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Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. In this environment, the epithelium has evolved effective mechanisms to cope with microbial products and to provide appropriate responses to potential pathogens. Although our understanding of these mechanisms is clearly in its infancy, a number of recent findings provide insight into phenotypic characteristics that allow for this discrimination. Here, we briefly review some of these mechanisms, with particular attention to epithelial expression of the anti-infective molecule bactericidal/permeability-increasing protein.
- mucosa
- infection
- inflammation
- eicosanoid
mucosal surfaces such as the lung, intestine, and kidney are lined by a single layer of epithelial cells. Epithelial cells are uniquely positioned to serve as a direct line of communication between the immune system and the external environment. In their normal state, mucosal surfaces are exposed to high concentrations of foreign antigens, while at the same time they are intimately associated with the immune system via subepithelial lymphoid tissue. Consequently, the epithelium forms an important barrier, preventing the free mixing of lumenal antigenic material with the lamina propria that houses the mucosal immune system. This latter capability is attributable to intercellular tight junctions, present as gaskets that circumferentially join epithelial cells at their apices. Tight junctions regulate the passive permeation of hydrophilic solutes through the "paracellular" space. Tight junctions are dynamic structures, the permeability of which is a highly regulated process. A second important function of the epithelium is the maintenance of mucosal hydration. A coordinated series of signaling events to epithelial stimuli (secretagogues) results in the activation of membrane ion channels and transporters. Depending on the net effect of such events (absorption or secretion of ions), an epithelial osmotic gradient is established and provides the driving force for paracellular water transport. Similar to many aspects of cell biology and immunology, this view has changed dramatically in the past decade. The epithelium is now viewed as an active player in normal homeostatic mechanisms of mucosal immunity. Here, we will briefly summarize current thinking regarding the many functional roles of epithelial antimicrobial peptides, with a particular emphasis on the recent discovery of epithelial-expressed bactericidal/permeability-increasing protein (BPI).
The lumenal surface of many epithelia is exposed to an exceptionally large bacterial population. Surprisingly little is known about how epithelial cells adapt to such an environment. It is now well accepted that epithelial cells of broad origin express a variety of antimicrobial peptides, including peroxidases, lactoferrin, lysozyme, and defensins (7). Only recently have we come to appreciate the extent to which these peptides contribute to the health of mucosal tissues (16). For example, it is thought that defensin expression in Paneth cells of the small intestine maintains the crypt as an essentially sterile environment (16). Moreover, it was shown that animals genetically null of matrilysin, the metalloproteinase that processes defensin precursors, and thus lacking mature defensins, are more susceptible to microbial invasion of the intestinal epithelium. These mice succumb more rapidly and to lower doses of Salmonella typhimurium than wild-type mice (25).
BPI is a 55- to 60-kDa protein originally found in neutrophil azurophilic granules, on the neutrophil cell surface, and, to a lesser extent, in specific granules of eosinophils (3). BPI selectively exerts multiple anti-infective actions against gram-negative bacteria, including cytotoxicity through damage to bacterial inner/outer membranes, neutralization of bacterial LPS (endotoxin), as well as serving as an opsonin for phagocytosis of gram-negative bacteria by neutrophils (3). A growing number of proteins with primary structural homology to BPI and roles in lipid recognition and host defense is being identified. The plasma LPS-binding protein (LBP) is a product of the liver with an anionic net charge that serves to greatly amplify responses to LPS by delivering LPS monomers to a monocyte receptor-complex containing CD14, MD2, and Toll-like receptor 4 (11). Whereas LBP recruits LPS monomers for delivery to CD14, BPI stabilizes LPS aggregates thereby preventing LBP-mediated LPS monomer delivery (23). Thus BPI and LBP are functionally antagonistic. It is the COOH-terminal domains of LBP and BPI that determine the route and host responses to LPS complexes. Whereas LBP predominates in resting plasma, the higher affinity of BPI for LPS coupled with the greater concentration of BPI at neutrophil-rich inflammatory sites favors BPI-mediated endotoxin neutralization (4).
In addition to BPI and LBP, humans also express cholesterol ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which apparently also maintain LPS-interactive properties (10). Homologues of BPI/LBP have recently been described in the head kidney and liver of a teleost fish (rainbow trout), suggesting that the BPI/LBP family is evolutionarily conserved. Of note, the BPI superfamily recently underwent a major expansion with the identification of homology to a murine epithelial expressed gene named plunc (palate, lung, and nasal epithelium clone) (1). The PLUNC family includes proteins with extended structures corresponding to holo-BPI [long (L)PLUNC] as well as smaller proteins with homology corresponding only to the NH2-terminal half of BPI [short (S)PLUNC]. The primary amino acid sequences of the PLUNC proteins reveal substantial divergence in the NH2-terminal region with greater homology (among the LPUNCS) in the region corresponding to the COOH-terminal half of BPI. Overall, the PLUNC family has modest amino acid sequence homology to BPI but very similar predicted fold and genomic organization to BPI. Rat and human PLUNC are secreted in nasal mucus, and rat PLUNC is upregulated in the nasal respiratory epithelium after bulbectomy, suggesting roles in host defense subsequent to injury.
The inflammatory bowel diseases (IBD), including both Crohn's disease and ulcerative colitis, are especially complex disorders. IBD is often a progressive and mutilating disease primarily localized to the gastrointestinal tract, although systemic complications are frequent. Despite extensive efforts, the basis of IBD has yet to be established. A number of etiologies for IBD have been proposed, including impaired epithelial barrier function, persistent infectious processes, abnormal regulation of intestinal immune responses, and multifocal vasculitis (20).
The hypothesis that human IBD might somehow be related to normal bacterial flora was first proposed more than 30 years ago. Accumulating evidence indicates that the lumenal microflora is central to the development of IBD. First, studies in murine models of colitis have indicated that clinical manifestation of symptoms similar to those in human patients is less severe, if at all, in animals maintained in germ-free environments (5). If colonized with commensal bacteria, these same animals rapidly develop symptoms consistent with IBD (5). Second, studies in humans and in a variety of animal models have indicated that broad-spectrum antibiotics alleviate some of the symptoms associated with IBD, suggesting that lumenal flora (or their byproducts) contribute to ongoing inflammatory disease. Third, recent studies detailing the chromosome 16 map identified a gene responsible, at least in part, for genetic linkage of IBD to a large number of families. This gene, designated NOD2 (also referred to as caspase activation and recruitment domain 15, or CARD 15), encodes an intracellular protein that functions as a so-called pattern-recognition receptor for bacterial peptidoglycan. Although IBD patients appear to manifest increased activation, variants of NOD2 function result in a paradoxical reduced activation by bacterial products (5). This latter aspect remains to be explained. Nonetheless, significant recent evidence indicates that constituents of microbial antigens present within commensal flora may contribute to the IBD process. Studies directed at understanding endogenous protective strategies may aid in identification of future therapies for IBD.
Our recent studies identified, for the first time, expression of BPI in human intestinal epithelia (2). This observation was based on transcriptional profiling studies aimed at identifying differentially expressed genes elicited by epithelial exposure to analogs of endogenously occurring anti-inflammatory eicosanoids [aspirin-triggered lipoxins (ATLa)]. Lipoxins are bioactive eicosanoids derived from membrane arachidonic acid by the combined action of 5-lipoxygenase (LO) and 12-LO or 15-LO involving two different cell types (i.e., transcellular metabolism). A number of recent in vitro and in vivo studies have revealed that lipoxins, and specifically lipoxin A4 (LXA4), serve as an innate "stop signal," functioning to control local inflammatory processes. For example, LXA4 has been demonstrated to inhibit polymorphonuclear neutrophil transmigration across both endothelia and epithelia, in vitro and in vivo (22). Synthetic lipoxin analogs exhibit greater potency for these actions than the native compound, likely due to decreased metabolism to inactive compounds. In particular, the synthetic LXA4 analog 15 (R/S)-methyl-LXA4, the structure of which resembles that of epimeric derivatives of lipoxin (15-epi-LXA4), a native lipoxin generated in vivo in the presence of aspirin, may partially contribute to the anti-inflammatory actions of aspirin. Similarly, the epi-lipoxin analogs have proven effective in vivo.
Interestingly, the original microarray suggested that a prominent gene cluster elicited by ATLa included a number of antimicrobial peptides. In addition to BPI, this cluster identified ATLa-dependent induction (threshold >3-fold increase) of several known epithelial antimicrobials, including lysozyme, defensin-5, and cathepsin E (unpublished data). In parallel, recent transcriptional profiling studies suggest that at least two antimicrobial peptide genes (phospholipase A2 and lysozyme) are induced in human IBD tissues (12). Nonetheless, we pursued the finding that BPI might be expressed in epithelia, particularly because BPI had previously been associated only with cells of the myeloid lineage. Initial studies directed at verifying microarray analysis revealed that a broad range of intestinal epithelial cells express BPI and each was similarly regulated by anti-inflammatory lipid mediators. Studies aimed at localization of BPI revealed that such expression occurs on the cell surface of cultured epithelial cell lines and dominantly localizes to epithelia in healthy human mucosal tissue. Functional studies employing a BPI-neutralizing antiserum revealed that surface BPI blocks endotoxin-mediated signaling in epithelia and kills S. typhimurium. Our studies identified a previously unappreciated "molecular shield" for protection of mucosal surfaces against gram-negative bacteria and their endotoxin. These studies will be described in detail later. Of note, BPI expression had also been reported in human nasolacrimal duct epithelium (17).
Ongoing studies within the laboratory have revealed that intestinal epithelial cell lines as well as native epithelia prominently express BPI. We have concentrated our efforts in the colon, but recent work (2) indicates that such BPI expression was not confined to the colon and was more widely distributed within the alimentary tract (e.g., squamous epithelia of the esophagus also expressed BPI). BPI localizes to both the crypt and villus and, unlike other colonic antimicrobial peptides (16), is not preferentially expressed in Paneth cells. These histological studies indicate the likelihood that BPI has a multifactorial function within epithelial cells along the alimentary tract. Of interest, it appears that BPI can exist on the cell surface. For such direct localization, we have concentrated on cultured cell lines (2), but in other cell types (e.g., human neutrophils), BPI has been demonstrated on the outer leaflet of the plasma membrane (16). Given the complexity of whole tissue, our studies in human epithelial tissues have not allowed for such detailed analysis. Nonetheless, the possibility exists that surface BPI could provide a direct bacterial-epithelial conduit for sensing and responding to bacterial signals. Present studies are aimed at better understanding how BPI expression is distributed along the length of the intestine and how epithelial BPI expression is regulated under inflammatory conditions.
Mucosal epithelial cells harbor a number of antimicrobial factors that form a biochemical barrier to microbial colonization (7, 16). Numerous studies have indicated that these antimicrobial factors are critical to maintenance of host-microbe homeostasis at the mucosal surface (7, 16). Initial studies in the present work identified the expression of BPI mRNA in epithelial cells, and extensions of these findings revealed broad expression on epithelia of diverse origin. Before its discovery in epithelium, BPI expression had been described only in cells of myeloid lineage (7). Two conceptual points exemplify the potential importance of BPI expression on mucosal epithelia. First, epithelia provide the initiation point for host-microbial interactions. Although microbial flora are necessary and beneficial to the host, some degree of selectivity is also prerequisite for homeostasis. Epithelial-expressed BPI could provide such a role. BPI is remarkable for its potent (nanomolar) and selective bioactivity against gram-negative bacterial species (14). Moreover, the finding that functional BPI is expressed on the epithelial surface, and not in the soluble milieu, could provide an additional degree of selectivity for invasive/host-interactive pathogens. Second, a basic feature of many mucosal surfaces is the presence of high concentrations of endotoxin. Previous work (18) has indicated that under appropriate conditions, certain epithelial cells can respond to endotoxin, and recent studies have clearly defined the existence of LPS receptors (e.g., CD14 and Toll-like receptors) on epithelial surfaces (11), the latter of which may be differentially regulated in selective mucosal diseases. In this context, an elegant recent study demonstrated that commensal bacteria and bacterial components such as LPS, via activation of Toll-like receptor, are necessary for homeostatic processes in the intestine (19). Thus a tenuous balance may exist between LPS recognition and activity, and endogenous mechanism(s) likely exist to diminish aberrant activation of epithelial cells. Our present findings indicate that surface-expressed BPI could provide an innate dampening mechanism against endotoxin by effectively competing for the binding of endotoxin, as such, preventing endotoxin binding to such proinflammatory receptors. Indeed, endotoxin activation of epithelia (i.e., ICAM-1 induction) was significantly enhanced by the addition of functionally inhibitory anti-BPI sera, suggesting a protective role for BPI in mucosal endotoxin homeostasis. In summary, epithelial BPI may contribute to the innate biochemical barrier characteristic of mucosal surfaces but may also provide a degree of selectivity necessary for effective host responses.
From this vantage point, we proposed that one function of epithelial BPI is to modulate responses to bacterial endotoxin. The addition of endotoxin to epithelial cells in the presence of 5% heat-inactivated normal human serum induced a concentration-dependent induction of ICAM-1 mRNA. Having shown that epithelial cells respond to endotoxin, we determined whether inhibition of epithelial BPI might function to enhance endotoxin-mediated induction of ICAM-1 surface protein. To this end, epithelial cells preexposed to anti-BPI and subsequently activated with a combination of endotoxin and human serum (source of soluble CD14) revealed that anti-BPI significantly increased endotoxin-induced ICAM-1, suggesting that BPI provides an endotoxin-neutralizing function for epithelial cells and that surface-expressed BPI might normally function to dampen epithelial endotoxin responses. Taken together, such findings implicate epithelial BPI as a direct line of bacterial-epithelial communication to submucosal tissues in this setting.
One function of the epithelium is to provide a barrier to prevent the free flow of lumenal contents to submucosal tissues. Included within the barrier property of the epithelium is the modulation of bacterial-epithelial interactions and the modification of bacterial localization along the intestinal wall. For example, antimicrobial peptides produced and released by Paneth cells at the base of the crypt determine bacterial populations within the crypt lumen, and for all intents and purposes, this is considered a sterile space (16). Although not well understood, the epithelium is thought to possess a surveillance mechanism(s), which is likely to comprise an important part of the innate immune response.
As part of the original characterization of epithelial BPI, we determined whether intact, adherent epithelial cells kill BPI-sensitive bacteria. To do this, confluent Caco-2 epithelial cells were exposed to S. typhimurium and examined for bacterial killing in standard colony-forming unit (CFU) analysis. Such analysis revealed a nearly 1-log order reduction in CFU over a 90-min period and that anti-BPI significantly inhibits bacterial killing compared with control normal goat serum. Parallel experiments assessing epithelial killing of a gram-positive bacterium (e.g., Enterococcus faecalis) revealed no influence of anti-BPI.
The high affinity of BPI for the lipid A region of LPS targets its cytotoxic activity to gram-negative bacteria. Binding of BPI to the gram-negative bacterial outer membrane is followed by a time-dependent penetration of the molecule to the bacterial inner membrane where damage results in loss of membrane integrity, dissipation of electrochemical gradients, and bacterial death (14). The actions of BPI are amplified by extracellular factors including the complement system and secretory phospholipase A2 (4). Members of the defensin and cathelicidin antimicrobial peptide families synergistically enhance the antibacterial activity of BPI (14). Whether this is of relevance to intestinal immunophysiology remains to be determined. Although the anti-infective properties of BPI are best defined with respect to gram-negative bacteria, BPI congeners and BPI-derived peptides have also shown activity against cell wall-deficient gram-positive bacteria and fungal organisms.
BPI binds the lipid A region of LPS with high affinity (14) and thereby prevents its interaction with other (proinflammatory) LPS-binding molecules, including LBP and CD14 (8). Because BPI binds the lipid A region common to all LPS, it is able to neutralize endotoxin from a broad array of gram-negative pathogens (14). Thus BPI is capable of inhibiting all of the many proinflammatory activities of LPS, including induction of cytokine release, activation of the neutrophil oxidase enzyme, and nitric oxide formation (14). The opsonic activity of BPI occurs via binding of the NH2-terminal domain to gram-negative bacteria and promotion, via the COOH-terminal portion of BPI, of bacterial attachment to neutrophils and monocytes (4). Whether such opsonic effects occur via ligand receptor interactions between the COOH-terminal half of BPI and membrane receptors or other mechanisms is unclear.
The selective and potent action of BPI against gram-negative bacteria and their LPS is fully manifest in biological fluids including plasma, serum, and whole blood (14). In multiple animal models of gram-negative sepsis and/or endotoxemia, administration of BPI congeners is associated with improved outcome, and these properties have rendered BPI an attractive target of biopharmaceutical development (15). BPI has proven safe and nonimmunogenic in phase I trials and has demonstrated potent anti-endotoxic activity in phase II trials (9). In a large, multinational phase III double-blinded, placebo-controlled trial, adjunctive treatment with rBPI21 was associated with reduced complications, including limb amputation, due to meninogococcal sepsis (13). Additional indications for the use of BPI congeners are being actively explored, as are activators of epithelial BPI. For instance, stable lipoxin analogs have recently proven protective in murine models of colitis (6). Given their size (<400 Da), stability, and composition, the lipoxins look especially promising as future therapeutic modalities for mucosal inflammation, for which some of this protection may be afforded by induction of epithelial BPI.
Of interest, BPI has been suggested as a marker molecule for IBD. For example, high levels of neutrophil-associated BPI are found in the colonic mucosa of patients with ulcerative colitis, and autoantibodies directed against BPI are proposed seromarkers for the IBDs (21). Indeed such autoantibodies have recently been shown to inhibit BPI bioactivity, indicating that the blocking of BPI could be involved in the disease process (21). Moreover, BPI congeners are currently being evaluated as novel therapies for diseases in which endotoxin is thought to play a role. Considering that IBD may be caused by a persistent reaction to antigen(s) secondary to a failure of normal immunoregulatory mechanisms and the observations that the ability of the epithelium to "hold back" flora in IBD may be abrogated, it is desireable to elucidate the contribution of proteins such as BPI to intestinal immunity.
In conclusion, the initial encounter of microbes with human tissue frequently takes place at mucosal surfaces. If the microbes survive, proliferate, and reach sites not normally colonized by microbial flora, the influx of neutrophils and other inflammatory cells into the affected area ensues. Normal host responses include the initiation of counterregulatory measures, including the local production of anti-inflammatory lipids (Fig. 1). The effectiveness of host defenses as innate mechanisms of adaptation to a microbial world is now an area of intense investigation. Studies in recent years have focused much attention on microbicidal peptides and proteins as common components of both epithelial and phagocytic innate host defenses. Intestinal epithelial cells form a single layer of cells that isolate the host from the potentially hostile gut lumen and are recognized as important immune effector cells, capable of responding to a wide array of biologically active agents commonly found in the intestinal environment. With its antibacterial and endotoxin-neutralizing properties, epithelial BPI may play a significant role in innate defense at the mucosal interface.
The studies reviewed here were supported by National Institutes of Health Grants DK-50189, DK-065768, and DE-13499 and by a grant from the Crohn's and Colitis Foundation of America.
The authors extend special thanks to Drs. O. Levy and C. Serhan for many contributions to this work.
- Copyright © 2005 the American Physiological Society


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Quadir 'Avon' Taylor, 29, is on trial for the 2012 death of 76-year-old Carrie Smith in Wilson Borough. Full story »
Quadir Taylor, 29, of Easton, is charged with helping to murder Carrie Smith in Wilson Borough. Full story »
Lehigh Valley Crime Stoppers on Tuesday announced the offer of up to $2,000 for information leading to the arrest of Quadir S. "Avon" Taylor. Full story »
Carrie Smith, 76, suffered a heart attack in the January 2012 holdup, leading to her death about two months later, authorities said. Full story »
Quadir "Avon" Taylor is wanted on homicide and other charges in the January 2012 home invasion that led to the death of Carrie Smith, 76, authorities said Thursday. Full story »
Investigators are still searching for a fourth suspect involved in the robbery and death of Carrie Smith in 2012. Full story »

subset: commoncrawl


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Fantasy baseball is a year-round activity these days. Gone are the days when you could simply buy a magazine in mid-March and expect to know what happened since October. Doesn't work that way. It especially doesn't work that way for me, because I end up drafting a few teams in November and December anyway. Plus, it's fun to follow what the Detroit Tigers are thinking about for their desolate bullpen around Thanksgiving time.
Let's cut to the chase: We'll be following all movement involving MLB's relief pitchers in this space all fall and winter long, leading up to and including our Spring Training coverage. Want my updated top-40 reliever rankings? Look further down. Want to see a team-by-team look at bullpen hierarchy? Bookmark this page. Want random references to former fantasy heroes like Antonio Alfonseca? Don't go away.
Below you'll see every major league team's bullpen represented, with its current closer and next-in-line candidates. And the rankings are to the right. The page will be updated as new information warrants, and we'll even tell you when we updated it. Here we go.
Note: Teams that have made recent moves have been moved to the top; after that, teams remain in alphabetical order until updates are needed.
Closer: Trevor Hoffman
Next in line: David Riske
Don't forget: Carlos Villanueva
Thoughts (Updated Jan. 8): Wow, is it going to be strange to see Hoffman pitching for this team! As I wrote the day Hoffman signed here, his numbers might not seem like it on the surface, but they are in decline, and leaving Petco Park will not help him. Still, he's clearly the closer, and he should get saves. The Brewers really had no other options in the wake of the stunning retirement of Salomon Torres. I think Villanueva could have done the job, and maybe in a year he gets the chance. Hoffman isn't perfect, but then again, look at whom this team employed in the role recently -- Eric Gagne, Derrick Turnbow, Dan Kolb -- and Hoffman might become beloved. I mean, who wants to see David Riske close?
Closer: Jonathan Broxton
Next in line: Cory Wade
Don't forget: Hong-Chih Kuo
Thoughts (Updated Jan. 8): I wanted to update this situation because it sure looked like the Dodgers were going after Trevor Hoffman, and that obviously would have affected the value for Broxton. Maybe the Dodgers add another arm or two and Broxton keeps his job, but the fact the team was even talking to Hoffman is a red flag. The other news is that it sure looks like underrated Takashi Saito won't be back in L.A. Saito was very good as a Dodger, but he's no youngster and his elbow appears to be a problem. He's gone. Wade and Kuo still make for nice setup men, for now, but it wouldn't shock me if help is still on the way.
Closer: Brian Fuentes
Next in line: Jose Arredondo
Don't forget: Scot Shields
Thoughts (Updated Jan. 7): The K-Rod era was obviously over, but I really thought the Angels would deal with the problems on offense, rather than sign another closer. Arredondo had a terrific season, and it's not like the team has depth problems in the bullpen, with Shields and other veterans lurking. I was surprised Fuentes ended up in Anaheim, but now that he's there, we have to embrace this. The Angels don't look like a team that will score a lot of runs, which is good news for providing save opportunities. I mean, isn't that part of the reason K-Rod saved 62 games, that every game was 4-2 in the ninth inning? Fuentes doesn't need help, either, as the southpaw can retire right-handed hitters, so Arredondo now becomes merely a strikeout middle reliever, one of the top ones off the board. If I sound a bit disappointed, well, I am. At least five other teams really needed Fuentes more, but you can never have enough top relievers.
Closer: Tyler Walker
Next in line: Roy Corcoran
Don't forget: Miguel Batista
Thoughts (Updated Jan. 7): No, I don't think former San Francisco Giant Walker is going to be a successful closer, but his January signing to a one-year deal is very significant. I think it does signal Brandon Morrow will continue with his transformation to becoming a fine starting pitcher. When J.J. Putz was traded to the Mets, that didn't leave much in the Seattle bullpen. Who are we kidding, there still isn't much, and Walker is likely to win and lose the job a few times, I think. At least Morrow can resume his Joba Chamberlain impression. I don't think Aaron Heilman will close; he wants to start, but will likely end up in the seventh or eighth innings. Other than that, Seattle needs to develop some arms within its system and not simply let its guard down and push Morrow back to closing. If you're going to lose 100 games anyway, might as well let Walker or Batista get 30 saves with a 5 ERA. It's happened before.
Closer: Chris Perez
Next in line: Jason Motte
Don't forget: Chris Carpenter
Thoughts (Updated Jan. 7): When I mentioned Carpenter as a "don't forget" guy back before Thanksgiving, I think we all had a chuckle and that was it. Now that manager Tony La Russa is actually discussing his former Cy Young winner as a possible closer, in a John Smoltz-type way because of injury concerns, it tells me Carpenter could save games, and that there are concerns about Perez. Could Perez save 30 games? Sure, he could, and Carpenter could start 30 games or not pitch at all. There's just some doubt now, that's all. Perez and Motte are strikeout right-handers apparently capable of taking that next step, but definitive word might not come on this situation until late March, if at all. La Russa has options. Ryan Franklin could end up with 20 saves for all anyone knows.
Closer: Brad Lidge
Next in line: Ryan Madson
Don't forget: Chad Durbin
Thoughts (Updated Jan. 7): The Phillies probably didn't intend to do much this offseason with the NL's top bullpen, but the new year brought bad news in the form of J.C. Romero's 50-game suspension for testing positive for a banned substance. When you figure the champs lose Romero for a quarter of the season, and Durbin doesn't exactly have a strong résumé, the Phils might look to add depth now, rather than finding internal help. It shouldn't change fantasy much, though; Lidge and Madson are reliable. Lidge is not going to be perfect in 2009; it's just unreasonable to expect it. Hard to believe Brett Myers was closing a year prior. Someday, when Lidge's deal is over, keep an eye on Tommy John survivor Scott Mathieson. For now, Romero becomes less of an option in NL-only leagues.
Closer: Carlos Marmol
Next in line: Kevin Gregg
Don't forget: Jeff Samardzija
Thoughts (Updated Jan. 7): When I first wrote about the Cubs officially parting ways with Kerry Wood, I thought it was a given Marmol would close. My stance didn't change when Gregg was acquired from the Marlins for a younger, harder-throwing prospect who will probably outperform him by 2010. But now I'm getting the feeling there might be a competition here in the spring between Marmol and Gregg. Plenty of times before we've seen managers opt to use their top relievers as setup men, and the team's third or fourth best reliever to close. How else to explain Joe Borowski and Antonio Alfonseca, among many others, leading their leagues in saves this decade? Borowski saved 40-plus games in a season he wouldn't have made half the bullpens in the majors! Anyway, Marmol could be dominant as a closer, but there remains some doubt if he'll get the chance. I hedged a bit, and ranked him 10th, and Gregg is ranked later. By the way, Marmol might have ended up, statistically, as the best closer in fantasy baseball had those seven saves been more like 37. His 114 strikeouts and 0.93 WHIP are pretty special. Meanwhile, Samardzija still has rookie eligibility, but figures to be the seventh-inning option.
Closer: Matt Lindstrom
Next in line: Leo Nunez
Don't forget: Jose Ceda
Thoughts (Updated Jan. 7): Lindstrom converted all five of his save chances in September, after Kevin Gregg lost the job due to a sore knee. I updated this section when Joe Nelson, arguably the team's top reliever in 2008, was cut loose when he could have been retained for one year and at a relatively cheap price. The Marlins' loss is Tampa Bay's gain now. The Marlins thought it was a good idea to bring in former Yankee Scott Proctor, who you might remember was abused by Joe Torre in 2006, and has struggled since. Proctor and Nunez now appear the most likely right-handers for the eighth inning, but keep an eye on Ceda. Acquired from the Cubs in the Gregg deal, Ceda is projected to close for the Marlins at some point, and that could come in 2009.
Closer: Francisco Rodriguez
Next in line: J.J. Putz
Don't forget: Eddie Kunz
Thoughts (Updated Dec. 11): Not a shocker here, as the Mets really needed K-Rod, and they got the prime closer on the market. For more on what the signing means, click here. The Mets wisely weren't done yet; What, you thought Luis Ayala was going to be the main setup dude? The day after announcing K-Rod had joined the Mets, Putz was stolen from the Mariners for prospects, bad relievers (farewell, thee Aaron Heilman) and energetic Endy Chavez. Putz is no lock, though. For one, if you owned him in fantasy this is horrible news for his value. He's not going to get saves. He could be one of the top five setup men in the biz, a major strikeout guy who gets 30 holds. He could also succumb to injury. I wouldn't bother drafting him now, and he leaves the rankings to the right. Man, Billy Wagner has to be wondering why he never had any help.
Closer: Kerry Wood
Next in line: Jensen Lewis
Don't forget: John Meloan
Thoughts (Updated Dec. 10): As expected when I wrote this column a month ago, Lewis wasn't long for the closer role, but then again, I do think he's going to get a few saves because the Tribe didn't sign the most durable guy around. Wood had a terrific season with the Cubs, finding a role he could thrive and avoid injury (for the most part) in, and one would think Wood does a nice job with the Tribe. Remember, this team once gave Joe Borowski enough save chances for him to lead the league, despite how poorly he pitched. Wood shouldn't pitch poorly. Lewis might not be the prime setup man, because Rafael Betancourt, could easily bounce back, and Rafael Perez figures to play an eight-inning role against lefties.
Closer: Mike Gonzalez
Next in line: Rafael Soriano
Don't forget: Jeff Bennett
Thoughts (updated Dec. 10): The Braves are likely to be active in free agency, and it appears bullpen help will be coming. A healthy Gonzalez should keep the closer job, but Soriano has proven he can't be used like a top closer, and the Braves believe he's too brittle to be relied on as the main setup guy. I originally named John Smoltz as a potential "don't forget" option, but he seems to be set on starting again, not closing, and it's not even a given he returns to Atlanta. A name from the past to remember: Aussie Peter Moylan is coming back from Tommy John surgery, and could be ready in May 2009. He's got skills, and after seeing B.J. Ryan return effectively in less than a year, who knows?
Other teams in alphabetical order until updated...
Closer: Chad Qualls
Next in line: Tony Pena
Don't forget: Jon Rauch
Thoughts: Qualls wouldn't have been my first choice to close, but the Diamondbacks are saying it's his job to lose. Pena and Rauch are innings-eaters who could handle the role. Bottom line on this team is it might not matter who starts the year with the job. Jose Valverde saved a ton of games in 2007, and Brandon Lyon managed to keep the job most of this past season. Forget about Max Scherzer; he's the No. 3 starter, at worst.
Closer: George Sherrill
Next in line: Chris Ray
Don't forget: Dennis Sarfate
Thoughts: Sherrill was among the league leaders in saves for much of 2008, so he gets first shot. Ray missed pretty much all of the season after Tommy John surgery, but should be healthy in the spring. I'm going to continue to expect something, someday, of Sarfate, a really hard thrower who shouldn't be starting and needs to harness his control. Reminds me of Washington's Joel Hanrahan.
Closer: Jonathan Papelbon
Next in line: Hideki Okajima
Don't forget: Manny Delcarmen
Thoughts: Since there's no real intrigue for who hurls in the ninth inning, I think it comes down to what happens with Justin Masterson. He's got a killer sinker and, on most teams, a future in the rotation. On this team that's deep with starting pitchers and able to sign more, Masterson could follow Papelbon's path. The acquisition of Ramon Ramirez from the Royals could push Masterson to starting, but in place of whom?
Closer: Bobby Jenks
Next in line: Octavio Dotel
Don't forget: Matt Thornton
Thoughts: While it seemed like a few members of this bullpen ran out of gas in October, it's still pretty deep. Not only does Dotel have closing experience in case Jenks' dropping strikeout rate is a harbinger, but Scott Linebrink could save games. Thornton might be the best pitcher in this bullpen, and let's not forget prospect Aaron Poreda could end up in the bullpen as well.
Closer: Francisco Cordero
Next in line: Jared Burton
Don't forget: Bill Bray
Thoughts: Cordero is safe, and would always have a long leash because of his contract. Burton takes over the David Weathers role, and keep an eye on one-time college closer Bray, who was used as a lefty specialist but doesn't need to be.
Closer: Manuel Corpas
Next in line: Huston Street
Don't forget: Taylor Buchholz
Thoughts: The Brian Fuentes era is over, but what about Street, who came over in the Matt Holliday deal? Corpas didn't have a strong 2008 season, but then again, neither did Street, who could be on the move again. Chances are whomever pitches better in March would earn the job. Poor Buchholz did have a good season, but he's a deep No. 3 for saves. If you're wondering why I didn't name former top pick Casey Weathers, we won't see him until 2010 after Tommy John surgery.
Closer: Fernando Rodney
Next in line: Joel Zumaya
Don't forget: Kyle Farnsworth
Thoughts: How does a team possibly move on when the Todd Jones era ends? OK, seriously, you don't think Rodney will start 2009 as the closer, do you? Jason Isringhausen could be a short-term option, or even David Weathers, whose name has been discussed. I'd guess the Tigers bring in a veteran type who could also set up if needed, then unleash Zumaya. If he's healthy and throwing well, Zumaya could be a closer steal.
Closer: Jose Valverde
Next in line: LaTroy Hawkins
Don't forget: Bud Norris
Thoughts: Valverde has led the NL in saves for different teams the past two seasons, so there's little reason to think he'll fall apart. There is, however, reason to think the Astros might be willing to make it three teams in three seasons, if they get starting pitching back. He'd better not get moved, considering who's setting him up. Prospect Norris should make the Astros out of the spring, and he's got closer stuff, eventually.
Closer: Joakim Soria
Next in line: Joel Peralta
Don't forget: Luke Hochevar
Thoughts: Soria is better than most people think, and the Royals have enough depth that any rumors of his moving to the rotation should end. What they don't have, after trading Leo Nunez (for Mike Jacobs) and Ramon Ramirez (for Coco Crisp), is a deep bullpen. Hochevar projects as the No. 5 starter, and while I think he made strides and should improve, a team like the Royals might sign a free agent for that spot and use Hochevar for a year setting up. Could happen.
Closer: Joe Nathan
Next in line: Jesse Crain
Don't forget: Jose Mijares
Thoughts: Nathan remains one of the top closers in the game, a top-5 fantasy pick for saves, but the Twins are often a hunting ground for fantasy owners to get solid middle relief. Watch Mijares, the large, unhittable, Venezuelan lefty become a J.P. Howell-type whom fantasy owners love, even if he doesn't get saves.
Closer: Mariano Rivera
Next in line: Damaso Marte
Don't forget: Joba Chamberlain
Thoughts: First of all, I think Chamberlain should and will be a starting pitcher, but certainly the possibility exists that his arm won't comply. Also, one would expect the Yankees to acquire a veteran right-hander to help set up Rivera, someone more experienced than Jose Veras.
Closer: Joey Devine
Next in line: Brad Ziegler
Don't forget: Santiago Casilla
Thoughts: Who was the closer in September, and why am I dissing him? I'm not, really. The submariner Ziegler came out of nowhere and was terrific, but Devine has "closer" stuff, whatever that is. He misses bats. He strikes people out. He keeps people off base. I think this is an open competition, but if I was drafting today, I think Devine wins the job.
Closer: Matt Capps
Next in line: John Grabow
Don't forget: Craig Hansen
Thoughts: The underrated Capps has 40 career saves. It wouldn't surprise me if he garnered that many in 2009 alone. He has the ability. The Pirates just need to get him more leads. As for Hansen, until he can throw strikes consistently, avoid him at all costs. I just think the Pirates will -- and can -- be patient with him.
Closer: Heath Bell
Next in line: Mike Adams
Don't forget: Cla Meredith
Thoughts: Bell has been one of the top set-up men in fantasy for two seasons, compiling 57 holds. In a bandbox ballpark, I might be concerned and think that Adams, once upon a time a closer candidate in Milwaukee, would have a shot. Adams did have a better 2008, you know. Trevor Hoffman is gone, and sometime in May, I think Padres fans will be longing for security in the pen.
Closer: Brian Wilson
Next in line: Jeremy Affeldt
Don't forget: Sergio Romo
Thoughts: Wilson didn't have the greatest numbers, but the low-scoring Giants delivered plenty of save chances. The free-agent signing of Affeldt should help bridge the gap from Tim Lincecum's leads better. Keep an eye on the hard-throwing Romo, as he could pile up the holds.
Closer: Troy Percival
Next in line: Dan Wheeler
Don't forget: Grant Balfour
Thoughts: Very odd situation here, because the Rays gave Percival a two-year deal, and if he's healthy, I think they feel obligated to let him pitch the ninth inning. For most of 2008, Percival did pitch well. Health is, of course, the big issue. Balfour looks to me like the team's best reliever by far, and I could see him vault into the role over homer-prone Wheeler. If I'm projecting save totals for 2009, I could see all three right-handers get double digits, which is obviously not what fantasy owners want. By the way, forget about David Price in the bullpen. He's the future ace.
Closer: Frank Francisco
Next in line: C.J. Wilson
Don't forget: Eddie Guardado
Thoughts: Francisco was terrific after the All-Star break, allowing 13 hits in 25 1/3 innings, but you might look at his low save total and assume he can't close. He can. So can Wilson. The Rangers might take a look at older, veteran closers for a year, like Trevor Hoffman, and Guardado could be brought back and vault everyone.
Closer: B.J. Ryan
Next in line: Jesse Carlson
Don't forget: Brandon League
Thoughts: There's little reason to be concerned about Ryan's health at this point, and the Blue Jays will have depth behind him, meaning if you try to guess who's next, chances are you'll miss. Carlson and Scott Downs are portsiders, and the emerging right-hander League fills a void the injured Jeremy Accardo couldn't in 2008. If only the Jays had rotation depth.
Closer: Joel Hanrahan
Next in line: Saul Rivera
Don't forget: Steven Shell
Thoughts: Hanrahan is a big strikeout right-hander who remains a bit prone to wildness and the home-run ball, but there's not much here to make him fear for his job. He should threaten for 30 saves in 2009. Any good arms the Nats have are ticketed for the rotation.
Eric Karabell is a senior writer for ESPN.com who covers fantasy baseball, football and basketball. He has twice been honored as fantasy sports writer of the year by the Fantasy Sports Writers Association. His new book, "The Best Philadelphia Sports Arguments," was published by Source Books and is available in bookstores. Contact Eric by e-mailing him here.


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Decision makers
- President Barack Obama
President Barack Obama STOP the immediate suffering that deportations are causing deeply in our community.
- President Barack Obama
President Barack Obama,
As Congress takes up the work of including the 11 million who call the US home but are yet to be fully included because of their immigration status, more than 1,100 people are deported – separated from their families and loved ones – each day that the debate goes forward. Now that a bi-partisan framework has been presented in Washington, it only makes sense to provide relief from deportations for those who would be included in the bill.
The immigration reform debate is not just policy; it is our future in this country. We are not just numbers!. We are our families and entire communities!. And it is our voices, fully at the table, that will prevent the debate from becoming any more toxic.
President Barack Obama STOP the immediate suffering that deportations are causing deeply in our community.
A suspension of deportations while Congress seeks immigration reform would extend the relief your Mr. President has granted Dream-eligible youth to their families and broader community. It moves us down the road to citizenship and removes the deportation and unjust enforcement from being barriers to reform.
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Freezing A Cake Change Quality Of Cake?
Decorating By AngelinaMomof3 Updated 13 Sep 2010 , 2:23pm by AngelinaMomof3
I am making my first carved car cake.. It's a dirt racing car and the top is not like a nascar car that can be filled with cake.. I plan on making the top out of hardened fondant so that it's see thru. My question is, does freezing a cake change the taste, texture, or it's structural integrity? Since it's my first I want to bake it and carve it now so that I can get it just right. Also if I bomb at it I have time to make another. I also need to have the dimensions of the top right so that I can have the 'roof' dried before I put the cake together. I really can't do this unless I have the bottom part to work with. I want to bake the cakes today and start carving tomorrow and then freeze it so that next Tuesday I can decorate it.. Any help is greatly appreciated. Thank you!
Hopefully the image attached. This is the car I am making.
I have recently started freezing my cakes, they seem to be just fine, even more moist than before you freeze them.
Im not sure about carving from frozen/ after its been froze. But I have one in the freezer right now that I have to do a simple carve on, on Thursday, I'll let you know how well it did.
I plan on carving it after it's frozen because everyone says it's much easier. I just didn't want the cake to not taste fresh or end up tasting like a freezer.. I have freezer wrap and aluminum foil to wrap it in but wanted opinions on how other peoples cakes have turned out!
Thank you!!
Honestly, I believe it changes the quality of the cake...makes it moister!
I get rave compliments and have noticed it myself when I freeze first. Ironically, I only don't freeze if I don't have enough time. I try to bake ahead on purpose so I can freeze.
I always freeze, wrapped well, and the cake benefits from it. Good luck on your car, can't wait to see the pictures!
Thank you all!! My daughters kindergarten teacher wants it for her husband. It's going to be modeled after his actual race car. They want strawberry and chocolate.. You guys made my decision easy! I'm baking today!


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I can design a PCB that can fullfill any electronic function you need. For example a control board for an automatic candy dispenser that can produce sounds and flashing lights. I am able to design from scratch or from your electrical schematic. Consultation is free and there is minimal cost to you during the design process. You will only pay for the final product / PCBs. Tell me what electronic function you need and I will produce a PCB that can fullfill your needs.
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Dynamic. Diverse. Unified. Imaginative. That's the spirit of Europe, evoked by 10 posters created to celebrate Europe Day, 9 May 2010.
Now it's your turn to pick the winning poster that best captures your feelings about Europe. The winning poster will be used for the annual Europe Day celebration, a day for Europeans to mark the achievements of the European Union in bringing the citizens of 27 nations together in a common cause and to debate the future.
Before you vote, here is what you need to know:
• Europe Day is the EU's birthday. The date of 9 May has been chosen because on that day in 1950 the French politician Robert Schuman presented his proposal to create an organised and peaceful Europe.
• The 10 posters have been chosen by an independent jury from among 1,703 submitted by graphic design students from across Europe in a competition to create the best poster to represent Europe Day.
• Using the theme "I love Europe", the students were asked: what does Europe mean to you today? What exactly is it that you love about Europe and the European Union? And how would you express your feelings?
• The winning poster will be published in the EU's 23 official languages.
Join in the fun by viewing the 10 posters and voting online.


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Making pizza from scratch, frozen, or the type that appears at your door an about an hour.
Shows: The Office and Bored to Death. Battlestar Galactica, Psych, Burn Notice, Food Network, Football, Warehouse 13, AMC The Walking Dead, Being Human, Eureka.
Movies: I like these a lot, frankly discussing favorite movies would be better than for me to list them.
Books: Bill Shakespeare, Dan Brown, Ms. Rowling, Don Miguel Ruiz, Klosterman, Randolph Lalond, more to come as I read. Recent title's The Wind Up Girl, The Hunger Games Trilogy, and many articles from Men's Health. DC comics and Image.
Artistic movement: Impressionism. Kinda the standard answer.
Cultural experience.
Great friends.
A comfortable bed
Plenty of time to dream large while awake and asleep.


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Pork Steak
Recipe by Barb G.
My husband LOVES this pork steak. It is fork tender, tasty & easy to make.
Top Review by Chef 920429
Barbara,this recipe is delicious!! It really is fork tender,and my husband says it's a keeper. I changed one thing~~~I must be the only person in the world that dosen't like dry onion soup mix,I used instead a can of french onion soup. I didn't use the water,and the gravy turned out perfect.Oh,I did chop the mushrooms. I want to thank you very much for sharing this recipe.Also thank you for the review on my Chicken Ala Booze.I posted a thank you on the Message Board and Thank You's.But I guess you never check in.Come join in the forum's it's a lot of fun.
See Discussion:60 Reviews 1 Tweak
Ingredients Nutrition
- 2 tablespoons canola oil
- 4 pork steaks
- salt and pepper
- garlic powder
- 1 large onion, chopped
- 1 cup fresh mushrooms, sliced or 2 (4 1/2 ounce) cans sliced mushrooms
- 2 (10 3/4 ounce) cans cream of mushroom soup
- 1 3⁄4 cups water
- 1 (1 ounce) package dry onion soup mix
- 1 tablespoon Worcestershire sauce
Directions See How It's Made
- Preheat oven to 350 degrees.
- Heat oil in large skillet over medium-high heat.
- Brown steaks on each side.
- While browning, season steaks with salt, pepper, and garlic powder.
- Transfer steaks to a 9x13 inch casserole dish.
- Sauté the onions and mushrooms in the same skillet.
- Add water, Worcestershire sauce, dry soup mix, and mushroom soup; mix together until sauce forms.
- Pour sauce over steaks.
- Cover dish with aluminum foil.
- Bake in preheated oven for 90 minutes.


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Question: What s the difference between a secured bond and an unsecured
What's the difference between a secured bond and an unsecured bond?
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text: Home iOS Slideshow The Week in iPad Cases: Twelve South's classic BookBook gets an update This week's roundup of new iPad cases brings you a mix of fancy backpacks, padded sleeves, folios, and transparent shells. By Emanuela Corso and Marco Tabini, Macworld | Feb 7, 2016 7:00 AM PT Share All Slides SLIDEFEATURED PRODUCTS ...plus, a cool new carry-all from Waterfield Designs, and... Case Logic Griffin HEX Incase Just Mobile Spigen Targus Twelve South Waterfield Designs Share this Slideshow Direct link: ...plus, a cool new carry-all from Waterfield Designs, and more This week's roundup of new iPad cases brings you a mix of fancy backpacks, padded sleeves, folios, and transparent shells. Read on! See larger image Case Logic The Evolution Backpack (all iPad models and iPad Pro; $43) is roomy and designed to keep all of your gear safe. It comes with a dedicated sleeve for your iPad, a front pocket panel for smaller items, and top and bottom grab handles for extra convenience. You can even keep a water bottle within reach, thanks to its mesh pockets on the sides. See larger image Griffin To make your commute easier, the Survivor Briefcase (all iPad models and iPad Pro; $190) gives you plenty of padded room for your iPad, MacBook, and iPhone.This weatherproof briefcase has been tested to withstand drops from up to six feet, sports a sealed zipper to keep out excess moisture, and comes with a number of compartments to neatly organize all your belongings. The Survivor also features a removable shoulder strap and a handle, and its velcro back pad slips let you easily attach the bag to a luggage handle. HEX The Calibre Black Sneaker Duffel (all iPad models and iPad Pro; $159.95) is a duffel bag tailor-made for all your high-tech equipment.Finished with a water-resistant coating, the bag includes a faux-fur lined main compartment for your iPad, two side pockets for your sneakers, and a detachable shoulder strap for hands-free carrying. See larger image Incase The Slim Sleeve (iPad Pro; $49.95) features a soft lining that helps protect against scratches and prevent damage from bumps and drops. It comes with a zippered closure to keep your iPad in place, and is available in a heather pattern in black or khaki. See larger image Just Mobile The barely-there TENC (iPad Pro; $49.95) is a self-healing back shell that keeps your iPad in pristine condition without adding unnecessary bulk.Compatible with the Smart Cover and the Smart Keyboard, this transparent case features cutouts for the iPad's ports, buttons, and camera. See larger image Spigen The Klasden 3 (all iPad models and iPad Pro; $100) is a modern-looking backpack that doesn't skimp on functionality.Available in gray or black, the Klasden 3 features a synthetic fur-lined sleeve for your iPad, several zippered and open pockets for your accessories, and padded shoulder straps for a confortable fit. See larger image Targus The Safe Fit (iPad Air 2; $30) features a folio layout with shock-absorbing corners for extra protection against everyday accidents.Tested to withstand drops from up to four feet high, the case doubles as a stand with support for multiple angles in landscape or portrait orientation, and is compatible with the iPad Air 2's magnetic sleep/wake feature. See larger image Twelve South The newly upgraded BookBook (iPad, iPad Air, iPad Air 2, iPad mini, and iPad mini 4; $80) sports two hardback covers, reinforced corners, and a handmade spine designed to disguise your iPad as a gorgeous vintage book.The leather case doubles as a stand in landscape orientation for typing and viewing, features a dual zipper with leather pulls for safety, and comes in brown, black, or red. See larger image Waterfield Designs The Zip Brief (iPad Pro; $189) is a carry-all with a dedicated enclosure for your iPad Pro and two plush pockets for your accessories. It features handles and a shoulder strap, and sports an additional front pocket for your iPhone. It comes in Black Leather/Black Ballistic, Chocolate Leather/Black Ballistic, Grizzly Leather/Black Ballistic, Black Leather/Waxed Canvas, Chocolate Leather/Waxed Canvas, or Grizzly Leather/Waxed Canvas. Next Up: Check out these related slideshows The Week in iOS Accessories and Cases: Baby's got HandL's... The Week in iOS Apps: Listen to your favorite longform... The Week in iOS Accessories and Cases: Louis Vuitton brings... The Week in iOS Apps: A Microsoft app that sees for you The Week in iOS Accessories and Cases: Pi Case does a... Get over 26 hours of professional photography training for under $35 - Deal... 65% off Etekcity 2 Pack Portable Collapsible LED Camping Lantern - Deal Alert Amazon Temporarily Discounts Echo from $179 to $100 - Deal Alert Related Slideshows The Week in iOS Accessories and Cases: Baby's got HandL's new phone... The Week in iOS Apps: Listen to your favorite longform articles on... The Week in iOS Accessories and Cases: Louis Vuitton brings luxury to... The Week in iOS Apps: A Microsoft app that sees for you The Week in iOS Accessories and Cases: Pi Case does a little bit of... 12 sweet cases for the new 10.5-inch iPad Pro You Might Like Email a friend To Use commas to separate multiple email addresses From Privacy Policy Thank you Your message has been sent. Sorry There was an error emailing this page.


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Check results of a key sixth race
ARCADIA, Calif. - Every race 2-year-old filly Major Idea runs is better than the one before. Friday at Santa Anita, she must continue improving in order to win the $50,000 Hidden Light Stakes.
Six juvenile fillies entered the mile turf race, which is the seventh on the card. By post time, Major Idea's form lines will be easily deciphered. That is because the filly Major Idea beat by a length in a maiden race at Del Mar - Alashir's World - was scheduled to start favored in Wednesday's sixth race. A win by Alashir's World would flatter Major Idea. A poor effort by Alashir's World may send handicappers looking elsewhere.
There are five alternatives. They include Bobby Frankel-trained European imports Chope Mockery and Gotdream; Mac Melody, whose European form is stronger than that of either Frankel shipper; Margaret's Fancy, who had a troubled trip in her U.S. debut; and longshot Skippingtomontana.
Major Idea is a daughter of Cherokee Run, owned by The Thoroughbred Corporation and trained by Neil Drysdale. She finished sixth to Buffythecenterford in her debut; second to Santa Catarina next out; then stretched to two turns and won a maiden turf race by a length. In the nearly two months since, Major Idea has worked steadily at Hollywood Park, while shipping twice to Santa Anita for turf works over the local surface.
The Hidden Light is the principal prep for the Grade 3 Miesque Stakes on Nov. 29 at Hollywood, the first day of Hollywood's autumn turf festival. The three-day turf festival includes six graded turf stakes, and typically attracts several European imports. Two showed up early, and will race Friday for Frankel.
Chope Mockery won 2 of 4 at minor tracks in France, and makes her U.S. debut for owner Edmund Gann. Gotdream also won 1 of 2 at minor tracks, and starts for owner John Amerman. Mac Melody won 2 of 3 in Europe, including a $75,400 stakes in Italy, and returns to her preferred surface after being overmatched in the Del Mar Debutante on dirt.
Margaret's Fancy was eliminated early in her U.S. debut last month. She steadied hard on a roughly-run first turn at Fairplex, tried to re-rally, and missed by a half-length. She previously won 2 of 3 on minor European tracks, and is unproven over a distance of ground.
* A two-day pick six carryover into the Wednesday card attracted pick six wagers of $1,947,163. Including the $520,536 carryover, the gross pick six pool was $2,467,699.
:: Subscribers: to purchase past performances for Santa Anita.
:: Non-subscribers: to purchase past performances for Santa Anita.


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Puducherry, May 4: As part of its initiatives to set up Energy Education Park in each State and Union Territory across the country, Union Ministry of New and Renewable Energy has established one such park in Puducherry.
An official release said that the purpose of the park was to provide play way method of education on importance of energy, different types of energy, their renewable sources and generation technologies.
The park has been set up on the precincts of the Puducherry Science Centre cum Planetarium. The park has been set up in association with the Renewable Energy Agency Puducherry at a cost of Rs 2 crores and the cost of the project has been equally shared by the Central Ministry and Puducherry government, the release said.
The park consists of an exhibition hall for indoor exhibits, a lush green landscaping for outdoor exhibits. The exhibition hall has been designed as a green building which utilises the natural sources for lighting and cooling.
Puducherry government has planned to establish a training centre in the exhibition hall to impart hands on training to the students of Industrial Training Institutes and Polytechnics to bring to focus the importance of sustainable energy.


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New car registrations in the 29 European markets covered by JATO Dynamics showed the current positive sales trend continued during April, with 1.32m units sold, which is 108,000 units more than the total recorded in April 2015. This was higher than the growth seen in March 2016 (+5.6%) and in April 2015 (+6.9%). YTD volume totalled 5.25m cars, which is 8.3% higher than total registrations between January and April 2015. The March SAAR came in at 15.38m units.
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Former United States President Jimmy Carter has reportedly come out in support of National Security Agency whistleblower Edward Snowden.
According to German news source Spiegel Online, Jimmy Carter has not only defended the NSA leaker but has also condemned U.S. global 'spying' efforts.
Carter said, "America has no functioning democracy," while speaking at a meeting of the "Atlantic Bridge" in Atlanta. Ex-US President also added, "I think the invasion of privacy has gone too far," Carter reportedly told CNN. "And I think that is why the secrecy was excessive." Praising Snowden's effort to help bring out the classified information through the leaks could be useful (and not treacherous) because they inform the public."
This is a very important statement for the reason that it is coming from a former United States president, and a "democrat" president for that matter. This gives much weight to the anti-NSA snooping argument that U.S. was wrong to carry out unauthorized mass surveillance programs.
Jimmy Carter has been quite vocal about his views regarding United States abandoning its role as the global champion of human rights. Last year, he wrote an op-ed in The New York Times pointing out that 'certain laws had canceled the restraints in the Foreign Intelligence Surveillance Act of 1978 to allow unprecedented violations of [Americans'] rights to privacy through warrantless wiretapping and government mining of our electronic communications.'
And that's what exactly has been happening. The top secret, mass 'snooping' surveillance programs such as PRISM and Boundless Informant, according to Snowden's leaks, were being used to not only spy on American people but also on people (and governments) of other countries of the world.
Although, according to the German news source, Jimmy Carter expressed his pro-Edward Snowden views to CNN, there is not much (or any) reporting found on his statement in the mainstream media. The news is however being shared on social media platforms such as Reddit and Twitter and people are wondering as to why major news organizations are not interested in covering former U.S. president's statement over the NSA scandal which undoubtedly holds a lot of impact and importance in U.S. politics.
Or perhaps this is not at all surprising given the fact that several attempts are being made to 'tailor' news stories being manufactured and going into the U.S. But this is just an assumption. Just an assumption.


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AgustaWestland and Kanematsu Corporation announced lasr week they were awarded a contract by the Japan National Police Agency (JNPA) to supply a further five AW109 Power Law Enforcement Helicopters as part of an on-going program to modernize the Police helicopter fleet.
The 2008 order represents selection of the AW109 Power for the fourth consecutive year. This order will bring the total number of AW109 helicopters in service with the JNPA to twenty-one and continues AgustaWestland´s growing share of the Japanese light twin engine market. AgustaWestland expects this growth to continue over the coming years.
The order also builds upon the recent order by the Tokyo Metropolitan Police for a second AW139 helicopter. In March 2008, the first AW139 maritime patrol and search and rescue helicopters were delivered to the Japan Coast Guard bringing the number of AW139 helicopters operating in Japan to four.
According to Aero-News.Net


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Just as all of us in Chicago were beginning to recover from the city's rejection by the International Olympic Committeecomes news that is even harder to swallow:
"Leafy greens, eggs and tuna are on the top of a list of the 10 riskiest foods regulated by the Food and Drug Administration," according to a release by the Center for Science in the Public Interest.
As we mull our menu selection for lunch, try a forkful of this information: Between 1990 and 2006, The Center for Science in the Public Interest used data collected from the Centers for Disease Control and Prevention as well as other sources to identify 363 outbreaks linked to iceberg lettuce, romaine lettuce, spinach and other leafy greens "variously contaminated with E. coli, Norovirus or Salmonella." This caused at least 13,568 people get sick. Possible culprits in the contamination include the old standard -- manure, plus contaminated irrigation water and poor handling practices, according to the CSPI. For those of us who do not routinely sprinkle our salads with flecks of manure, this is a cause for concern.
Over the same time frame, the CSPI found a linkage between eggs, 352 outbreaks and 11,163 illnesses thanks to that E. coli thing. Tuna? Some 268 outbreaks and 2,341 illnesses were found. Over the past 17 years of research the CSPI also noted that despite what it calls a "limited consumption," oysters could be linked to 132 outbreaks causing 3,409 illnesses. The center doesn't explain its view that consumption of oysters is limited but I'm betting that any food with the consistency of phlegm usually starts off with a disadvantage in the food-consuming sweepstakes.
Potatoes, yes even potatoes, were linked to 108 outbreaks and 3,659 illnesses. Rounding out the top (or bottom) ten are cheese, ice cream, tomatoes, sprouts and berries. And keep in mind, most food-borne illnesses are never reported, so the center says this is the tip of the iceberg (lettuce.)
It makes one think of what could possibly be a safe lunch. Two slices of white bread with nothing between them?
And all of this comes on the heels of the disturbing New York Times expose on the ground beef industry, which should have been the biggest boost for a vegetarian lifestyle in history were it not for this new study I'm writing about that tells us you can get really, really sick from vegetables too.
I should point out that the CSPI release says this is no reason to forgo the occasional salad Nicoise, but because so many of these supposedly healthy foods are supposedly being regulated by the Food and Drug Administration, the Senate must follow the House and pass legislation pending now that would reform food safety laws.
Out here in the Midwest, farmers grow a lot of leafy vegetables. So this report will probably be met with considerable consternation, if not outright opposition to implementation of more federal regulation. Besmirching tuna as a credible edible is also probably going to generate some blowback from the fishing industry.
But the CSPI says these outbreaks "give the best evidence of where and when the food safety system is failing to protect the public." It would seem to suggest that the failure is glaring and widespread.
Think about that the next time you have a yen for tuna salad. Me? I've lost my appetite.


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|Reviews for Unicorns
| smut1956 chapter 1 . 9/9/2010
At least you give us dramatic hormonal true adults and for that I say: Go Team! Clever twist on a cruel realty for Mac/Stella fans.
Fun and funny.
One small correction for you: in this case you mean "rein" instead of "reign" unless you have Mac as the ruler of the lab which could also work.
Thanks for sharing.
| DNAisUnique chapter 1 . 5/23/2010
Okay, I loved this quote when you first mentioned it, but it's hella funny coming from Mac. I can actually see him saying that.
Loves me some SMacked. Yipee!
Bahaha, way to turn the Twilight stuff around and make it SMac-esque.
Team Stella FTW!
Excellent fic. *bows to a master*
| messermonroeforever125 chapter 1 . 5/19/2010
HAHAHAHA that was so great. I loved that you were also able to tie in Reed...oh Twilight. Fantastic job :)
| BAUMember chapter 1 . 5/19/2010
This was a lovely wee story i really liked it cuteness so much,,,team smacked rocks love them ...
| xShippyAngelx chapter 1 . 5/19/2010
wow, babygurl0506. that was indeed a short one-shot... but *really* awesome! ;) nice work!
| Go Smacked chapter 1 . 5/19/2010
I really love it! Very nicely written and I love the " team Stella" part. Very well incorporated!
I'm on Team Stella too!
| shawdoo chapter 1 . 5/19/2010
Loved it! Very cute!
| ab89us chapter 1 . 5/19/2010
| Andorian Ice Princess-AIP chapter 1 . 5/19/2010
hmm shoulda read this yestserday b/c nothing can lift my mood right now. however you did put a much needed smile on my face so thank you :D
| SMackedCaskett chapter 1 . 5/19/2010
Cute :)
but well, really, who's not Team Mac or Team Stella? ;) or Team Mac/Stella possibly.
| Lime Sweet Pea chapter 1 . 5/18/2010
Hey! This was too cute. I definitely enjoyed it. I liked the humorous side of Mac you wrote!
Great job!
| piper maru duchovny chapter 1 . 5/18/2010
I'm Team Mac as well. :D
Loved it, Darling
| Miyukiseta chapter 1 . 5/18/2010
My God, this was so cute!
As much as I hate Twilight, I liked the reference to it. "Hormonal, dramatic young adults." So true! (lol)
Thanks for the dedication!
| SMackedFan chapter 1 . 5/18/2010
lol! This made my night! I loved it! "I just have to tell myself they're only horses that stab people" haha! Oh Mac...
And btw; I'm with Stella, Team Mac is where it's at ;) hehe. Jacob and Edward got nothin on Mac ;)


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This property has been removed by the agent. It may be sold or temporarily removed from the market
2 bedroom lodge for saleOre, Hastings, East Sussex
Property Description
Key features
- 2 Bedrooms
- Double Glazing
- Gas Central Heating
- Bar and Restaurant
- Fishing Lakes
- 2016 Site Fees Included
- Woodland Location
- Swimming Pool
- 50 Week Season
Full description
Tenure: Leasehold
***QUOTE `LONGSONS 10` FOR A FURTHER 500 POUNDS OFF PURCHASE PRICE (not to be used in conjunction with any other promotional offers)***
Finance packages available with low cash deposits and affordable monthly repayments.
The park is uniquely set in 1066 Country on the edge of the ancient coastal Cinque Port town of Hastings and is the perfect location for your luxury holiday home.
The park is hidden in a gently sloping valley stretching out over 100 acres of woodland, which is host to an abundance of wildlife and beautiful natural flora and where you can explore with a myriad of footpaths. Our indoor pool is unique and gives the impression you could be swimming through underground caves!
Take a stroll around the fabulous fishing lake, the parks centre piece and the perfect setting for the family picnics on long summer days.
The Holiday Park offers a warm welcoming atmosphere in which families feel safe - a pedestrian friendly environment in which cars take second place! Children can play away from busy roads, whilst parents and grandparents can relax and spend time with friends old and new, without the worry of who`s driving home.
Facilities to include:-
-Stunning Fishing Lake (NRA license required)
- Boating Lake
- Crazy Golf Course
-Unique Indoor Pool with Spa Bath and Sauna
-Family Entertainment Bar with Great Food and Sky TV
-Free WI-FI Internet Access in Club Area
-Amusements and Small Paly Area
-Small Shopping Kiosk for Essentials
Please note we have not tested any apparatus, fixtures, fittings, or services. Interested parties must undertake their own investigation into the working order of these items. All measurements are approximate and photographs provided for guidance only.
Listing History
Map & Street View
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Market Info
Disclaimer - Property reference 6288. The information displayed about this property comprises a property advertisement. Rightmove.co.uk makes no warranty as to the accuracy or completeness of the advertisement or any linked or associated information, and Rightmove has no control over the content. This property advertisement does not constitute property particulars. The information is provided and maintained by Harvey Longsons, Swaffham. Please contact the selling agent or developer directly to obtain any information which may be available under the terms of The Energy Performance of Buildings (Certificates and Inspections) (England and Wales) Regulations 2007 or the Home Report if in relation to a residential property in Scotland.
Map data ©OpenStreetMap contributors.


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It looks like I my only internet access over the next 2 weeks will be over UMTS with my 智能手机 (zhìnéng shǒujī) smartphone.
Despite the amazing screen, I probably won't be able contribute news, but I will be preparing a raft of new phonetic character maps to upload in January.
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|Home > Erwinn
♂ Erwinn
What does Erwinn mean?
Erwinn [er-winn] as a name for boys is of Old English derivation, and the meaning of Erwinn is "boar friend". Erwinn is a version of Irwin (Old English): author Irwin Shaw.
ASSOCIATED WITH old english, friend
VARIANTS Irwyn, Irwinn, Erwyn, Erwin▼CREATIVE FORMS
(female) MIDDLE NAME PAIRINGS
Erwinn Eamon (E.E.), ..
How popular is Erwinn?
Erwinn is an unusual first name for males. Erwinn is an equally unusual last name for all people. (2000 U.S. DEMOGRAPHICS)
Which version is better?with its source form and related names. Irwin and Erwin are the popular related forms of Erwinn (NOT RANKED). Other variants, like Erwyn, are seldom used. Adoption of these forms of Erwinn was at its highest in the 1920s (MEDIAN #270). (TOP 2000 NAMES, 2015)
Similar Names
Erwinn is pronounced similarly to Arian▲, Arien, Arin, Arion, Arrin, Arwin, Arwyn, Eirian, Eirwyn, Eran, Erin▼, Eron, Erron, Erwynn, Eurion, Orin, Orion▲, Orrin, Orwin and Orwynn. Other recommended names are Aswinn (see Aswin), Corwinn (see Corwin), Eadwinn, Edwin▼, Elwin▼, Elwinn (see Elvin), Elwynn, Erling, Ermin, Ermino, Ern, Ernie▼, Ernin, Erno, Ervin▼, Ervine, Erving, Ewin, Ewing, Ewynn, Gwinn, Kerwinn, Merwinn (see Mervin), Norwinn (see Norvin), Oswinn and Unwinn (see Unwin). These names tend to be more frequently used than Erwinn.See names in meaning and etymology.


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Fluffy Cream Cheese Frosting
READY IN: 5mins
Recipe by Pismo
I found this recipe on the America's Test Kitchen (Cooks Illustrated) website. I like it because it has a very light cream cheese flavor and isn't too sweet or overpowering.
Ingredients Nutrition
- 4 tablespoons unsalted butter, softened but still cool
- 1 cup confectioners' sugar
- 4 ounces cream cheese, softened
- 3⁄4 teaspoon vanilla extract
Directions See How It's Made
- With electric mixer on medium-high speed, beat butter, sugar, cream cheese, and vanilla until light and fluffy and no lumps remain.


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Watch: Bill Hader and Kristen Wiig Are Better Reporters Than Local News Guy
Young journalists take note: if you're interviewing talent for a movie he or she is in, watch the movie first.
Apparently, this is something foreign to Denver reporter Chris Parente, who talked to Bill Hader and Kristen Wiig about The Skeleton Twins last week.
… More »


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Restaurants and Clubs
We interviewed thousands of people and prepared a list of places which are loved by most of you. We contacted them all and what you see here is how many of them will be happy to serve Club Insomnia Members with discounts, offers and much more!
List Of Restaurants
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