Fight fans will get a nice treat this week when the UFC holds three events in three days, culminating with a stacked card for UFC 194. UFC Fight Night 80, which takes place in Las Vegas, kicks off the three-day extravaganza.
This is the card for prospects. The UFC brings a ton of talent to UFC Fight Pass that could turn out to be top names in the future of their respective divisions. Of course, the biggest prospect on that list, Paige VanZant, headlines this card against the first-ever UFC strawweight title challenger, Rose Namajunas. VanZant has garnered many headlines in the lead-up to this fight, but she will get a tough submission specialist in Namajunas. Namajunas is a replacement for Joanne Calderwood, who pulled out of the fight due to injury.
The co-main event features another budding star on the UFC roster. Sage Northcutt looks to continue building on his hype against Cody Pfister. Northcutt blasted onto the scene with a quick TKO victory over Francisco Trevino in his UFC debut. At 6-0 and only 19 years old, Northcutt has been highly touted and marketed for a fighter who only just made his Octagon debut. Now, he gets to prove his debut wasn't a fluke against Pfister. Pfister is coming off a unanimous decision victory in his last fight over Yosdenis Cedeno.
Also on the main card, New Jersey native Jim Miller takes on The Ultimate Fighter 15 winner Michael Chiesa in a lightweight tussle. And at middleweight, Elias Theodorou will look to make it four straight victories in the UFC and keep his undefeated record going against Brazilian knockout artist Thiago "Marreta" Santos.
UFC Fight Night 80 starts with preliminary-card action beginning at 6:45 p.m. ET on UFC Fight Pass. The main card will also air on the UFC's exclusive online-streaming service beginning at 10 p.m. ET. This edition of Toe-to-Toe is brought to you by the creative Combat Press minds of Vince Carey and Sal DeRose.
The UFC brass really likes Paige VanZant. They've already started pushing her as a top star and now she's headlining a card opposite Rose Namajunas. If VanZant can get past Namajunas, she'll have four straight UFC wins. Will the UFC continue to bring her along slowly, or will there be too much temptation to insert the young star into a title fight?
Carey: I'm really liking what VanZant is bringing to the table so young in her MMA career. She's only 21 years old, yet she possesses an "it" factor that already earned her a Reebok sponsorship and comparisons to Ronda Rousey. She currently holds a 3-0 record inside the Octagon and she seems to get better every time we see her. There's a lot to like. Plenty of fight fans look at her and see a future star, and not only do I completely agree, but I'm starting to look at her as a future champion as well. Of course, before PVZ can even think about wrapping gold around her waist, she needs to get past Namajunas on Thursday night. That's going to be a tough outing.
VanZant has been great at pushing the pace and taking control of the cage during her UFC career. Her clinch work especially stands out as a major weapon in her arsenal. Her game plan against the smaller and exceptionally dangerous Namajunas is likely going to be to take the same approach as Carla Esparza did in her title bout against Namajunas. VanZant, like Esparza, will look to completely shut down Namajunas with her strength and grappling prowess before capitalizing once her opponent's gas tank starts to give out. Obviously, that's a lot easier said than done against a tough submission artist like Namajunas, but if "12 Gauge" can wear her out against the fence early, this fight could easily end inside the first few rounds. VanZant's cardio and pressure are the best in the division and Namajunas isn't going to be able to keep up.
VanZant will take home the victory in relatively dominant fashion, so the real question lies in where she ends up next. As badly as the UFC would love to jump on the hype train and make a Joanna Jędrzejczyk-VanZant title fight, it's a bit too early for that. VanZant could use a little more seasoning before jumping straight into the deep end, and besides, the promotion already has a couple of title challengers on deck. Claudia Gadelha has been next in line for Jędrzejczyk for a while now. Even if the Brazilian can't get healthy in time to fight the champ, then Tecia Torres just needs to pull off a win as a favorite this Saturday against Jocelyn Jones-Lybarger to put her name in the hat. With Torres ranked third in the division and having handed VanZant her only loss, it only makes sense for "The Tiny Tornado" to get the next shot at the belt if Gadelha can't go.
VanZant has to win one more before getting a shot at gold, and she needs to earn it against someone else with a little star power. Michelle Waterson's name comes to mind. Waterson was forced to pull out of a fight against Torres recently. If the timing works out for a fight between the former atomweight and VanZant, it would make sense and could be a lot of fun. It could also provide PVZ a chance to earn another marquee victory before being thrown to the wolves.
DeRose: My colleague mentioned the Rousey comparison. Well, VanZant might have one more thing in common with the former champion after meeting Namajunas: a loss in the UFC. I've been on the VanZant hype train as much as anybody. She really is a good fighter, but she's not a great fighter. When it was announced a few months ago that VanZant was facing Joanne Calderwood, I originally had VanZant slated to win. However, while I felt that it was a good step up for VanZant, but thought back then that it's not like they were feeding VanZant to Namajunas or anything. Yeah, so I might have foreseen this coming. I can predict these things.
For all the reasons my colleague sees VanZant winning, I see it in favor of Namajunas. Look, we all know VanZant likes to make the striking game a brawl and uses that aggression well to set up her takedowns and progress into grappling. VanZant doesn't have the strength of Esparza nor the wrestling skills to completely neutralize Namajunas.
Now, here's the thing with VanZant. She has good grappling, but she loses a ton of positions on the ground. Namajunas isn't Felice Herrig, Alex Chambers or Kailin Curran. Namajunas has some solid grappling skills, especially off of her back. VanZant could get away with losing against her past opponents, but against Namajunas, who is known for crazy submissions, that is a huge no-no.
VanZant isn't all that technical when it comes to her game. That will be a huge problem against somebody like Namajunas, who pounces on the mistakes of her opponent. Just look at her fight against Calderwood on The Ultimate Fighter. Namajunas really dominated the fight. The 23-year-old made Calderwood look like she had never grappled more than a day in her life and eventually submitted Calderwood in the second round. Randa Markos, another heavy-pressure grappler, was also submitted by Namajunas on the show.
If VanZant wins this fight, it will be due to her heavy output on the ground that may open up a cut or really work on the cardio of Namajunas. However, it seems inevitable that VanZant will make a mistake and Namajunas will steal back the guard to quickly submit VanZant off her back.
However, if VanZant does manage to win, then the UFC really does need to hold off on granting the young prospect a title shot. Jędrzejczyk would eat her alive if they were to throw the two of them together in the Octagon right now. We've seen what the champ can do to fighters like Valerie Letourneau, Jessica Penne and the aforementioned Esparza. That trend would likely continue against VanZant, who is still green in some areas. VanZant is only 21 years old, so there is plenty of time for her to develop to eventually get a title shot. The UFC would be smart to capitalize on VanZant's momentum to bring in some high profits in a new marketable division, but common sense says the company keeps building a fighter with this kind of popularity among fans.
Jim Miller was a consistent presence near the top of the lightweight division until he ran into Donald Cerrone and Beneil Dariush and suffered back-to-back losses. He has picked up a recent win, but can he continue to rebound when he meets Michael Chiesa? Are Miller's days as a top lightweight done?
DeRose: A split decision victory is still a win, regardless of how you look at it. Sure, it was a close fight against Danny Castillo, probably one of the better middle-tier lightweights in the division, but it isn't definitive proof that Jim Miller's prior losses were just flukes against top competition. It also isn't definitive proof he is on the decline, though. This fight should tell us exactly where the 32-year-old stands in his career.
Michael Chiesa is a tough out for just about any fighter. His two losses came against some pretty good fighters in Joe Lauzon and Jorge Masvidal. Chiesa is going to look to use his size advantage here. The 27-year-old holds a five-inch edge in height and reach. Chiesa will most likely seek to make this a grind for Miller by using his size to bully Miller against the cage. Chiesa also has very solid grappling that he can use if he wants to bring the wrestler to the mat.
The size disadvantage might make it harder for Miller to use his wrestling to avoid being grinded out. Miller might also be the better striker of the two and is much more able to take a beating. There's a reason he only has one loss by knockout, which happens to have come at the hands of Cerrone, a talented striker.
The lightweight division is just far too stacked for Miller to be considered a top lightweight anymore, especially if he loses this fight. A loss will make it insanely difficult for him to make the climb back up the ladder.
Carey: It kind of bums me out that Miller isn't going to end up fighting for a UFC title. This is a guy who has won 14 fights inside the Octagon and been in some of the most exciting lightweight bouts we've ever seen, but every time he was on brink of getting a shot at gold he was shut down by one of the elite at 155 pounds. His career isn't quite over yet and he's still likely got a few years of fighting for the UFC left in him, but it's safe to say his time as a contender is gone. The back-to-back losses to Cerrone and Dariush aren't too troubling, because those are a couple of really good fighters, but the Miller we've seen in the cage during his last few outings isn't the same guy who was running roughshod through the division a few years ago.
There's a chance for Miller to get things back on track and maybe make one final push for UFC gold with a win this weekend, but it's unlikely to happen. Chiesa is reminiscent of a younger Miller at this stage of his career, and it's not just the beards. Both men have underrated wrestling and submission skills, neither is afraid to stand toe-to-toe and slug it out, and they've both been covered in blood while fighting Joe Lauzon. OK, that last one probably doesn't mean much, but you get my point. These are two pretty similar fighters, and while picking youth over experience is a risky play in most forms of life, it's not a bad idea in MMA when the fighters seem this close. Chiesa is younger, bigger and probably stronger than Miller, and he should have no problem dictating where and how this fight takes place.
Still, this is a Jim Miller fight, so we can expect to see a pretty wild and entertaining 15 minutes. The Jersey native is one of the best in the division at getting into brawls and making an otherwise inconsequential fight the one that people remember when the card is through, and that's his future in this sport. With Clay Guida and Diego Sanchez having left the 155-pound division, there's a spot open for a UFC veteran who's tough as nails and willing to fight anyone and everyone as long as they can entertain the fans and earn a paycheck. I wouldn't be surprised if Miller was the guy who ended up filling that void.
Since we've talked about Paige VanZant, we have to talk about one of the UFC's other most marketable fighters: Sage Northcutt. Is the UFC doing the right thing by easing him through the ranks? How long until he makes the jump up to face the best in the division and even contend for a title?
Carey: You know what? I'm 100 percent on board with how the UFC is treating Sage Northcutt so far. The kid is 19 years old and has gobs of potential, that much is obvious. He came off like a future star the second he entered the cage for his fight against Francisco Trevino a few months ago. After his subsequent performance set the internet on fire for a minute, the UFC easily could have overreacted and thrown him in the cage against a known commodity and sat back to see how he dealt with the pressure. Instead, Zuffa did the right thing and continued to bring him up slowly, giving him this fight with Cody Pfister to gauge exactly where he's at in the crowded lightweight division.
I'm all for building up Northcutt slowly, but I have a feeling his performance this weekend is going to fast-track him a little too much. Pfister has a chance to be a game opponent, though, and his win over Yosdenis Cedeno at UFC 189 was proof that he deserves an opportunity to make a name for himself in the UFC. However, if we're being honest, he has essentially been picked as a sacrificial lamb for Northcutt to slaughter on his way up the 155-pound ladder. I'm not necessarily saying to expect Pfister to get slaughtered on Thursday night, but the UFC is almost always uncannily good at providing its up-and-coming stars with winnable match-ups. It's obvious the company is expecting Northcutt to walk away with this one.
Northcutt will get a decent step up in competition with a win this week. Once that happens, we should have a better idea of how quickly "Super Sage" is going to be able to contend at lightweight. I'm still not completely convinced that Northcutt is the future title contender everyone is making him out to be, so don't expect any speculation here on how long it could take him to get to that point. However, I will say that I'd be extremely surprised if he was in the lightweight rankings at this time next year. Northcutt is a hell of a prospect, but he can't be crowned as the future of the division until he beats an opponent or two that can legitimize him a bit.
DeRose: Yeah, the UFC really needs to take its time with Northcutt in this division. Lightweight is arguably the deepest division in the UFC, and there are handfuls of title challengers that deserve title fights before Northcutt.
There aren't many stars who can sell cards on their own, but Northcutt seems likely to bolster that list. However, I, too, am not totally ready to crown Northcutt as future of the division. The 19-year-old got a knockout win over Trevino, who was then cut from the promotion. Whether Trevino's release was due to the weight-cut issue in his fight against Northcutt or his performance in said fight, who knows. Regardless, Northcutt needs some victories over talented opponents who are mainstays on the UFC roster.
Within the next few fights, we should see him face some middle-tier lightweights. The UFC needs to gradually raise the level of play just a little bit in each fight before finally allowing Northcutt to crack into top-10 opponents. Northcutt would probably have some tough fights against the wrestlers in the division, and we haven't really seen him tested against a top wrestler yet.
The UFC needs to continue at its current pace to help Northcutt grow as a fighter and potential face of the promotion. Some fans might not like it and say the UFC is protecting Northcutt, but, considering his age, that should be the norm. Eventually he'll have to face the best, but it won't happen for a couple of years at the least.
Aljamain Sterling and Johnny Eduardo are both currently sitting inside the top 10 of the UFC's bantamweight division, yet somehow they've found themselves buried on the prelims of a Fight Pass card. Was the UFC right in placing this bout so far down on the card and, more importantly, is there anything the winner can do to ensure this won't happen again?
DeRose: I have no earthly idea why this is on the prelims portion of a Fight Pass card. When you consider just how good Aljamain Sterling is as a fighter and the future of the division, that alone should be reason enough to put this on the main card or, at the very least, near the top of the preliminary portion of the lineup. What it may come down to is the weight class. The bantamweight division hasn't exactly received a heavy marketing push from the UFC, nor has it drawn in as many eyes as it should draw. Maybe the UFC doesn't find either fighter very marketable, but it's difficult to imagine how this could be the case.
There isn't much more either fighter can do to raise their profile with this single fight. Sterling should win this fight. He is a better overall fighter than Johnny Eduardo. Coming from the Serra/Longo camp, Sterling is very highly trained by some of the best coaches in the sport. Whether it be on the ground or striking, Sterling is the complete package. I'm very, very high on him as a potential title challenger one day. If a potential future title challenger isn't enough to make the UFC market this fight more and put it in a more prominent spot in the lineup, then nothing will.
Perhaps the UFC brass would change its mind if Sterling went on the mic and had some insane Conor McGregor-esque charisma and called out everybody in the division and their moms. Maybe he needs to go on a streak of devastating finishes, but he already has seven in his career, including two in the UFC. One of those finishes came against Takeya Mizugaki, who has been a bantamweight top-10 gatekeeper.
If the UFC wants a more marketable bantamweight division, it should start by featuring fights like this one rather than burying it on the prelims. Sage Northcutt, in just his second UFC appearance, is in the co-main event and he isn't even ranked. If anything, this division-changing fight should have been up there, but it wouldn't sell as many tickets. Gee, I wonder why. Maybe it's due to the underwhelming advertisement of the 135-pound division outside of T.J. Dillashaw?
Carey: I'm offended to the point of almost being angry about where this fight was placed on the card. Sterling is the No. 5-ranked bantamweight in the world and he can't get on a main card? Was it that important to let Elias Theodorou get some of the spotlight? I mean no disrespect to "The Spartan," who has an undefeated record and some wicked awesome hair, but come on, man. Sterling is undefeated and might be the prospect with the most potential on this entire card, and Eduardo is coming off of the biggest win of his career after knocking out Eddie Wineland last year. This is a pay-per-view main-card fight on some of the UFC's weaker offerings, and the fact that it's not even the featured prelim is more than a little ridiculous.
Ordinarily, I wouldn't be quite so amped up over something as trivial as the bout order, but I'm every bit as on board the Sterling hype-train as my colleague. There's no other way to say it: "Funk Master" is just really damn good for having less than a dozen fights to his name. After seeing him dispatch Mizugaki with relative ease earlier this year, the MMA community started to pay attention. Getting stuck on the prelims of a Fight Pass card isn't going to help him gain any notoriety, and since I've got a pretty good feeling Sterling's going to be fighting for a belt at some point in the next two years, that seems like a mistake.
As for making sure this doesn't happen again, I'll second my colleague. Sterling (if you haven't guessed, he's obviously my pick to win this one) either needs a highlight-reel stoppage win or he needs to get on the stick and cut some WWE-style promos to get the ball rolling. He has all of the talent in the world and a top-notch camp that should only make him better, but if he wants to become a name in the sport and get opportunities at big-money fights, then he needs to start speaking up.
Carey: The prelim headliner between Tim Means and John Howard is bound to be a ton of fun. Both men like to stand and trade punches, and Means is aggressive enough that the sometimes hesitant Howard is going to have no choice but to either answer "The Dirty Bird's" output or suffer another UFC loss. Howard has had a fight or two that have had the potential for excitement, but which have resulted in more than their fair share of boos from the live crowd. It's doubtful that Means is going to let that happen in this contest, though, and an aggressive "Doomsday" is the best kind of "Doomsday." Enjoy the slugfest.
DeRose: Elias Theodorou against Thiago "Marreta" Santos. This fight may be on the main card, but this is probably the best part of the card. Theodorou has been impressive so far in his UFC career. He has scored two of his three victories by way of TKO. He's undefeated and may be the bright spot in the middleweight division, especially because of his undefeated record. Theodorou could have used a step up in competition following his win over Brian Ebersole, but Santos can be as dangerous as anybody else. Whether it's his hands or his feet, Santos has knockout power. He devastated Steve Bosse in his last fight with a wild head-kick knockout. This could be a wild one, but it will go in favor of the man with the pound-for-pound best hair in the UFC, Theodorou.
DeRose: Creed. Definitely the movie Creed. You have a three-day stretch of UFC cards, and what better way to kick this off than with the next installment in the Rocky franchise? Creed was an excellent movie with some excellent and outstanding acting between Michael B. Jordan and Sylvester Stallone. Make a trip over to watch boxing — I know, I know, that other combat sport — to get you hyped up for some fights.
Carey: You know what? I second that suggestion. Creed is just awesome. It's a must-see for anyone remotely interested in combat sports, Rocky and movies in general. In fact, pair this card with Creed and then pair Creed with a friend so you can discuss the movie in between fights. Oh, and pair this card with the other two cards this weekend, too. This is a UFC fan's dream weekend, so you might as well enjoy every second of it.
MW: Kevin Casey vs. Antonio Carlos Junior Carlos Junior Carlos Jr.


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Understanding the inner workings of the human heart
August 30, 2020 August 25, 2020 northbrookdesignscom
Researchers have investigated the function of a complex mesh of muscle fibers that line the inner surface of the heart. The study, published in the journal Nature, sheds light on questions asked by Leonardo da Vinci 500 years ago, and shows how the shape of these muscles impacts heart performance and heart failure.
In humans, the heart is the first functional organ to develop and starts beating spontaneously only four weeks after conception. Early in development, the heart grows an intricate network of muscle fibers—called trabeculae—that form geometric patterns on the heart's inner surface. These are thought to help oxygenate the developing heart, but their function in adults has remained an unsolved puzzle since the 16th century.
"Our work significantly advanced our understanding of the importance of myocardial trabeculae," explains Hannah Meyer, a Cold Spring Harbor Laboratory Fellow. "Perhaps even more importantly, we also showed the value of a truly multidisciplinary team of researchers. Only the combination of genetics, clinical research, and bioengineering led us to discover the unexpected role of myocardial trabeculae in the function of the adult heart."
To understand the roles and development of trabeculae, an international team of researchers used artificial intelligence to analyse 25,000 magnetic resonance imaging (MRI) scans of the heart, along with associated heart morphology and genetic data. The study reveals how trabeculae work and develop, and how their shape can influence heart disease. UK Biobank has made the study data openly available.
Leonardo da Vinci was the first to sketch trabeculae and their snowflake-like fractal patterns in the 16th century. He speculated that they warm the blood as it flows through the heart, but their true importance has not been recognized until now.
"Our findings answer very old questions in basic human biology. As large-scale genetic analyses and artificial intelligence progress, we're rebooting our understanding of physiology to an unprecedented scale," says Ewan Birney, deputy director general of EMBL.
The research suggests that the rough surface of the heart ventricles allows blood to flow more efficiently during each heartbeat, just like the dimples on a golf ball reduce air resistance and help the ball travel further.
The study also highlights six regions in human DNA that affect how the fractal patterns in these muscle fibers develop. Intriguingly, the researchers found that two of these regions also regulate branching of nerve cells, suggesting a similar mechanism may be at work in the developing brain.
The researchers discovered that the shape of trabeculae affects the performance of the heart, suggesting a potential link to heart disease. To confirm this, they analyzed genetic data from 50,000 patients and found that different fractal patterns in these muscle fibers affected the risk of developing heart failure. Nearly five million Americans suffer from congestive heart failure.
Further research on trabeculae may help scientists better understand how common heart diseases develop and explore new approaches to treatment.
"Leonardo da Vinci sketched these intricate muscles inside the heart 500 years ago, and it's only now that we're beginning to understand how important they are to human health. This work offers an exciting new direction for research into heart failure," says Declan O'Regan, clinical scientist and consultant radiologist at the MRC London Institute of Medical Sciences. This project included collaborators at Cold Spring Harbor Laboratory, EMBL's European Bioinformatics Institute (EMBL-EBI), the MRC London Institute of Medical Sciences, Heidelberg University, and the Politecnico di Milano.
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redpajama_set_name: RedPajamaCommonCrawl


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Robin Wright is at the helm when House of Cards returns for its sixth and final season in Fall 2018
Posted by Jimmy Shah | Mar 7, 2018 | Movies & TV | 0 |
Robin Wright is at the helm when House of Cards returns for its sixth and final season in Fall 2018 — check out the new spot here:
House of Cards stars Golden Globe winner and Emmy Award nominee Robin Wright, as well as Michael Kelly, Diane Lane, Greg Kinnear, Jayne Atkinson, Patricia Clarkson, Cody Fern, Constance Zimmer, Derek Cecil, Campbell Scott and Boris McGiver.
House of Cards executive producers are showrunners Melissa James Gibson and Frank Pugliese, and Robin Wright, David Fincher, Joshua Donen, Dana Brunetti, Eric Roth, Michael Dobbs and Andrew Davies.
The series was created by Beau Willimon and is produced by Donen/Fincher/Roth.
MRC – also behind the hit Netflix series Ozark – is the studio producing House of Cards, the first original series produced for Netflix.
In 2013, House of Cards became the first original online series to receive major nominations from the Primetime Emmy Awards. The series has received 53 Emmy nominations to date, with seven wins — including the first major Emmy for a streaming service for David Fincher's win for "Outstanding Directing for a Drama Series." House of Cards received six Golden Globe nominations, and two wins. The historic series has received 11 Screen Actors Guild nominations with two wins; an AFI Award; four Writers Guild Award nominations, with one win; two BAFTA nominations; four Producers Guild Award nominations; two Directors Guild Award nominations; and a Peabody Award, among other accolades.
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Meet Outlook for Android, the application that helps millions of users connect all their email accounts, calendars and files in a convenient place. Recently redesigned, Outlook for Android allows you to do more from a powerful inbox. See what matters most first with the Focused Inbox that keeps important messages on top. Alternate between your emails and the calendar to schedule your next meeting or share your availability with just a few taps. Or take a document from your list of Files and attach it to an email with no problems.


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ANTIMICROBLAL AGENTS AND CHEMOTHERAPY, Oct. 1992, p. 2108-2117 0066-4804/92/102108-10$02.00/0 Copyright © 1992, American Society for Microbiology
In Vitro and In Vivo Antibacterial Activities of AM-1155, a New 6-Fluoro-8-Methoxy Quinolone MASAKI HOSAKA, TOKUTARO YASUE, HIDEYUKI FUKUDA, HIROSHI TOMIZAWA, HIROSHI AOYAMA, AND KEIJI HIRA*
Central Research Laboratones, Kyorin Phannaceutical Co., Ltd., Nogi-machi, Shimotsuga-gun, Tochigi, 329-01, Japan Received 6 January 1992/Accepted 17 July 1992
AM-1155 is a new quinolone with a wide spectrum of antibacterial activity against various bacteria including anaerobes and Mycoplusma pneumoniae. AM-1155 was 2- to 16.fold more active than ciprofloxacin and ofloxacin against Staphylococcus aureus including methicillin-resistant strains, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis; its MICs for 90%o of strains tested were 0.10 to 0.78 ,g/ml. The activity of AM-1155 was comparable to that of ciprofloxacin against members of the family Enterobacteriaceae, Branhamella catr*als Haemophilus influenzae, and Neisseria gonorrhoeae, but was fourfold less than that of ciprofloxacin against Pseudomonas aerugios. Against Xanthomonas maltophiia, Acinetobacter cales, and Campylobacter jejuni, AM-1155 was two- to fourfold more active than ciprofloxacin. At a concentration of 1.56 ,ig/ml, AM-1155 inhibited 901% of Bdcteroidesfragilis strains tested; its activity was 8- to 10-fold higher than those of ofloxacin and ciprofloxacin. Development of resistance to AM-1155 in S. aureus and S. epidermidis occurred at a lower frequency than did that to ciprofloxacin after eight transfers in the presence of drug. In the oral treatment of mouse systemic infections, AM-1155 was four- to eightfold more effective than ciprofloxacin against gram-positive cocci and was as active as ciprofloxacin against gram-negative rods. The efficacy of an oral or a subcutaneous dose of AM-llSS was two- to fivefold greater than that of ofloxacin. Against experimental pneumonia with Kiebsiella pneumoniae and P. aeruguiosa, AM-1155 was two- to fourfold more active than ciprofloxacin and ofloxacin. AM-1155 also had good efficacy against mouse ascending urinary tract infections with Escherichia coli and P. aeruginosa. These results suggest that AM-llSS may be a potent antibacterial agent applicable to various infections. ,
A number of new quinolones with a broad spectrum of activity against gram-positive and gram-negative bacteria have been developed during the past decade; and some compounds, such as norfloxacin (12), ofloxacin (17), and ciprofloxacin (18), have been introduced into clinical practice and have proven to be efficacious in the therapy of bacterial infections. Nevertheless, these new quinolones show only moderate activity against gram-positive and anaerobic bacteria. AM-1155, 1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid, is a new quinolone that has been developed by Kyorin Pharmaceutical Co., Ltd., Tokyo, Japan (Fig. 1). In the study described here, we compared the in vitro and in vivo antibacterial activities of AM-1155 with those of ciprofloxacin, norfloxacin, and ofloxacin. (This work was presented in part at the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy
[91.)
MATERIALS AND METHODS Antibacterial agents. AM-1155, ciprofloxacin, norfloxacin, and ofloxacin were synthesized at the Central Research Laboratories of Kyorin Pharmaceutical Co., Ltd. Nalidixic acid was obtained from Sigma Chemical Co., St. Louis, Mo. Organisms. The organisms used in this study were laboratory strains and clinical isolates which were collected between 1986 and 1990 from several hospitals in Japan. The *
organisms were kept as stock cultures in 10% skim milk at -40°C in our laboratory. Quinolone-resistant mutants of Escherichia coil and Pseudomonas aeruginosa-E. coli KEA12 (8), E. coli KEA13 (8), E. coli KE7 (7), P. aeruginosa KH4023 (10), P. aenrginosa KH4013E (10), and P. aeruginosa KH4014a (2)-were used for the study on susceptibility and inhibition of DNA gyrase supercoiling activity. E. coli MH5 and N-51 were provided by M. Inoue (Gunma University, Gunma, Japan) and S. Nakamura (Dainippon Pharmaceutical Co., Ltd., Osaka, Japan), respectively. Determination of MICs. The MICs of the compounds were determined by the twofold agar dilution method (6) with Mueller-Hinton medium (Difco), which was supplemented with 5% defibrinated horse blood for streptococci, enterococci, and Campylobacter jejuni. Chocolate agar was used for Haemophilus influenzae and Neisseria spp. GAM agar (Nissui Seiyaku Co., Tokyo, Japan) and buffered starchyeast extract agar were used for obligate anaerobes and Legionella pneumophila, respectively. The inocula were prepared as follows. All strains except streptococci, enterococci, H. influenzae, Neisseria spp., L. pneumophila, and Bacteroidesffragilis were grown overnight in Mueller-Hinton broth (Difco). Streptococci and enterococci were grown overnight in Mueller-Hinton broth supplemented with 5% defibrinated horse blood. H. influenzae and B. fragilis were grown in brain heart infusion broth plus 5% Fildes extract (Kanto Kagaku Co., Tokyo, Japan) and GAM broth (Nissui Seiyaku Co.), respectively. Neisseria spp. and L. pneumophila were grown overnight on chocolate agar or buffered starch-yeast extract agar plates. Bacterial colonies were removed just before use and were suspended in saline. The 2108
ANTIBACTERIAL ACTIVITY OF AM-1155
VOL. 36, 1992 0
#H33 FIG. 1. Chemical structure of AM-1155.
overnight broth cultures and bacterial suspensions of Neisseria spp. and L. pneumophila were diluted in fresh broth to a final concentration of approximately 106 CFU/ml, and final inoculum, 5 x 103 CFU per loopful) one loopful (5 of each bacterial suspension was applied onto the agar plates with an inoculater (Microplanter; Sakuma Seisakusho, Tokyo, Japan). The plates were incubated at 37°C for
18 h; plates containing C jejuni and L. pneumophila incubated for 48 h. Neisseria spp., H. influenzae, and C. jejuni were incubated in the GasPak system (BBL Microbiology Systems), and obligate anaerobes were incubated in an anaerobic chamber (Forma Scientific). The drug susceptibility of Mycoplasma pneumoniae was determined by the twofold broth dilution method described previously (13). The MIC was defined as the lowest concentration of antimicrobial agent that inhibited visible growth. Determination of MBCs. The MBCs for 10 strains each of Staphylococcus aureus, E. coli, and P. aeruginosa were determined by the method of Pearson et al. (15). Before determination of MBCs, the MICs were determined by the twofold broth dilution method with Mueller-Hinton broth. For the MIC determination, the final inoculum ranged from 2 x 105 to 2 x 106 CFU/ml. The MBCs were determined by transferring 50 ,ul of culture broth from each MIC tube without visible growth onto drug-free Mueller-Hinton medium plates. After 18 h of incubation at 37°C, the number of bacterial colonies occurring on the plates was determined. The MBC was defined as the lowest concentration of drug which killed >99.9% of the inoculum. Time-kill study. The bactericidal activity of AM-1155 was measured by the method described previously (6). Representative organisms incubated in Mueller-Hinton broth (Difco) for 18 h at 37°C were diluted with fresh broth to about 105 CFU/ml, and the diluted cultures were incubated for 2 h at 37°C with shaking. After 2 h of preincubation, AM-1155 was added to the culture at various concentrations around the MIC. Portions (0.1 ml) of the cultures were removed at the indicated times and were plated onto drug-free MuellerHinton medium (Difco) plates, after dilution as necessary. The number of colonies were counted after 18 h of incubation at 37°C. Inhibition of DNA gyrase. Bacterial DNA gyrase was purified from E. coli KL16 (5.9 x 10' U/mg of protein), E. coli N-51 (gyrA) (2.5 x 105 U/mg of protein), P. aeruginosa PA01840 (4.4 x 104 U/mg of protein), and P. aeruginosa PKH-T477 (gyrA) (4.9 x 104 U/mg protein) as described previously (3, 4, 11, 16). The DNA gyrase of Micrococcus luteus ATCC 4698 (100 U/13 pl) was obtained from a commercial source (Bethesda Research Laboratories, Gaithersburg, Md.). The assay of inhibition of DNA supercoiling
activity of DNA gyrase was performed as described by Gellert et al. (5). Relaxed plasmid pBR322 substrate DNA was prepared by treatment with calf thymus topoisomerase I as recommended by the manufacturer (Bethesda Research Laboratories). One unit of gyrase activity was defined as the amount of enzyme that catalyzed the conversion of 50% of the relaxed closed-circular pBR322 DNA to the supercoiled form in 2 h at 37°C in a gyrase reaction mixture. Mutation frequency of resistance. The test organisms were grown in Mueller-Hinton broth at 37°C with shaking until the midexponential growth phase was achieved. The bacteria were then concentrated by centrifugation, and approximately 108 to 109 CFU of bacteria was plated onto MuellerHinton medium plates containing each test compound at the concentration of four times the corresponding MIC. Colonies were counted after 48 h of incubation at 37°C. The frequency of spontaneous mutations selected by each compound was calculated as the ratio of the number of cells growing on drug-containing agar plates to the number of inoculated cells. Development of resistance. AM-1155 and ciprofloxacin were prepared as twofold dilutions in Mueller-Hinton broth. The test strains were inoculated into a dilution series of each agent with an inoculum of 105 CFU/ml. After overnight incubation at 37°C, the broth with the highest concentration of the drug showing turbidity in each series was subcultured into a new dilution series of the same agent. This was done for 8 consecutive days. Mouse protection test. Male ICR mice weighing about 20 g (SLC Japan Inc., Shizuoka, Japan) were infected intraperitoneally with bacterial suspensions. S. aureus and P. aeruginosa were injected as suspensions in 5% gastric mucin (Difco). The other strains were used as suspensions in saline. The test compounds were administered orally or subcutaneously 1 h after challenge. Untreated and treated groups at each dose were composed of 10 mice each. The 50% effective doses (ED50s) were calculated by the probit (1) method on the basis of the number of survivors at 7 days after infection. Experimental pneumonia in mice. Experimental pneumonia in mice was induced by Kiebsiella pneumoniae B54 and P. aeruginosa S51 as described previously (6). Male ICR mice weighing about 20 g (SLC Japan Inc.) were placed in an exposure chamber (Ikemoto Rika, Tokyo, Japan) and were infected by exposure to aerosol which was produced by nebulization of 10 ml of the bacterial suspension (1.1 x 109 CFU/ml) at a pressure of 1 kg/cm2 for 30 min. For P. aeruginosa pneumonia, we used leukopenic mice, which were prepared by intraperitoneal injection of cyclophosphamide (250 mg/kg of body weight) at 4 days before infection. The test compounds were administered orally to groups of five mice each at 18, 42, and 66 h after K pneumoniae infection or 8 h after P. aeruginosa infection. The ED50s were calculated by the probit method from the number of survivors at 6 and 7 days after infection for K pneumoniae and P. aeruginosa, respectively. Pharmacokinetics in mice. The tissue distribution and urinary excretion of AM-1155 and ciprofloxacin in male ICR mice weighing 24 to 34 g (SLC Japan Inc. and Clea Japan Inc., Tokyo, Japan) were determined following administration of a single oral dose of 10 mg/kg. At 0.5, 1, 2, 4, 6 and 8 h after administration, blood and tissue samples such as lung and kidney were collected from five mice. Serum was obtained from blood by centrifugation at 1,870 x g for 20 min. Tissue samples were homogenized in 1/15 M phosphate buffer (pH 7.4). After centrifugation, the super-
ANTrMICROB. AGENTS CHEMOTHER.
HOSAKA ET AL.
TABLE 1. Comparative in vitro activities of AM-1155, ciprofloxacin, norfloxacin, and ofloxacin against clinical isolatese
Organism (no. of isolates)
DrugRange
MIC (pg/ml) 5
Staphylococcus aureus (34)
AM-1155 CPFX NFILX OFLX
0.05-0.20 0.20-0.78 0.39-3.13 0.20-0.78
Methicillin-resistant Staphylococcus aureus (30)
AM-1155 CPFX NFLX OFLX
0.05-0.20 0.39-3.13 1.56-25 0.39-1.56
0.20 3.13 12.5 1.56
NFLX- and CPFX-resistant Staphylococcus aureus (10)
3.13 50 100 25
6.25 100 100 50
Staphylococcus epidemnidis (26)
1.56-6.25 12.5-100 50-100 6.25-50 0.05-0.39 0.20-1.56 0.39-12.5 0.20-1.56
NFLX- and CPFX-resistant Staphylococcus epidennidi (26)
AM-1155 CPFX NFLX
0.20-50 1.56-100 12.5-100 1.56-100
1.56 50 100 12.5
OFLX Staphylococcus haemolyticus (25)
OFLX Staphylococcus hominis (15)
OFLX
Staphylococcus saprophyticus (8)
AM-llSS CPFX NFLX OFLX
Steptococcus pneumoniae (15)
AM-l155 CPFX
NFL:X OFLX Enterococcusfaecalis (14)
AM-l155 CPFX NFLX
OFLLX Enterococcusfaecium (12)
Escherichia coli (26)
AM-l155 CPFX NFX OFLX AM-l155 CPFX
Klebsiella pneumoniae (24)
NFLX OFLX AM-l155 CPFX NFLX OFLX
0.10-6.25 0.20-100 0.39-> 100 0.20-50
3.13 12.5 100 12.5
0.10-12.5 0.10->100 0.39->100 0.20-100
6.25 100 >100 50
0.20-6.25 0.20-100 0.78->100 0.39-50 0.20-0.39 0.39-1.56 3.13-12.5 1.56-3.13
0.39 0.39-0.78 1.56-3.13 1.56
0.39-3.13 0.78-6.25 6.25-25 3.13-12.5 0.0125-0.05 0.0063-0.05 0.05-0.10
0.05-0.20 0.05-0.78 0.025-0.39 0.10-1.56
0.78 1.56 25 6.25 0.78 1.56 3.13 1.56 12.5 6.25 12.5 6.25 0.05 0.025 0.025 0.025 0.10 0.10 0.10 0.10 0.39 0.05 0.39 0.05 0.20 1.56 1.56 0.20 Continued on foUowing page 0.39 0.78 3.13 1.56
TABLE 1-Continued Organism (no. of isolates)
Drug Range
Enterobacter cloacae (25)
0.025-0.20 0.0125-0.10 0.05-0.78 0.05-0.39
Serratia marcescens (25)
AM-llSS
0.39-6.25 0.10-3.13 0.20-12.5 0.39-12.5
CPFX NFLX OFLX
MIC (,ug/ml) 50%
0.05 0.025 0.20 0.10
Citrobacterfreundii (12)
0.05-1.56 0.0125-1.56 0.05-6.25 0.10-6.25
Proteus vulganis (11)
0.10-0.39 0.025-0.10 0.05-0.39 0.10-0.39
Proteus mirabilis (10)
Morganella morganii (13)
0.05-0.20 0.0125-0.025 0.025-0.05 0.05-0.20
0.10 0.0125 0.05 0.10
AM-1155 CPFX
0.10-100 0.0125->100 0.05->100 0.10->100
1.56 6.25 25 6.25
6.25 12.5 100 25
rettgeri
NFLX OFLX
Pseudomonas aeruginosa (35)
0.78-12.5 0.10-1.56 0.39-6.25 0.78-12.5
NFLX- and CPFX-resistant Pseudomonas aeruginosa (34)
6.25-> 100 3.13-100 12.5->100 12.5-> 100
Xanthomonas maltophilia (13)
Acinetobacter calcoaceticus (17)
0.025-0.10 0.10-0.39 0.78-3.13 0.20-0.39
Alcaligenes faecalis (15)
Branhamella catarrhalis (20)
Haemophilus influenzae (16)
0.78-25 0.78-100 3.13->100 0.78-50 0.025-0.05 0.025-0.05 0.10-0.20 0.05-0.10 0.0125-0.025 0.0125-0.025 0.05-0.10 0.025-0.05
6.25 25 100 25 0.025 0.025 0.20 0.10
100 50 >100 >100
12.5 25 >100 25 0.05 0.05 0.20 0.10
0.025 0.0125 0.025 0.025 0.10 0.05 0.05 0.05 Continued on following page
ANTIMICROB. AGENTS CHEMOTHER.
TABLE 1-Continued MIC (1g/ml)
(no. of isolates)
Neisseria gonorrhoeae (10)
0.0063-0.0125 0.0063-0.0125 0.025-0.05 0.0125-0.025
0.0063 0.0063 0.05 0.0125
0.0125 0.0063 0.05 0.025
Flavobacterium spp. (26)
0.20-> 100 0.78-> 100 1.56-> 100 0.78-> 100
Campylobacterjejuni (21)
Bacteroides fragilis (23)
0.39-3.13 3.13-> 100 25-> 100 1.56-25
CPFX, ciprofloxacin;
>100 > 100 > 100 > 100
0.39 12.5 100 3.13
1.56 25 >100 12.5
NFLX, norfloxacin; OFLX, ofloxacin.
natants were obtained. Urine was collected for 24 h after administration of drug. Samples were assayed for bioactivity by the cup diffusion procedure with Bacillus subtilis ATCC 6633 or E. coli NIHJ JC-2 as the test organism by the method described by Oomori et al. (14).
RESULTS Antibacterial activit. The antibacterial activity of AM1155 was determined for 516 clinical isolates and was comTABLE 2. Antibacterial activities of AM-1155 against the obligately anaerobic bacteria L. pneumophila and M. pneumoniae Organism
CPFX
0.39 0.39 0.39 1.56 1.56 0.78 0.78 3.13 3.13 0.78 0.39 0.39 0.20 3.13 0.78 3.13 1.56
6.25 3.13 6.25 6.25 25 12.5 1.56 12.5 12.5 1.56 0.78 0.78 0.39 12.5 0.78 12.5 1.56
50 25 50 50 >100 >100 25 100 100 6.25 6.25 6.25 3.13 100 1.56 >100 25
0.39 100 100
CPFX, ciprofloxacin; NFLX, norfloxacin.
pared with those of ciprofloxacin, norfloxacin, and ofloxacin (Tables 1 and 2). Table 1 summarizes the MIC ranges and the MICs for 50 and 90% of the strains tested (MIC50s and MIC90s, respectively). AM-1155 was very active against S. aureus including methicillin-resistant strains, Staphylococcus epidermidis, streptococci, E. coli, K pneumoniae, Enterobacter cloacae, Proteus spp., Morganella morganii, Acinetobacter calcoaceticus, Branhamella catarrhalis, H. influenzae, Neisseria gonorrhoeae, and C. jejuni, with MIC90s of 800 100 800 NA, nali-
P. aeruginosa IF0 1 2689
E. coli NIHJ JC-2
S. aureus 209P 10 E 9 0 8
6 U 5 U
039 Ig/mi
0.78I g/ml
CR cn a
4 na 3 2 :3 S
._
0.20 Lg/ml
g/ml
\01
limit of assay L
-2 0 2 4
Time (h)
Lg/m
IX0.025 g/m
limit of _I L ' | *
\\ 0.0125 g/ml (MIC) 0.05
assay .
_I,L
\.t56 ILg/ml (MJIC)
limit of assay I
FIG. 2. Bactericidal activity of AM-1155 against S. aureus, E. coli, and P. aeruginosa.
cept P. aeruginosa, and B. fragilis and had slightly greater activity against enterococci, streptococci, and C. jejuni. The activity of AM-1155 against the majority of the members of
the family Enterobacteriaceae, B. catarrhalis, H. influenand N. gonorrhoeae was almost the same as that of ciprofloxacin. AM-1155 was more potent than ofloxacin and norfloxacin against these strains. AM-1155 inhibited 50% of norfloxacin-resistant S. aureus and S. epidermidis strains at concentrations of 3.13 and 1.56 jig/ml, respectively. Against P. aeruginosa, the activity of AM-1155 was similar to those of norfloxacin and ofloxacin, but it was fourfold less than that of ciprofloxacin. AM-1155 was inactive against norfloxacin- and ciprofloxacin-resistant P. aeruginosa. The antibacterial activities of AM-1155 against the obligately anaerobic organisms L. pneumophila and M. pneumoniae are given in Table 2. AM-1155 inhibited Bacteroides spp., Fusobacterium spp., Eubacterium spp., Propionibacterium acnes, Peptococcus magnus, Clostridium spp., Peptostreptococcus spp., and VeilloneUla paruvula at concentrations of 0.20 to 3.13 jig/ml. The MICs of AM-1155 for L. pneumophila GIFU2522 and M. pneumoniae Mac were s0.0063 and 0.10 ,g/ml, respectively. In vitro activity against quinolone-resistant mutants. The drug susceptibilities of DNA gyrase mutants (KEA12 and MH5 of E. coli [8], KH4023 of P. aeruginosa [10]) and outer membrane permeability mutants (KEA13 and KE7 of E. coli [7, 8], KH4013E and KH4014a of P. aeruginosa [2, 10]) are given in Table 3. E. coli KEA12 (norA) and MH5 (gyrA) and P. aeruginosa KH4023 (nfxA) were fourfold less susceptible than the respective parent strains to AM-1155. Their susceptibilities to other quinolones such as ciprofloxacin and norfloxacin were also decreased. E. coli KEA13 and KE7, OmpF-deficient mutants, were two- to fourfold less susceptible than the parent strains to quinolones, including AM1155. The MICs of AM-1155 for P. aeruginosa KH4013E (nfxB) and KH4014a (nfxcC) were 1.56 and 3.13 ,g/ml, respectively, which were four and eight times the MIC, respectively, for the parent strain PA04009. MBCs. The MBCs of AM-1155 and ciprofloxacin for 10 zae,
clinical isolates each of S. aureus, E. coli, and P. aeruginosa were determined. There was no difference or only a twofold difference in the MIC90s and MBCgos. The bactericidal activity of AM-1155 was similar to that of ciprofloxacin (data not shown). Killing-curve studies. Killing-curve studies were performed with AM-1155 against S. aureus 209P, E. coli NIHJ JC-2, and P. aeruginosa IF012689. The rapid bactericidal activity of AM-1155 against these bacteria at concentrations greater than the MIC is shown in Fig. 2. More than 99% of the initial number of viable bacteria were killed within 1 or 2 h of incubation with AM-1155 at concentrations equal to or twice the MIC. Inhibitory effects on DNA gyrase. The inhibitory effects of AM-1155 and ciprofloxacin on DNA gyrase from test strains are given in Table 4. The 50% inhibitory concentrations (IC50s) of AM-1155 on the supercoiling activities of DNA gyrases from M. luteus ATCC 4698, E. coli KL-16, and P. aeruginosa PA01840 were 8.3, 0.38, and 23.3 ,ug/ml, respectively. The DNA gyrases from gyrA mutants of E. coli KL-16 and P. aeruginosa PA01840 were resistant to AMTABLE 4. Inhibition of supercoiling activity of DNA gyrases by AM-1155 DNA gyrase from:
M. luteus ATCC 4698
AM-1155 MIC IC50
CPFXa
IC50 (,ug/ml) 14.0
(1lg/ml) 0.025
(11g/ml) 8.3
(pg/ml) 0.20
0.025 0.39
0.38 13.5
KL-16 (wild type) N-51 (gyrA)
P. aeruginosa
PA01840 (wild type)
PKH-T477 (gyrA) a CPFX, ciprofloxacin.
8.0 >400
TABLE S. Frequencies of spontaneous mutants resistant to AM-1155, ciprofloxacin, and norfloxacin Organism
Original (ILg/min)MIC
CPFX NFLX
Mutation frequency
In vitro and in vivo antibacterial activities of a new quinolone, OPC-17116.
In vitro evaluation of a new quinolone antibacterial.
In vitro antibacterial activity of a new quinolone, NM394.
In-vitro activity of tosufloxacin, a new quinolone antibacterial agent.
Ceftizoxime (FK 749), a new parenteral cephalosporin: in vitro and in vivo antibacterial activities.
SCE-963, a new broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities.
In vitro and in vivo activities of a new quinolone, WIN 57273, possessing potent activity against gram-positive bacteria.
Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro.
In vitro and in vivo activities of SCE-2787, a new parenteral cephalosporin with a broad antibacterial spectrum.
Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin.
In vitro and in vivo antibacterial activities of E-4497, a new 3-amine-3-methyl-azetidinyl tricyclic fluoroquinolone.
In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin with a broad antibacterial spectrum.
In Vitro antibacterial and in Vivo cytotoxic activities of Grewia paniculata.
In vitro and in vivo antibacterial activity of T-1220, a new semisynthetic penicillin.
Synthesis and antibacterial activity of new tetracyclic quinolone antibacterials.
SCE-129, antipseudomonal cephalosporin: in vitro and in vivo antibacterial activities.
Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity.
In vitro antibacterial activities of a thiazolyl peptide antibiotic PM2409.
In vitro antibacterial activities of PD 131628, a new 1,8-naphthyridine anti-infective agent.
Comparative in vitro activities of a new quinolone, WIN 57273, and piperacillin plus tazobactam against anaerobic bacteria.
In vitro and in vivo activities of LJC10,627, a new carbapenem with stability to dehydropeptidase I.
Comparative in vitro activities of a new quinolone, OPC-17116, possessing potent activity against gram-positive bacteria.
In vivo antibacterial activity of MRX-I, a new oxazolidinone.
Carfecillin: antibacterial activity in vitro and in vivo.
In vitro and in vivo antibacterial activities of AM-1155, a new 6-fluoro-8-methoxy quinolone.
AM-1155 is a new quinolone with a wide spectrum of antibacterial activity against various bacteria including anaerobes and Mycoplasma pneumoniae. AM-1...


Located three hours by bus from Medellín, Jericó offers much more than religious tourism, including paragliding, hiking, and horseback riding.
Sonja takes us to the mountain village of Minca, which is a hiker's paradise located in Colombia's Sierra Nevada near Santa Marta.
Ryan tells us the best day trips you can take from Medellín, including popular stops such as Guatapé and Santa Elena and the somewhat unknown San Rafael.


We at Brindavani are thrilled to announce our very first chamber concert! We invite you to join us on Sunday, May 13th for an exciting morning of music with concerts given by Carnatic America's talented youth.
All are welcome to RSVP at tinyurl.com/brindavani-rsvp. Space is limited, so you must do so in order to enter! We hope to see everyone there!


With Oscar fever beginning to sweep in, accompanied by the justified criticism over their complete lack of diversity, I feel its only right that we turn our gaze to the big screen and its portrayal of tattoos.
Though both online and on the small screen tattoos are the focus for many shows, Hollywood's glamour does not seem so keen to embrace the topic.
What started with Miami Ink, "the gold standard" of tattoo shows as AV Club labels it, has now grown, for better or worse, into a multi-million pound industry of tattoo-related output for television audiences.
Ami James, Chris Nunez and co pioneered the standard format for tattoo television and paved the way for a host of other artists to make their mark on their clients, and the public, with AV Club stating that Miami Ink "spawned the whole subgenre".


I can print through my cellphone using android app and also using web browser, but not on astroprint desktop… any help?
As far as I can tell, that feature really does not work. I have tried it multiple times with the printer on and off the same network; neither works.


This workshop developed by the Merrithew™ team demonstrates dynamic movement sequences that take full advantage of the body's own weight and gravity. These moves are guaranteed to develop ultimate strength and stability particularly through the core, including the lumbo-pelvic region. The workshop features an intense abdominal series, sequences with rotation and mobilization as well as a section dedicated to front and side planks.


Do you need financial help for a specific purpose?
There are numerous charities which make grants to individuals. However, their funds are under great pressure, and it can be hard to find a charity which will fund the need you have. You will need to look for organisations which fund the kind of need you have.
Turn2Us is a charity which helps people to access financial help from benefits, and from charities. They have a simple search engine for charities on their website. If you are looking for financial help from a charity, go to Turn2Us.
A couple of common queries are about help to buy computers, and help with the cost of a holiday.
Home Farm Trust – guide to holidays for people with learning disabilities includes a section on help with funding a holiday.
The Family Fund gives money to buy equipment or services for children who need extra help because of a severe disability or long-term illness. Grants are means-tested.
You can apply to the Family Fund if you are the parent or carer of a child or young person aged 18 or under and you have the legal right to live in the UK. Go to the Family Fund for information.
Health benefits – help with prescriptions, fares to hospital, etc.


text:
Super Monster Novels
Monsters and Superheroes
Category Archives: Superheroes
Red Hot and Green
Posted on December 15, 2019 by Eerie Searleman
In my opinion, She-Hulk is the best superhero name Stan Lee ever thought up. The hyphenated personal pronoun succeeds at being funny and dumb and smart and provocative all at the same time. She-Hulk could easily be a monster from a 1950s movie or the topic of a women's studies class. Take your pick.
She-Hulk is a six-foot-seven, 680-pound jade-green party animal. And as her name implies, she's hell on wheels and an indefatigable physical presence. But in Marta Acosta's novel from 2013 she isn't nearly as interesting as her host, Jennifer Walters, a woman who is described as a beautiful disaster—all luminous eyes and existential grief. Walters is, according to her spunky best friend, "a perplexing blend of kick-ass chick and honor-roll nerd." The She-Hulk Diaries could easily have been called The Jennifer Walters Diaries instead.
But no worries; Even with "She-Hulk" in the title, Walters establishes herself as the real hero of the book. Her quest to find a good job, secure an affordable apartment in Manhattan and hook up with an awesome boyfriend represents her version of a hero's journey.
Naturally, there are plenty of obstacles in Walters' way. She must grapple with duplicitous coworkers, limited rental options and an ex-lover who insists on writing embarrassing songs about their weekend tryst (sample lyric: "I'll crawl from the primordial sludge for you. I'll give up my gills and prehensile appendage for you"). Dr. Doom even shows up to make things more complicated. It's sort of like Sex and the City (or maybe Breakfast at Tiffany's) with a little superhero action on the side. There's a lot of navel-gazing in The She-Hulk Diaries, but it's mostly well written and relentlessly jokey. Added bonus for those who care: the sex talk is surprisingly frank.
With all the real world drama surrounding Walters, there's not much for She-Hulk to do. We are told that "Shulky" is a righteous superbabe and a sex object for millions of teenage boys, but the author keeps her on the sidelines most of the time.
Regardless of her costarring status, She-Hulk succeeds in retaining her brutish charm wherever she goes. She is, I admit, pretty good with the zippy one-liners. "I'd rather be tasty than tasteful," she brags at one point. And later, when her boobs pop out of her outfit, she says, "It pays to advertise!"
Even when she's serious (which is not very often), She-Hulk is able to express herself with surprising aplomb. For example, every time she visits the Avengers Mansion she feels the sting of sexism (especially from ex-boyfriend Tony Stark). She may be red hot and green, but she's not happy about being marginalized because of her sex. "Male is not the default gender for superhero," she huffs. The Sensational She-Hulk deserves a little more respect.
[The She-Hulk Diaries / By Marta Acosta / First Printing: June 2013 / ISBN: 9781401311018]
Posted in Superheroes
Loki the Enchantress
Posted on November 17, 2019 by Eerie Searleman
There's no timestamp on Mackenzi Lee's latest novel. Readers aren't told how old Loki and Thor are. All we know is that All-father Odin has yet to name an heir to the Asgardian throne.
Later, when Loki visits London, the details are somewhat vague as well. When exactly does Lee's novel take place? Does it transpire during the early days of the Industrial Revolution? Or is it set in a bleak nineteenth century Dickensian milieu?
Even Loki is confused by the squishy timeline. On Asgard he's a young prince and an artful dodger. But on Midgard he's already the Lord of Darkness and Mischief and Chaos and Everything Evil.
Loki doesn't know it at the time, but humans on Earth are keenly aware of the mighty Aesir. Stories of Odin and Frigga and the Twilight of the Gods are a big part of popular culture.
As it turns out, these myths from the past are also inextricably tied to Asgard's future. Like it or not, Loki never gets to be the hero. It is his brother Thor who eventually ascends to the throne. "My story has already been written," he cries in frustration. "It's been told and retold. Humans know everything about me."
Which begs the question: If Loki can't be the hero, what else is left? Lots of things, apparently. He can be the witch, the trickster, the schemer, the self-serving God of Chaos. He can prove the mythology books right, that he was rotten from the start. Says the author: "He would serve no man but himself, no heart but his own. That would be his choice."
Loki's partner in crime is Amora, known to comic book readers as the Enchantress. In possession of five highly coveted Norn Stones, the pair hatch a plot to storm Asgard with an army of human zombies. For some reason, this seems like a totally reasonable thing to do.
As a couple, Amora and Loki are two sides of the same coin. They're both dissatisfied with Asgard's rigid caste system. Amora is a powerful sorceress who resents living in the shadow of her mentor Karnilla, the Queen of Norns. "I do not want to be controlled," she says. "I am powerful, so let me be powerful!"
Likewise, Loki considers himself cleverer, sharper and quicker than everyone else in Odin's court. He knows, however, that he'll never win his father's favor. Secretly he wishes for a hammer just like the one his brother wields. "I want to break something," he says.
Good or bad, hero or villain, Loki and Amora are ultimately undone by social expectations. Like Esther Greenwood (look it up), they can't break out of the bell jar. "There are some things that cannot be taught," says Odin, "and one is how to change our hearts. Our true selves always show themselves in the end."
[Loki: Where Mischief Lies / By Mackenzi Lee / First Printing: September 2019 / ISBN: 9781368022262]
Posted on September 26, 2019 by Eerie Searleman
Witchblade was certainly a big part of the "bad girl" movement in comic books during the 90s. And author John DeChancie doesn't back away from the sexy witch's infamous eye-popping transformation in his prose adaptation from 2002.
She was, he wrote, a paradox of dress and undress. "Her metamorphosis produced a filigree of delicate metal work of swirls and arabesques crawling up her body and covering her full breasts and neither portions but leaving little else unexposed. She was nude and yet somehow completely covered."
Even without the Witchblade gauntlet, Sara "Pez" Pezzini was an eyeful. She dressed like a tomboy, said the author, but she always looked good. "Her jeans were tight and the T-shirt under her jacket was inevitably undersized, allowing her feminine lineaments to come through nicely. She was tall, thin, well proportioned, and had a face that could launch several navies. Legs up to the neck. Oh, those legs! And there were other parts of her body that shaped up just as well."
Comic books have always been slightly disreputable, and Witchblade along with similar titles such as Vampirella and Lady Death unquestionably took advantage of the media's lowbrow reputation. This is not a criticism from me btw. Over the years, the character has become iconic and (dare I say it) beloved around the world. She appeared on television in 2001 and even made the transition to anime in 2006.
Witchblade: Talons was a tie-in novel written specifically to supplement the TV series, but DeChancie doesn't let himself get derailed by continuity minutia. Detective Pezzini wore her Witchblade gauntlet, she seemed comfortable with it, and characters (old and new) coexisted without a hitch. There's no origin story to speak of, but the supernatural tenor of the comic book series was preserved.
Pezzini finds herself in a sticky situation involving a "magical" supercomputer, a werewolf, a "mahjong dragon," a supernatural assassin, a Romanian crime boss and a bunch of religious zealots from an alternative dimension. Vlad Tepys (the Impaler himself) even shows up for some decapitating fun.
The whole thing is silly and beyond criticism. True believers will be happy to discover that Witchblade retains her bad girl charm in prose format (Pezzini even briefly considers launching a personal website with nude pictures of herself). The details of her ongoing story, however, are rendered inconsequential. But that's okay. Nobody ever bought a Witchblade comic for the story.
[Witchblade: Talons / By John DeChancie / First Printing: January 2002 / ISBN: 9780743435017]
Kaiju Canon
Posted on June 9, 2019 by Eerie Searleman
It's 1964 and Earth is heading toward a large-scale daikaiju extinction event in author Ryan George Collins's enjoyable first novel. Dinosaurs, reptiles (not dinosaurs), sea monsters and insects have all united to "enact some Old Testament wrath" on mankind.
These "large strange beasts" have been around since the beginning of time and they most likely will be here at the end of it. And guess what? They don't particularly like the fact that they no longer rule the world. Now operating under a loose confederacy, they're eager to wipe humanity off the map. As it turns out, resistance to change isn't a trait exclusive to men. Monsters don't like it either.
When these giant creatures shamble toward Japan or Chile (!), the first responders are a highly specialized covert action team. Operation Red Dragon is an international paramilitary unit that was forged during WWII and tasked with keeping kaiju activity under wraps.
On the agency's payroll are two genetically engineered super soldiers: Gen. Ishiro Tsujimori, who is able to conduct, generate and unleash electrical energy, and Special Agent X, the world's only human cyborg. Also available for duty is C.I.G.O.R. (not cigar), a 26-feet-tall cybernetically integrated giant ornithology robot thingy, and a human yokai named Chakra. They're the monsters protecting mankind from the monsters who want to destroy it.
So far, so good. Operation Red Dragon is the first volume of a planned Daikaiju Wars series, and it dutifully introduces a riot of monsters and superheroes and establishes the alliances that will propel upcoming sequels, Even though it's a thin book, there's plenty of retro tokusatsu action to keep readers (like me) happy.
Be forewarned, however. There's a smattering of religious jibber jabber sprinkled throughout this book. Certainly many writers have used Biblical allegory to magnify their monster narratives over the years. But author Collins needs to be careful. His writing isn't exactly subtle. "Maybe some humility before God is what mankind needs," he says bluntly at one point. For goodness sakes, he even anoints a prophet by the end of the book. Hopefully Collins will steer clear of turning his Daikaiju War into a Daikaiju Holy War.
[Operation Red Dragon / By Ryan George Collins / First Printing: April 2018 / ISBN: 9781925711790]
Posted in Monsters, Superheroes


The next print issue of PCR is going to be our Distribution special, which hits desks at the beginning of March.
Whether is for business, consumer and pro gaming, this sector guide will cover the latest desktop computers on the market. If you're a vendor or distributor in this arena, get in touch!
We'll also be showcasing the latest networking gear in this issue, so if you want your products to get in front of retailers and resellers, show us what you've got.
As this is our distribution special, the March issue will be packed with profiles on the biggest tech distributors in the channel. Get in touch if you'd like to be considered for a profile.
In keeping with the theme, this issue will also look at the latest technology that's helping distributors do their job – from tech for warehouse workers to custom inventory software. If you would like to provide commentary on this subject, we'd love to hear from you.
If you would like to be considered for any of these features, email Laura Barnes at laura.barnes@biz-media.co.uk before Wednesday 13th February.
If you would like to get involved commercially in this issue there will be a variety of packages available. Please contact Beccy Barr on 07703 503 101 and at Beccy.Barr@biz-media.co.uk or Rob Baker on 0203 143 8778 and at Rob.Baker@biz-media.co.uk before Monday 18th February.


Rod and reel fishing also spoonbill snagging when in season. Overnight camping on sandbars on the river, log lines and limb lines also trout lines. Two day one night & three day two night camping available.


OUR LANDSCAPE AND VISUAL ASSESSMENT SERVICES ARE STRUCTURED THROUGH PEOPLE EXPERTISE, software and SECTOR KNOWLEDGE.
Whether you are looking to design a new public amenity area, or conduct a landscape and visual impact assessment for a large scale renewables project or housing development, Cogeo partner varied industries to address all Landscape and Visual requirements.
Our Landscape Architects provide design and assessment services for all Landscape and Visual aspects of a project. They collaborate with clients in both public and private sectors over many different types of projects, ensuring developments stay on track with our proactive approach. All our assessments follow best practice guidance, including the 'Guidelines for Landscape and Visual Impact Assessment' (third edition).
With design and assessment software packages including AutoCAD, GIS, Windfarm and SketchUp, we deliver across all scales of development. We also use high specification equipment for field surveys.
Smaller scale developments, such as garden design or amenity planting are covered within this service also.


Colebrook, N.H. – Two Berlin men got lucky only suffering minor and non-life threatening injuries after a failed jump attempt of an ATV in Colebrook. Yesterday afternoon 39-year-old Eric Lebeau and 40-year-old Robert Maider, crashed an Arctic Cat Wildcat side-by-side in a field in Corridor C of the "Ride the Wilds Trail" just north east of Route 145 and Hughes Road. According to NH Fish and Game Lebeau stated that he asked Maider if he wanted to "jump the berm" that was in the field. Maider agreed, and the vehicle went airborn off of the berm and nose dived into the ground. Neither Lebeau nor Maider had helmets on and neither was wearing seatbelts. Maider was ejected from the machine before it came to rest on its roof with Maider's arm pinned underneath it. Lebeau also sustained injuries that were non-life threatening. At around 2:15 PM on Monday Colebrook Dispatch contacted New Hampshire Fish and Game Conservation Officers to report the crash. The 45th Parallel EMS, Colebrook Fire and Rescue along with many volunteers assisted in assessing the patients, getting them to the ambulances, and transporting them to Upper Connecticut Valley Hospital in Colebrook. Fish and Game Conservation Officer Glen Lucas said Speed was the contributing factor in the crash, and Lebeau will be cited for the violation.


My client an established Insurance company based in Dorset are looking for a Legal Counsel for a 6-12-month contract supporting an exciting strategic project within the business.
The legal department is well regarded within the business and is an integral part of the business.
This opportunity will start ASAP for a 6-12-month period with the opportunity of working 2 days per week remotely.
To work closely with the Senior Legal Counsel within the business providing support to the General Counsel and external solicitors in regard to the project.
Drafting and negotiating commercial contracts (including financial services distribution arrangements technology and general supplier contracts), managing disputes as and when required.
Provide advice on commercial matters within the business.
Open to PQE Level, candidates from both In-House and Private Practice will be considered. You must have a strong Corporate background. The key to this role is handling a broad range of corporate caseloads.


The WeatherTech SportsCar Championship (USC) is a sports car racing series based in the United States and Canada and organized by the International Motor Sports Association (IMSA). It is a result of a merger between two existing North American sports car racing series, the American Le Mans Series and Rolex GrandAm Sports Car Series.
· Prototype (P): the flagship class, combining Grand-Am Daytona Prototype with the American Le Mans Series P2 prototypes and DeltaWing cars, built to 2014 specifications.
· Prototype Challenge (PC): a spec class carried over directly from the American Le Mans Series, featuring Le Mans Prototype Challenge cars built by Oreca with engines supplied by Chevrolet and tires from Continental.
· GT Le Mans (GTLM): a continuation of the ALMS GT class, consisting of cars matching the Automobile Club de l'Ouest's GTE specification, including the Ferrari 458 GT2.
· GT Daytona (GTD): a class that combines the Grand-Am GT & GX classes with the Ferrari 458 GT3, Porsche 911 GT3 Cup cars from the ALMS GTC class and cars built to FIA GT3 specifications.
Some races may only use selected classes of cars, for example: Any class car may be permitted entry into the Rolex 24, while at the Grand Prix of Long Beach only the Prototype (P) and GT Le Mans (GTLM) will be entered.
Ferrari is represented by two teams in the GTLM class and 5 team in the GTD class.
The 2016 United SportsCar Championship (TUSC) season will be the second season of the International Motor Sports Association's WeatherTech Sportscar Championship. It will begin in January with the 24 Hours of Daytona.
2016 will see the introduction of the two awards for the top-finishing Pro-Am drivers in Prototype, while the Bob Akin Award will be for the top GTLM pairing. The top Pro-Am pairings from these classes at the end of the year will be given automatic entries to the 2017 24 Hours of Le Mans, with the Trueman award winner eligible for the LMP2 class, while the Akin Award winner would be for the LM GTE Am class. To be eligible for these awards, the drivers must at a minimum contest the North American Endurance Cup events.


Love isn't what you say.
How do you get such thin and neat lines?
very stunning good use of colors and comp.
This is gay and I love it.
Very pretty and makes me think what's their story about.
This is gorgeous. So passionate and full of life! I love the colors and the shading and thr folds.


Benefits of the Tutorial Day to tell your Boss!
Asking your line manager or team leader about going on the Tutorial Day 30th September, might be an awkward conversation to start. Here are a few ideas that you might want to raise with them so that you can attend the Tutorial Day and perhaps get the company to pay for you as part of your development.
Within a dedicated classroom environment, the tutors focus on the developers in the room exclusively for the entire time of the tutorial. It's not quite 1:1, but it is a small group with plenty of opportunities for you to get hands-on learning and support from experts in their field. We have kept the cost of the tutorial day as small as we can (at cost) none of the tutors gets paid, so everyone involved undertakes this for the love of the community and to help improve people's skills.
The tutors will take the developers through in-depth teaching, with opportunities for group learning, individual coaching, and questions throughout the sessions. Your developers will come away with new skills and knowledge, that they can apply to their work.
We are all aware that people learn in different ways. The tutorial day enables the tutor to teach the group via various learning methods including – traditional lecture teaching, building practical and real software there and then, question and answer sessions, demonstrations and more. Getting all of this with a real life tutor for a day is a fantastic opportunity to learn skills quickly and thoroughly to then take back to your company on Monday!
Tutorials tend to accelerates learning. Learning together in a group enables your staff member to benefit from the shared experience and knowledge in the room. A developer on their own or with the usual people they work with – will not give them that wider experience and knowledge that they will get from a room full of new people and an experienced tutor. The value for money is great, as your team member gets the benefit from the shared experience in the room of developers from different organisations and experience.
Many developers state that peer learning is very enjoyable and motivating for them. Sharing knowledge and teaching others is a valuable way for everyone to learn. The developers who attend PHPNW each year, report back to us that they have not only discovered masses of great stuff, but they cannot wait to get back to work on Monday to try it out. Attending a tutorial day and the conference is a great value for money way of motivating your staff.
CPD (continuous professional development) is a major and useful way for a company to measure and improve the performance and skills of its team members. Committing to support developers to attend Tutorial Days and Conferences can be an extremely positive experience for both the individual and the employer.


How Does A Young Child Learn to do Math?
by Bright Kids Inc. | Dec 3, 2015 | Smart Kids Math!
One way young children solve math problems is to use a counting procedure. To solve 6 + 4, the child first counts to 6, using either their fingers or other counters, and then they count out 4 more to make 10. This procedure requires a lot of effort and is time consuming.
In a somewhat shortened procedure the child starts with a closed fist and refers to the fist as the bigger number (they do not count out the bigger number) and then adds on the smaller number. For example, to solve 6 + 4, the child would start with a closed fist at 6 and count out 4 fingers one at a time (7 – 8 – 9 – 10) to make 10.
An even more efficient way to solve the problem is simply to retrieve the answer from memory, rather than working it out. Younger children rely more on counting procedures. Older children are more apt to use retrieval. It is important to note that children of all ages use a variety of procedures. There is not an orderly, stage-like progression from counting to retrieval. Even young children can use retrieval for some problems (2 + 1). The manner of solving math problems varies.
NUMERACY, NUMBER SENSE and PROBLEM SOLVING start with parents teaching numbers. Create a working knowledge of how to count forwards by 1's to 100.
Parents can do a variety of activities to enhance a numeracy, number sense and problem-solving curriculum.
Use MATH VOCABULARY to communicate mathematical thinking.
Ask your child HOW they solved a problem.
Practice mental mathematics in addition and subtraction.
Mental mathematics enables students to determine answers without paper and pencil. It improves computational fluency by developing efficiency, accuracy and flexibility.
Work on estimation with your child.
Show and talk about what numbers represent, use concrete materials to compare.
Investigate fractions and money amounts; estimate, measure, and describe length, time, and temperature.
Engage your child in mathematical discussions.
Connect mathematical ideas and concepts in to everyday experiences.
Encourage your child to reflect on and extend their understanding of mathematics as it occurs in their everyday activities, play, and conversations.
Encourage your child to TALK MATH, and make Learning Math FUN FUN FUN!
by Bright Kids Inc. | Nov 5, 2015 | Positive Parenting Tips!
Children don't come with a manual!
Self-esteem is the value a child places on oneself. It is seeing oneself with positive characteristics. It is the feeling children have about all the things they see themselves to be or someone who will do well in the things that are important to them.
Children cannot be quickly injected with self-esteem. Many of the steps necessary for building a child's self-esteem is ongoing and it is continually being refined as one progresses through life.
Parents play a crucial role in nurturing the development of their child's self-confidence and self-esteem. As a parent, you have the greatest influence in shaping your children's sense of self-esteem, positive outlook and a healthy view of themselves; you are their first and most important teacher.
Teach your child to work towards a goal, and to have pride in their success. It is important to set achievable and realistic goals so your child experiences a sense of satisfaction with their accomplishments.
Give them an opportunity to succeed.
Encourage them to face challenges and take risks.
Encourage them to say "NO" to negative pressures.
Verbalize confidence in your child and their abilities. It is extremely important to give children support and approval.
Children who have confidence in themselves and their abilities will be more likely to lead happy and productive life.
It is important for you to help your child discover their talents and abilities. (School, sports, music, drama, science, etc.). Once they do identify what they excel at, they need to value their strengths.
Children need to know they are important. Show love and acceptance through your daily expressions of affection. Give lots of HUGS!
Play, work and relax together. When children feel loved by their parents (i.e. the important people in their lives), they feel comfortable, safe and secure, and open to communication.
Children will develop respect for themselves and for others if they learn that what they think, feel and do is important.
Set a Good Example – have a POSITIVE and CHEERFUL ATTITUDE!
by Bright Kids Inc. | Oct 20, 2015 | Fun For Kids!, Helping your child with homework!
Spending time helping your child with their learning will pay back HUGE dividends. Studies show that children who achieve academic success early in life go on to higher paying jobs, and more satisfying careers. Helping your child with their homework, and making it enjoyable time together will help both of you. In the majority of homes "Homework" is a painful experience for both parent and child. Work WITH them! Help Them With Their Homework! Make it fun! The more kids feel good about the work they're doing, the more they'll enjoy learning, and the more successful they'll be over the coming years.
How Children Learn To Read and Comprehend?
by Bright Kids Inc. | Oct 6, 2015 | Smart Kids Language Arts!
Did you know learning to read involves decoding and comprehension?
Decoding – translating the print into sounds and words.
Comprehension – understanding the meaning of what is being read.
Be able to decode print.
Beginning readers often put so much effort into decoding that it reduces their comprehension.
There are two main approaches to early reading instruction.
PHONICS emphasizes decoding where children might be taught to look for sound patterns and to sound out words. Children are taught to recognize speech sounds, called phonemes, alone and in combination. This is called PHONEMIC AWARENESS.
The other approach is WHOLE LANGUAGE LEARNING, emphasizes the teaching of reading in a meaningful context. The children might be taught to memorize a few familiar words, called SIGHT WORDS, so that they can quickly learn to read familiar texts. There is less emphasis on learning to decode unfamiliar words.
Children need BOTH a phonics approach AND a whole language approach that incorporates phonemic awareness and learning basic sight words. Developing phonemic awareness is critical to reading difficult words. Breaking down difficult words into sounds can help your child identify new words. New words eventually become new sight words for your child.
Tips for Parents to help motivate with phonics, phonemic awareness and whole language reading in the HOME.
Help your child learn word lists for their grade and the letters and sounds in each word.
Attend to spelling; use phonics and phonemic awareness knowledge and skills, the meaning and function of words in context, and spelling generalizations to spell with accuracy.
Have them spell the words on their word list for you.
Play word games – challenge your child to explain the meaning of a word.
Have a word of the day. Extend the word choice through knowledge of synonyms, antonyms and homonyms.
Experiment with words, phrases and sentences. Enhance the clarity and artistry of communication.
Encourage your child to write a story using their word lists; have them read you their story and ask them questions about the story.
Review and proofread their story and help your child edit their work.
Take your child to the library OFTEN and share your love of literacy with your child.
Read to your child and have them read to you.
Parents can ensure that significant literacy learning is included in day-to-day activities, daily routines, and playtime and family time experiences. In so doing, parents create an effective environment to support their child's learning and success in literacy, spelling, reading and writing.
PARENT TIPS to HELP Young Children Learn to do Math!
by Bright Kids Inc. | Sep 18, 2015 | Fun For Kids!
NUMERACY, NUMBER SENSEand PROBLEM SOLVING start with parents teaching numbers. Create a working knowledge of how to count forwards by 1's to 100.
Use MATH VOCABULARYto communicate mathematical thinking.
Practice mental mathematics inaddition and subtraction.
Work on estimationwith your child.
Encourage your child to reflect on and extend their understandingof mathematics as it occurs in their everyday activities, play, and conversations.
EDUCATING OUR CHILDREN IS THE BEST INVESTMENT WE CAN MAKE!
Fun With Play Dough – The Moppet Recipe!
by Bright Kids Inc. | Sep 15, 2015 | Fun For Kids!
Teach with LAUGHTER – Send Your Students Home Smiling!
by Bright Kids Inc. | Sep 7, 2015 | Fun For Kids!
Did you know the study of laughter is called GELOTOLOGY?
BE THE REASON FOR YOUR STUDENTS' SMILE!!
Laughter can soothe a teacher's and a student's tension; it can also make it easier to cope with difficult situations.
Laughter helps you connect with other people.
Laughter can help reduce your anxiety and make you feel happier.
It can improve your mood and outlook on life.
It benefits your creativity, confidence and self-esteem.
It provides an opportunity for FUN as students learn to cope with the complexities of their world.
Being a teacher can be one of life's most CHALLENGING yet joyful and rewarding experiences!
Laugh together and give compliments often! Engage in jokes and humorous activities with your students.
Make it a habit to share a laugh with your student before school, during school and after school. And have them share a funny story or jokes with you.
Helpful Tips for Teachers to Include HUMOR in the CLASSROOM. Humor changes developmentally.
During the Preschool years, play and humor are often linked. For example just being bounced up and down or shouting BOO often conjures up shouts of joy and laughter from a child.
Primary school age children enjoy riddles, jokes and rhymes.
Middle school children learn the meaning of more words; their riddles, jokes and humor become more sophisticated.
With each advancing stage children become more aware, more knowledgeable. They play with language, tell jokes and indulge in horseplay.
What do you call an injured TYRANNOSAURUS REX?? — A DINO – SORE!!
Why did the boy eat the lamp?? — His mother told him to have a LIGHT snack!!
What did the cat say when she spilled her milk?? — Nobody is PURR – FECT!!
What did the sun say when it was introduced to the earth?? — It is nice to HEAT you!!
Why do birds go to the library?? — To look for BOOK WORMS!!
What did one flea say to the other flea, as they were getting ready to go to a movie?? — Shall we walk, or take a DOG!!
What do you say to a BUNNY on the day he was born?? — HOPPY Birthday!!
KEEP SMILING 🙂 and Live Happily Ever Laughter!
Parent with LAUGHTER – Send Your Kid to School Smiling!
by Bright Kids Inc. | Sep 5, 2015 | Fun For Kids!
BE THE REASON FOR YOUR CHILD'S SMILE!!
Laughter can soothe a parent's and a child's tension; it can also make it easier to cope with difficult situations.
It provides an opportunity for FUN as children learn to cope with the complexities of their world.
Being a parent can be one of life's most CHALLENGING yet joyful and rewarding experiences!
Laugh together and give compliments often! Engage in jokes and humorous activities with your children.
Make it a habit to share a laugh with your child before school, after school and before bed. And have them share a funny story or jokes with you.
Helpful Tips for Parents to Include HUMOR in the HOME. Humor changes developmentally.
During the Preschool years, play and humor are often linked. For example just being bounced up and down or shouting BOO often conjures up shouts of joy and laughter from your child.
Helping your child with homework!


text:
Q: Are the Sith completely gone? According to an answer to this question, Kylo Ren is not a true Sith.
As we saw in the end of episode VI

Palpatine and Vader are both killed.

Does this mean there are no longer any Sith in the galaxy? If there are no current Sith alive, how would the Sith come back?
Clearly there are followers of the dark side, but I get a bit confused on what the true difference is and why Kylo Ren could not simply re-start the Sith and claim to be one unless there was someone to dispute that claim.

A: I think the implication is that yes, the Sith are gone, though it wouldn't be the first time in Star Wars universe that people thought that.
The most compelling evidence for this is two-fold:

*

*The main antagonist of The Force Awakens doesn't call himself a Sith, he's a Knight of Ren.

*At one point, Maz rattles off a list of "Dark Side of the Force" users from the past and she includes the Sith on that list.

The only thing that's not entirely clear is the identity of the power behind The First Order, Supreme Leader Snoke, who's background remains intentionally vague as of the first movie.

A: According to Visual Dictionary, the implication is that the Sith are gone. Kylo Ren's page (#24) states:

... His ability to use the Force grants him many impressive combat skills, but Kylo Ren is no Jedi, nor is he a Sith.
He is the archetype of a new generation of Dark Side users that have emerged to fill the void left by the Sith's demise

"Demise" seems to strongly imply that they are gone.

*

*
what the true difference is

Disney canon doesn't see very clear on this, but I think it's more of a doctrinal thing. Catholics, Mormons, Protestants and SDAs are all Christians (i don't mean to imply any equivalence of Christianity to Dark Side, but more use Christianity as example of doctrinally branched religion); but they have some fairly major doctrinal differences in their beliefs and practices.

*
why Kylo Ren could not simply re-start the Sith and claim to be one unless there was someone to dispute that claim

In theory, he could - Darth Krayt did just that in old Legends canon.
In practice, he was subservient to Snoke, so he would do what Snoke told him to do, not hare off and do his own thing.

A: No
In The Rise of Skywalker we found out that

 Darth Sidious is alive, so the Siths are still out there. If Rey would do what he wanted, she would probably also become a Sith.

After this movie

 where Darth Sidious died, it seems that now they're really over (and the other answers are valid again). But hey, it is Star Wars, so probably they're not.

redpajama_set_name: RedPajamaStackExchange


The navy and air force will be deployed to monitor a shipment of radioactive fuel as it makes its way through the Irish Sea to Sellafield later this month, it emerged today.
Patrol ships and reconnaissance aircraft will watch over the five tonne cargo of plutonium and uranium mixed oxide (MOX) which is being shipped to the Cumbrian installation from Takahama in Japan.
"The Department of Defence will be deploying resources as appropriate on an ongoing basis as regards the MOX shipment," a department spokesman said.
"It would obviously involve the use of Naval Service ships and Air Corps reconnaissance aircraft."
The decision, following a meeting of the Government's Emergency Task Force yesterday, comes amid public outcry about the shipment.
It also marks a U-turn in Dublin as last week Marine Minister Dermot Ahern rejected calls by the environment group Greenpeace for the defence forces to be deployed.
But the defence spokesman said today that the decision to deploy had been made following fresh consultation between Defence Minister Michael Smith and Mr Ahern.
The spokesman was unable to confirm how many vessels or aircraft would be used, saying it was an "operational matter". But he said: "There will be some deployment."
The cargo ships, the Pacific Pintail and the Pacific Teal, are to arrive in the Irish Sea within the next two weeks but are highly unlikely to enter territorial waters, which stretch 12 miles out to sea, as such a move would probably spark a diplomatic incident.
The material on board was rejected by the Japanese nuclear industry when it arrived in 1999 after it emerged that quality control data at Sellafield, operated by British Nuclear Fuels Ltd (BNFL), was incorrect.
Opposition groups in the Dáil have in recent days stepped up the pressure on Taoiseach Bertie Ahern to demonstrate Ireland's anger at the shipment.
Enda Kenny, leader of Fine Gael, called yesterday for "immediate unconditional war" on the British nuclear industry.
He said on board the Greenpeace flagship, the Rainbow Warrior, which is docked in Dublin: "We've crept around BNFL for too long. It's a matter of fact - not opinion - that BNFL cannot be trusted."
He added: "I'm not happy to put the lives of any Irish child, including my own, in the hands of BNFL."
The Rainbow Warrior is to lead a flotilla of boats which will protest in the Irish Sea when the nuclear cargo arrives.


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Villa Brancatelli is a building of the fourteenth century surrounded by vineyards of its property. Its location is perfect to spend some relaxing moments or as starting point to visit the wonders of Tuscany.
The apartments are fully furnished and offer self-contained accommodation.
At Villa Brancatelli you can enjoy wonderful walk on the beach and a breathtaking landscape on the Elba Island. The possibilities of tours on the territory are numerous and varied: you can discover the paths and the surroundings by foot or rent a bike. Or, why not, simply enjoy some relax by the pool.
Our restaurant will give you the possibility to taste the traditional tuscan cuisine accompanied by the best Brancatelli wines.
The family Brancatelli will be here for you to ensure you an unforgettable experience during your staying.


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Q: compare and sort header based on presence of equal match, python Compare line in file 1 to line in files 2 and 3, if there's a match, list that value as first entry on the header. Is there a way to sort and order the file 1 so that its arranged in way
file1 entries
winter|mountain|snow
skate|slide
ice|water|freeze|melt

file2 entries
water
juice
mountain

file3 entries
sea
ocean
slide
climb

output file with sorted header
mountain|winter|snow
slide|skate
water|ice|freeze|melt

file1 = open('some_file_1.txt', 'r')
file2 = open('some_file_2.txt', 'r')
file3 = open('some_file_3.txt', 'r')

FO = open('some_output_file.txt', 'w')

for line in file1:
    file1_list = line.split(|)
        for i in file1_list:
            for line2 in file2:
                if i == line2:
                    i.insert(0,line.pop(i.index(line2))) # how to sort order of header in file1?
            else: # look at file 3 for match entries between fil3\e1 and file3
                if i == line3:
                    i.insert(0,line.pop(i.index(line2)))

    FO.write("%s\n" %(line1))

want output to look like this
output file with sorted header
mountain|winter|snow
slide|skate
water|ice|freeze|melt

A: I would first create a set of the words in the files 2/3, then sort the words based on their inclusion in the set:
S = set()
for name in ['some_file_2.txt', 'some_file_3.txt']:
    with open(name, 'r') as f:
        S.update(f.read().split('\n'))

with open('some_file_1.txt', 'r') as f, open('some_output_file.txt', 'w') as fo:
    for line in f:
        fo.write('|'.join(sorted(line.strip().split('|'), key=lambda x: x not in S))+'\n')

Output:
mountain|winter|snow
slide|skate
water|ice|freeze|melt

Content of S:
{'climb', 'juice', 'mountain', 'ocean', 'sea', 'slide', 'water'}