text:
I got a kick out of Rohan's comment on my previous blog (How do you define DFM?). It is too easy to assume that anyone knows what you are talking about when you say DFM. Just because everyone has been talking about it doesn't mean any of them know what they are talking about.
You could probably infer from my approach to the previous blog that my background is primarily on the manufacturing side. I was responsible for yield and reliability improvement in the wafer fab. We measured yield and reliability by counting the difference between the total number of die (chips) that we started at the beginning of the manufacturing process vs the number of die that passed a series of electrical and physical tests at the end of the process. You can measure this as a percentage, but this is misleading because different designs have different die sizes which builds in a bias towards large die sizes yielding lower. It is simply a matter that big die have more surface area and circuit content so they have a higher chance of getting impacted by any particular issue than a small die. Because of this issue, a metric called Defect Density (Dd or D0) is used to normalize yield across different die sizes. The chart below shows the expected yield by die size for a specified Dd. For a given die size you can predict the percent yield assuming a exposure to a constant fab defect rate.
This Dd provides a very simple single measurement to track yield across product lines. It also provides a convenient hammer for management to beat you with:) However, making the numbers get better is a whole different ball game. With hundreds of process steps from beginning to end, it is like chasing cats trying to tune out and control all the variation. That is why we were so focused on measuring data at every step along the way.
The thing that ultimately led to my transition into EDA was that we began to notice that some designs didn't follow this curve. In the following chart you can see some of the data from my previous life in which we plotted a wide assortment of our designs on this curve. Each point on the chart represents the yield for a given "lot" of wafers (25 wafers) run through the fab.
You can see in the chart that products 1,2 & 3 have very similar die sizes but dramatically different average yields compared to each other even though they were running on the same process in the same fab at the same time. They yield consistently but differently. Clearly, something was fundamentally different between them that make product 3 much more sensitive to the fab issues than product 2. Also note product 7. It yielded very inconsistently from lot to lot. In other words, slight variation differences from one process run to the next would have dramatic effects on its yield. You can't blame these problems on the fab because they all got the same process and the other products fit the curve as they should.
The take away for the non-PhD is that design can make a difference on yield and just passing DRC, LVS & timing does not account for this difference . The trick is figuring out what variations in design lead to these variations and determining ways of eliminating these variations. The process, tools and methods for doing this are DFM. In my next blogs I will discuss how this manifest itself in reliability problems as well and the various types of design variations that cause these issues.


text:
- About this Journal ·
- Abstracting and Indexing ·
- Advance Access ·
- Aims and Scope ·
- Annual Issues ·
- Article Processing Charges ·
- Articles in Press ·
- Author Guidelines ·
- Bibliographic Information ·
- Citations to this Journal ·
- Contact Information ·
- Editorial Board ·
- Editorial Workflow ·
- Free eTOC Alerts ·
- Publication Ethics ·
- Reviewers Acknowledgment ·
- Submit a Manuscript ·
- Subscription Information ·
- Table of Contents
Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 954602, 8 pages
Cytotoxic CD4 T Cells in Antiviral Immunity
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Received 2 July 2011; Accepted 9 September 2011
Academic Editor: Julie Curtsinger
Copyright © 2011 Nikki B. Marshall and Susan L. Swain. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
CD4 T cells that acquire cytotoxic phenotype and function have been repeatedly identified in humans, mice, and other species in response to many diverse pathogens. Since CD4 cytotoxic T cells are able to recognize antigenic determinants unique from those recognized by the parallel CD8 cytotoxic T cells, they can potentially contribute additional immune surveillance and direct effector function by lysing infected or malignant cells. Here, we briefly review much of what is known about the generation of cytotoxic CD4 T cells and describe our current understanding of their role in antiviral immunity. Furthering our understanding of the many roles of CD4 T cells during an anti-viral response is important for developing effective vaccine strategies that promote long-lasting protective immunity.
1. Introduction
CD4 T cells are well known for their helper roles including those that promote antibody class switching, enhancing the development of cytotoxic T lymphocyte (CTL) activity of CD8 T cells and their ability to be functional memory cells, as well as inducing the phagocytic activity of innate immune cells to name a few (Figure 1). To perform these important roles, CD4 T cells differentiate into unique effector helper subsets characterized by their expression of specific cytokines and transcription factors as outlined in Figure 2. A lesserknown role for CD4 T cells, however, is their ability to acquire cytotoxic activity and directly kill infected, transformed, or allogeneic MHC class II+ (class II) cells. Cytotoxic CD4 T cells (ThCTL) identified by cytotoxic phenotype and/or function have been repeatedly identified over the past three decades and shown to recognize a diversity of pathogens. ThCTL were once thought to be an anomaly associated with long-term in-vitro culturing of CD4 T cell lines and clones generated from both humans [1–4] and mice [5, 6]. However, ThCTL have also been identified in the peripheral blood mononuclear cells (PBMCs) of humans seropositive for chronic viral infections including human cytomegalovirus (HCMV) [7–10], hepatitis viruses [11], and human immunodeficiency virus 1 (HIV-1) [7, 12, 13]. ThCTL have also been identified in mice infected with chronic viruses including lymphocytic choriomeningitis virus (LCMV) [14] and gamma-herpes virus [15]. The generation of ThCTL, however, is not just restricted to conditions of chronic antigen stimulation or chronic viral stimulation, as we have also identified ThCTL in the lungs of mice 7 days following primary infection with influenza virus A (unpublished results). Despite these observations, there is still much we do not know about ThCTL, including the specific events that occur during infection that induce the acquisition of cytotoxic function, and whether ThCTL can play a significant protective role during an antiviral immune response. In particular, we can postulate that ThCTL could aid in viral clearance and the fact that they and CD8 T cells recognize distinct epitopes could make selection of viral variants much less likely. Moreover, ThCTL may have different properties that make them less inflammatory including a faster contraction and secretion of cytokines and chemokines that promote repair, although this has not been established. As we analyze the potential of ThCTL to enhance antiviral immunity, we will want to evaluate these possibilities.
2. Class II-Restricted Cytotoxic Activity
Unlike CD8 CTL that recognize cognate antigen in the context of ubiquitously expressed MHC class I molecules, the cytotoxic function of ThCTL is restricted to class II antigen-presenting cells (APCs) such as the professional APCs that include dendritic cells, macrophages, and B cells, as well as a number of infected tissue types. One of the most extensively studied ThCTL subsets in humans are those generated against Epstein Barr Virus (EBV), a herpes virus typically harbored in latent form by B cells. ThCTL have been found to recognize both lytic and latent EBV class II antigens presented by conventional and transformed B cells [16–19]. ThCTL have also been identified in HIV-1 seropositive individuals [7, 12], a lentivirus that infects professional APCs and CD4 T cells that can also express class II upon activation in humans but not in mice [20–22]. CD4 T cell clones from macaques infected with another lentivirus, Simian immunodeficiency virus (SIV), were found to eliminate SIV-infected macrophages but not infected CD4 T cells in-vitro [23]. Also, CD4 T cells from the PBMCs of individuals vaccinated against poliovirus were shown to kill poliovirus-infected macrophages and dendritic cells [24]. Other nonprofessional APCs that harbor viruses and support their replication can also express class II such as the epithelial cells that line the respiratory tract that are infected by viruses such as influenza and parainfluenza, as well as endothelial cells and glial cells which can harbor CMV. ThCTL clones derived from HCMV-seropositive individuals were shown to kill glial cells expressing HCMV glycoprotein B [25] and lympoblastoid cell lines expressing CMV antigen [26].
In-vivo class II-restricted killing has also been demonstrated in virally infected mice. First shown by Jellison et al., splenocytes pulsed with LCMV GP61 class II peptide and not irrelevant peptide were specifically eliminated in LCMV-infected mice [14]. This was also shown for spleen cells pulsed with influenza HA126 peptide in influenza-infected mice [27], and spleen cells pulsed with West Nile Virus (WNV) NS31616 peptide in WNV-infected mice [28]. Taken together, the majority of studies that have measured the cytotoxic activity of ThCTL have either used peptide-pulsed transformed B cells or splenocytes as target cells, hence we still know very little about the diversity of target cell types that human or mouse ThCTL can recognize and kill. Also unknown is whether there are key attributes of infected target cells that promote ThCTL generation and what host and viral factors favor their induction.
3. Role for ThCTL When CD8 CTL Are Impaired
One of the challenges of identifying ThCTL in situ is that they are overshadowed and seemingly inhibited by the presence of CD8 CTL which outnumber them [29, 30]. Thus it is not surprising that ThCTL have also been identified in virally infected mice deficient in, or depleted of, CD8 T cells. Stuller and Flaño showed specific killing of spleen cells pulsed with γHV68 in gamma herpes virus-infected mice depleted of CD8 T cells [15]. In beta-2 microglobulin KO (β2m) mice that lack most class I MHC expression and hence have very few CD8 T cells and NK cells, ThCTL were identified in the respiratory tract during Sendai parainfluenza virus infection [31], and also in β2m mice infected with LCMV [32, 33]. ThCTL can also arise from naïve TCR transgenic CD4 T cells transferred to a lymphopenic host and kill adoptively transferred splenocytes presenting cognate pepide (unpublished results). Moreover, lymphopenia-induced ThCTL have been shown to eradicate melanoma tumors in mice [34, 35], highlighting a potential therapeutic role for ThCTL in antitumor immunity.
ThCTL could also play a role in compensating for age-related decline in CD8 CTL activity or when CD8 CTL activity is impaired. Interestingly, Zhou and McElhaney found that the cytolytic function of influenza-specific CD4 T cells was preserved in aged individuals at least 10 weeks postvaccination, however, the CD8 CTL response was significantly impaired within 4 weeks postvaccination compared to younger individuals [36]. Moreover, ThCTL may be found to play a prominent role in antiviral responses to pathogens that have evolved mechanisms to evade detection by CD8 CTL. Many viruses including HIV-1, HSV, and HCMV employ mechanisms that inhibit normal MHC class I antigen processing and presentation [37, 38], enhancing their ability to evade detection by CD8 CTL. During the latent stage of infection, EBV expresses a limited number of proteins including Epstein-Barr Nuclear Antigen 1 (EBNA1) that is expressed in B cells as well as the EBV-associated malignancy, Burkitt's lymphoma (BL). EBNA1 inhibits its own degradation and translation thus preventing presentation of EBNA1 antigens on MHC class I molecules [39, 40]. Interestingly, EBNA1 does gain access to endogenous MHC class II processing by the process of autophagy [16, 41]. EBNA1 contains a dominant EBV CD4 T cell epitope, and EBNA1-specific ThCTL have been shown to kill BL cells [42, 43]. As ThCTL have been repeatedly described in EBV carriers, one may speculate they play a role in controlling EBV infection, or control the development of EBV-associated malignancies. Interestingly, the loss of EBV-specific functional CD4 T cells has been found to correlate with the development of EBV-associated lymphomas in some individuals [44–46].
4. ThCTL Cytotoxic Effector Mechanisms
The cytotoxic effector mechanisms reported thus far to be utilized by ThCTL are shared with those used by CD8 CTL including cytotoxic granule exocytosis and Fas/Fas ligand- (FasL-) mediated apoptosis. The cytotoxic mechanism considered the dominant mechanism utilized by ThCTL is the directed exocytosis of cytotoxic granules into a target cell to induce apoptosis. Contained within these granules are granzymes that are serine esterases that target various substrates to initiate and mediate cellular apoptosis [47]. The granzymes gain intracellular access into target cells with the help of the protein perforin that polymerizes to form channel pores through the plasma membrane [48]. Perforin-mediated cytolytic activity has been suggested for virus-specific ThCTL clones that recognized peptides derived from EBV latent membrane proteins [49], HIV-1 gag protein [50], poliovirus [24], and dengue virus capsid protein [51]. Granulysin, an enzyme with both cytolytic and antimicrobial properties, is also found in cytotoxic granules in NK cells and activated T cells in humans [52]. Granulysin was found to play an important role in the killing of the yeast Cryptococcus neoformans by ThCTL [53]. No homolog for granulysin has been identified in mouse. The binding of Fas receptor on target cells to FasL expressed on effector cells initiates the formation of a death-inducing signaling complex and induction of target cell apoptosis [54]. Expression of Fas on target cells has been shown to lend them susceptible to lysis by ThCTL [55]. Furthermore, a lack of Fas expression on target cells impairs killing by ThCTL generated in mice infected with LCMV [14, 33] and WNV [28]. A third cytotoxic mechanism we should mention is the induction of apoptosis via the binding of TNF-related apoptosis-inducing ligand (TRAIL) to death receptors DR4 and DR5 expressed on target cells. T cells have been shown to induce apoptosis of bystander cells via this pathway, however, the relevance of this apoptotic pathway for class II-mediated killing is not yet known.
Differential regulation of cytotoxic gene expression in CD8 T cells compared to CD4 T cells has been described. Unlike CD4 T cells, single positive CD8 thymocytes express perforin mRNA transcript [56] and likely maintain this expression once they emigrate out into the periphery, while CD4 T cells require activation through their T cell receptor to induce perforin expression [57, 58]. CD4 T cells also require TCR stimulation to upregulate their expression of granzyme B [59]. We also found that naïve mouse CD8 T cells cultured with IL-2 for 72 hours expressed increased granzyme B protein, however, CD4 T cells required the addition of TCR activation (N. B. Marshall, S. L. Swain; unpublished observations). Thus it is possible that CD8 T cells are better primed for the immediate development of cytotoxic function when in a naïve state, while further stimuli are necessary to convert CD4 T cells into killers. Whether the CTL program in CD4 T cells once activated is maintained into memory has not to our knowledge been reported, but this is clearly of interest. If it is, it would support the concept that the CD4 T cells that become cytotoxic represent a separate polarized functional subset.
5. ThCTL Phenotype
Degranulation is required for perforin- and granzyme-mediated killing of target cells. The core of the cytotoxic granules contains the effector proteins granzymes and perforin; the membrane of the cytotoxic granules contains lysosomal-associated membrane glycoproteins (LAMPs) including CD107a (LAMP-1) and CD107b (LAMP-2) [60]. During degranulation, the granule membranes merge with the outer cellular membrane, thus the transient transfer of LAMP proteins onto the surface of a cell is currently considered to be a marker of degranulation. Nemes et al. found that approximately half of HIV-1 gag-specific CD4 T cells in infected individuals expressed CD107a [61]. Casazza et al. identified CD107a+ perforin+ granzyme+ CD4 T cells in HCMV-seropositive individuals with cytolytic activity [62]. CD107a+ ThCTL have also been identified in mice infected with gamma herpes virus [63] and in mice infected with influenza virus A (unpublished results). ThCTL are thus currently identified by the coexpression of perforin, granzyme B, and surface expression of CD107a. One of the challenges of identifying ThCTL in mice, however, is the lack of a reliable antibody that can be used to stain for perforin expression in mouse cells [58].
In individuals with chronic viral infections, ThCTL have a phenotype consistent with that of differentiated effector T cells including the loss of expression of the TNF receptor family member, CD27, and the costimulatory molecule, CD28. However, CD28neg CD27neg perforin+ ThCTL were identified in the PBMCs of HIV-1 seropositive individuals [12], and in individuals with viral hepatitis [11]. In HCMV-seropositive individuals, ThCTL that expressed granzyme B, perforin, and CD107a were CD27neg and CD28neg [8, 62], and they were further identified to coexpress the killer lectin-like receptor (KLR) NKG2D [9]. Engagement of NKG2D has been shown to activate the cytolytic activity of NK cells and gamma delta T cells [64–66]. A role for NKG2D or other KLRs in ThCTL cytotoxic activity is not yet known. Consistent with the phenotype of ThCTL in humans, ThCTL in mice infected with gamma herpes virus were also found to be CD27neg [15]. EBV-specific CD4 T cells, however, were both CD27+ and CD28+ in EBV-seropositive individuals [67]. We have also found that ThCTL generated in the lungs of mice during primary influenza virus A infection are CD27+/- [68] and CD28+ (unpublished results). Thus the expression of CD27 and CD28 by virus-specific ThCTL is determined by the particular viral response which is also true for CD8 T cells [69]. Also, the anatomical site in which ThCTL are generated may help to determine their unique signature phenotype as is the case for other types of effector CD4 and CD8 T cells. For example, ThCTL generated in the lungs of influenza-infected mice express high levels of CD103, a receptor for epithelial cadherin, which is not expressed by the CD4 T cells found in the spleen and draining lymph nodes (unpublished results). Thus phenotypic variation of ThCTL across different anatomical sites and pathogenic infections is expected.
6. ThCTL Generation
Although CD4 T cells with cytotoxic activity have been identified within Th0- [70–72], Th2- [73, 74], and Treg- [75] effector T cell subsets, ThCTL are most often described as being Th1-like, characterized by the production of IFN-γ or as polyfunctional with production of some combination of the cytokines IFN-γ, TNF-alpha, and IL-2 [8, 12, 28, 49, 51, 62, 76]. Th1-polarized or Th1-like CD4 T cells are known to demonstrate cytotoxic activity [27, 43, 72, 77], however, the expression of these cytokines is not required for their cytotoxic function [14, 27, 31, 63]. Th1-polarizing conditions include the presence of IL-12 and neutralizing anti-IL-4 antibody which, respectively, have been shown to enhance (IL-12) and inhibit (IL-4) cytotoxic activity. IL-12 enhances cytotoxic activity by increasing expression of perforin and granzymes through the activation of STAT4 [78–81]. Conversely, IL-4, which activates STAT6, has been shown to inhibit the cytotoxic activity of in-vitro generated ThCTL [72].
Th1-polarizing conditions, however, are not the optimal conditions for generating ThCTL. CD4 T cells differentiated under Th1-polarizing conditions do express perforin, however, the transcript levels are still >20-times less than that of activated CD8 T cells [82]. The cytotoxic activity of CD4 T cells is further enhanced when polarized under Th0 conditions in the presence of IL-2 [72]. For CD8 CTL, IL-2 has been shown to increase the expression of perforin and granzymes and enhance cytotoxic activity [83, 84]. The activation of STAT5 by IL-2 has been shown to enhance perforin expression in CD8 CTL [85], and also in EBV-specific ThCTL clones [57]. IL-2 also strongly induces the expression of the transcription factor, Eomesodermin (Eomes) [86]. The transcription factors Runx3 and Eomes promote CTL development and are sufficient to induce IFN-gamma, perforin, and granzyme B expression [87, 88]. Eomes was required for the upregulation of granzyme B expression in cytotoxic Th1 cells responding to staphylococcal enterotoxin A in the presence of agonist antibodies to CD134 (OX40) and CD137 (4-1BB) [89]. The requirement for Eomes in ThCTL development and cytotoxic activity is still not yet well established. IL-15, a cytokine structurally similar to IL-2, binds the IL-2/IL-15 beta chain and common gamma chain also activating STAT5 and was recently shown to enhance the expression of granzyme B and perforin in human CD28neg CD4 T cells [90].
By analogy to conditions inducing other T cell subsets, it is likely that in addition to IL-2, other factors will be found to act in concert to promote the development of ThCTL. For example, heat shock protein 70 was shown to induce the cytotoxic activity of CD4 T cells that was further enhanced in the presence of IL-15, as well as IL-12 or IL-7 [91]. Costimulatory pathways may also play a role in inducing optimal ThCTL. Costimulation through OX-40 and 4-1BB was recently found to enhance the cytotoxic activity of Th1 cells [89]. Antigen dose and persistence may also affect ThCTL generation. In influenza-infected mice, ThCTL are only found in the lung suggesting maximum or repeated antigen stimulation may be necessary. We have also found that low antigen dose favors in-vitro ThCTL generation, but with the addition of exogenous IL-2 [72].
7. Role of ThCTL in Antiviral Activities
There are few studies of the contribution of ThCTL in immune protection. We found that perforin-dependent cytotoxicity played a key role when in-vitro-generated Th1 effectors were introduced into unprimed mice infected with high-dose influenza virus [27]. Moreover, when we analyze the protective mechanisms used by Th1 memory cells, we find that monoclonal memory cells drive the selection of virus variants and that this mechanism is perforin-dependent (T. M. Strutt, K. K. McKinstry, S. L. Swain, unpublished results). Thus CD4-mediated cytotoxicity seems to be one of several key mechanisms that contribute to viral control and elimination. A key complication of the multipronged strategy that CD4 T cells use to combat pathogens is that individual mechanisms may be redundant except when virus titers rise to very high levels. Thus, further studies are needed to define the role of ThCTL in response to different pathogens.
8. Summary
A subset of CD4 T cells can acquire cytotoxic activity during an antiviral immune response and kill target cells presenting cognate viral antigen. A role for ThCTL is highlighted when the generation and/or immune surveillance by CD8 CTL is impaired, which can occur when immune evasion mechanisms are employed by the virus. Furthermore, ThCTL may also play a role in controlling the development of viral-associated malignancies including EBV-associated lymphomas. ThCTL are identified phenotypically by their expression of markers of cytotoxic granule exocytosis including perforin, granzyme B, and surface expression of degranulation marker, CD107a. We still know little about the factors necessary to generate ThCTL, although TCR activation is required for the upregulation of granzyme B and perforin expression. The expression of cytotoxic mediators is further enhanced by the addition of cytokines including IL-12, IL-2, and IL-15. Although ThCTL often share characteristics with Th1 cells, there is evidence that Th1-polarizing conditions do not produce optimal killers, thus ThCTL may represent a distinct CD4 T cell effector subset. We propose that CD4 T cell-mediated cytotoxicity is one component of the antiviral arsenal of T cells and will in time be seen as a valuable player in antiviral responses where destruction of target cells is an important aspect of protective immunity.
This work was supported by the National Institutes of Health Grant no. P01AI46530.
- H. Wagner, A. Starzinski-Powitz, H. Jung, and M. Roellinghoff, "Induction of I region-restricted hapten-specific cytotoxic T lymphocytes," Journal of Immunology, vol. 119, no. 4, pp. 1365–1368, 1977. View at Scopus
- C. Feighery and P. Stastny, "HLA-D region-associated determinants serve as targets for human cell-mediated lysis," Journal of Experimental Medicine, vol. 149, no. 2, pp. 485–494, 1979. View at Scopus
- B. Fleischer, "Acquisition of specific cytotoxic activity by human T4+ T lymphocytes in culture," Nature, vol. 308, no. 5957, pp. 365–367, 1984. View at Publisher · View at Google Scholar · View at Scopus
- J. P. Tite and C. A. Janeway Jr, "Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: Ia restriction and cognate vs. noncognate interactions in cytolysis," European Journal of Immunology, vol. 14, no. 10, pp. 878–886, 1984. View at Scopus
- M. M. Maimone, L. A. Morrison, V. L. Braciale, and T. J. Braciale, "Features of target cell lysis by class I and class II MHC-restricted cytolytic T lymphocytes," Journal of Immunology, vol. 137, no. 11, pp. 3639–3643, 1986. View at Scopus
- A. E. Lukacher, L. A. Morrison, and V. L. Braciale, "Malissen B and braciale TJ: expression of specific cytolytic activity by H-21 region-restricted, influenza virus-specific T lymphocyte clones," Journal of Experimental Medicine, vol. 162, no. 1, pp. 171–187, 1985. View at Scopus
- J. J. Zaunders, W. B. Dyer, B. Wang et al., "Identification of circulating antigen-specific CD4+ T lymphocytes with a CCR5+, cytotoxic phenotype in an HIV-1 long-term nonprogressor and in CMV infection," Blood, vol. 103, no. 6, pp. 2238–2247, 2004. View at Publisher · View at Google Scholar · View at Scopus
- E. M. van Leeuwen, E. B. Remmerswaal, M. T. Vossen et al., "Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection," Journal of Immunology, vol. 173, no. 3, pp. 1834–1841, 2004. View at Scopus
- A. Sáez-Borderías, M. Gumá, A. Angulo, B. Bellosillo, D. Pende, and M. López-Botet, "Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus," European Journal of Immunology, vol. 36, no. 12, pp. 3198–3206, 2006. View at Publisher · View at Google Scholar · View at Scopus
- M. A. Suni, S. A. Ghanekar, D. W. Houck et al., "CD4+CD8dim T lymphocytes exhibit enhanced cytokine expression, proliferation and cytotoxic activity in response to HCMV and HIV-1 antigens," European Journal of Immunology, vol. 31, no. 8, pp. 2512–2520, 2001. View at Publisher · View at Google Scholar · View at Scopus
- N. Aslan, C. Yurdaydin, J. Wiegand et al., "Cytotoxic CD4+ T cells in viral hepatitis," Journal of Viral Hepatitis, vol. 13, no. 8, pp. 505–514, 2006. View at Publisher · View at Google Scholar · View at Scopus
- V. Appay, J. J. Zaunders, L. Papagno et al., "Characterization of CD4+ CTLs ex vivo," Journal of Immunology, vol. 168, no. 11, pp. 5954–5958, 2002. View at Scopus
- P. J. Norris, H. F. Moffett, O. O. Yang et al., "Beyond help: direct effector functions of human immunodeficiency virus type 1-specific CD4+ T cells," Journal of Virology, vol. 78, no. 16, pp. 8844–8851, 2004. View at Publisher · View at Google Scholar · View at Scopus
- E. R. Jellison, S. K. Kim, and R. M. Welsh, "Cutting edge: MHC class II-restricted killing in vivo during viral infection," Journal of Immunology, vol. 174, no. 2, pp. 614–618, 2005. View at Scopus
- K. A. Stuller and E. Flaño, "CD4 T cells mediate killing during persistent gammaherpesvirus 68 infection," Journal of Virology, vol. 83, no. 9, pp. 4700–4703, 2009. View at Publisher · View at Google Scholar · View at Scopus
- R. Khanna, S. R. Burrows, P. M. Steigerwald-Mullen, D. J. Moss, M. G. Kurilla, and L. Cooper, "Targeting Epstein-barr virus nuclear antigen 1 (EBNA1) through the class II pathway restores immune recognition by EBNA1-specific cytotoxic T lymphocytes: evidence for HLA-DM-independent processing," International Immunology, vol. 9, no. 10, pp. 1537–1543, 1997. View at Publisher · View at Google Scholar · View at Scopus
- D. Adhikary, U. Behrends, A. Moosmann, K. Witter, G. W. Bornkamm, and J. Mautner, "Control of Epstein-barr virus infection in vitro by T helper cells specific for virion glycoproteins," Journal of Experimental Medicine, vol. 203, no. 4, pp. 995–1006, 2006. View at Publisher · View at Google Scholar · View at Scopus
- E. Landais, X. Saulquin, E. Scotet et al., "Direct killing of Epstein-barr virus (EBV)-infected B cells by CD4 T cells directed against the EBV lytic protein BHRF1," Blood, vol. 103, no. 4, pp. 1408–1416, 2004. View at Publisher · View at Google Scholar · View at Scopus
- H. M. Long, T. A. Haigh, N. H. Gudgeon et al., "CD4+ T-cell responses to Epstein-barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines," Journal of Virology, vol. 79, no. 8, pp. 4896–4907, 2005. View at Publisher · View at Google Scholar · View at Scopus
- T. M. Holling, N. van der Stoep, E. Quinten, and P. J. van den Elsen, "Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III," Journal of Immunology, vol. 168, no. 2, pp. 763–770, 2002. View at Scopus
- H. S. Ko, S. M. Fu, R. J. Winchester, D. T. Yu, and H. G. Kunkel, "Ia determinants on stimulated human T lymphocytes. Occurrence of mitogen- and antigen-activated T cells," Journal of Experimental Medicine, vol. 150, no. 2, pp. 246–255, 1979. View at Scopus
- C. H. Chang, S. C. Hong, C. C. Hughes, C. A. Janeway Jr, and R. A. Flavell, "CIITA activates the expression of MHC class II genes in mouse T cells," International Immunology, vol. 7, no. 9, pp. 1515–1518, 1995. View at Scopus
- J. B. Sacha, J. P. Giraldo-Vela, M. B. Buechler et al., "Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection," Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 24, pp. 9791–9796, 2009. View at Publisher · View at Google Scholar · View at Scopus
- R. Wahid, M. J. Cannon, and M. Chow, "Virus-specific CD4+ and CD8+ cytotoxic T-cell responses and long-term T-cell memory in individuals vaccinated against polio," Journal of Virology, vol. 79, no. 10, pp. 5988–5995, 2005. View at Publisher · View at Google Scholar · View at Scopus
- N. R. Hegde, C. Dunn, D. M. Lewinsohn, M. A. Jarvis, J. A. Nelson, and D. C. Johnson, "Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL," Journal of Experimental Medicine, vol. 202, no. 8, pp. 1109–1119, 2005. View at Publisher · View at Google Scholar · View at Scopus
- E. M. M. van Leeuwen, E. B. M. Remmerswaal, M. H. M. Heemskerk, I. J. M. Ten Berge, and R. A. W. van Lier, "Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection," Blood, vol. 108, no. 9, pp. 3121–3127, 2006. View at Publisher · View at Google Scholar · View at Scopus
- D. M. Brown, A. M. Dilzer, D. L. Meents, and S. L. Swain, "CD4 T cell-mediated protection from lethal influenza: perform and antibody-mediated mechanisms give a one-two punch," Journal of Immunology, vol. 177, no. 5, pp. 2888–2898, 2006. View at Scopus
- J. D. Brien, J. L. Uhrlaub, and J. Nikolich-Zǔgich, "West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection," Journal of Immunology, vol. 181, no. 12, pp. 8568–8575, 2008. View at Scopus
- N. S. Williams and V. H. Engelhard, "Perforin-dependent cytotoxic activity and lymphokine secretion by CD4+ T cells are regulated by CD8+ T cells," Journal of Immunology, vol. 159, no. 5, pp. 2091–2099, 1997. View at Scopus
- I. Bourgault, A. Gomez, E. Gomrad, F. Picard, and J. P. Levy, "A virus-specific CD4+ cell-mediated cytolytic activity revealed by CD8+ cell elimination regularly develops in uncloned human antiviral cell lines," Journal of Immunology, vol. 142, no. 1, pp. 252–256, 1989. View at Scopus
- S. Hou, M. Fishman, K. G. Murti, and P. C. Doherty, "Divergence between cytotoxic effector function and tumor necrosis factor α production for inflammatory CD4+ T cells from mice with Sendai virus pneumonia," Journal of Virology, vol. 67, no. 10, pp. 6299–6302, 1993. View at Scopus
- D. Muller, B. H. Koller, J. L. Whitton, K. E. LaPan, K. K. Brigman, and J. A. Frelinger, "LCMV-specific, class II-restricted cytotoxic T cells in β 2-microglobulin-deficient mice," Science, vol. 255, no. 5051, pp. 1576–1578, 1992. View at Scopus
- A. J. Zajac, D. G. Quinn, P. L. Cohen, and J. A. Frelinger, "Fas-dependent CD4+ cytotoxic T-cell-mediated pathogenesis during virus infection," Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14730–14735, 1996. View at Scopus
- S. A. Quezada, T. R. Simpson, K. S. Peggs et al., "Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts," Journal of Experimental Medicine, vol. 207, no. 3, pp. 637–650, 2010. View at Publisher · View at Google Scholar · View at Scopus
- Y. Xie, A. Akpinarli, C. Maris et al., "Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanoma," Journal of Experimental Medicine, vol. 207, no. 3, pp. 651–667, 2010. View at Publisher · View at Google Scholar · View at Scopus
- X. Zhou and J. E. McElhaney, "Age-related changes in memory and effector T cells responding to influenza A/H3N2 and pandemic A/H1N1 strains in humans," Vaccine, vol. 29, no. 11, pp. 2169–2177, 2011. View at Publisher · View at Google Scholar
- A. Alcami and U. H. Koszinowski, "Viral mechanisms of immune evasion," Immunology Today, vol. 21, no. 9, pp. 447–455, 2000. View at Publisher · View at Google Scholar · View at Scopus
- J. L. Petersen, C. R. Morris, and J. C. Solheim, "Virus evasion of MHC class I molecule presentation," Journal of Immunology, vol. 171, no. 9, pp. 4473–4478, 2003. View at Scopus
- J. Levitskaya, M. Coram, V. Levitsky et al., "Inhibition of antigen processing by the internal repeat region of the Epstein-barr virus nuclear antigen-1," Nature, vol. 375, no. 6533, pp. 685–688, 1995. View at Scopus
- Y. Yin, B. Manoury, and R. Fåhraeus, "Self-inhibition of synthesis and antigen presentation by Epstein-barr virus-encoded EBNA1," Science, vol. 301, no. 5638, pp. 1371–1374, 2003. View at Publisher · View at Google Scholar · View at Scopus
- C. Paludan, D. Schmid, M. Landthaler et al., "Endogenous MHC class II processing of a viral nuclear antigen after autophagy," Science, vol. 307, no. 5709, pp. 593–596, 2005. View at Publisher · View at Google Scholar · View at Scopus
- C. Münz, K. L. Bickham, M. Subklewe et al., "Human CD4+ T lymphocytes consistently respond to the latent Epstein-barr virus nuclear antigen EBNA1," Journal of Experimental Medicine, vol. 191, no. 10, pp. 1649–1660, 2000. View at Publisher · View at Google Scholar · View at Scopus
- C. Paludan, K. Bickham, S. Nikiforow et al., "Epstein-barr nuclear antigen 1-specific CD4+ Th1 cells kill Burkitt's lymphoma cells," Journal of Immunology, vol. 169, no. 3, pp. 1593–1603, 2002. View at Scopus
- E. Piriou, K. van Dort, N. M. Nanlohy, M. H. J. van Oers, F. Miedema, and D. van Baarle, "Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin lymphoma," Blood, vol. 106, no. 9, pp. 3166–3174, 2005. View at Publisher · View at Google Scholar · View at Scopus
- O. Gasser, F. K. Bihl, M. Wolbers et al., "HIV patients developing primary CNS lymphoma lack EBV-specific CD4+ T cell function irrespective of absolute CD4+ T cell counts," PLoS Medicine, vol. 4, no. 3, p. e96, 2007.
- K. N. Heller, F. Arrey, P. Steinherz et al., "Patients with Epstein-barr virus-positive lymphomas have decreased CD4+ T-cell responses to the viral nuclear antigen 1," International Journal of Cancer, vol. 123, no. 12, pp. 2824–2831, 2008. View at Publisher · View at Google Scholar · View at Scopus
- D. Chowdhury and J. Lieberman, "Death by a thousand cuts: granzyme pathways of programmed cell death," Annual Review of Immunology, vol. 26, pp. 389–420, 2008. View at Publisher · View at Google Scholar · View at Scopus
- M. E. Pipkin and J. Lieberman, "Delivering the kiss of death: progress on understanding how perforin works," Current Opinion in Immunology, vol. 19, no. 3, pp. 301–308, 2007. View at Publisher · View at Google Scholar · View at Scopus
- T. A. Haigh, X. Lin, H. Jia et al., "EBV latent membrane proteins (LMPs) 1 and 2 as immunotherapeutic targets: LMP-specific CD4+ cytotoxic T cell recognition of EBV-transformed B cell lines," Journal of Immunology, vol. 180, no. 3, pp. 1643–1654, 2008. View at Scopus
- P. J. Norris, M. Sumaroka, C. Brander et al., "Multiple effector functions mediated by human immunodeficiency virus-specific CD4+ T-cell clones," Journal of Virology, vol. 75, no. 20, pp. 9771–9779, 2001. View at Publisher · View at Google Scholar · View at Scopus
- S. J. Gagnon, F. A. Ennis, and A. L. Rothman, "Bystander target cell lysis and cytokine production by dengue virus- specific human CD4+ cytotoxic T-lymphocyte clones," Journal of Virology, vol. 73, no. 5, pp. 3623–3629, 1999. View at Scopus
- C. Clayberger and A. M. Krensky, "Granulysin," Current Opinion in Immunology, vol. 15, no. 5, pp. 560–565, 2003.
- C. F. Zheng, L. L. Ma, G. J. Jones et al., "Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients," Blood, vol. 109, no. 5, pp. 2049–2057, 2007. View at Publisher · View at Google Scholar · View at Scopus
- M. E. Peter and P. H. Krammer, "The CD95(APO-1/Fas) DISC and beyond," Cell Death and Differentiation, vol. 10, no. 1, pp. 26–35, 2003. View at Publisher · View at Google Scholar · View at Scopus
- T. Stalder, S. Hahn, and P. Erb, "Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity," Journal of Immunology, vol. 152, no. 3, pp. 1127–1133, 1994. View at Scopus
- X. Liu, B. J. Taylor, G. Sun, and R. Bosselut, "Analyzing expression of perforin, Runx3, and Thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes," Journal of Immunology, vol. 175, no. 7, pp. 4465–4474, 2005. View at Scopus
- H. Niiya, I. Sakai, J. Lei et al., "Differential regulation of perforin expression in human CD4+ and CD8+ cytotoxic T lymphocytes," Experimental Hematology, vol. 33, no. 7, pp. 811–818, 2005. View at Publisher · View at Google Scholar · View at Scopus
- M. E. Pipkin, A. Rao, and M. G. Lichtenheld, "The transcriptional control of the perforin locus," Immunological Reviews, vol. 235, no. 1, pp. 55–72, 2010. View at Publisher · View at Google Scholar · View at Scopus
- W. J. Grossman, J. W. Verbsky, B. L. Tollefsen, C. Kemper, J. P. Atkinson, and T. J. Ley, "Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells," Blood, vol. 104, no. 9, pp. 2840–2848, 2004. View at Publisher · View at Google Scholar · View at Scopus
- M. R. Betts and R. A. Koup, "Detection of T-cell degranulation: CD107a and b," Methods in Cell Biology, vol. 2004, no. 75, pp. 497–512, 2004. View at Scopus
- E. Nemes, L. Bertoncelli, E. Lugli et al., "Cytotoxic granule release dominates gag-specific CD4+ T-cell response in different phases of HIV infection," AIDS, vol. 24, no. 7, pp. 947–957, 2010. View at Publisher · View at Google Scholar · View at Scopus
- J. P. Casazza, M. R. Betts, D. A. Price et al., "Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation," Journal of Experimental Medicine, vol. 203, no. 13, pp. 2865–2877, 2006. View at Publisher · View at Google Scholar · View at Scopus
- K. A. Stuller, S. S. Cush, and E. Flano, "Persistent γ-herpesvirus infection induces a CD4 T cell response containing functionally distinct effector populations," Journal of Immunology, vol. 184, no. 7, pp. 3850–3856, 2010.
- S. Bauer, V. Groh, J. Wu et al., "Activation of NK cells and T cells by NKG2D, a receptor for stress- inducible MICA," Science, vol. 285, no. 5428, pp. 727–729, 1999. View at Publisher · View at Google Scholar · View at Scopus
- A. Diefenbach, A. M. Jamieson, S. D. Liu, N. Shastri, and D. H. Raulet, "Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages," Nature Immunology, vol. 1, no. 2, pp. 119–126, 2000. View at Scopus
- D. Cosman, J. Müllberg, C. L. Sutherland et al., "ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor," Immunity, vol. 14, no. 2, pp. 123–133, 2001. View at Scopus
- E. Amyes, C. Hatton, D. Montamat-Sicotte et al., "Characterization of the CD4+ T cell response to Epstein-barr virus during primary and persistent infection," Journal of Experimental Medicine, vol. 198, no. 6, pp. 903–911, 2003. View at Publisher · View at Google Scholar · View at Scopus
- D. M. Brown, "Cytolytic CD4 cells: direct mediators in infectious disease and malignancy," Cellular Immunology, vol. 262, no. 2, pp. 89–95, 2010. View at Publisher · View at Google Scholar · View at Scopus
- V. Appay, P. R. Dunbar, M. Callan et al., "Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections," Nature Medicine, vol. 8, no. 4, pp. 379–385, 2002. View at Publisher · View at Google Scholar · View at Scopus
- T. Kaneko, "Human autoreactive (Th0) CD4+ T-cell clones with cytolytic activity recognizing autologous activated T cells as the target," Human Immunology, vol. 61, no. 8, pp. 780–788, 2000. View at Publisher · View at Google Scholar · View at Scopus
- M. Yasukawa, H. Ohminami, J. Arai, Y. Kasahara, Y. Ishida, and S. Fujita, "Granule exocytosis, and not the Fas/Fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4+ as well as CD8+ cytotoxic T lymphocytes in humans," Blood, vol. 95, no. 7, pp. 2352–2355, 2000. View at Scopus
- D. M. Brown, C. Kamperschroer, A. M. Dilzer, D. M. Roberts, and S. L. Swain, "IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells," Cellular Immunology, vol. 257, no. 1-2, pp. 69–79, 2009. View at Publisher · View at Google Scholar · View at Scopus
- M. D. McKisic, D. W. Lancki, and F. W. Fitch, "Cytolytic activity of murine CD4+ T cell clones correlates with IFN-γ production in mouse strains having a BALB/c background," Journal of Immunology, vol. 150, no. 9, pp. 3793–3805, 1993. View at Scopus
- D. W. Lancki, C. S. Hsieh, and F. W. Fitch, "Mechanisms of lysis by cytotoxic T lymphocyte clones: lytic activity and gene expression in cloned antigen-specific CD4+ and CD8+ T lymphocytes," Journal of Immunology, vol. 146, no. 9, pp. 3242–3249, 1991. View at Scopus
- D. A. Vignali, L. W. Collison, and C. J. Workman, "How regulatory T cells work," Nature Reviews Immunology, vol. 8, no. 7, pp. 523–532, 2008. View at Publisher · View at Google Scholar · View at Scopus
- B. P. Mahon, K. Katrak, A. Nomoto, A. J. Macadam, P. D. Minor, and K. H. Mills, "Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor," Journal of Experimental Medicine, vol. 181, no. 4, pp. 1285–1292, 1995. View at Publisher · View at Google Scholar · View at Scopus
- P. Erb, D. Grogg, M. Troxler, M. Kennedy, and M. Fluri, "CD4+ T cell-mediated killing of MHC class II-positive antigen-presenting cells. I. Characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells," Journal of Immunology, vol. 144, no. 3, pp. 790–795, 1990. View at Scopus
- K. Yamamoto, F. Shibata, N. Miyasaka, and O. Miura, "The human perforin gene is a direct target of STAT4 activated by IL-12 in NK cells," Biochemical and Biophysical Research Communications, vol. 297, no. 5, pp. 1245–1252, 2002. View at Publisher · View at Google Scholar · View at Scopus
- T. W. Salcedo, L. Azzoni, S. F. Wolf, and B. Perussia, "Modulation of perforin and granzyme messenger RNA expression in human natural killer cells," Journal of Immunology, vol. 151, no. 5, pp. 2511–2520, 1993. View at Scopus
- D. F. Deblaker-Hohe, A. Yamauchi, C. R. Yu, J. A. Horvath-Arcidiacono, and E. T. Bloom, "IL-12 synergizes with IL-2 to induce lymphokine-activated cytotoxicity and perforin and granzyme gene expression in fresh human NK cells," Cellular Immunology, vol. 165, no. 1, pp. 33–43, 1995. View at Publisher · View at Google Scholar · View at Scopus
- M. Aste-Amezaga, A. D'Andrea, M. Kubin, and G. Trinchieri, "Cooperation of natural killer cell stimulatory factor/interleukin-12 with other stimuli in the induction of cytokines and cytotoxic cell-associated molecules in human T and NK cells," Cellular Immunology, vol. 156, no. 2, pp. 480–492, 1994. View at Publisher · View at Google Scholar · View at Scopus
- M. E. Pipkin, B. Ljutic, F. Cruz-Guilloty et al., "Chromosome transfer activates and delineates a locus control region for perforin," Immunity, vol. 26, no. 1, pp. 29–41, 2007. View at Publisher · View at Google Scholar · View at Scopus
- M. L. Janas, P. Groves, N. Kienzle, and A. Kelso, "IL-2 regulates perforin and granzyme gene expression in CD8+ T cells independently of its effects on survival and proliferation," Journal of Immunology, vol. 175, no. 12, pp. 8003–8010, 2005. View at Scopus
- M. J. Smyth, J. R. Ortaldo, Y. I. Shinkai et al., "Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells," Journal of Experimental Medicine, vol. 171, no. 4, pp. 1269–1281, 1990. View at Scopus
- J. Zhang, I. Scordi, M. J. Smyth, and M. G. Lichtenheld, "Interleukin 2 receptor signaling regulates the perforin gene through signal transducer and activator of transcription (Stat)5 activation of two enhancers," Journal of Experimental Medicine, vol. 190, no. 9, pp. 1297–1307, 1999. View at Publisher · View at Google Scholar · View at Scopus
- M. E. Pipkin, J. A. Sacks, F. Cruz-Guilloty, M. G. Lichtenheld, M. J. Bevan, and A. Rao, "Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells," Immunity, vol. 32, no. 1, pp. 79–90, 2010. View at Publisher · View at Google Scholar · View at Scopus
- F. Cruz-Guilloty, M. E. Pipkin, I. M. Djuretic et al., "Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs," Journal of Experimental Medicine, vol. 206, no. 1, pp. 51–59, 2009. View at Publisher · View at Google Scholar · View at Scopus
- E. L. Pearce, A. C. Mullen, G. A. Martins et al., "Control of effector CD8+ T cell function by the transcription factor eomesodermin," Science, vol. 302, no. 5647, pp. 1041–1043, 2003. View at Publisher · View at Google Scholar · View at Scopus
- H. Z. Qui, A. T. Hagymasi, S. Bandyopadhyay et al., "CD134 plus CD137 dual costimulation induces eomesodermin in CD4 T cells To program cytotoxic Th1 differentiation," Journal of Immunology, vol. 187, no. 7, pp. 3555–3564, 2011.
- R. Alonso-Arias, M. A. Moro-Garcia, J. R. Vidal-Castineira et al., "IL-15 preferentially enhances functional properties and antigen-specific responses of CD4+CD28null compared to CD4+CD28+ T cells," Aging Cell, vol. 10, no. 5, pp. 844–852, 2011. View at Publisher · View at Google Scholar
- C. Figueiredo, M. Wittmann, D. Wang et al., "Heat shock protein 70(HSP70) induces cytotoxicity of T-helper cells," Blood, vol. 113, no. 13, pp. 3008–3016, 2009. View at Publisher · View at Google Scholar · View at Scopus

subset: commoncrawl


text:
Google, Asus to hook up on 7-inch Android tablet, says report
Google will partner with Asus on a 7-inch tablet. Another in a string of reports on the rumored tablet.
Yet another report is claiming an imminent 7-inch Google tablet. And add Asus to the mix as that company will make and co-brand the device.
Google and Asus will unveil a 7-inch co-branded tablet PC as early as May, said DigiTimes in a report dated March 9.
NPD DisplaySearch analyst Richard Shim told CNET last month that the tablet will have a 1280x800 resolution 7-inch display and production is slated for April. The initial production run is between 1.5 million to 2 million units, Shim said.
And another report earlier this month said at least one model will retail for $199, run stock Android 4.0 Ice Cream Sandwich, and use a quad-core Tegra 3 processor from Nvidia.
The last part is interesting because at CES Asus announced the 7-inch Eee Pad MeMO 370T , which is slated to sell for only $250. That also uses the Tegra 3 processor.
On paper, this would be a step up from the $199 Amazon Kindle Fire, which, by comparison, has a 1024x600 display, runs Android 2.3, and uses a Texas Instruments dual-core OMAP 4430 chip .


text:
Steak and Tomato Sauté
From Good Housekeeping
triple-tested at the Good Housekeeping Research Institute
Served on a bed of spicy arugula, the sirloin in this saute is full of rich, bold flavors from being cooked with red wine, garlic, and mushrooms.
Be the first to rate this recipe
You must be logged in to use this feature.
Username: | |
Password: | |
Forgot your username or password? |
Not a member? Register
Nutritional Information
(per serving)
Calories | 310 |
Total Fat | 13g |
Saturated Fat | 3g |
Cholesterol | 85mg |
Sodium | 320mg |
Total Carbohydrate | 12g |
Dietary Fiber | 3g |
Sugars | -- |
Protein | 36g |
Calcium | -- |
Kate Mathis
Serves: 4
Yields: 4 main-dish servings
Total Time: 30 min
U.S. | Metric | Conversion chart |
- 2 tablespoon(s) vegetable oil
- 1 pound(s) top sirloin beef steak, trimmed and thinly sliced into 2-inch-long pieces
- 1 medium (6- to 8-ounce) onion, thinly sliced
- 1 container(s) (10-ounce) sliced mushrooms
- 1 pint(s) grape tomatoes
- 2/3 cup(s) dry red wine
- 2 clove(s) garlic, crushed with press
- 6 cup(s) (about 4 ounces) arugula
- In 12-inch skillet, heat oil on medium-high until hot, but not smoking. Sprinkle beef with 1/8 teaspoon salt and 1/4 teaspoon freshly ground black pepper. Add beef to skillet; cook 2 minutes or until browned, stirring occasionally.
- With slotted spoon, transfer beef to medium plate. To same skillet, add onion and 1/3 cup water. Cook 2 minutes, scraping up browned bits. Add mushrooms, tomatoes, and 1/4 teaspoon salt. Cook 3 to 4 minutes or until onion softens.
- To skillet, add red wine and garlic. Cover and cook 5 to 7 minutes or until tomatoes begin to burst, stirring occasionally. Return beef to skillet along with any accumulated juices. Cook 1 minute or until beef is heated through (145 degrees F).
- To serve, divide arugula among serving plates. Top with beef mixture.
Loading photos...
Here are some alternate versions of this recipe created by our wonderful community of chefs!
More from Good Housekeeping
Special Offer
Special Offers


text:
The Industrial Revolution happened between around 1750 and 1850; it's often considered the most important event in human history since the domestication of plants and animals. It paved the way for the prosperity much of the Western world takes for granted today.
The revolution was born in England, but it spread quickly all over the world – never before have so many people's lives changed so fast. Many of the technologies that enabled the revolution stemmed from the invention of the steam engine in 1784. Its efficiency and power lifted industry from modest workshops to high-speed factories.
Advances in one sector spurred greater activity in another. Increased factory demand for supplies meant better transportation was needed. Canals and railways meant raw materials and finished goods could be moved quickly and in bulk.
The Industrial Revolution caused huge problems as well as benefits. Burning coal polluted the air in cities causing health problems. Inadequate sanitation and refuse collection created horrifying outbreaks of disease; factory workers were poisoned by hazardous materials. Yet despite its toll on nature and on humans, the revolution moved steadily forward, and in time it has affected almost every society on the planet.


text:
South Jersey Marina to host Strictly Boaters Boat Show
Written by Staff Reports Friday, April 20, 2012 12:39 pm
< Prev | Next > |
Three years ago, South Jersey Marina hosted a new in-water boat show designed to appeal to the serious boating enthusiast. For the first three years, the show was called the Strictly Jersey Boat Show.
This year the show's focus has been expanded to make it more accessible to buyers in neighboring states, and the name has been changed to the Strictly Boaters Boat Show.
The show continues to be open only to boat manufacturers, dealers and companies that furnish products and services used by boaters.
The three-day show runs 10 a.m.-4 p.m. Friday through Sunday, May 4-6 at South Jersey Marina, 1231 Highway 109, Cape May. Admission $15.
Every in-water vessel shown will be available for sea trials. Land-based exhibits will feature a wide variety of boating-related products, services and supplies.
For information visit www.strictlyjersey.com.


text:
Quality Inn & Suites Watertown
Description provided by Quality Inn & Suites Watertown
FREE wireless high speed Internet access. FREE Deluxe Continental Breakfast with hot items. Indoor pool, whirlpool, excercise room, and business center on premises. Cinema 5 Theater, parks, walking and bike trails, Thunder Road, Terry Redlin Art Center, restaurants and shopping nearby. Fresh baked cookies each evening Sunday through Thursday. Pet accommodation: 20.00/stay.
List of Amenities for Quality Inn & Suites Watertown
· Air conditioning · Bus parking · Business center · Cable television · Coffee/Tea maker · Continental breakfast · Exercise gym · Hairdryer · Ice machine · Indoor pool · Iron · Iron · Laundry/Valet service · Onsite laundry · Outdoor parking · Parking · Pets allowed · Safe deposit box · Telephone · Truck parking · Wireless internet connection |
Restaurant Information
2nd Street Station Applebees Lunker's McDonalds Green Emerald IHOP Country Casino Dempseys Pub Mr. Ts Sportsbar The Drake / Tues - SatRecreation Information
Indoor pool
Area Attractions
Watertown Arpt.Sioux Falls Regional Airport
Bramble Park Zoo
Cinema 5 Theatre
Codington County Museum
Dakota Sioux Casino
Golf Course
Lake Pelican
Mellette House Museum
Redlin Art Center
Thunder Road Amusement Park
Watertown Event Center
Lake Kampeska
Watertown Mall
Kid Zone Indoor Amusement
High School Rodeo Grounds
Watertown Family Aquatic Cen
Room Information for this hotel
Handicap room, Microwave, Non-smoking, RefrigeratorMiscellaneous Information provided by Quality Inn & Suites Watertown
· American Dollars is the native currency.
· Check in time is 3:00 PM
· Check out time is 11:00 AM
· Renovated in 01/01/1999
· 59 rooms.
· 0 suites.
· 2 floors.
This Hotel's Guarantee Policy
This Hotel's Cancellation Policy
Reservations not cancelled by deadline will be charged 1 night's stay, or full amount of stay for reservations requiring prepayment.


text:
Homemade Applesauce
My mother in law makes wonderful applesauce. It's spicy like cider, and as sweet as pie filling. Each autumn, she collects the fruit that falls from the apple trees in her backyard (it takes two trees to produce fruit, how poetic is that?), and makes jars of applesauce for me. I love the smell of cinnamon wafting through the air as I heat her applesauce on our stove. It's so yummy I eat bowlful after bowlful, leaving not much to store for the winter. Only this year, rather than applesauce, she gave me a box of apples. What am I supposed to do with a box of apples? I'm not a cook. I can cook, but it requires advance planning: finding a recipe, shopping for the ingredients, and hiring a baby sitter to watch the kids so I don't splatter grease on them.
I called my mother in law for her applesauce recipe and she laughed. I don't think she's ever used a recipe. Her mother in law taught her how to make applesauce. "Boil the apples in water," she said. "And then squeeze them through your ricer. Add sugar, cinnamon and nutmeg to taste." To taste? Whose taste? Mine?
But I went for it. I boiled the apples on the stove for two hours.
When they softened (i.e. exploded), I dumped them into a colander. The water ran out, thick and creamy, and I realized I was supposed to keep it. Oh well.
We added nutmeg and cinnamon to taste, but skipped the sugar. Then I put some vanilla extract in there to make it mine.
As the smell of cinnamon wafted through our kitchen, suddenly I felt as if my mother in law was with us. And it wasn't just her, but the people we had shared meals with at her table. Making applesauce was like preserving a part of our family's history: the farm where two apple trees grew, and the people who planted them. It made me realize the point of a meal wasn't the speed at which food gets to your table, but the community you find there. And tonight we had past generations with us.
The applesauce may not be perfect, but at least its ours.
No related posts.
Related posts brought to you by Yet Another Related Posts Plugin.
One Comment
I'm SO behind on blogs! The applesauce looks and sounds so easy and fun and delicious and now I want to make sure I get the boys (including husband) and I to an orchard before it's too late! Love your addition of vanilla. Also love that you left out the sugar. I only buy unsweetened as it sure doesnt' need it, huh!
Love the picture of your son with his tongue sticking out as he scoops away.
Also, too funny about kissing Rocco. I felt just a little out of place not drinking wine at the winery, but the evening was great fun and I still can't believe I met Rocco either! (I enjoy meeting famous people.)
Thanks for stopping by my blog!


text:
You must be logged in to save your search, you can Register an account with SciCrunch to save your searches.
orIf you have forgotten your password, please enter your account email below and we will reset your password and email you the new password.
Biologists possess the detailed knowledge critical for extracting biological insight from genome-wide data resources, and yet they are increasingly faced with nontrivial computational analysis challenges posed by genome-scale methodologies. To lower this computational barrier, particularly in the early data exploration phases, we have developed an interactive pattern discovery and visualization approach, Spark, designed with epigenomic data in mind. Here we demonstrate Spark's ability to reveal both known and novel epigenetic signatures, including a previously unappreciated binding association between the YY1 transcription factor and the corepressor CTBP2 in human embryonic stem cells.
Welcome to NIF. Explore available research resources: data, tools and materials, from across the web
Search for resources specially selected for NIF community
Search across hundreds of additional biomedical databases
Search Pub Med abstracts and full text from PubMed Central
Enter your search terms here and hit return. Search results for the selected tab will be returned.
Click here to login or register and join this community.
Narrow your search by selecting a category. For additional help in searching, view our tutorials.
Displays the total number of search results. Provides additional information on search terms, e.g., automated query expansions, and any included categories or facets. Expansions, filters and facets can be removed by clicking on the X. Clicking on the + restores them.
Displays individual records and a brief description. Click on the icons below each record to explore additional display options.


text:
I was going through a code which has a series of test video's. My question is not relevent to the application. Its with the video. The video that I saw in it were test videos, very short and kind of customised (had a text describing the file name and a little bar moving signifying that its a video. The file is xyz.mp4). It felt as though the developer has put those as a stop-gap, only to fill them with the real video's later.
My question : is it possible to make such tiny test videos?? whats the time frame that needs invested in it? tools available? any more information you think might help me understand this issue.
Thanks in advance for pondering over my question...


text:
I bought this for myself, and I have to say it is fabulous. There are two versions, one for men, one for women, and the women's one is great. It is not too strong, it is very clean smelling, and nothing that is overpowering. I wore it today and several people complimented me on my perfume, and for the price it is a great buy. Will definitely buy again!
This fragrance rivals those that cost three times the cost. The smell is clean & citrusy but has deep woodsy notes that gives the smell dimension. The bottle design has a great artsy look to it. I love it for myself! Great value, smell is comparable to those high-end fragrances.


text:
Thanks for your blog and great information on Shrove Tuesday.
It's the last day before Lent and a time when people used up all their treats before the six weeks of Lent started.
We've been busy making pancakes today – the French crepe types. They are so easy to make and enjoyed by all the family. --Jules B.


text: Slot Friends Premium gamesBookmark the permalink. Release date: Sep 26th, 2012 Price: 1.99 Version: 1.4 Seller: Jesse Manuel Buy Now STP SCORE: Not yet reviewed Description Screenshots Pull the slots in this turn-based friends-to-friend direct slot machine game. Related Games Card Wars – Adventure Time Rivals for Catan Star Trek Rivals Heads Up! TRANSFORMERS Legends Injustice: Gods Among Us Solitaire Blitz Order & Chaos Duels – Trading Card Game King Cashing 2 Penny Arcade The Game: Gamers vs. Evil


text:
Found the same room at a different price? Tell us, and we'll offer to match it.
The Atherstone Red Lion Hotel
3 | Self Classified Hotel | Ratings explained |
During your stay we implore you to relax in the library or conservatory before enjoying both local and international cuisine in the Queens Restaurant or Wine Bar. For those who enjoy a more lively atmosphere the Sports Bar is the place with Sky Sports available along with a wide range of local ales and bar meals.
All rooms offer wireless Internet connection for the business traveller with the majority of rooms also having double beds.


text:
Simply Exquisite.
At Elichai Fine Jewelry we consider every piece of jewelry we craft a work of art — a personal expression of elegance, grace, and enduring beauty. From initial concept to gem setting, we strive to create heirloom-quality jewelry that will last for generations.
Don't just dream…
let us design it!


text:
The Jazz Giants Play Cole Porter: Night And Day
Various Artists
1. Dream Dancing 3:59 2. Just One Of Those Things 3:56 3. You'd Be So Nice To Come Home To 5:26 4. Love For Sale 4:48 5. All Of You 4:31 6. Night And Day 7:35 7. I Love Paris 5:08 8. I've Got You Under My Skin 3:16 9. Begin The Beguine 6:48 10. I Love You 5:28 11. Easy To Love 1:47 12. Ev'ry Time We Say Goodbye 3:20 13. From This Moment On 6:14
Jazz players like those on this album had, in the Fifties and early Sixties, been nourished on swing and bop and were enjoying relatively good gigs in clubs and studios, and were still feeling like their form was new and open to exciting exploration. When not airing their own soon-to-be classic original compositions, they were leafing back a couple of decades to an earlier creative era. That was the time between the Wars, when Cole Porter, basking in the well-financed attentions of Broadway and Hollywood, had managed to live in the posh style to which he'd been born while pouring out what's perhaps the richest, most effervescent combination of music and lyrics to ever gush from one mind. His output, which continued after the Second World War, helped to illuminate the world's recovery from the Depression and to substitute an image of a stimulating lifestyle blessed with romance and adventure.
–from the liner notes by Jeff Kaliss
Find out more about Various Artists


text:
Ask A ScientistChemistry Archive |
name Brandon D. status student age 20s Question - i need to know how much water is produced for each gallon of gasoline burned. the actual question I am trying to answer is..."for each gallon of fuel burned, more than ______ of water is formed." this question pertains to motor vehicles, so that is the reason i specified gasoline. ------------------------------------------------------- The inquiry has no specific answer because gasoline is a mixture of hydrocarbons, and in some places up to 10% ethanol. In addition, the composition of gasoline is different in different climates. For example, in the northern states in winter there must be a higher ratio of more volatile components. Otherwise the car will not start at -20F. There are also some aromatic hydrocarbons present in gasoline. There is also the complicating factor that combustion is not always complete, so the mix of products will change. You may find the following equation useful to find the approximate amount of water produced, that you could use in some model calculations. For a linear aliphatic hydrocarbon the general formula is:C(n)H(2n+2). For octane n=8 so the formula is C8H18. Octane is typical of the hydrocarbons found in gasoline. So, the general chemical equation for combustion is: C(n)H(2n+2) + [(3n+1)/2] O2 -------> (n) CO2 + (n+1) H2O It would be fairly easy to set this up on a spread sheet (e.g. Excel) and look at various compositions. The mass units need not be metric, so you could look at the lbs of H2O produced per lb of hydrocarbon, and the density conversion for water is: 8.33 lbs./ gal. Vince Calder ========================================================= Gasoline is a complex mixture of hydrocarbons, and other ingredients, so there is not an exact answer, but assuming that gasoline is octane (C8H18) the complete combustion (which does not occur in the real world) chemical reaction is: 2C8H18 + 25O2 = 16CO2 + 18H2O Assuming octane has a density of 0.8 kg/liter and liquid water has a density of 1.0 kg/liter, you can calculate the volume of water produced by a given volume of hydrocarbon. Vince Calder ========================================================== By now, you have probably received this answer from others, but if my resources and calculations are correct, (at room temperature) LESS than one gallon of water is formed in a complete, clean reaction of gasoline with oxygen to produce water and carbon dioxide. Actually, it's only around five milliliters less. Tim Spry
Back to Chemistry | Ask A Scientist Index |
NEWTON Homepage | Ask A Question |


text:
Bus Directions
Bus Directions
- Take Major Deegan Expressway which becomes New York State Thruway North Rt. 87
- Continue to Exit for Rt. 287 East (Cross Westchester Expressway) to Exit #1 (Route 119) At Exit, turn left onto 119 East
- Continue on until you see the sign for 9A North (traffic light) – approx ½ mile.
- Turn left onto 9A North, Pleasantville Road
- Turn right onto Pleasantville Road
- Make a left onto Chappaqua Road and follow for approximately 2 miles.
- When you see a small lake and cabins on the right side, the conference center will be just ahead and up the road on the left.


text:
Filed under: Betas, Sci-fi, Trailers, Video, MMO industry, New titles, News items, Free-to-play, City of Steam
If you've been wanting to get a look at the upcoming steampunk MMO City of Steam but haven't been able to procure a closed beta spot, there are still two days until the Autumnwane testing round. However, if you can't wait that long, Mechanist Games has a new trailer showing off the game to tide you over.On top of that, the studio has announced that City of Steam has kicked off its Greenlight campaign on Steam. What does this mean for fans? It means that if the game gets enough votes, it will be made available on Steam, which will in turn add a number of new features to the game, including pets, new dungeon types, new steambikes, extra character customization options, and more!
To get your City of Steam fix, be sure to watch the creatively done trailer after the break, and then don't forget to watch Massively TV this Friday night, December 14th, at 9:00 p.m. EST to see the game live!
[Source: Mechanist Games press release]
Continue reading City of Steam double feature: A beta trailer and a Steam Greenlight campaign
City of Steam double feature: A beta trailer and a Steam Greenlight campaign originally appeared on Massively on Wed, 12 Dec 2012 17:15:00 EST. Please see our terms for use of feeds.


text:
Austin Amateur Radio Supply occasionally sends out emails on new items, special pricing, in store promotions, manufacturer's promotions & other announcements that are of interest to the Amateur Radio community. You can view a sample here.
You can always safely unsubscribe. We never share or sell our email list.
Do we have permission to send them to you?
Sign up here.


text:
Job openings rate in October 2009
December 10, 2009
The job openings rate was unchanged in October at 1.9 percent. After falling steeply from mid-2007 through February 2009, the job openings rate has been steady at 1.8 percent or 1.9 percent since March 2009.
The number of job openings fell by 2.3 million from the most recent peak in June 2007 to April 2009, but has declined by only 7,000 since.
The job openings rate was essentially unchanged in every industry and region in October.
These data are from the Job Openings and Labor Turnover Survey. Data for October are preliminary. To learn more, see "Job Openings and Labor Turnover—October 2009" (HTML) (PDF), news release USDL-09-1499.
Bureau of Labor Statistics, U.S. Department of Labor, The Economics Daily, Job openings rate in October 2009 on the Internet at http://www.bls.gov/opub/ted/2009/ted_20091210.htm (visited March 06, 2015).
Three recent editions of Spotlight on Statistics
Housing: before, during, and after the Great Recession
looks at consumer expenditures on household items, employment in residential construction, prices for household items, and injuries in occupations involved in building and maintaining our homes. -
Women veterans in the labor force examines the demographic, employment, and unemployment characteristics of women veterans.
BLS Statistics by Occupation provides an overview of occupational employment and wages with an emphasis on STEM jobs and occupational data by typical entry-level education required.


text:
MP3 of the Day from the Axe and the Oak, Playing Electric Pickle on Thursday
The track does a good job of conveying eeriness and paranoia but it's deeply rooted in that old time rock and roll fun. Great production levels here too -- the instruments are crisp and the rhythm section of Myles (bass) and Fernando (drums) creates a good base for Sander's vocals and guitar work. Check them out Thursday night at the Electric Pickle where they'll be performing for a film crew from WLRN.
The Axe and the Oak. Thursday, February 25. Electric Pickle, 2826 N. Miami Ave., Miami. Show starts at 10 p.m., admission is free. 305-456-5613; electricpicklemiami.com
MP3: The Axe and the Oak - "Dancing on the Grave of Jack the Ripper"
Sponsor Content


text:
I'll repeat that: Tight Credit Is Causing Housing Prices to Rise.
Yes I know. I'll explain.
This week the Federal Reserve released it's January 2013 Senior Loan Officer Opinion Survey on Bank Lending Practices and it continued to show little movement in mortgage underwriting standards but demand was up. The increase in demand has not softened mortgage lending standards. In fact, mortgage standards have remained essentially unchanged since Lehman collapsed in 2008.
On the household side, domestic banks reported that standards for both prime and nontraditional mortgages were essentially unchanged over the past three months. Respondents indicated that demand for prime residential mortgages increased, on net, while demand for nontraditional residential mortgages was unchanged.
Tight lending standards has prevented many sellers from listing their homes because they don't qualify for the trade up, holding supply off the market. The shortage is manifesting itself by also keeping people unaffected by tight credit from listing until they find a home they wish to purchase. Record low mortgage rates keep the demand pressure on as affordability is at record highs. Rising prices are not really based on anything fundamental like employment and a robust economy.
Tight credit + record low mortgage rates => reduced supply + steady demand => rising prices.
Like I said before…
Tight Credit Is Causing Housing Prices to Rise.
I'll repeat that….
Tight Credit Is Causing Housing Prices to Rise.
January 2013 Senior Loan Officer Opinion Survey on Bank Lending Practices [Federal Reserve]
Falling Inventory Has Created a Housing "Pre-Covery," not "Recovery" [Miller Samuel Matrix]
Tags: Lehman
18 Responses to "Tight Credit Is Causing Housing Prices to Rise"
Good observation! I agree. I'm working up my forecasts for the AL Markets and reviewing last year's have found more interesting correlations, hint it is not interest rates though But I do agree that interest rates are impacting pricing. Perhaps more precisely due to the inflationary and inverse relationship between interest rates and pricing of financial assets.
[...] Streeters use when ripping people off (Fortune) • Tight Credit Is Causing Housing Prices to Rise (Miller Samuel Inc.) • Predicting Markets, or Marketing Predictions (Advisor Perspectives) see also Perils of [...]
This observation is erroneous at its core. As a 40 year lender and student of mortgage markets, I can assure you that lenders have been and continue to tighten underwriting standards. I do expect that tren will reverse in 2013 as more and more lenders return to mortgage originations.
The increase in value is due primarily to low interest rates and a dimunation of worries about job security on thbe part of 75% of potential buyers. The housing recovery has been dramatically dampenedd by credit standards tightened to catch the horses that left the barn between 2007 and 2009. At today's housing price levels, the downside risk in pricing is minimal. The increase in demand has to do with buyers who feel that the economy has been wrung out, that inflation is on the way and they need to act now while rates and prices are low. The duration of this housing slump was exacerbated by the underwriting pendulum swing too far. I could not agree less with the conclusion that tighter credit standards are contributing to rising home prices. The exact opposite is true.
[...] – Tight Credit Is Causing Housing Prices To Rise (appraiser & analyst Jonathan Miller, Matrix) [...]
[...] Tight Credit Is Causing Housing Prices to Rise | #MillerSamuel @jonathanmiller VT Reply With Quote [...]
The same standards which apply to would-be sellers not being able to move up apply to would-be buyers. Your premise would be accurate if tighter credit standards affected more would-be sellers than would-be buyers.
I believe that prices are moving up because of supply inelasticity and that inelasticity is induced by would-be sellers having negative of little equity. No one wants to bring $75,00 to escrow to sell their home.
[...] while the cause of this price increase may seem elusive in the current economy, a recent article by Jonathan Miller of Miller Samuel, Inc. suggests that it is in fact the tight credit market that [...]
[...] while the cause of this price increase may seem elusive in the current economy, a recent article by Jonathan Miller of Miller Samuel, Inc. suggests that it is in fact the tight credit market that [...]
[...] where home appreciation was fueled by loose underwriting. It's actually the opposite, where tight underwriting plus low rates push home inventory down and prices up. And right now loan underwriting is as tight as it gets, leading to the loan quality stats noted [...]


text:
Bobby Flay Fit, Episode 3: Mix It Up
by Joseph Erdos in Bobby Flay Fit, January 16, 2013Bobby Flay manages to stay fit and healthy even with a busy lifestyle as a chef, and he's eager to share his healthy eating and fitness plan with fans in a seven-part Web series, Bobby Flay Fit.
The focus of Episode 3 is mixing it up: It's easy to get bored with your exercise routine. That's why it's important to mix it up, try something new and get out of your comfort zone.
In Episode 3 of Bobby Flay Fit, Bobby and his pal, Iron Chef Michael Symon, get together in the gym to try some new exercises. Bobby isn't as familiar with weight training, so Michael shows him some techniques to mix things up a bit. On the way to the gym, they share a healthy snack that Bobby made — Chocolate-Coconut Granola.
Takeaways from Episode 3:
- Eat a little something before you exercise to fuel your workout.
- Get advice from someone in the know before starting a new workout.
- Workouts are more effective if you keep yourself interested and engaged by trying new things: Alter your routine or try a new sport.
Make it at home:
Chocolate-Coconut Granola
Similar Posts
Bobby Flay Fit, Episode 11: Inspire Others by Example
Bobby Flay manages to stay fit and healthy even with a busy lifestyle as a chef, and he's eager to share his healthy eating and fitness plan wit...Comments (
1,010 )-
My favorite smoothie ingredients are strawberries, bananas, acai, and blueberries.
That type of slow weight lifting does nothing for you. The concentric portion of an excercise should be faster and the eccentric portion slower and more controlled. Aslo Michael Symon looks like he has never touched a weight so I'm not sure it is a good idea to take strength training advice from him. Just my opinion.
since your schedule is so busy why don't you and Michael Symon try CrossFit! It's much better than the weight training Michael Symon was teaching you and easier to learn. If you combine CrossFit with the cardio that you are doing now you will really like looking in the mirror and be the Fittest you have ever been Check it out! I am sure there are CrossFit gyms in NYC maybe even in the Reebok gym where you and Michael Symon recorded the video. Try it you'll get hooked!
[…] Episode 3: Mix It Up Change Up Your Workout: Try new things to keep yourself from falling into an exercise rut. But remember, enthusiasm is key, and so is safety. Get advice from someone who knows before starting a new activity. […]
[…] Episode 3 of Bobby Flay Fit, Bobby's friend, Iron Chef Michael Symon, joins Bobby in the gym for a […]
[…] who knows about fitness, like a trainer, when beginning a new exercise routine is important. In Episode 3 of Bobby Flay Fit, Michael Symon takes Bobby to Reebok Sports Club in New York to teach him some […]
[…]always a major fan of linking to bloggers that I appreciate but really don't get quite a bit of link enjoy from[…]…
[…]below you'll find the link to some websites that we think it is best to visit[…]…
[…]Sites of interest we have a link to[…]…
The Birch of the Shadow…
I believe there might become a number of duplicates, but an exceedingly useful list! I have tweeted this. Quite a few thanks for sharing!…


text:
Fallbrook Girls Rugby Club continues its winning waysThursday, February 13th, 2014 Issue 07, Volume 18.
The tournament was held at Heritage Park over the weekend of Jan. 23-25. The Fallbrook under 18 team (U18) won games against Snow Canyon (Utah), Bishop O Dowd (NorCal), and Lashburn Lucky (Saskatchewan, Canada) twice. Playing 15-a-side rugby, Fallbrook ended the weekend with a 266-5 points difference. The tournament allowed Fallbrook to begin its season by successfully introducing the new, younger players into the U18 division with the experience of the returning players. A rewarding weekend was had by all. The Durbin sisters, Johni and Lilly, had a fruitful weekend scoring 11 tries each. The new leadership team, led by Captain Taylor Duncan, created a positive and unifying environment in which all players were able to feel comfortable and thrive. Fallbrook players Rachel Bell, Kayla Canett, and Michel Navarro played in the sevens division for an elite team, the Serevi select side, made up of players from across the country. Fallbrook Girls Rugby Club appreciated all its supporters who traveled to Las Vegas and coordinated behind the scenes events to ensure their success. If anyone is interested in the teams upcoming schedule or in sponsorship, they can contact the coaches at firstname.lastname@example.com. 2 comments
Well done ladies! Good luck with your season.
These ladies just kill it. They are awesome.
The Fallbrook Village News has tightened its' policy regarding comments. While we invite you to contribute your opinions and thoughts, we request that you refrain from using vulgar or obscene words and post only comments that directly pertain to the specific topic of the story or article. Comments that are derogatory in nature have a high likelihood for editing or non-approval if they carry the possibility of being libelous. The comment system is not intended as a forum for individuals or groups to air personal grievances against other individuals or groups. Please, no advertising or trolling. In posting a comment for consideration, users understand that their posts may be edited as necessary to meet system parameters, or the post may not be approved at all. By submitting a comment, you agree to all the rules and guidelines described here. Most comments are approved or disregarded within one business day. |
Valley NewsAnza Valley OutlookFallbrook.orgSourcebookPDF VersionCoupon CornerSign up for iNewsEarthquake Info Most Commented 359 Medical marijuan... 267 Arrests now numb... 246 13-year-old Fall... 218 Vote yes on Pr... 205 Arrests now tota... 170 UPDATE: Authorit... 168 Man hit, killed ... 166 Marine commits s... 153 13-year-old Fall... 153 Little Mexico in... 148 EXCLUSIVE UPDATE... 145 Increased Noise ... 137 Fallbrook reside... 133 Methamphetamine ... 125 Mother-in-law ar... |
The Fallbrook Village News All contents copyright ©2015 |
About Us Earthquake Information Business Listings |
Contact Us Letter to the Editor Report a website error |
Sitemap Online Digital Edition RSS Feeds Login |


text:
You are here >
Caritas advocates for environmental justice for present and future generations.
Our understanding that we are stewards of God's creation, our solidarity with the poor, and our respect for the common good make the issue of environmental justice the responsibility of every person.
- New Zealand Catholic Bishops Conference, 2006
Caritas' environmental advocacy includes raising awareness on the impact of climate change on many of the world's poorest and most vulnerable communities. We have also written submissions on biofuels and raised concerns about the future for those likely to be displaced by climate change, especially in the Pacific.
Read more:
See how a rural community in Syangja, Nepal, is working together
to confront the challenge of climate change.
Without Rain from Splashroom Media on Vimeo.
RSS Feed Contact Us | SiteMap | Privacy | Copyright 2012 Caritas Aotearoa New Zealand Charities Registration No:CC36055.


text:
Price: $0.99
Version: 1.1
App Reviewed on: iPhone 3GS
Graphics / Sound Rating:
User Interface Rating:
Gameplay Rating:
Re-use / Replay Value Rating:
Overall Rating:
When a game attempts to mash-up elements from other titles and genres, the results tend to go one of two ways. It can be a jack-of-all-trades, master of none, providing players with several options to mess around with but never quite meeting or exceeding similar mechanics found in more focused releases. Or it can somehow pull it off and leave everyone completely befuddled. not to mention thoroughly entertained. Vanessa Saint-Pierre Delacroix sits somewhere in the middle of these two extremes: better than "okay," but still lacking in a few areas. Not that this makes it any easier to actually stop playing, mind.
Poor little Vanessa is too eccentric and brilliant for her own good. She's constantly bullied by her classmates due to her peculiar nature, thus choosing to keep to herself most of the time. When an ancient and mysterious puzzle box is accidentally activated and sucks the entire city inside of itself, she'll have to put her smarts (and her tolerance for jerks) to the ultimate test in order to solve the unsolvable and put things right. In practice it's like an odd combination of box-pushing, gravity flipping puzzles and platforming.
It takes a little getting used to, but once everything started to click I found it near impossible to put Vanessa Saint-Pierre Delacroix down. Players will have to guide the unwilling heroine to each level's exit, navigating around inter-connected rooms on the outside of a six-sided cube. It's easier to understand by looking at the screens, below. Levels ramp-up in complexity at a steady pace, and new elements such as wall-climbing enemies and special red blocks (needed to clear blue obstructions) are introduced constantly.
It's unfortunate that the controls can feel a little stiff, however. Flipping rooms has a bit of a lag to it which can sometimes result in rotating more or less than intended. Often with unpleasant results. Similarly, being unable to flip while jumping (much less moving in any way) feels like a missed opportunity. My biggest gripe, though, is the rating system. Basically, it makes no sense. I've cleared a level using below the allotted number of flips while going over the time limit and gotten the best rank. I've done it on another level and gotten the worst. The same has happened when I've beaten a stage with time to spare but going over on flips. Like I said, it makes no sense.
Yet, while the controls can be a little fussy and the rating system seems totally nonsensical, I still can't seem to tear myself away. It's always "Just one more level," or "Just one more try." I can't explain it, but I suppose I don't really need to. It's simply a fun and very addicting iOS game.
Tagged with: $0.99, platform, platformer, platforming, platforms, puzzle, puzzle game, Puzzle Platformer, puzzlebox, puzzles, Replay Games, Vanessa Saint-Pierre Delacroix


text:
Welcome! Babes of Sweden is a links page, dedicated to listing websites with free pictures of Swedish babes, models and celebrities, such as the Graaf sisters, Victoria Silvstedt, Vendela Kirsebom, Janna Svensson etc.
Our chief concern is to list free sites that feature nude photos of Swedish women. But we feel that we can't be too strict on this criteria. There are a lot of babe photos out there on the web, where the girl in question has great looks and a sexy body but doesn't appear stark naked. Therefore we also link pages with Swedish babes who are partly naked (seminudes), dressed in swimsuit/bikini, or clad in something revealing, like lingerie.
Below are an extensive list of names on some Swedish models, babes and celebrities to give you an impression of the sort of images you can expect to see at the listed sites.
Finally, if you operate a site with nude, semi-nude or bikini pictures of Swedish babes and/or celebs, and want to get it listed with Babes on Sweden, then please use this submit form.


text:
I'd heard of a pessary being used to treat uterine prolapse, but had no idea they were ever used to treat incontinence. Wonder how that works?
I always thought of a pessary as a sort of medieval or Victorian method of treating some disorders, but I suppose it has a use in modern medicine, too. Very interesting.


text:
We want to ensure that making a return is as easy and hassle-free as possible! If for any reason you decide that your purchase just isn't for you, simply return the item within 30 days of receipt and we'll cover the return shipping when you choose our FREE Pre-Paid Return Shipping Label. Learn more about our return policy.
Shop now and get Free Value Shipping on most orders over $49 to contiguous 48 states, DC and to all U.S. Military APO/FPO/DPO addresses.
by Liz on Mon Feb 02, 2009 6:52 pm
by tancho on Mon Feb 02, 2009 7:13 am
by Liz on Mon Jan 12, 2009 12:33 pm
by haastyle on Sun Jan 11, 2009 4:43 pm


text:
While in the early Principate period, Roman penal law distinguished primarily between citizens and non-citizens and this was the criterion in terms of personal rights for the determination of punitive measures, from the end of the 2nd cent. AD social rank determined the treatment of individuals by the courts. The differentiation in punishments is linked in the legal texts and in modern research primarily with two terms, honestiores and humiliores. The honestiores were the members of the privileged classes (senators, equites, decurions, veterans); they were e…
Honestiores/Humiliores(878 words)
Cite this page
Krause, Jens-Uwe (Munich). "Honestiores/Humiliores." Brill's New Pauly. Antiquity volumes edited by: Hubert Cancik and , Helmuth Schneider. Brill Online, 2015. Reference. 04 March 2015 <http://referenceworks.brillonline.com/entries/brill-s-new-pauly/honestiores-humiliores-e517020>
First appeared online: 2006
First Print Edition: 9789004122598, 20110510
▲ Back to top ▲


text:
Hello All, I've been lurking these forums for months and would like to thank all the members for contributing their advice and experiences. Your posts have helped me become a better ccp holder. So now I would like to help the next new ccp holder.
I've had my ccp since march, and I remember being scared to death of printing. My first carry gun was a G26 in a Smart carry. Then traded up to G36 in an IWB, now i'm jumping up to the G21sf in OWB set up.
what i'm trying to say here is that Don't worry about printing to much.
You're not printing as bad as you think you are.


text:
GL: Has the recent E. coli outbreak in Europe had any impact on your farm or farming methods (not using pesticides)?
MG: No. In fact, the European outbreak seems to be attributed to a non–O157 form of E. coli, and in our program, we test for non–O157 pathogens.
GL: What advice would you give people who are concerned about eating organic produce for fear of being more susceptible to E. coli and other bacteria?
MG: I would say that organic simply is no more susceptible to foodborne contamination than food produced with chemicals. Even the U.S. Food & Drug Administration has said it has no data showing any higher or lesser risk for adulteration with foodborne pathogens for growing products using organic versus conventional farming techniques. I think this concern may arise out of the thought that organic farmers may be using manure. What many people don't know is that the use of manure is specifically regulated in certified organic operations so that it must be composted to a certain heat for a certain length of time to kill pathogens.
But I certainly understand overall concern for safer food. That's why we grow food organically and that's why we have such a rigorous food–safety program. From the very first days of Earthbound Farm, we've been committed to growing food without toxic and persistent chemicals, and it's becoming increasingly clear that some of these chemicals have harmful effects. That's an important factor in choosing safer food.
If you add the value of keeping chemicals out of our food supply with our extremely rigorous food–safety program, I think it's really a statement about how strongly committed we are to producing the safest food possible. I encourage people to know who's producing their food and how it's being produced.
GL: What's next? Are you branching out into more produce lines? Stores? Packaged goods?
MG: We are in the midst of developing some exciting new product lines that will either complement current lines (such as salad dressings and toppings) or find other ways to use organic fruits and vegetables in delicious and wonderful products. At the end of July, we'll be rolling out a couple of new products, including Earthbound Farm's organic triple–washed Mixed Baby Kale. The Environmental Working Group's "Shopper's Guide to Pesticides" has kale on its list of the 12 produce items most likely to be contaminated with pesticide residues and an important item to choose organic. All these factors will help make kale, which is intriguing to many, more accessible and approachable.
We've also got our organic Power Lunches coming out, which are powerfully delicious, naturally nutrient–dense salad meal kits that are ready–to–eat, and they include such combinations as Blueberry Quinoa Protein Balance, Cranberry Wheat Protein Boost, and Tomatillo Black Bean Protein Energy.


text:
These Pics Of Jennifer Lawrence Getting High In Hawaii Are Giving Me A Boyfriend-Style Boner
You know I was on the fence about this girl for a while. Lotta talk going around about whether her cute personality was manufactured or whatever. Well I think these pictures just won me over. You know why? It's because of how she's holding the joint. She's got it going underhand style, as opposed to your classic overhand technique. Love it. Just something so innocent and girly about it. Makes me want to buy her ice cream and eat it in bed with her while we watch Terminator 2, then just fuck right through our dinner reservations and call room service instead.


text:
Ace That Interview, Metro Campus
Type: | Workshop |
Date: | Wednesday, July 25, 2012 |
Time: | 10am - Noon |
Location: | Metro Campus, MSS 404 2900 Community College Ave.., Cleveland, OH 44115 |
Hosted by: | The Career Centers |
Deadline: | Tuesday, July 24, 2012 |
Review general guidelines to improve your interviewing skills and gain a "behind the scenes" insight into the interview process. Learn about the different types of interviews, overcoming obstacles and avoiding common mistakes. Practice your interviewing skills and receive valuable feedback pertaining to your strengths and areas for improvement. Topics to be covered are Basic Guildelines, Traditional Questions, Behavioral Based Questions and Telephone Interviews.
Go to: http://www.tri-c.edu/careerservices
This event requires that you sign up in order to attend.
You must log in to your College Central Network account in order to do so.
© 1997 - 2015 College Central Network, Inc. All rights reserved. | ||


text:
Turkey has disbanded its first squadron of McDonnell Douglas F-4E Phantom strike aircraft, under a transition plan leading to its future operation of Lockheed Martin's F-35 Joint Strike Fighter. Continue reading…
Tag Archives | JSF
Lockheed Martin F-22 production line
Earlier this month Stephen Trimble's blog The DEW Line reported that the US Secretary of Defense Robert Gates recommended halting the Lockheed Martin F-22 Raptor production at 186 aircraft. Pictured here is the F-22 production line. In the meantime, the US Air Force has cleared a five-year upgrade project to allow the Lockheed Martin F-22A Raptor to communicate with other […]
F-22 to communicate with stealth and non stealth aircraft
The US Air Force has cleared a five-year upgrade project to allow the Lockheed Martin F-22A Raptor to communicate with other stealthy – and perhaps some non-stealthy – aircraft types. The project will cost roughly $900 million. Continue reading…
US Department for Defense want new vertical lift technology
The US Department of Defense has assigned a key architect of the project that became the F-35 Joint Strike Fighter programme to look at launching an all-new, "future vertical lift" (FVL) aircraft to enter service after 2020. A key goal will be to reduce the danger of aircraft operating in vertical lift mode. Operations in […]
Cookies & Privacy
Recent Posts
Recent Comments
- Lorna on Bristow hits the bullseye
- Criminal Attorney Naperville on Bristow hits the bullseye
- www.youtube.com on Ryanair girls in another "charity" calendar
- spanish grammar exercises free on A320 Wataniya Airways pic of the week
- biurorachunkowopodatkowe.pl - tania rachunkowość i księgowość on Eclipse owners aim for rescue act


text:
uTorrent 3.2 Beta 27272
- Fix: video slider steps should be small for fine control and visual smoothness
- Fix: fixed lack of window frame for popped-out video; returning to embedded video works fine too;
- Fix: heap corruption
- Fix: Fix rendering of stats dialog. First line was formatted as header text.
- Feature: minimal support for pad-files (deselect them by default)
- Fix: Improperly formatted torrent vote messages
- Fix: Only request IPV4 addresses for udp tracker DNS resolution
- Feature: sanity check on how many uTP connections we allow
- Feature: retry http connection when host resolves into multiple ips and the first fails


text:
EasternWakeNews.com copyright notice
Material published on EasternWakeNews.com, including articles, photos, graphics, videos, bulletin board postings and other content, is copyrighted by Eastern Wake News or by other information providers who have licensed their content for use on EasternWakeNews.com. The entire contents of EasternWakeNews.com are also copyrighted as a collective work under the United States copyright laws.
For more information, please read our Terms of Service.