targets were incubated with either RSV- or SeV-dervived peptides (10 μg/ml) overnight. Respiratory syncytial virus peptide-loaded targets were then labeled with 5 μM carboxyfluorescein diacetate succinimidyl ester (CFSE) and control targets with 0.5 μM CFSE before mixing them at a 1:1 ratio. Mixed targets were then incubated at the indicated effector/target (E/T) ratios with lung cells from mice infected with RSV for 8 days. Cells were incubated at 37°C for 4 h and then were analyzed by flow cytometry. Percent specific lysis was calculated as 100 − (100 × Percent CFSEhigh [at E/T of 2 or 20)/Percent CFSEhigh [at 0:1]).
More information on materials and methods, including statistical analyses, can be found in SI Text.
We thank Dr. Nitin Karandikar, James Forman, and John Schatzle for much invaluable advice. We thank Dr. Nitin Karandikar (University of Texas Southwestern, Dallas) for the 2.43 hybridoma and Dr. Lijun Sun (University of Texas Southwestern, Dallas) for help with antibody purification. This work was supported by grants from the National Institutes of Health (Grant AI-09919) and the Welch Foundation. V.G.B. was supported in part by a National Institute of Allergy and Infectious Diseases training grant (Grant 5T32 AI005284–30). Z.J.C. is a Burroughs Wellcome Fund Investigator of Pathogenesis of Infectious Diseases and an Investigator of the Howard Hughes Medical Institute.
¶To whom correspondence should be addressed. E-mail: zhijian.chen{at}utsouthwestern.edu
Author contributions: V.G.B., O.R., and Z.J.C. designed research; V.G.B., Q.S., E.J.B., and X.C. performed research; Q.S., C.S., J.-P.T., A.M., A.M.G., and H.J. contributed new reagents/analytic tools; V.G.B., A.M.G., O.R., and Z.J.C. analyzed data; and V.G.B. and Z.J.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0804717105/DCSupplemental.
Freely available online through the PNAS open access option.
© 2008 by The National Academy of Sciences of the USA
Pichlmair A,
Reis e Sousa C
(2007) Innate recognition of viruses. Immunity 27:370–383.
Akira S,
Uematsu S,
Takeuchi O
(2006) Pathogen recognition and innate immunity. Cell 124:783–801.
Seth RB,
Sun L,
Chen ZJ
(2006) Antiviral innate immunity pathways. Cell Res 16:141–147.
(2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314:997–1001.
Hornung V,
(2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314:994–997.
Kawai T,
(2005) IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6:981–988.
Meylan E,
(2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167–1172.
Xu LG,
(2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19:727–740.
Ea CK,
(2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122:669–682.
Banchereau J,
Steinman RM
(1998) Dendritic cells and the control of immunity. Nature 392:245–252.
Simoes EA,
Carbonell-Estrany X
(2003) Impact of severe disease caused by respiratory syncytial virus in children living in developed countries. Pediatr Infect Dis J 22:S13–S18, discussion S18–S20.
Murata Y,
Falsey AR
(2007) Respiratory syncytial virus infection in adults. Antivir Ther 12:659–670.
Welliver RC
(2003) Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr 143:S112–S117.
Openshaw PJ
(2005) Antiviral immune responses and lung inflammation after respiratory syncytial virus infection. Proc Am Thorac Soc 2:121–125.
Collins PL,
Murphy BR
(2005) New generation live vaccines against human respiratory syncytial virus designed by reverse genetics. Proc Am Thorac Soc 2:166–173.
Sun Q,
(2006) The specific and essential role of MAVS in antiviral innate immune responses. Immunity 24:633–642.
Kato H,
(2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23:19–28.
Kumagai Y,
(2007) Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. Immunity 27:240–252.
Jafri HS,
(2004) Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice. J Infect Dis 189:1856–1865.
Rudd BD,
(2007) MyD88-mediated instructive signals in dendritic cells regulate pulmonary immune responses during respiratory virus infection. J Immunol 178:5820–5827.
Koyama S,
(2007) Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol 179:4711–4720.
Graham BS,
Bunton LA,
Wright PF,
Karzon DT
(1991) Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest 88:1026–1033.
Rutigliano JA,
Rock MT,
Johnson AK,
Crowe JE, Jr,
Graham BS
(2005) Identification of an H-2D(b)-restricted CD8+ cytotoxic T lymphocyte epitope in the matrix protein of respiratory syncytial virus. Virology 337:335–343.
Jung A,
(2008) Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T cell response via MyD88. J Virol 82:196–206.
Jewell NA,
(2007) Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol 81:9790–9800.
Smit JJ,
Lukacs NW
(2006) Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J Exp Med 203:1153–1159.
Wang H,
Peters N,
Schwarze J
(2006) Plasmacytoid dendritic cells limit viral replication, pulmonary inflammation, and airway hyperresponsiveness in respiratory syncytial virus infection. J Immunol 177:6263–6270.
Medzhitov R,
Janeway CA, Jr
(1999) Innate immune induction of the adaptive immune response. Cold Spring Harb Symp Quant Biol 64:429–435.
Hoebe K,
Janssen E,
Beutler B
(2004) The interface between innate and adaptive immunity. Nat Immunol 5:971–974.
Schulz O,
(2005) Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433:887–892.
Schwarze J,
(1999) CD8 T cells are essential in the development of respiratory syncytial virus-induced lung eosinophilia and airway hyperresponsiveness. J Immunol 162:4207–4211.
Thank you for your interest in spreading the word on PNAS.
You are going to email the following MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus
Message Subject (Your Name) has sent you a message from PNAS
Message Body (Your Name) thought you would like to see the PNAS web site.
Vijay G. Bhoj, Qinmiao Sun, Elizabeth J. Bhoj, Cynthia Somers, Xiang Chen, Juan-Pablo Torres, Asuncion Mejias, Ana M. Gomez, Hasan Jafri, Octavio Ramilo, Zhijian J. Chen
Proceedings of the National Academy of Sciences Sep 2008, 105 (37) 14046-14051; DOI: 10.1073/pnas.0804717105
News Feature: Do hosts and their microbes evolve as a unit?
A group of evolutionary biologists sees evidence for a hologenome. Others dismiss it entirely. One thing's certain: The debate remains heated.
Image credit: Shutterstock/Piriya Gutsch.
Hints of ayahuasca in pre-Columbian rituals
Chemical evidence suggests ritual use of psychoactive plants used to brew ayahuasca in pre-Columbian Bolivia.
Image courtesy of Juan Albarracin-Jordan and José M. Capriles.
Kinship and violence in Neolithic Poland
Researchers present evidence of Neolithic kinship and violence based on remains from a mass grave in Poland.
Image courtesy of Piotr Włodarczak.
Brain fluid shifts following spaceflight
Volume of cosmonauts' brain ventricles increased by an average of 12% after spaceflight—a potential mechanism to cope with increased brain fluid volume, a study suggests.
Image courtesy of R. Maxine Rühl.
PNAS Profile of NAS member and cell biologist Junying Yuan
Image courtesy of Aaron Washington for Harvard Medical School.
PNAS Portals
PNAS Updates
Feedback Privacy/Legal
Copyright © 2019 National Academy of Sciences. Online ISSN 1091-6490

redpajama_set_name: RedPajamaCommonCrawl


text:
MPS Supports Cowgirls with Cameras Film Camp
by Meredith Stephens | Jun 13, 2018 | MPS News, News | 0 comments
MPS Studios is honored to sponsor the first-ever Cowgirls with Cameras film camp. The camp, which takes place on Thursday, June 14, and Friday, June 15, is a film experience during which girls in high school, ages 14-18, gain exposure to filmmaking by shooting a documentary short film alongside local industry professionals.
Applicants were to write an essay describing their interest in attending the camp, and six of the highest-qualified candidates were chosen. The girls get to learn from nine film industry volunteers, meaning they will have lots of one-to-one mentorship opportunities.
The National Cowgirl Museum and Hall of Fame and the Lone Star Film Society came together initially to make the camp happen.
"The Museum had recently honored Callie Khouri, the writer of 'Thelma and Louise' and the series 'Nashville', who noted that not many women have jobs behind the camera; opportunities for women and girls to learn are few," said Diana Vela, Associate Executive Director of Exhibitions and Education at the Cowgirl Museum. "Knowing that Lone Star Film Society was right in our backyard, we wanted to take advantage of their expertise and offer an opportunity for young girls to learn about what happens behind the camera."
The Cowgirl Museum reached out to the Lone Star Film Society, and the partnership was born. They began putting their heads together to build an education program that involved documentary filmmaking for their participants.
The collaboration grew even further when Chad Mathews, Festival and Film Society Director for LSFS, enlisted the help of Four Thirds Creative – a woman-owned production company focused on creating videos with social and emotional impact.
"Four Thirds Creative will provide an overview of the post-production process at the end of the camp and is charged with editing the participants' hard work into a documentary," said Karen Ryan, Post Master General at Four Thirds Creative. "The final piece will be shown at the Lone Star Film Festival in November."
The camp will be held at Wings of Hope Equitherapy in Cleburne, Texas.
"One of the founders of Wings of Hope, Margaret Dickens, is a Museum Hall of Fame Honoree," said Vela. "We honored her due to her non-profit work with equitherapy – at a time when very few were doing it. We wanted to highlight the incredible work of Wings of Hope while also allowing the girls an opportunity to learn filmmaking skills."
Wings of Hope provides equine-assisted activities for children and adults with unique physical, mental, and emotional challenges.
"Our mission is so out of the ordinary, and we live outside of the box, so this was a perfect fit for our organization," said Allison L. Gross, Development Director for Wings of Hope. "Our goal is to best serve individuals with disabilities and challenges through the partnership of a horse, so any time we can collaborate and stretch that service it allows us to enhance our mission."
Four Thirds brought MPS on as a sponsor, and MPS's own Executive Vice President, Meredith Stephens, will be volunteering both days of the camp to mentor the girls. "It's exciting that MPS gets to be a part of the inaugural year of the Cowgirls with Cameras camp, and we hope the collaboration will continue for years to come."
"Once we complete this camp, we will evaluate it and hopefully begin planning for 2019," said Mathews. "Depending on the success of this year, expansion is definitely something we are very interested in exploring."
MPS is honored to be a part of this community rising together, working in tandem to support and promote area organizations and the growth of the next generation of filmmakers.
ABOUT MPS STUDIOS
For nearly 40 years, MPS Studios has provided the equipment and support services to production companies making movies, commercials, and television shows. A staff of highly specialized, factory-trained, and industry-savvy technicians provide world-class service to clients around the corner and around the globe. The company offers cameras, lighting/grip/electric, sound stages, and lighting repair. Inventory includes ARRI, RED, Canon, Panasonic, and Sony cameras, along with, hundreds of lenses, and thousands of filters. Lighting inventory includes ARRI SkyPanels, ARRI M-series HMI's, Kino Flo, Mole Richardson. Contact MPS Camera & Lighting Austin, MPS Studios Dallas, or MPS Denver to have a rental package customized for your next project. www.mpsfilm.com
Storytelling With Large Format Cameras
The ARRI Orbiter: Everything You Need To Know
MEET THE CREW: DYLAN MCELVEEN
MPS Studios Celebrates ARRI Authorized Repair Center Partnership


There is nothing better than a serving of good mashed potatoes. You know the kind: all white and fluffy and loaded with a buttery, creamy richness that is irresistible. That said, there is nothing worse than a serving of bad mashed potatoes. Sadly, I am sure you also know them: all gloppy, starchy and thick and such a patent culinary disappointment. Any cook out there knows that the road to good mashed potatoes can be frought with peril. What starts out as a simple side quickly turns into heavy, rocky goo. It shouldn't be this way- after all, what's so hard about boiling some potatoes and mixing them up with butter, milk, salt and pepper? Plenty, that's what.
I started all this thinking about mashed potatoes because Julia requested them for her 6th birthday celebration. And, for me, someone who fancies herself a good cook, this was a bit of a challenge. See, I have never been able to really guarantee how my potatoes would come out. They could be fabulous or they could be wretched. There was no predicting. And, now that she had asked for them for her birthday dinner, I felt the need to conquer the mashing of potatoes! After all, the least I should be able give my daughter on her birthday was good potatoes!
I began by reading every cookbook I had to see what they had to say. And, I quickly came to the conclusion, that in most cases, the mashing of potatoes suffers from a gross lack of attention to detail. We peel the potatoes, put them in a pot- have it boil…but aren't really focused on how long. We add milk or cream- but aren't really focused on how much we add or the temperature of the milk. We add butter, salt. We beat, but aren't really focused on how hard and long. Oh, and we do it at the last minute- as we are doing a million other things to get dinner on the table. And, guess what? The results show it. This is a dish that needs focus. It also needs a ricer- but more on that later!
My research- both in books and practice confirmed that there are several keys to making a yummy, light, mashed potatoes. The first (and most important) step is paying attention. To facilitate this, I recommend that you make your potatoes in advance- storing them in a simmering double boiler covered with foil until you are ready to eat. (I made mine 1.5 hours early and they were fabulous.) In the same vein, make sure you really watch the potatoes as they boil- you want to get them right when they soften. You don't want to overcook them. And, if you don't have a ricer, get one! Mashing your potatoes through a ricer helps make them light and fluffy. The rest, the milk or cream, butter, salt and pepper is to taste. One note: I can never bring myself to go the cream route- that said, it makes for an amazing potato and is more forgiving than straight milk. It is also more fattening. But cream or no cream, if you are focused on the details- chances are you will knock this side out of the park!
If peeling the potatoes, do so. Cut the potatoes in 3 pieces each. Boil the potatoes until a knife goes cleanly and easily in-about 17-22 minutes on my stove. Drain. Meanwhile, warm the milk. Using a ricer, rice the potatoes. Gradually add the milk or cream and butter while mixing with a spatula until the potatoes reach the desired consistency. Season with salt and pepper. May be stored in the top of a simmering double boiler until ready to use- be sure to cover with foil though!
This entry was written by Caroline, posted on October 5, 2010 at 5:32 am, filed under comfort food, cooking, entertaining, kid friendly, sides, vegetarian. Bookmark the permalink. Follow any comments here with the RSS feed for this post. Post a comment or leave a trackback: Trackback URL.
C-line! I just realized you have your own blog going – who knew. Things in Oz are truly spectacular, but I'm already a bit worried about introducing our Aussie friends to Thanksgiving without my ricer! Ha. Please give my best to the fam and see you on the other side of this adventure.


The Gordon County Board of Commissioners held their Regular Meeting on Tuesday, August 7, 2012, at 10:00 a.m. in the Conference Room of the Administration Building.
Chairman Bailey read the list of employees with anniversary hire dates in August.
Commissioner Long drew the name of Patricia Bedford as employee of the month.
Chairman Bailey asked if there were any additions, omissions, or deletions to the Minutes for the Work Session July 17, 2012, the Regular Meeting July 17, 2012, and the Special Meeting July 24, 2012. Commissioner Long made a motion to approve the minutes. Commissioner Steward seconded the motion and all voted aye. Minutes approved.
County Administrator Dowling advised that this is for Board approval of the Local Option Sales Tax Certificate of Distribution. This is a State requirement every ten years according to the Census. Following several meetings with the municipalities, and going through the State mandated procedure, the Board has approved the method of distribution strictly by population. This certificate must be completed by August 26th.Commissioner Long made a motion to approve the LOST Certificate of Distribution and authorize the Chairman to sign. Commissioner Steward seconded the motion and Commissioners Long, Steward, and Bailey voted aye. Motion passed.
County Attorney Smith advised that this is the first reading of an amendment to the Malt Beverage Wine and Liquor ordinance. The amendment is for the Event Permit Application section of the ordinance which called for any event permit application to be submitted at least 15 days prior to the event. Based upon staff recommendations, the request is for the Board to consider an amendment requiring the application to be submitted at least 30 days prior to the event. The amendment will be on the next agenda for a second reading and the Board's consideration for approval.
Commissioner Long made a motion to adjourn the meeting. Commissioner Steward seconded the motion and all voted aye. There being no further business, the meeting was adjourned at 10:10 a.m.


I have been listening with the utmost interest to the words of Bishop Forte and of Cardinal Martini, and it is difficult for me to put forth yet another topic of discussion after two such intense interventions. The latter focused especially on the future, urging us to gaze beyond past events, whereas I shall attempt to examine the reasons for the theological and religious opposition between Judaism and Christianity. Therefore I shall concentrate in a special manner on the past. At the same time, I would like to project this topic from the past into a future that concerns us both and towards which we are going together. Considering the complexity and the controversial nature of the problems under discussion, as well as the short time we have today, my talk shall be very brief.
I would like to preface my considerations with a general observation that is also meant to be an expression of hope for the future. Jewish-Christian dialogue – despite the limits, the flaws, the disappointments, the criticisms and the attacks which it continues to cause – is a dynamic reality; we are not in a situation of stasis. And I would like to quote, applying it to us, a verse from the Book of Deuteronomy (5, 3): "We, all of us who are alive here this day," are armed more with good will and hope than with wisdom and certainties. The comparison between Christianity and Judaism typical of the past centuries is not that of today; yesterday there were theological disputes, and the Jews were unilaterally asked to attend public assemblies where they had to justify their continued allegiance to the faith of their fathers. Today, Jews and Christians in the spirit of dialogue meet in very different circumstances and with markedly different attitudes. It is nonetheless difficult to deny that from a part of the Jewish world, rabbinical and not rabbinical, there is still a certain resistance, a difficulty about entering into a relationship with Christianity in the context of the initiatives of dialogue. This happens for a series of reasons; some of them are clear and evident, some are less so but do nonetheless exert a determining influence on our relations.
There is of course still the fear or the suspicion that the true goal of the Christians is to attract the Jews to Christianity through dialogue, or that through these contacts those Jews who are less religiously motivated, and thus are more fragile, may be induced to abandon their religion and to embrace Christianity. I have the impression that, from a preliminary and substantial point of view, the true reason behind this resistance is not tied to a subliminal fear or reluctance, but is connected with considerations of a doctrinal type: unlike Christianity in relation with Judaism, Judaism does not need Christianity to understand or to comprehend itself. Today there is a tendency to talk of an "asymmetrical relation" that connects Jews and Christians at the level of dialogue. In other words, for a Christian the encounter with Israel means the rediscovery of one's own roots, so that Christianity is more clearly defined, understood, and, so to speak, better justified. For a Jew the encounter with Christianity does not carry the same significance. On the contrary, in this second case, the encounter with the other becomes a source of tension and contradiction as soon as the figure of Jesus comes under discussion (and how could it be otherwise?) – a figure that, understood as divine and messianic, contrasts with Israel's monotheistic or messianic conception. It is also necessary to add that within Christianity's religious doctrine, where we meet with openness and readiness to change as well as with resistance and hesitation, there are still serious difficulties whenever one tries to define and to indicate the role of the people of Israel. As an example, I am thinking of the interpretation given by the Church of the return of Israel to its land after two thousand years of galut (exile); is it a providential event within a theological vision or a historical and contingent event within a political perspective?
I could continue to discuss these issues, adding yet other considerations, but I am not going to do so, since this is not the issue on which I intend to focus tonight. I would like to bring the discussion to a different level, no longer assessing the Christian theological understanding of Judaism, but rather, starting from inside the Jewish tradition, attempting to outline and evaluate the main points of a Jewish theological understanding of Christianity. The latter, even if essential, is not univocal; it is contradictory, and is still being worked out. Its elaboration is certainly a very difficult and delicate task, whose starting point is the study of the definitions of Christianity given by the Jews in the past; and I am thinking here especially of the Talmudic and the Medieval period.
The question where all discussions arrived and converged, and thus also the main problem to be solved, was whether the Christians had to be considered idolaters or not. In the Talmud we find a distinction between the goyim (including the Christians) living in the land of Israel and the goyim living outside the land of Israel. In order to absolve the former from the accusation of idolatry, it was necessary to make sure that they truly did not practice idolatry; for the second, the presumption that they were not idolaters was sufficient. There is a passage in the Talmud (b. Hullin 13b) that seems to say this: "The idolaters outside Israel are not idolaters, since what they do is to practice, out of habit, the rituals of their fathers." I have translated [into standard Italian] a technical expression that means this: "performing certain practices," they do not show a clear intention of celebrating idolatrous rituals. Why do we find this difference of evaluation between those living in the land of Israel and those who are outside of it? Most likely, the Christians of the Holy Land mentioned in the Talmud are the first Christians, the Judeo-Christians, the church of Jerusalem, the church of Jacob, those who had known and practiced the Jewish religion and had subsequently abandoned it. These ones, therefore, knew what they were doing, they knew that they were violating the precept of the yihud ha-Shem (the unity of God), according to which God (ha-Shem) is One (ehad), a precept that concerns those who are born Jews and not those who are outside the people of Israel. According to some, there is a subtle distinction: the descendants of Noah (those non-Jewish individuals who, like the Christians, obey universal moral laws) are subject to the prohibition of idolatry, but are not obliged to embrace monotheism. Thus shittuf (the association of other divine figures to the one God, as in the case of Jesus) can be practiced by them without breaking the prohibition of idolatry, considering that they are not obliged to profess monotheism.
With the passing of time, especially in Medieval Europe, the situation would undergo a radical change. On one hand, idolatry in the proper sense of the term would disappear, and with it also the necessity to fight it. Christians and Muslims would control Europe (the Muslims until the fall of Grenada in 1492). The Jews would have to deal with them in their different roles as rulers and as representatives of different religions. What is the Jewish approach towards Christians and Christianity in the Medieval period? Does this approach change in comparison with the Talmudic period, or does it remain unvaried? In general, one must distinguish between the (Sephardic) rabbis residing in areas under Islamic influence and the (Ashkenazi) rabbis residing in areas under Christian influence.
The Sephardic front is authoritatively represented by Maimonides, who, if compared with the diversified position of the Talmud, takes a more radical and univocal stance, eliminating the distinction between the inhabitants of the land of Israel and those living outside Israel, treating all Christians as "idolaters" tout-court. Next to this negative vision of Christian theology, Maimonides does however give a more open and moderate assessment of the Messianic role of Christianity and Islam in the world. Here is for instance a passage of the Treatise on Kings, which does not appear in all editions (of the Mishneh Torah), because in most of them it is censored: "To understand the thoughts of the Creator of the world is not possible to man, because our ways are not His ways and our thoughts are not His thoughts (Is 55,8); nevertheless, all the words of Jesus of Nazareth and of the son of Ishmael [Mohammed] who came after him are aimed at paving the way to the King-Messiah and at preparing the whole world to serve God together, as it is written: 'because I shall then transform the language of the peoples into a pure language, so that all shall invoke the Name of the Lord shall serve him in a sole unit [all together, in harmony]' (Sof. 3,9)". Following the line of thought begun by Yehuda ha-Levy in the Kuzari, Maimonides lets Christianity and Islam, so to speak, do a "qualitative leap": he includes the two religions within a sole providential plan that sees them as protagonists of a preparatory itinerary of humanity as a whole towards the Messianic event.
In the so-called Ashkenazi world, where we find personalities such as Rashi, the Tosafists, and other rabbinical authorities who carry much weight in the French-Germanic environment, it is emphasized that the Christians (in the countries where the Jews lived) are not idolaters. We can therefore see a rather marked distinction between the evaluation of the Christians given by the Sephardic world represented by Maimonides and the evaluation given in general by the highest authorities of the European Ashkenazi world. According to the latter, the Christians are not idolaters, or they do not know of any idolatrous practice, or – echoing the well-known claim by Rabbi Yohanan mentioned earlier (from the treatise Hullin of the Talmud) – " what they do is to practice out of habit the rituals of their fathers," without any intention of thereby carrying out idolatrous practices. In such a delicate context, we ought to mention a rather odd circumstance. In a very important halakhic text (the Tur by Ya'aqov ben Asher), the controversialist and jurist Joseph Caro explicitly mentions that "at the present time [we are in the 16th century], the Christians believe in the Creator of the world and thus are not to be considered idolaters." In another work of his, the codifying treatise Shulhan Arukh, the same Joseph Caro does however fail completely to mention his conviction as a halakhic norm.
Within this complex horizon, a special case is represented by the position of a famous 14th century scholar from Provence, Rabbi Menachem ben Shelomò ha-Meiri (1249-1315). He thinks that Christianity has nothing to do with idolatry and that the prohibitions mentioned in the Talmud about the idolaters do not concern the Christians. Thus he writes: "even if their faith is different from ours, they do not belong to the category of idolaters"; "they believe in the existence of God the Blessed One, in His uniqueness and omnipotence, even if in some respects, from the point of view of our faith, they incur in some errors"; and later, "in our time, in the majority of cases, even if sometimes they share oaths in the name of important dead personages [the saints], they nonetheless do not consider them deities [and thus there is no idolatry]". Meiri's position is certainly remarkable and authoritative, even if these conclusions of his, which appear wholly to exclude Christianity from the problematic of idolatry, seem to be rather unique.
In such a tormented context, characterized by contradictory positions and thoughts, sometimes oriented towards a more moderate appraisal, sometimes towards a more critical judgment of the Christian religion, Maimonides' ambivalent opinion – negatively on the theological level, but positively open in its Messianic perspective – appears to be the clearest and most straightforward affirmation of the involvement of Christianity in a providential role of a Messianic-providential type. And this opinion continues to represent a major stepping stone in the path that Christianity and Judaism make together, though along parallel and distinct planes. Maybe even the category of the "descendants of Noah," which is admittedly rather inadequate and weak, may still be used to think of Christianity in Jewish terms and to reconcile conceptually (and not only conceptually) the two religions.
Let us not forget that in the past century, in the heart of a European continent that some thought most civilized, we witnessed the explosion of the Shoah, with its burden of suffering and death – and the idea of dialogue came as a consequence of the Shoah. As I said, dialogue continues and must be sustained because it is a unique occasion to think and to speak together: the only open road which we can both follow so as to be present, together, whenever God shall so desire. "Things that are hidden belong to the Lord our God" (Deut. 29, 28). As far as we are concerned, and as was just emphasized by Cardinal Martini, we should not behave as if we were in a rush; we ought not to have too many certainties (personally, I have more questions to make than answers to offer); we ought not to be tempted to "wake up love" (Song of Songs 2, 7) before it is time. Thanks to our faith, we must be optimistic; we must be trusting and we must be convinced that, when the moment shall come, God shall open our eyes and our hearts, showing us the truth. Thus, we must be "alive" and walk together in the direction of that goal, with sentiments of love, respect and humility.


text:
"Stokesay Castle - a model maker's inspiration?" Topic
Please do not post offers to buy and sell on the main forum.
Back to the English Civil War Message Board
Back to the War of the Roses Message Board
Back to the Medieval Discussion Message Board
OMM: New Rules, Books, Wargames & Magazines
Junior Generals
Battle for Britain: Wargame the English Civil Wars 1642-1651
Oddzial Osmy's 15mm Teutonic Crossbowmen 1410
The next Teutonic Knights unit - Crossbowmen!
The Joy of Minis
Editor in Chief Bill ponders nirvana.
1,233 hits since 28 Jan 2022
Warspite1 28 Jan 2022 2:50 p.m. PST
For any of you not lucky enough to visit it, I give you Stokesay Castle in Shropshire, on the borders of England and Wales:
I was there is 2008 and found it a delight. A single tower (small keep) and a great hall with another tower at the other end. This second tower had a half-timbered upper-storey added later.
The black and yellow gatehouse is pure 16th century; there would have been a simple gate tower and a drawbridge there before. The bailey wall was once higher but was reduced after a brief English Civil War siege.
Modelling inspiration for the 13th to 17th centuries!
See also: link
Grelber 28 Jan 2022 4:51 p.m. PST
I like the great hall with the balcony and staircase. If there was a rope hanging nearby, you could swing down to attack the sheriff's men below (I've clearly seen too many versions of Robin Hood movies over the years).
Grelber
20thmaine 28 Jan 2022 5:23 p.m. PST
Good pick.
I've visited a few times and each time I've thought "I have to model this".
It's perfect – the mix of architecture and everything snugly fitting together on a relatively small plot of land.
AussieAndy 28 Jan 2022 10:47 p.m. PST
Loved our visit. While castles are great to visit, a fortified manor house is a lot more unusual and perhaps more interesting. Would love to see a model.
Huscarle 29 Jan 2022 2:13 a.m. PST
Tried to visit many years ago when we were walking Offa's Dyke, but it was unfortunately shut for the day. We didn't have a lot of luck with castles on that walking holiday as we also went over to Rhuddlan, and it was shut for renovation work. At least we got to get into Manorbier castle at the end of the holiday
Warspite1 29 Jan 2022 4:43 a.m. PST
@all:
I am glad you liked it. I originally posted those pictures in 2008 but, mysteriously, they had disappeared from Flickr.
Still one of the 'dinkiest' little castles and a treat to behold in my book!
Darrell B D Day 29 Jan 2022 4:46 a.m. PST
Used to pass by regularly when I lived in Herefordshire and it was always a treat to see.
I remember trading at a show in Shrewsbury some time in the early noughties and someone had made a gorgeous model of it. I wonder what happened to that model.
DBDD
SHaT1984 29 Jan 2022 8:00 a.m. PST
Both amazing and bizarre~ never seen anything quite like this.
I only spent a month in UK way back when… so apaet from
'thr Tower' I saw verlittle outside the mainstream attractions.
More on the other side of the channel where I spent the remaining 6 months of tour and research!
thanks for great pics! dave-
Midlander65 30 Jan 2022 9:00 a.m. PST
Those are very good photos. I completely agree: it is lovely place to visit and ideal inspiration for modelling a fortified manor / small castle.
It seems to be popular.
OSCS74 30 Jan 2022 7:53 p.m. PST
Thanks for posting your great pictures.
KeepYourPowderDry 31 Jan 2022 8:47 a.m. PST
Thanks for the pictures. On my list of places to visit (and has been for a long time)
Warspite1 01 Feb 2022 7:48 a.m. PST
For those that did not spot it, this Stokesay picture may have a story to tell.
The arrow loop has clearly been rounded to make an embrasure for a handgun, heavy handgun (wall piece) or musket.
This may have happened in the Medieval period but is more likely to have happened during the English Civil War.
Stoppage 06 Feb 2022 8:30 a.m. PST
Aha! The last picture shows what the randomly placed pieces of stone projecting from the walls were for!


text:
package org.apache.thrift.server;

import java.io.IOException;
import java.nio.ByteBuffer;
import java.nio.channels.SelectionKey;
import java.nio.channels.Selector;
import java.nio.channels.spi.SelectorProvider;
import java.util.HashSet;
import java.util.Set;
import java.util.concurrent.atomic.AtomicLong;
import org.apache.thrift.TAsyncProcessor;
import org.apache.thrift.TByteArrayOutputStream;
import org.apache.thrift.TException;
import org.apache.thrift.protocol.TProtocol;
import org.apache.thrift.transport.TIOStreamTransport;
import org.apache.thrift.transport.TMemoryInputTransport;
import org.apache.thrift.transport.TNonblockingServerTransport;
import org.apache.thrift.transport.TNonblockingTransport;
import org.apache.thrift.transport.TTransport;
import org.apache.thrift.transport.TTransportException;
import org.apache.thrift.transport.layered.TFramedTransport;
import org.slf4j.Logger;
import org.slf4j.LoggerFactory;

/** Provides common methods and classes used by nonblocking TServer implementations. */
public abstract class AbstractNonblockingServer extends TServer {
  protected final Logger LOGGER = LoggerFactory.getLogger(getClass().getName());

  public abstract static class AbstractNonblockingServerArgs<
          T extends AbstractNonblockingServerArgs<T>>
      extends AbstractServerArgs<T> {
    public long maxReadBufferBytes = 256 * 1024 * 1024;

    public AbstractNonblockingServerArgs(TNonblockingServerTransport transport) {
      super(transport);
      transportFactory(new TFramedTransport.Factory());
    }
  }

  /**
   * The maximum amount of memory we will allocate to client IO buffers at a time. Without this
   * limit, the server will gladly allocate client buffers right into an out of memory exception,
   * rather than waiting.
   */
  final long MAX_READ_BUFFER_BYTES;

  /** How many bytes are currently allocated to read buffers. */
  final AtomicLong readBufferBytesAllocated = new AtomicLong(0);

  public AbstractNonblockingServer(AbstractNonblockingServerArgs args) {
    super(args);
    MAX_READ_BUFFER_BYTES = args.maxReadBufferBytes;
  }

  /** Begin accepting connections and processing invocations. */
  public void serve() {
    // start any IO threads
    if (!startThreads()) {
      return;
    }

    // start listening, or exit
    if (!startListening()) {
      return;
    }

    setServing(true);

    // this will block while we serve
    waitForShutdown();

    setServing(false);

    // do a little cleanup
    stopListening();
  }

  /**
   * Starts any threads required for serving.
   *
   * @return true if everything went ok, false if threads could not be started.
   */
  protected abstract boolean startThreads();

  /** A method that will block until when threads handling the serving have been shut down. */
  protected abstract void waitForShutdown();

  /**
   * Have the server transport start accepting connections.
   *
   * @return true if we started listening successfully, false if something went wrong.
   */
  protected boolean startListening() {
    try {
      serverTransport_.listen();
      return true;
    } catch (TTransportException ttx) {
      LOGGER.error("Failed to start listening on server socket!", ttx);
      return false;
    }
  }

  /** Stop listening for connections. */
  protected void stopListening() {
    serverTransport_.close();
  }

  /**
   * Perform an invocation. This method could behave several different ways - invoke immediately
   * inline, queue for separate execution, etc.
   *
   * @return true if invocation was successfully requested, which is not a guarantee that invocation
   *     has completed. False if the request failed.
   */
  protected abstract boolean requestInvoke(FrameBuffer frameBuffer);

  /**
   * An abstract thread that handles selecting on a set of transports and {@link FrameBuffer
   * FrameBuffers} associated with selected keys corresponding to requests.
   */
  protected abstract class AbstractSelectThread extends Thread {
    protected Selector selector;

    // List of FrameBuffers that want to change their selection interests.
    protected final Set<FrameBuffer> selectInterestChanges = new HashSet<FrameBuffer>();

    public AbstractSelectThread() throws IOException {
      this.selector = SelectorProvider.provider().openSelector();
    }

    /** If the selector is blocked, wake it up. */
    public void wakeupSelector() {
      selector.wakeup();
    }

    /**
     * Add FrameBuffer to the list of select interest changes and wake up the selector if it's
     * blocked. When the select() call exits, it'll give the FrameBuffer a chance to change its
     * interests.
     */
    public void requestSelectInterestChange(FrameBuffer frameBuffer) {
      synchronized (selectInterestChanges) {
        selectInterestChanges.add(frameBuffer);
      }
      // wakeup the selector, if it's currently blocked.
      selector.wakeup();
    }

    /**
     * Check to see if there are any FrameBuffers that have switched their interest type from read
     * to write or vice versa.
     */
    protected void processInterestChanges() {
      synchronized (selectInterestChanges) {
        for (FrameBuffer fb : selectInterestChanges) {
          fb.changeSelectInterests();
        }
        selectInterestChanges.clear();
      }
    }

    /**
     * Do the work required to read from a readable client. If the frame is fully read, then invoke
     * the method call.
     */
    protected void handleRead(SelectionKey key) {
      FrameBuffer buffer = (FrameBuffer) key.attachment();
      if (!buffer.read()) {
        cleanupSelectionKey(key);
        return;
      }

      // if the buffer's frame read is complete, invoke the method.
      if (buffer.isFrameFullyRead()) {
        if (!requestInvoke(buffer)) {
          cleanupSelectionKey(key);
        }
      }
    }

    /** Let a writable client get written, if there's data to be written. */
    protected void handleWrite(SelectionKey key) {
      FrameBuffer buffer = (FrameBuffer) key.attachment();
      if (!buffer.write()) {
        cleanupSelectionKey(key);
      }
    }

    /** Do connection-close cleanup on a given SelectionKey. */
    protected void cleanupSelectionKey(SelectionKey key) {
      // remove the records from the two maps
      FrameBuffer buffer = (FrameBuffer) key.attachment();
      if (buffer != null) {
        // close the buffer
        buffer.close();
      }
      // cancel the selection key
      key.cancel();
    }
  } // SelectThread

  /** Possible states for the FrameBuffer state machine. */
  private enum FrameBufferState {
    // in the midst of reading the frame size off the wire
    READING_FRAME_SIZE,
    // reading the actual frame data now, but not all the way done yet
    READING_FRAME,
    // completely read the frame, so an invocation can now happen
    READ_FRAME_COMPLETE,
    // waiting to get switched to listening for write events
    AWAITING_REGISTER_WRITE,
    // started writing response data, not fully complete yet
    WRITING,
    // another thread wants this framebuffer to go back to reading
    AWAITING_REGISTER_READ,
    // we want our transport and selection key invalidated in the selector
    // thread
    AWAITING_CLOSE
  }

  /**
   * Class that implements a sort of state machine around the interaction with a client and an
   * invoker. It manages reading the frame size and frame data, getting it handed off as wrapped
   * transports, and then the writing of response data back to the client. In the process it manages
   * flipping the read and write bits on the selection key for its client.
   */
  public class FrameBuffer {
    private final Logger LOGGER = LoggerFactory.getLogger(getClass().getName());

    // the actual transport hooked up to the client.
    protected final TNonblockingTransport trans_;

    // the SelectionKey that corresponds to our transport
    protected final SelectionKey selectionKey_;

    // the SelectThread that owns the registration of our transport
    protected final AbstractSelectThread selectThread_;

    // where in the process of reading/writing are we?
    protected FrameBufferState state_ = FrameBufferState.READING_FRAME_SIZE;

    // the ByteBuffer we'll be using to write and read, depending on the state
    protected ByteBuffer buffer_;

    protected final TByteArrayOutputStream response_;

    // the frame that the TTransport should wrap.
    protected final TMemoryInputTransport frameTrans_;

    // the transport that should be used to connect to clients
    protected final TTransport inTrans_;

    protected final TTransport outTrans_;

    // the input protocol to use on frames
    protected final TProtocol inProt_;

    // the output protocol to use on frames
    protected final TProtocol outProt_;

    // context associated with this connection
    protected final ServerContext context_;

    public FrameBuffer(
        final TNonblockingTransport trans,
        final SelectionKey selectionKey,
        final AbstractSelectThread selectThread)
        throws TTransportException {
      trans_ = trans;
      selectionKey_ = selectionKey;
      selectThread_ = selectThread;
      buffer_ = ByteBuffer.allocate(4);

      frameTrans_ = new TMemoryInputTransport();
      response_ = new TByteArrayOutputStream();
      inTrans_ = inputTransportFactory_.getTransport(frameTrans_);
      outTrans_ = outputTransportFactory_.getTransport(new TIOStreamTransport(response_));
      inProt_ = inputProtocolFactory_.getProtocol(inTrans_);
      outProt_ = outputProtocolFactory_.getProtocol(outTrans_);

      if (eventHandler_ != null) {
        context_ = eventHandler_.createContext(inProt_, outProt_);
      } else {
        context_ = null;
      }
    }

    /**
     * Give this FrameBuffer a chance to read. The selector loop should have received a read event
     * for this FrameBuffer.
     *
     * @return true if the connection should live on, false if it should be closed
     */
    public boolean read() {
      if (state_ == FrameBufferState.READING_FRAME_SIZE) {
        // try to read the frame size completely
        if (!internalRead()) {
          return false;
        }

        // if the frame size has been read completely, then prepare to read the
        // actual frame.
        if (buffer_.remaining() == 0) {
          // pull out the frame size as an integer.
          int frameSize = buffer_.getInt(0);
          if (frameSize <= 0) {
            LOGGER.error(
                "Read an invalid frame size of "
                    + frameSize
                    + ". Are you using TFramedTransport on the client side?");
            return false;
          }

          // if this frame will always be too large for this server, log the
          // error and close the connection.
          if (frameSize > trans_.getMaxFrameSize()) {
            LOGGER.error(
                "Read a frame size of "
                    + frameSize
                    + ", which is bigger than the maximum allowable frame size "
                    + trans_.getMaxFrameSize()
                    + " for ALL connections.");
            return false;
          }

          // if this frame will push us over the memory limit, then return.
          // with luck, more memory will free up the next time around.
          if (readBufferBytesAllocated.get() + frameSize > MAX_READ_BUFFER_BYTES) {
            return true;
          }

          // increment the amount of memory allocated to read buffers
          readBufferBytesAllocated.addAndGet(frameSize + 4);

          // reallocate the readbuffer as a frame-sized buffer
          buffer_ = ByteBuffer.allocate(frameSize + 4);
          buffer_.putInt(frameSize);

          state_ = FrameBufferState.READING_FRAME;
        } else {
          // this skips the check of READING_FRAME state below, since we can't
          // possibly go on to that state if there's data left to be read at
          // this one.
          return true;
        }
      }

      // it is possible to fall through from the READING_FRAME_SIZE section
      // to READING_FRAME if there's already some frame data available once
      // READING_FRAME_SIZE is complete.

      if (state_ == FrameBufferState.READING_FRAME) {
        if (!internalRead()) {
          return false;
        }

        // since we're already in the select loop here for sure, we can just
        // modify our selection key directly.
        if (buffer_.remaining() == 0) {
          // get rid of the read select interests
          selectionKey_.interestOps(0);
          state_ = FrameBufferState.READ_FRAME_COMPLETE;
        }

        return true;
      }

      // if we fall through to this point, then the state must be invalid.
      LOGGER.error("Read was called but state is invalid (" + state_ + ")");
      return false;
    }

    /** Give this FrameBuffer a chance to write its output to the final client. */
    public boolean write() {
      if (state_ == FrameBufferState.WRITING) {
        try {
          if (trans_.write(buffer_) < 0) {
            return false;
          }
        } catch (TTransportException e) {
          LOGGER.warn("Got an Exception during write", e);
          return false;
        }

        // we're done writing. now we need to switch back to reading.
        if (buffer_.remaining() == 0) {
          prepareRead();
        }
        return true;
      }

      LOGGER.error("Write was called, but state is invalid (" + state_ + ")");
      return false;
    }

    /** Give this FrameBuffer a chance to set its interest to write, once data has come in. */
    public void changeSelectInterests() {
      switch (state_) {
        case AWAITING_REGISTER_WRITE:
          // set the OP_WRITE interest
          selectionKey_.interestOps(SelectionKey.OP_WRITE);
          state_ = FrameBufferState.WRITING;
          break;
        case AWAITING_REGISTER_READ:
          prepareRead();
          break;
        case AWAITING_CLOSE:
          close();
          selectionKey_.cancel();
          break;
        default:
          LOGGER.error("changeSelectInterest was called, but state is invalid ({})", state_);
      }
    }

    /** Shut the connection down. */
    public void close() {
      // if we're being closed due to an error, we might have allocated a
      // buffer that we need to subtract for our memory accounting.
      if (state_ == FrameBufferState.READING_FRAME
          || state_ == FrameBufferState.READ_FRAME_COMPLETE
          || state_ == FrameBufferState.AWAITING_CLOSE) {
        readBufferBytesAllocated.addAndGet(-buffer_.array().length);
      }
      trans_.close();
      if (eventHandler_ != null) {
        eventHandler_.deleteContext(context_, inProt_, outProt_);
      }
    }

    /** Check if this FrameBuffer has a full frame read. */
    public boolean isFrameFullyRead() {
      return state_ == FrameBufferState.READ_FRAME_COMPLETE;
    }

    /**
     * After the processor has processed the invocation, whatever thread is managing invocations
     * should call this method on this FrameBuffer so we know it's time to start trying to write
     * again. Also, if it turns out that there actually isn't any data in the response buffer, we'll
     * skip trying to write and instead go back to reading.
     */
    public void responseReady() {
      // the read buffer is definitely no longer in use, so we will decrement
      // our read buffer count. we do this here as well as in close because
      // we'd like to free this read memory up as quickly as possible for other
      // clients.
      readBufferBytesAllocated.addAndGet(-buffer_.array().length);

      if (response_.len() == 0) {
        // go straight to reading again. this was probably an oneway method
        state_ = FrameBufferState.AWAITING_REGISTER_READ;
        buffer_ = null;
      } else {
        buffer_ = ByteBuffer.wrap(response_.get(), 0, response_.len());

        // set state that we're waiting to be switched to write. we do this
        // asynchronously through requestSelectInterestChange() because there is
        // a possibility that we're not in the main thread, and thus currently
        // blocked in select(). (this functionality is in place for the sake of
        // the HsHa server.)
        state_ = FrameBufferState.AWAITING_REGISTER_WRITE;
      }
      requestSelectInterestChange();
    }

    /** Actually invoke the method signified by this FrameBuffer. */
    public void invoke() {
      frameTrans_.reset(buffer_.array());
      response_.reset();

      try {
        if (eventHandler_ != null) {
          eventHandler_.processContext(context_, inTrans_, outTrans_);
        }
        processorFactory_.getProcessor(inTrans_).process(inProt_, outProt_);
        responseReady();
        return;
      } catch (TException te) {
        LOGGER.warn("Exception while invoking!", te);
      } catch (Throwable t) {
        LOGGER.error("Unexpected throwable while invoking!", t);
      }
      // This will only be reached when there is a throwable.
      state_ = FrameBufferState.AWAITING_CLOSE;
      requestSelectInterestChange();
    }

    /**
     * Perform a read into buffer.
     *
     * @return true if the read succeeded, false if there was an error or the connection closed.
     */
    private boolean internalRead() {
      try {
        return trans_.read(buffer_) >= 0;
      } catch (TTransportException e) {
        LOGGER.warn("Got an Exception in internalRead", e);
        return false;
      }
    }

    /** We're done writing, so reset our interest ops and change state accordingly. */
    private void prepareRead() {
      // we can set our interest directly without using the queue because
      // we're in the select thread.
      selectionKey_.interestOps(SelectionKey.OP_READ);
      // get ready for another go-around
      buffer_ = ByteBuffer.allocate(4);
      state_ = FrameBufferState.READING_FRAME_SIZE;
    }

    /**
     * When this FrameBuffer needs to change its select interests and execution might not be in its
     * select thread, then this method will make sure the interest change gets done when the select
     * thread wakes back up. When the current thread is this FrameBuffer's select thread, then it
     * just does the interest change immediately.
     */
    protected void requestSelectInterestChange() {
      if (Thread.currentThread() == this.selectThread_) {
        changeSelectInterests();
      } else {
        this.selectThread_.requestSelectInterestChange(this);
      }
    }
  } // FrameBuffer

  public class AsyncFrameBuffer extends FrameBuffer {
    public AsyncFrameBuffer(
        TNonblockingTransport trans, SelectionKey selectionKey, AbstractSelectThread selectThread)
        throws TTransportException {
      super(trans, selectionKey, selectThread);
    }

    public TProtocol getInputProtocol() {
      return inProt_;
    }

    public TProtocol getOutputProtocol() {
      return outProt_;
    }

    public void invoke() {
      frameTrans_.reset(buffer_.array());
      response_.reset();

      try {
        if (eventHandler_ != null) {
          eventHandler_.processContext(context_, inTrans_, outTrans_);
        }
        ((TAsyncProcessor) processorFactory_.getProcessor(inTrans_)).process(this);
        return;
      } catch (TException te) {
        LOGGER.warn("Exception while invoking!", te);
      } catch (Throwable t) {
        LOGGER.error("Unexpected throwable while invoking!", t);
      }
      // This will only be reached when there is a throwable.
      state_ = FrameBufferState.AWAITING_CLOSE;
      requestSelectInterestChange();
    }
  }
}

redpajama_set_name: RedPajamaGithub


text:
The Burning of the Library of Alexandria
The loss of the ancient world's single greatest archive of knowledge, the Library of Alexandria, has been lamented for ages. But how and why it was lost is still a mystery. The mystery exists not for lack of suspects but from an excess of them.
The Development of Union Strategy
This article explores the strategic environment facing Lincoln in 1860-61, and his development of Union strategy to suppress the rebellion.
The Duchy of Burgundy, Medieval Powerhouse
During the fourteenth century the French State was not cohesive and united. The existence of pseudo independent principalities created conflict and instability. The most powerful of these principalities was the duchy of Burgundy located between France and the German Empire.
The Early Civil War Perspectives of an Illinois Soldier as Reflected in His Letters: Galesburg to Vicksburg.
This essay provides a window into the thoughts, perspectives, attitudes and opinions of a soldier who fought in the war and left a legacy of twelve unpublished letters - letters that are probably unread outside his family. This collection of correspondence provides a wealth of materials for students of the war over 130 years later.
The Escape of the Harriet Lane through the Union blockade of Galveston.
My Grandfather's account of the escape of the Harriet Lane through the Union blockade of Galveston. The letter is addressed to "Friend Phillips" the then editor of the North Adams Transcript, North Adams, Massachusetts.
The Evolution of US Army Tactical Doctrine, 1946-1976
Chapter Seven from Evolution of U.S. Army Tactical Doctrine discusses how army tactics in Vietnam changed from the way the army fought previous wars.
The Fighting Ellets: Ingenuity, Courage, Nepotism and Corruption?
In early 1862, the Union forces operating along the Mississippi River faced a potentially grave new threat from Confederate ironclads. Major General Charles Halleck, in command of the Department of Missouri in St. Louis, sent an urgent request to Secretary of War Edwin Stanton requesting assistance. Stanton had just the man to solve Halleck's problem.
Simone J. Pace's story about Jack Lucas, tthe only high school freshman to hold the Medal of Honor.
The Greatest Inventions In The Past 1000 Years
What where the greatest inventions of the past millennium?
The Handsome Young Irishman of the 95th IL Infantry
The Life of Jennie Hodgers


5.1 What if I was Willful?
5.3 I Knew I Should have Filed Tax Returns, but Did not Know About FATCA or FBAR?
5.4 What if the IRS disagrees with Me and Believes I was Willful?
5.5 Is there an Attorney-Client Privilege with a Non-Attorney?
5.6 My CPA told me there is a Privilege?
5.7 Which Three (3) Years of Tax Returns do I have to Amend?
5.8 Is it True I can still be Audited for the Prior 3 years of Tax Returns?
5.9 On my Original Schedule B I Indicated I had no Foreign Accounts?
5.10 So if I marked No on Schedule B, I may still Qualify for Streamlined?
5.11 I received a FATCA Letter, now what?
5.12 What if I Do Not Respond to the FATCA Letter?
5.13 What if I have an Unreported Foreign Gift (Form 3520)?
5.14 What if I Failed to Report a Foreign Trust (Form 3520-A)?
5.16 I have a PFIC and/or Foreign Mutual Fund that I never Reported (Form 8621)?
5.18 I do not Have to Pay Tax on These Accounts Overseas?
5.19 I already Paid Taxes on These Earnings Overseas?
5.20 Are There Penalties on the Outstanding Tax Liability?
5.21 How is the 5% Penalty Calculated?
5.22 I live Overseas, Do I Qualify for the IRS Penalty Waiver?
5.23 Is my Foreign Real Estate Calculated into the Equation?
5.24 What Type of Accounts Must be Reported?
5.25 Must Foreign Insurance Policies be Reported?
5.26 What if I am Under IRS Audit or Examination?
5.27 What is a Reasonable Cause Statement?
5.28 But I have no tax liability?
5.30 Does my Foreign Inheritance Count Toward the Penalty?
5.31 Do I Receive Criminal Protection under the Streamlined Program?
Streamlined Domestic Offshore Procedures: "IRS Streamlined Domestic" is for U.S. Resident Taxpayers who have not reported Foreign Accounts, Income, Investments or Assets to the Internal Revenue Service.
For many taxpayers, the domestic version of the Streamlined Offshore Procedures (SDOP) may be a good option.
SDOP is an IRS program designed for individuals who were non-willful and meet the other filing requirements. And, as the IRS continues to increase enforcement of offshore tax related issues (as well as issuing fines and penalties against individuals out of compliance) the number of people entering the program continues to grow.
One of the most common questions we receive daily is regarding penalties – specifically, how is the Streamlined Domestic Offshore Procedures Penalty calculated?
Here is a Brief Summary (But please keep in mind that you should consult with an experienced Offshore Disclosure Attorney when making proactive representations to the IRS, and there is no attorney-client privilege with a CPA).
1st: Compile the 12/31 balances on your Foreign Accounts, Insurance Policies and other 8938/FBAR qualified accounts for each year within the compliance period.
2nd: Determine the proper exchange rate for each year (For example: You cannot use the current exchange rate in 2017, for your 2013 accounts — sorry for those of you with accounts in Euros or Rupees).
3rd: Total the 12/31 balances on your previously unreported Foreign Accounts, Insurance Policies and other 8938/FBAR qualified accounts (Value of Real Estate is not included for the Streamlined Program).
4th: Pick the Year that has the highest 12/31 balance (not highest max year balance, which is the standard for OVDP).
5th: Multiply the above-value by 5%.
Example: Michael's highest year 12/31 aggregate balance in the six (6) year compliance period is 2013. In 2013 his 12/31 balances totaled $2,600,000. His penalty would be $130,000.
For example, if you literally had no idea that foreign accounts needed to be reported, and your actions, behavior, and history shows that you did not access the foreign accounts, withdraw any money from them, etc., then chances are you will be able to show you were non-willful.
Did your CPA or EA send you questions in writing asking about Foreign Accounts or Income?
*If you were willful, then you should never submit to the Streamlined Program. Unfortunately, there has been an influx of inexperienced attorneys who will prey upon you, and convince you to go streamlined instead of OVDP. They will make it seem that if you only have a small amount of income, or were only noncompliant for a few years, that you can still go streamlined.
Do I Include Closed Foreign Accounts on FATCA Form 8938?Streamlined Offshore Disclosure – Do I Amend Three Years of Tax Returns?


text:
Q: How to push objectId to mongodb schema field array of object using findByIdAndUpdate Everytime I hit api I am getting same error-
I have tried sending value as parameters also but failed. Any help would be appreciated. When i use $set it updates same value everytime the web service is called but it does work but not with $push.
MongoError: The field 'songId' must be an array but is of type objectId in document
 {_id: ObjectId('59709590380026118c22dd61')}

My Playlist schema code:-
var PlaylistSchema = new mongoose.Schema({
  name: String,
  coverphoto: { type: String, default: '' },
  userId: {
    type: ObjectId,
    ref: 'User'
  },
  songId: [{ type: ObjectId, ref: 'Song' }],
  updated_at: { type: Date, default: Date.now },
});

my Song Schema code
var mongoose = require('mongoose');
var Schema = mongoose.Schema,
ObjectId = Schema.ObjectId;

var SongSchema = new mongoose.Schema({
  audioName:{type:String,default:''},
  title: String,
  // coverphoto: { type: String, default: '' },
  singer: { type: String, default: '' },
  movie: { type: String, default: '' },
  album: { type: String, default: '' },
  lyricist: { type: String, default: '' },
  actors: { type: String, default: '' },
  lyrics: { type: String, default: '' },
  genre: { type: String, default: 'Random' },
  duration: { type: String, default: '' },
  size: { type: String, default: '' },
  userId: {
    type: ObjectId,
    ref: 'User'
  },
  categoryId: {
    type: ObjectId,
    ref: 'Category'
  },
  updated_at: { type: Date, default: Date.now },
});

module.exports = mongoose.model('Song', SongSchema);

My Api code
/* post api to add song in playlist */
router.post('/addSongToPlaylist', function (req, res, next) {
  Playlist.findOne({ '_id': req.body.playlistId }, function (err, playlist) {

    if (err) return next(err);

    console.log(playlist)
    console.log("req.body.songId", req.body.songId);
    if (playlist) {
      Playlist.findByIdAndUpdate(
         req.body.playlistId,
          { $push: { "songId": req.body.songId } },
          { new: true },
          function (err, playlistData) {
              if (err) return next(err);
              res.json({ message: 'New Song added successfully', playlist: playlistData, success: true });
          });
    } else if (!Song) {
      res.json({ message: 'Failed to add song', success: false });
    }

  });
});

redpajama_set_name: RedPajamaStackExchange