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US unemployment benefit claims rise, Fla. down 5,400
Published: Thursday, December 12, 2013 at 9:34 a.m.
Last Modified: Thursday, December 12, 2013 at 10:00 a.m.
WASHINGTON — The number of people applying for U.S. unemployment benefits rose 68,000 to a seasonally adjusted 368,000 last week.
It's the biggest increase in first-time applications in more than a year, a troubling sign if the trend lasts. But the increase likely reflects the difficulty adjusting for delays after the Thanksgiving holiday.
Read related story: US unemployment aid applications surge to 368,000
Here are the states with the biggest increases and decreases in applications. The state data are for the week ended Nov. 23, one week behind the national figures:
States with increases:
Wisconsin: Up 4,420, no reason given
Ohio: Up 2,597, due to layoffs in manufacturing and financial services
Kentucky: Up 1,538, no reason given
States with decreases:
California: Down 19,920, due to fewer layoffs in the services sector
Texas: Down 7,284, no reason given
Florida: Down 5,400, due to fewer layoffs in agriculture, construction, manufacturing, retail and wholesale trade
Pennsylvania: Down 5,145, due to fewer layoffs in construction, scientific services, health care, retail, and social services
Nevada: Down 3,295, no reason given
Michigan: Down 2,567, due to fewer layoffs in management
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Жилье целиком
3 гостя
1 спальня
2 кровати
Об этом жилье
Paradise inside the City Centre! 300 year old colonial house 2 blocks from the Plaza de Armas. Hot showers, central location and super safe. A beautiful place to spend your time in Cusco.
Read our reviews and see what others think about staying with us.
We go out of our way to make sure you have an amazing time in Cusco and make great memories.
This mini apartment is located inside of a 300 year old colonial house in the center of Cuzco on Saphi. Many airbnb listings in Cusco are hotels and we are proud that we offer you a real apartment inside of a real house, the way airbnb was meant to be. This home has been owned by the same family for the last 300 years. You will find many decorations from colonial times decorating the patio area and sleep on a bed that has a 100 year old carved frame.
You can walk out the door and be in the main square in only a few minutes. It's also ideally located near all the transport hubs.
There is a garden area where you can enjoy your morning cup of coffee and a gorgeous patio where you can sit an enjoy a glass of wine. It also has a comfortable living room, and a kitchenette with a microwave and a kettle for making coffee or tea. There is a mini fridge as well. The bed frame is hand carved and has been in the family for 100 years.
There is Wi-fi and HOT showers!
We live in the city center as well and you can ask any time to come over and get advice or get help planning your trip.
Most people are looking for the best experience in Cusco during their time here, we can help you accomplish that, we know the city, the best restaurants, the best day trips, the coolest bars, and how to arrange almost any trip on any budget. If you would like to do paragliding, 4 wheeling, the longest zip line in the world or one of the many awesome treks here in Cusco, hiking Salkantay, Ausangate, Choquequiroa, Inka trail, and Inca jungle, we can set it up. We have done it or know someone who has. (If you have not planned to have a few days or more in Cusco you will wish you did, so plan accordingly. There is lots to do in and around the Cusco area.)
We also ride some killer secret single track that we are more than happy to take experienced bikers on. We can also take you on our personal tour called A Day in the Life.... showing you Peru outside of the tourist spectrum. Our F B page has all kinds of pics of that tour and people who have done it. It is an all day experience and only runs on Sundays.
If you need a ride from the airport or bus station let us know, we can organize that for you, it costs 20-25 dollars, someone will drive there, wait, wait some more, hold a sign and even hold your hand if your scared, and then will get you to our house safe and sound without you having to haggle with the taxi drivers who love fresh tourists. However, if you find managing things like taxis in foreign counties no big deal take one here for 10-15 soles.
Our neighborhood is in a safe part of town very central and close to the Plaza de Armas. You can walk from this apt to all the sites in the city. It's always advisable to take a taxi if you are out late at night. They can drop you off at our door. It's a 3-4 minute walk from the Plaza de Armas. At rush hour however, you can walk faster than a taxi.
You can walk, take a cheap taxi for about $1.50 or take a public bus, which is an adventure in itself, zip your pockets. We know how to get just about anywhere here, so we can make sure you are getting on and taking the correct buses.
If you arrive before the 1:00 check in time and want to leave your bags at our house on Centenario, feel free. Also, if you need a place to leave things while you go on some big trek or to Macchu Picchu for the night you can do that too at our house on Centenario.
Доступно гостям
Wifi, hot showers, and a plethora of great restaurants, local ruins, and more....all while staying in a 8th generation Cusqueña house two minutes from the main square. There is a garden or patio you can enjoy a glass of wine in.
Общение с гостями
Our home is on Av. Centenario, also in the city center so it is easy to get together if you want. We always have you come to our house first and we go over to the apartment together. Then after that we can email, (SENSITIVE CONTENTS HIDDEN) or talk by phone. You get privacy and our advice anytime you want.
Другие важные подробности
We offer specialized, all inclusive trekking, real mountain biking, and off the beaten path adventures, if you want to do some really cool stuff in Cusco, stay with us and inquire.
~It's a shared patio in the back and in the front, please be respectful of others using the patio.
~No unknown guests in the house
~No smoking inside the apartment
~No parties
Если вы отменяете бронирование за 7 дней до поездки или раньше, то мы вернем 50% суммы бронирования. Если вы отменяете бронирование меньше чем за 7 дней до поездки, то деньги не возращаются.
102 отзыва
У этого хозяина 446 отзыва о другом жилье.Просмотреть другие отзывы
We moved to Peru with the desire to help in a third world country. We were complete volunteers for seven years. We both worked in schools for the poor. We arrived with minimal Spanish and a one year old. I would have to say we have come a long way since then. Not only are we fluent in Spanish but Bill has picked up Quechua from the locals he worked with in Andahuaylillas. Although we spent most of our time helping the poor we also took out time to search out some of the best single track, sweet day hikes, good camping spots and do the big treks around here. We love adventure and family which is why we do lots of family adventures.
We are both from Buffalo, NY but moved to Durango Colorado after we got married. We now live in the city center of Cusco Peru, ten minutes walking to the Plaza de Armas. We have decided to offer travelers a nice, safe, and relaxed stay in our house during their time here. After hearing about Airbnb from a friend, we thought it would be great to offer some of our extra rooms to the traveler who tires of cheap hotels and rowdy hostels. You should feel free to have a nice, safe, and relaxed stay in our house during your time here. We know the area, have done the trips, and know the best ways to enjoy Cusco, and its wonders. Plus we can help you do some off the beaten path stuff if you'd like. You'll be happy you stayed with us. Families are welcome!

subset: commoncrawl


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Empire State Youth Orchestras believes in the power of music to transform young lives. Since 1996, it has provided free, private music lessons during the school-day to talented middle-school students in inner city communities. In 2015, recognizing the importance of music training for even younger students, ESYO expanded its program to include an after-school, intensive, ensemble-based program for elementary school children.
ESYO CHIME provides free, daily ensemble-based music instruction to children residing in underserved communities in New York's Capital Region. It presents opportunities to excel in the field of music and make available clear progression routes to ensure every stage of the individual child is looked after.
The program starts with intensive music training at the elementary level and feeds into continued support at the middle school, leading into a seat on one of ESYO's outstanding, performance ensembles.
In addition to musical benefits, research consistently shows that engaging students in intense music training develops executive function skills, reduces violence, and increases both cognitive flexibility and working memory. Children involve in the arts are also four times more likely to be recognized for academic achievement and five times less likely to drop out of school. As the children begin to realize their talent their confidence, self-esteem, self-worth, concentration and renewed sense of pride for their community is fostered in significant ways.


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Noel Gallagher: I 'never had a problem' with cocaine
Noel Gallagher "never had a problem" with cocaine.
The former Oasis star claims he was never addicted to the drug and refused to take it after a while because it "stopped appealing" to him.
He said: "It was a bizarre few months when cocaine stopped appealing to me, because I was still hanging out with the same people.
"I was drinking more - people were still doing it in front of me, which didn't bother me in the slightest, and I've come to realise in the years since then that I never really had a problem with it."
The 48-year-old musician - who has been clean from the drug for a number of years - believes the "only really bad thing" that it made him do was tapping his foot continuously and admits after he stopped the drug, he started to reevaluate some of the friendships he had.
He told The Sunday Times' Style magazine: "The only really bad thing it made me do was tap my foot a lot. At one point, the downstairs neighbours where I was living sent me a note querying 'the loud and rhythmic banging on the ceiling every night' - it was only my foot!
"Towards the end, I had a few nights where I'd scan the room and think, 'How the f**k have I ended up here with these people? We've got nothing in common, it's just the drugs."


text:
You are playing Cute Pink Room Escape
The Escape Games- Cute Pink Room Escape is another point and click house escape game developed by The Escape Games. The motivation of this game has to escape from the cute pink house by using your fantasy skills. Imagine, You have wake up in your old house. That time you know about two thing, door was locked and door key was missing. So, you can find out the door key to escape from this house. This is to check your smart skills. I know, you are the intelligent person. So, you can easily find the way to escape from this house. Ok friends, are you ready to play this interesting Cute Pink Room Escape game?. The Escape Games have more exciting and amusing free online escape games, don't forget to tell your dear ones. All the best!!!. Have more fun!!!. Good Luck!!!. The motivation of this game has to escape from the Cute Pink room by using your fantasy skills. Have more fun. Good Luck.
Game loading!


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Gold prices edged lower Tuesday, weighed down by a stronger dollar and growing expectations for higher US interest rates.
Gold for February delivery fell as much as 0.9% through the early morning. It was last seen down $3.80, or 0.3%, at $1,190.00 a troy ounce at 4:59 pm ET.
The futures price staged a solid recovery Monday, reaching an intraday high of $1,200 a troy ounce. Gold's uptrend continues to be limited by a stronger US dollar, which has been supported by expectations of higher interest rates as soon as next month.
The dollar index, which tracks the greenback against a basket of other major currencies, was up as much as 0.3% Tuesday. It settled down 0.4% at 100.91. The index reached a new 14-year high last week.
Dollar-denominated gold becomes less affordable to foreign investors when the greenback rises. The month-long rally in the dollar has sent bullion tumbling to more than nine-month lows. Further losses could be on the radar should the Federal Reserve hike rates in December as expected.
Federal Funds futures rates, which have long been used to express the market's views on Us monetary policy, imply a more than 98% chance of a rate increase next month.
Rallying stock markets have also weighed on gold and other risk-off assets. The S&P 500, Dow Jones and Nasdaq set consecutive record highs last week, as investors continued to cheer Donald Trump's plan to stimulate the economy through infrastructure spending, deregulation and corporate tax cuts.
US stocks bounced back on Tuesday from a soft start to the week, with the S&P 500 finishing 0.2% higher.
In economic data, US third quarter GDP growth was revised up to 3.2% year-over-year, up from a preliminary estimate of 2.9%, the Commerce Department reported Tuesday. That was the fastest acceleration since the third quarter of 2014. Economists had forecast an upward revision to 3%. The economy is expected to gather strength in the final stretch of 2016, invoking greater confidence in the health of the recovery.
Comex Gold Futures (February 2017)


text:
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June 27, 2013 | Free Samples
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You work too hard for your money to throw it all away on full price when you don't have to!
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Singer Mika Singh, who turned 38 today has been wished a year full of success and good health by folks from Bollywood. Much before the actor turned 38, his friends from the industry put together a party to celebrate his birthday.
After the three day IIFA weekend, when Mika Singh and every other Bollywood celebrity was in Malaysia, the tinsel town decided to celebrate Mika Singh's birthday.
Hrithik Roshan apparently arranged for a cake and celebrated the singer's birthday along with the rest of the actors. Mika Singh tweeted, "@iHrithik thank U so much brother :) really had an awesome time in #malasiya .Thanx 4 the cake & fantastic party bro."
Watch Brothers Trailer: Akshay Kumar Vs Sidharth Malhotra
The 38-year-old singer, the younger brother of Punjabi singer Daler Mehndi, is known for a wide variety of hits he has given to Bollywood like Sawan mein lag gaye aag, Mauja hi mauja, Dhanno, Dhinka chika, Desi beat, Subah hone na de, Pungi, Chinta ta ta and Main tere agal bagal hun.
Some of his friends took to Twitter and wished him as well...
Raj Kundra: Happy birthday to my baby brother @MikaSingh love u praaaji keep the tunes coming!!
Pulkit Samrat: @MikaSingh Paaji wish you a very Happy Birthday!!! Have a kickass year!! Keep rocking us the way you do!
Ayushmann Khurrana: @MikaSingh happy bday paaji! Rab raakha!
Check out his birthday party pics...
Hrithik Roshan
It's inspiring 2 b around someone who always has d power 2 make people feel good. Happy birthday @MikaSingh d world shall always dance wth u
Sonakshi Sinha
Happy birthday to a fellow gemini, new singing partner and certified rockstar @MikaSingh! Brrrruuuaaahhh! Rock it!
Sunny Leone
Happy birthday @MikaSingh God bless!! Have a wonderful birthday!! Keep making all of us sing and dance to your tunes!!


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Sorcerer Mickey Mouse Snowflake Ornament - Walt Disney World 2017
Let it snow!
Cast a spell of snowflake sorcery on your holiday tree with this flat ceramic ornament featuring Mickey Mouse, for an unforgettable souvenir of your 2017 visit to Walt Disney World Resort! See more
It's added to your bag!
Not eligible for in-store reservation.
Magic in the details...
Created especially for Walt Disney World Resort?
- Flat snowflake disc design with Mickey icon cutouts
- Screen art center features Mickey and commemorative ''2017'' logo
- Walt Disney World logo
- Contrast edging
- Satin ribbon for hanging
- Mickey is costumed as The Sorcerer's Apprentice from Walt Disney's Fantasia
The bare necessities
- Ceramic
- 4'' Diameter
- Imported
Most items ordered via Standard Delivery will arrive within 5-7 business days, personalized items within 9-11 business days. Exceptions include items shipped from locations other than our main warehouse. Express Delivery is available for an extra charge.


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- Here is a breakdown of the latest patch fun I had with update 13.0. I pretty much have all of Hydroids parts now. Got them all in less than an hour. I don't know if that is the norm or extremely lucky. In other news Vay Hek seems a bit too easy for all the crap he talks. Or maybe the group of us were too strong. Shout out to the players who ran with me farming Hydroid.
- I have yet to find a stance for anything. So I think I'm not looking in the right place. Because Hek sure doesn't drop it lol. As for Melee 2.0 it makes me feel like a real ninja. Especially when you combine the Katana with the Kunai. And you have yourself an Ash WHOO ninja city. Do yourselves a favor and try the fist weapons too. You will lmao for like an hour using it. Hydroid won't be ready this week. But I'll have him in the next episode.
- I haven't gotten a taste of the Dark Sectors yet. But I don't think any rails are made yet. So we will see how that goes soon enough.
Play Warframe= http://full.sc/14rMMh1
So we had an excellent dev stream for update 13. You can see the low down of it all here. https://www.youtube.com/watch?v=THYFOn4hHdI
But I'm going to focus in on Melee 2.0 information we got from the stream. And how I'm preparing for it. The major blow in it is charge attacks will be no more. And replaced with Warframe energy charging. Some people might not like it but I love it. What that does is open up a whole lot of fun and variety.
We won't see a million Gala's running around like we do now. And it makes all of the weapons we currently have. More in line with all of the weapons. This means more choice and more fun. Without people questioning it and complaining. Me personally I'm leveling up now Dakkra Prime. I love the look of the weapon always have. It just wasn't as useful as Galatine was.
I'm also looking into using Hate and Orthos Prime. Now I may go as far as have several melee weapons. And rotate them based off of fun or boredom. And set certain weapons for certain enemies. Like fast weapons for infested because they sword. And keep big hitters for heavy armored guys. The number of fun possibilities is crazy now.
And I applaud DE for making it viable to use all melee weapons again. Rather than just the flavor of the week. Now we haven't seen it yet so I could just be jumping the gun. But as things look right now let's get it poppin. Also I'll be unretiring Ash just to try all of this out
This was a rough week for me. I have a infection on meds. Which made it close to impossible to do anything this week. I'm better no but now out of the woods. So I had to pick and choose where I did videos. I was happy to feel well enough today to get this video out today,
South Park Stick of Truth Cinematic LP Side Scroller Soul Saver Online Rust First Person Survival Game Closers Online Side Scroller Ecol tactics Online Rpg Maker 2014 Link Realms FreeSky2 Rift Creater Your own Pvp Dimensions Live Guild Wars 2 Feature Pack Warframe Melee 2.0 League of Angels Shadowrun Universe On Steam Animated Series "My name is MT" Ghost Recon Phantoms Remake Zero Online Mech MMO Final Fantasy 14 Patch 2.2 Elder Scrolls Online coming 4/4/2014 You Tuber to watch "Sophie Breca" Rant for the week "Oculus VR bought by Facebook"
The latest patch 10.3 is out for warframe. The quality of life in this game keeps getting better. The UI for the mods section shows slight streamline improvement. The way loot drops is now according to tier. It takes away a lot of the guessing and low level farming. It was a great patch exact patch notes are following.
Survival Mission Improvements:
- Items awarded at 5 minute intervals are now shown in the HUD below the Lotus transmissions.
- Reward items now stack as you play - all rewards are given at the end of the mission.
- As you play and survive, you will receive items at these times:
- 5m: Item from the first reward tier
- 10m: Item from the first reward tier again
- 15m: Guaranteed Void key (this is considered the second reward tier).
- 20m, 25m, 30m+: Item from the third reward tier
- Void mission Prime rewards are awarded at 15 minutes only.
- Mission rewards are now split into three distinct tiers of enemy level, instead of being based on faction.
- Expect better rewards based on the enemy tier you are fighting:
- Tier 1: Level 1-25
- Tier 2: Level 25-45
- Tier 3: Level 45+
- Void mission rewards are tied to the tier of the key.
- Extraction no longer triggers if only one player enters the extraction area.
- If the life support bar is still depleting, *all* players must be at extraction to complete the mission.
- The regular 60 second extraction timer starts if half the team is at extraction *after* the life support bar reaches zero.
- All doors in the level are now locked until you trigger the alarms.
- Added an effect to show the exact position of the next incoming support capsule.
- Improved management and feedback when equipping mods between weapons and sentinels.
- Bosses now have their blueprint drops as end-mission rewards (like Lephantis) instead of physical orbs in the level. (PSA: Known issue with BP's not appearing in Foundry will be Hotfixed.).
- Further improvements on the experimental multi-threaded rendering option. If you had this enabled, take note you will need to re-enable this in the settings area.
- Hid conclave scores from lobby UI; only reveal them in squad panel when someone votes on a Conclave node, and also provide name of player who doesn't meet Conclave rating requirement.
- Made Dojo prop decoration destruction give all your resources back.
- Hooked up sound to the Revive mechanic, falling downed allies now has audio feedback.
- Improved matchmaking to consider a player's "Loadout rank" when finding a suitable squad to join (sum of pistol + rifle + melee + powersuit rank) .
- Updated Dera and Sicarus firing sounds.
- Added missing mod card image for Quick Thinking.
- Improved camera motion under collision.
- Gloss maps added to Nekro's materials for more varied shininess.
- Added elemental FX for Kama.
- Added more colour variation to Infested Pistol FX.
- Acrid now uses energy color.
- Added sound for Trinity's Energy Vampire ability deactivating.
- Players can only sell their last remaining Sentinel weapon if they have no Sentinels in their inventory.
- Improved mini-map pathing to prevent misleading objective icons.
- Reduced impulse on stealth finishers.
- Balanced Nova's Molecular Prime ability for Conclaves only.
- Added unique casting sounds for Banshee abilities and updated Soundquake and Silence.
- Added new Volt Shield ability sounds.
- Updated Volt overload charge sounds to match animation.
- Added translations for some text that was English only.
- Added local and remote teleport sound slots for Ash's Bladestorm.
- Added small smoke effect to noxious crawlers.
- Fixed mobile-defense objective markers; they now stay on the active defense objective and only show the other terminal markers after the defense wave is complete.
- Prevented Vor's electrical attacks from hiting the invisible players (Loki, Ash).
- Improved spawning in multi-defense (and other modes that explicitly spawn enemies using custom spawn filters).
- Improved spawning logic in Corpus Ship Survival.
- Changed minimap marker settings to help with finding Survival capsules in Grineer Galleon.
- Added a limit to the number of Survival markers that appear onscreen at once; aside from making it easier to see the action this may also help with frame-rate.
- Removed elevators from Orokin Derelict Survival.
- Improved melee weapon accuracy vs. non-upright targets.
- Made sentinel flare visual effect use energy color.
- Removed redundant mission start VO after host migration.
- Changed pre-death (aka bleed-out) to disallow blocking or parrying.
- Changed all UPPERCASE Warframe and weapon names in descriptions to Capital Case.
- Improved Ash Teleport responsiveness – trimmed animation and added reaction to enemy being teleported to.
- Added Carrier Sentinel ambient FX.
- Added holster animation to Dual Zoren, Dual Ichor, and Dual Cleaver weapons after a jump attack.
- Replaced pagination with scrolling navigation for browsing available profile pictures.
- Revised player resurrection sounds.
- Added conclave values to Sentinels and Kama.
- Revised Clan leaderboard badges.
- Made Ignis flame effects use energy color.
- Added immediately display of cosmetic item loadout changes to on the main menu avatar; Backing out without equipping a cosmetic item will then revert to your actual loadout.
- Improved Mag Prime materials to better allow tinting.
- Improved logic for drawing enemy fire while using Rhino's Iron Skin ability and Djinn Sentinel Fatal Attraction precept.
- Improved ambient sound for Dojo Gardens.
- Conclaves now operate on best-of-three rounds instead of single round.
- A few Market weapons are being retired: Gorgon, Dual Ether Daggers, Boar, and Machete. You have 7 days to get them before they go into the retirement!
- Fixed various host migration issues found in Survival related to enemy spawning.
- Fixed Survival life support capsule and pickup timing.
- Fixed issue with news/alerts not displaying intermittently.
- Fixed mission nodes being selected in the background when clicking on alert popup.
- Fixed some highlight issues with consumables (buttons now disabled when not picking consumables).
- Fixed rare cases where an alarm panel outside of the spawn would be enabled instead of the one in the spawn room, changed how health drain works.
- Fixed Dual Ichor getting stuck in charge mode.
- Fixed Sure Footed mod that was not working on clients.
- Fixed issue where using chat while in a non-star node lobby will prevent the player from starting it, and when done in a star chart lobby, will start the match.
- Fixed bounding box on consoles that allowed players to walk up them.
- Fixed issue where player loses rewards in key-accessed defense missions if they do not claim and exit with host.
- Fixed missing intro/outro music in Conclaves.
- Fixed issue where Clans could build more than one of the same Clan Halls.
- Fixed changing regions while zoomed preventing alert panel from every showing up again.
- Fixed missing damage number reports for clients during Ember's Overheat ability.
- Fixed some issues with Warframe idles.
- Fixed (switched) Glaive mod names of Quick Return and Rebound to match the function.
- Fixed animation bug with Boltor if reload is interrupted by melee.
- Fixed Mag's Shield Polarize ability FX on enemies to use correct color.
- Fixed a "power in use" bug that occurred after using Nekros' Desecrate.
- Fixed issue with Soma where clip mesh during reload animation was rendering black
- Fixed Akimbo Bolto sound attenuation and missing reload sounds.
- Fix for Glaive mods to be shared between Glaive/Kestrel
- Fixed Conclave game type not counting in stats.
- Fixed Torid gas cloud not appearing when the projectile hits and kills an enemy.
- Fixed reported collision issues across all maps.
- Fixed clients not being able to damage ragdolled enemies with trace fire weapons.
- Fixed continuous fire AoE weapons (Ignis, Embolist) from hitting the same target multiple times per shot when in ragdoll.
- Fixed missing bodyfall event sounds for Grineer deaths.
- Fixed inbox not popping up after tutorial, if you have unread messages.
- Fixed issue that allowed Nova's Wormhole ability to teleport through rock walls.
- Fixed Loki's Radial Disarm that was removing limbs from Infested Runners.
- Fixed issue where after activating the first objective in Orokin mobile defense, the timer does not start.
- Fixed Dx11 being disabled in the launcher if you went to the settings panel before Dx11 had been auto-detected.
- Fixed enemies not always playing their death animations / ragdolls.
- Fixed weapons that played reload sounds twice (Ignis, Grakata, Embolist)
- Fixed Nekros "noble" pose with Lanka equipped.
- Fixed Survival reward that awarded a maxed Sentinel mod.
- Fixed weapon energy shader for dark (black) energy colors.
- Fixed issue where MOAs raised with Nekros Shadows of the Dead ability knocked down friendly players.
- Fixed Shadows of the Dead not applying effects on clones for clients when there is enough latency between them and the host.
- Fixed emblem deco positions on Carrier and Djinn sentinels.
- Fixed Torid gas cloud damage radius, which was larger than the actual visible cloud.
- Fixed Torid elemental damage not being affected by armor.
- Fixed issue where Mods won't apply to newly purchased weapons until you "touch" them in the arsenal.
- Fixed level 60+ Infested suicide runners surviving after they self-explode.
- Fixed Osprey's not being affected by Ember's Fireblast (even when flying right through the effects).
- Fixed multiple animation bugs reported in forums.
- Fixed mismatched translations of planet name for Phobos.
- Fixed Vor teleporting after targets he hasn't seen yet.
- Fixed ragdolled enemies not displaying a health bar.
- Fixed throwing animation (Kunai, Hikou) becoming jittery with fire rate increase.
- Fixed NPCs potentially falling through floor when activating panic-button.
- Fixed issue where Sentinels were destroyed during Lephantis battle phase switches.
- Fixed reload sounds for Dual Vastos with data mass reload animation.
- Fixed Reflection mod not working on Grineer Lancers.
- Fixed Infested chargers and ancients not being appropriately affected by Vauban's Vortex ability.
- Fixed issue where player could craft last remaining secondary weapon (for dual version) leaving the player with no secondary weapon available.
- Fixed Ignis and other weapons causing Pickups to go crazy if they had not come to rest in Conclave duels.
- Fixed the news and alerts blocking the mouse even when they are invisible.
- Fixed issue where users may be unable to rotate their camera after placing a decoration in the Dojo.
- Fixed perceived range issues with Galatine, and also fixed misaligned elemental FX.
- Fixed some reported issues with Rescue Target "stuck" spots.
- Fixed some gfx settings that would not actually take effect the 1st time you toggle if your reconfig required a device reset (ie: res change)
- Fixed issue where players could attack and kill each other between rounds in Neptune and Pluto Conclaves.
- Fixed issue where players were repeatedly teleported out of the duel area upon host migration.
- Fixed missing elemental FX for Dakra Prime and Plasma sword.
- Fixed issue where enemy Shield Osprey drones would shield friendly enemies controlled by Nyx or Nekros.
- Fixed Glaive Rebound mod to have improved rebounding (must travel specified distance before auto-recall)
- Fixed headshot stat tracking issues with all ranged weapons.
- Fixed issue where if a player dies during a survival mission, they will lose their previously acquired checkpoint.
- Fixed client not initiating lobby when joining sessions while zoomed in on a planet.
- Fixed "joined <player>" message unnecessarily appearing when returning to frontend after completing a mission.
- Fixed stat tracking to exclude enemy pet kills/deaths in Conclave duels.
- Fixed Ember's Fireblast light FX being independent of its power duration.
- Fixed spectating mode - spectators no longer spectate themselves.
- Fixed Conclave spawning to avoid players spawning on top of each other.
- Fixed Fatal Attraction precept error on clients, resulting in missing FX.
- Fixed player getting stuck in sprint without toggle sprint in some cases.
- Fixed akimbo animations related to crouching and hand positioning.
- Fixed issues with Ammo Mutation mods that were not functioning as intended.
Update 10 is live with a host of new changes. You can see the patch notes below. But I'm going to talk about what I liked. The UI is my favorite part of this content. It's sleek and easy to use. Makes things far more smooth and streamlined in the game.
Next thing I want to touch on is Nekro and Mag. I've seen a ton of Nekro running around already. Soul punch is the most awesome name and skill I witnessed so far. They did a really good job with him. I haven't seen Mag Prime yet ofcourse. But I am trying to farm her for my second frame.
I have to mention The Golem boss because it's too epic not to. He is a fun fight not to hard and not a push over. He is a very good beginning to epic large encounters in this game. I think he needs his own music though it would make the feel better.
The new sentinel Carrier is meh to me. I love shade so he is getting the deth cube's rifle. I want to see how epic or lame that will look. The new melee weapons look sick, cool additions to the game for sure. The new Rifle with that omg 100 bullet clip...I have to resist the urge on that.
Conclave is cool, although I can't seem to find any high enough for my full power. If I am mistaken someone please tell me which planet. I can fight 880 power on. Not that I'm super high. I know loads of people higher but where are we supposed to go?
Two things I dislike are simple. First thing the new mods to me are fluff. Unless we getting a new slot, I can't see me using them. Like the Intruder mod lol what? Yea I'm not wasting a slot that.
Second thing is the gating of the new maps. I think that should have been said before hand. Because all it did to all of us is rage us lol. They patched and made it better. But you still kinda have that hmm taste left right?


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October 10, 2016
Your brother kept on complaining about the trees' branches getting in your way. At first you laughed at him and asked him to look around. You let him say the place you're in and he got it right. You are in a forest. Both of you have some wilderness training and you want to try […] ...57 votes, average: 3.89 out of 5


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New Opportunity
3 Bedroom 1 Bathroom Crowdfunding Property in SUITLAND, MD
PeerStreet: 2415 Fort Dr SUITLAND, MD 20746
- Property Type: Single-family
- Investment: $1,000+
- Annual Return: Medium
- Term: Short
- CF Type: Debt
- Listed: 09/07/2016
Property Overview The subject property is a single-family home located in Suitland-Silver Hill, MD. It has three bedrooms, one bathroom, and a total of 972 square feet. Location Suitland-Silver Hill is a city in Prince Georges County, Maryland. It is located approximately 10 miles south of Washington, DC. According to Clear Capital, the values of homes in the subject property's zip code have increased 5.7% year-over-year (July, 2016) and are expected to decrease by 2.2% over the next 12 months and by 9.1% over the next 24 months. The loan has a remaining term of approximately 12 months and the current "As Is" LTV based on a PeerStreet-commissioned BPO is 66%. To analyze downside risk, PeerStreet applied the worst 12-month decline (32.2%) in the zip code over the last 20 years (data from Clear Capital) to the "As Is" value. If the worst 12-month price decline in the past 20 years were to occur again, the resulting "Stressed LTV" would be 97%. The 2014 estimated median household income of Suitland-Silver Hill was $56,951, approximately 23% lower than the estimate for the state of Maryland.
Security: Debt
Term: Short
Listed: 09/07/2016
Security: Debt
Term: Short
Listed: 09/07/2016


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Question: The adjusted trial balance of Wilder Company at December 31
The adjusted trial balance of Wilder Company at December 31, 2017, includes the following accounts: Owner's Capital $15,600, Owner's Drawings $7,000, Service Revenue $39,000, Salaries and Wages Expense $16,000, Insurance Expense $2,000, Rent Expense $4,000, Supplies Expense $1,500 and Depreciation Expense $1,300. Prepare an income statement for the year.
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Answer to relevant QuestionsPartial adjusted trial balance data for Wilder Company is presented in BE3-9. The balance in Owner's Capital is the balance as of January 1. Prepare an owner's equity statement for the year assuming net income is $14,200 ...Yang Co. was organized on April 1, 2017. The company prepares quarterly financial statements. The adjusted trial balance amounts at June 30 are shown below.(a) Determine the net income for the quarter April 1 to June 30.(b) ...Meghan Lindh, D.D.S., opened a dental practice on January 1, 2017. During the first month of operations, the following transactions occurred.1. Performed services for patients who had dental plan insurance. At January 31, ...Zac Brown Company has the following balances in selected accounts on December 31, 2017.Service Revenue ........... $40,000Insurance Expense .......... 2,700Supplies Expense ............ 2,450All the accounts have ...A review of the ledger of Remina Company at December 31, 2017, produces the following data pertaining to the preparation of annual adjusting entries.1. Prepaid Insurance $10,440. The company has separate insurance policies ...
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The Fuze Quattro is a great vibe-compatible butt plug for anyone who wants to engage in anal play. Just slide your favourite bullet vibrator into the hole in the base and you will feel the vibrations throughout the toy for extra pleasurable stimulation. Or you can use the base as a finger hole for manual adjustment and play.Always remember that the anus is not self-lubricating, so when using any toy here, be very generous with the lube.Happy Valley toys are made of pure platinum silicone. Silicone is non-porous, hypoallergenic and phthalate-free, making it an ideal body-safe material. Silicone toys can be boiled for up to 5 minutes in order to sterilize them. Always remember to stick with water-based lubricant when using a silicone toy.Vibrator not included. Made in the USA.Available in BlackLength: 10 cm / 4"Circumference: 8 cm / 3 1/4"
© 2016 Lovecraft Ltd. All rights reserved. No portion of this site may be reproduced or duplicated without the express permission of Lovecraft Ltd.
On our site you will be introduced to Canada's most comprehensive selection of highest quality sex toys, lubricants, massage lotions, books, and so much more. We carry the very popular Fleshlight toys for men, the well known prostrate massagers by Aneros, and the wonderful Japanese Tenga masturbators. We have the Cadillac Magic Wand as well as the Vibratex Rabbit Vibrators. Luxury vibrators from Lelo, We-Vibe, Fun Factory and Joy Division. We proudly carry Canadian sex toys from Aslan Leather, Happy Valley, LeatherBeaten and Love Bumper. We also have silicone dildos from Vixen Creations and Tantus and don't forget to check out or wonderful selection of lubricants and massage oils.


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O this learning, what a thing it is!
~William Shakespeare
The Robinson Shakespeare Company (RSC) was founded in 2008 with the objective of bringing high quality theatre instruction to children from diverse backgrounds. Over the years, the program has grown from 12 participants to over 30 and through a generous Community Foundation Grant from the Community Foundation of St. Joseph County, the RSC has been able to start an outreach into area schools that currently reaches approximately 430 students through after-school programs and in-class workshops.
Robinson Shakespeare Company
Community Partners


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Meet MELISSA....this pretty girl was found as a stray with Joan who is believed to be her mother. Melissa is a beagle/spaniel mix, approx. 5 years old and 30lbs. She is a happy soul who just needs some TLC and a patient owner. She does well with other dogs and will need one in her new home. Melissa will need a fenced yard to keep her from ever being a stray again. She is spayed, current on shots, heartworm negative & microchipped. Our online application can be found at http://members.petfinder.org/~VA231/Adoptions/Application.htm.
We require all animals in the potential adoptive home be altered, current on shots and heartworm. We do ask for permission to contact your vet to verify this information. Some dogs are required to have a fenced yard depending on temperment. We do not adopt out animals to be outdoor dogs only.
Thank You!
Your message has been sent to Hickory Hill K-9 Rescue.
You'll receive a copy, too, at to help you keep track of which pets you've inquired about, and which shelters and rescues you've emailed.
NOTE: Some shelters have physical locations you can visit; some of these shelters may only have pets for a limited time, so please do not wait for a reply—just go visit the shelter! Other organizations are rescue groups run by busy volunteers who may take a while to reply. You can find information about the shelter or rescue group caring for this pet, and their adoption procedures, on the pet's details page on Adopt-a-Pet.com.


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There is so much to love about Highlands. It has been a mountain respite for over a century and people still come here to get away from 'the real world' and the small year-round population of about 3,200 swells to over 30,000 in the summer months. Whether you are looking to relax or discover unique activities, the Playhouse joins the vibrant cultural arts scene with four live productions in the summer season and first-run movies throughout the year. The postcard downtown area itself boasts some of the finest amenities in the South with amazing shops, world-famous resorts and unforgettable restaurants. At 4,118 feet, Highlands has one of the highest elevations east of the Mississippi River.
Outdoor Activities
Arts & Culture


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Jotform API: how can i provide an update form for subscribers & integrate it with Jotform?Asked by actors2014 on September 09, 2015 at 08:49 PM
Many thanks in advance & apologies for basically asking the same question twice ;)
I'm a Php Webdeveloper, and I've been asked to provide an pre-populated "update" form for the existing subscribers of my clients website that can pass entries to both JotForm's server and to my client's server.
I'm a Jotform noob, but I've figured I need to use the API. Unfortunately, I'm stuggling to get my head around your documentation! I have very little time to do this (as usual) - hence the questions...
Currently, the client's site has a Jotform, linked to Stripe, that takes various details from new subscribers, together with their credit card details.
Now its planned, via a "Thank you" redirect to run a simple PhP script that passes the above details into a mysql DB.
The problem is, this method can only work for new subscribers; how can we securely update the details for existing subscribers in a way that updates both jotform's and our DB info in "one go"?; I am aware we can set up autoresponder emails with "edit" links but all this will do is enable the subscriber details to be changed on Jotform and miss out our DB altogether.
I know you can pass details via URLs, but this seems crazily insecure, particularly as credit card details may need to be passed.
So, now (probably erronously) I've come to the conclusion to use the JotForm API, but not getting very far with this ( I have a key & the API's working on my server) so using this (or not if you suggest) how do I:
1. grab a subcribers personal data,
2. display it via a prepopulated Jotform,
3. check everything is OK (including the Credit card details)
4. Pass the valid data back to Jotform (preferably via POST) & update our DB.
Anyone done this, or at least point me in the right diection here?
Any advice will be very gratefully recieved!
JotForm Support
If that's the case, there's two options that you can try.
Option 1: Create your own HTML form or page dedicated to only updating some details to the subscriber (I assume you are not requesting for payment again?).
With that in mind, here are the link to our API page using PHP:
1. Let's say user wants to get his subscription or submission details by entering a specific ID or name, you can then follow this guide on how to fetch the submission data and prepopulate the HTML form: http://api.jotform.com/docs/#submission-id
2. After that, you can then refer to this link to edit or update those submissions: http://api.jotform.com/docs/#post-submission-id
3. At the same time, you can run your own PHP script to update your MySQL database.
Option 2: Another way for this is using the edit link plus a Webhook. Instead of redirecting to a PHP script to run it, you can silently run it at the back end using WebHook, you can learn more about it here: https://www.jotform.com/help/245-How-to-Setup-Webhook-with-JotForm. However, I'm not sure if the Webhook will still trigger for edit link, I assume it will. You can have a PHP script in the Webhook that checks if it's a new or old submission.
I hope that helps. You can also contact the API team for more details, here's their email address firstname.lastname@example.com.
Cheers Charlie for the great answers. I'll try-out option one. Many thanks again ;)
JotForm Support
You're welcome. I'm glad it helped. Should you need any assistance again, please feel free to contact us anytime.
Thank you :)


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The SS Propulsion is a building in Civilization Revolution.
The Spaceship Propulsion Module is one of the four essential pieces needed to construct a Spaceship and win a Technology Victory! Building extra Propulsion Modules will make your Spaceship complete its journey faster!
- 200 Resources needed
- Tech Required - Space Flight
Civilopedia EntryEdit
Travel through the empty reaches of space is vastly different from traveling through a planetary atmosphere. An aircraft must constantly fight the dragging effect of the air around it, and must apply constant thrust to maintain altitude, course and speed. A space craft, on the other hand, is flying through vacuum - once it is moving it will continue to move without further energy required (until it crashes into something or comes within the gravitational pull of a sizeable object). Therefore, a colonizing spacecraft's engines are designed to provide massive thrust at the start of the voyage to set the ship on its course, then to remain largely dormant for the majority of the journey (except as needed to provide small course corrections to avoid stellar debris), and then to provide equally massive thrust to slow the ship down once it reaches its destination.
- While the major output of most engines, like those found in cars, is carbon dioxide, because a significant portion of rocket fuel is hydrogen and oxygen, the major output of the space shuttle is water.
- A space shuttle is able to reach speeds of roughly 17,000 mph (27000 km/h) in 8.5 minutes. This is the equivalent of going from 0 to 60 mph in a second and a half.


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Product Spotlight
Featured Research
Quick Stats
You are here
Expert Column: Seafood Sales Start Lent with a Bang
Comp retail promos up 42 percentBy John Sackton, SeafoodNews.com
There is a good chance seafood sales for Lent will be excellent this year. After a drop in 2014, retail seafood promotions during February surged by 42 percent, led by a 45 percent increase in shrimp promotions.
Urner Barry's retail index measures both the number of stores nationally engaged in promotion, and the number of seafood features published in a given week.
For this analysis, which originally appeared on our website, seafoodnews.com, we used the raw store numbers to determine retail interest. The data represent about 40 percent of U.S. metro areas, by population. In the major metro markets surveyed, 195,112 stores ran individual weekly seafood features in February 2015, versus only 137,690 in February 2014. Obviously retailers see seafood lent promotions as a bigger part of their business this year. We recognize that Lent in 2014 started three weeks later than Lent in 2015. However, comparing the first three weeks of Lent in each year shows the same strong improvement, with a 26 percent increase in total year-over-year store promotions. So we are confident that we are looking at a strong start to the main seafood sales season.
The surge in promotions applies to all products, but especially shrimp. The number of stores (again for the 16 surveyed major metro areas) with shrimp promotions increased from 43,577 to 63,291. However, prices were mostly unchanged. For example, a 26-30 raw EZ peel shrimp sold for $9.52 per pound in 2014, and for $9.31 per pound in 2015. This is a drop of only 2.2 percent.
Meanwhile, the last 90 day wholesale average for 26-30 Asian white shrimp has been $5.01, vs. $6.75 for the same period a year ago. So wholesale prices have come down 25.7 percent, and retail prices have come down about 2.2 percent. This suggests that part of the retail interest in shrimp is that margins are considerably higher this year than in 2014.
But the surge in promotion suggests that not only are retailers eager to buy shrimp, but they are selling to more customers. This is a positive development for suppliers, as it means that shrimp is moving through the pipeline. Of course it would move faster with lower retail prices, but that is likely what 's coming next.
The impetus will be retail competition, and once some banners start heavily promoting lower prices, others will follow suit.
This positive news on shrimp was repeated in other major categories as well, though less dramatically. Atlantic salmon promotions were up 12 percent over February 2014, and have continued a positive trend for three years.
Fillets, both fresh and frozen, also saw higher promotion. Fillet promotions were up 33 percent in February, vs. the same month last year. For Alaskan cod, average prices edged up from $5.62 to $6.09. For fresh/frozen Atlantic cod, prices were stable, with an average price of $6.75 in 2015 -- less than a penny difference compared with 2014.
Higher sales with little price reduction is an indication of improving seafood demand. Retail is clearly increasing its sales volume as more promotions translate directly to higher volume. Meanwhile, foodservice demand is climbing also, as restaurant traffic improves and the headwinds of unemployment and low wages abate a little, due partly to lower gas prices.
This will likely create quite a buzz at the upcoming Boston Seafood Show, as it's clear that this year's seafood sales will be firing on all cylinders.


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Thrive is our stress management programme. Released at the beginning of 2016, it has been created after over two years of development and research to pro-actively prevent and manage stress, anxiety and depression.
Find out how stressed you are with our questionnaire.
The Yerkes-Dodson Law explains the relationship between performance and stress, indicating that an optimal level of pressure needs to be applied to get the best from someone. However, once that optimal level becomes too much for a person to handle, performance decreases significantly. The management of stress and anxiety is imperative to us living a healthy, happy life.
Each of the clinical interventions used in the app have years of research behind them, and we've featured all of this within the app itself, as well as below. We have also carried out clinical research trials at the University of Roehampton, with another commencing in April 2016.
Start every day tracking your mood to receive the best recommendations to get through it. Based on your results the Mood Meter will recommend different activities. It will record your results on your progress so you can look back and see what works for you. It will learn itself what you find helpful and get better at advising you over time.
Our cognitive behavioural therapy based thought trainer is how we help you to re-frame your negative thoughts. We all have negative thoughts at times, but is there a better way we can think about things? That is what the thought trainer is here to do. It tracks how you feel, giving recommendations and helping you to see a positive in the negative. With everything tracked in Progress and the app learning more about you as you use it, the Thought Trainer will soon personalise itself to your experiences.
The evidence
Computerised Cognitive Behavioural (cCBT) therapy has accumulated 10 years of evidence. It has been shown to work as a self-directed treatment without intervention from a therapist. In 2016 Jill Newby and colleagues from St Vincent's Hospital in Australia undertook a review of all the evidence of cCBT used for depression and anxiety showing it is a very effective technique and comparable to face to face therapy. Here is a link to the study.
Progress keeps track of everything you do in the app. It is what the app uses to give you better and better tips. If you are working with a therapist you can use Progress as your full-fledged therapy journal.
This is the simplest technique, one that you can learn in the app and practice anywhere you are. It is based on the fact that increasing chest pressure by taking very slow and deep breaths, and then reducing by slowly breathing out, triggers a reflex. This reflex slows down your pulse and gives you a relaxed feeling in your body. As body and mind are connected this then results in relaxation in your mind. Give it a go for 3, 5, 7 or 10 minutes!
The evidence
Deep slow breathing is an essential technique incorporated in many relaxation exercises. It has been extensively examined in the literature in different setting. A good review of the evidence behind it and its uses can be found in General Principles and Empirically Supported Techniques of Cognitive Behavior Therapy, Chapter 14 by Hazlett-Stevens and Craske. You can read a preview of the chapter here.
In this technique we also take advantage of the mind-body connection. We will teach you to contract and relax various muscles progressively allowing you to enjoy the difference between the tense sensations in the muscle and the relaxed sensations that come after you have let the tension go
The evidence
Since its description by Jacobson in 1938 this technique has a record of proven efficacy. There is a 2007 review of the literature that summarises all the available evidence up to that date which you can find here.
Not for everyone but those of you who are able to reach a state of hypnosis can benefit greatly from this technique. We will try to teach you to put yourself into a hypnotic trance. If you are able to achieve it, he will help you teach yourself a word of phrase that will quickly bring you back to that state of relaxation whatever your circumstances.
The evidence
It has proven efficacy in anxiety related to many situations. It has been particularly studied in people going through different medical treatments like dialysis, chemotherapy, surgery and dentistry. There is a 2010 review that goes through all that evidence. The main issue with hypnosis is that the person must be suggestible to benefit from it. Here is a recent study on how suggestibility influences outcomes in using hypnosis to manage pain.
Simple to learn but hard to master this is quite a powerful technique for relaxation. It requires dedication and practice but if you persevere it can bring about the most benefits. You will need a quiet space and to achieve a sensation of comfort. You will be able todevelop a passive attitude that allows you to just watch your feelings, sensations and thoughts as they pass through your mind. You will also use word or phrase to help you refocus.
The evidence
This is probably the technique that has received the most attention recently. It requires practice to master but everyone can use it if they devote the time to learn it and practice it. There is a complete review and meta-analysis of all the evidence of meditation in the management of anxiety published in the British Journal of Psychology in 2012.
We all like a positive, feel good message – And that's why the message in a bottle was created. A completely confidential, anonymous social feature, the message in a bottle feature allows you to send and receive encouraging cards through the app. You can personalise the message in a number of ways from the images on the postcard to the stamp. Plus sending it is great fun - who will find your message in a bottle?
When feeling anxious or stressed, sometimes you need a distraction for 5 minutes to help you forget about what is going on around you. This is why the Zen Garden was created. Giving you a blank canvas to build a tranquil garden on the beach, this feature allows you to get creative and design your own peaceful paradise to take your mind off of things around you, when you need to.


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kevin steele Photographer
Shamar CamargoModel Female Santa Barbara, California, US
My MM URL: http://www.modelmayhem.com/ShamarCamargo
Mayhem # 895104
About Me
Moody, sensual, atmospheric, classical, alternative are some of the styles I work with.
Melding with nature is my forte. I like to evoke a sense of anthropomorphism in the landscape. My body can reflect everything from animal magnetism to the stillness of marble.
What I have to offer as a model:
-adventurous streak, i.e. body paint, experimental makeup,
climb trees or hike into location
-refined aesthetic, avant garde to classical
-natural tan, no tattoos
-phenomenal wardrobe
-all natural look (no plastic surgery)
-basic makeup to match my unusual skin tone
-experience with both fine art and photography modeling
-an eye for the artistic shot
-Dance and Martial Arts background
-know interesting locations
-experience designing shoots, post production
and being on other end of camera
-comfortable in the outdoors
-a true hourglass figure
Send me an email to discuss my rates and set something up...
Have you worked with Shamar Camargo? Add Credits for Shamar Camargo! >>
kevin steele Photographer
ChristopherW A L K E R Model
edwin souby Photographer
Erin Florence Photographer
Jafar M Pierre Photographer
Paquet Photography Photographer
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Introducing KDE 4, mini articles full of screenshots
I'm Mexican. If you find any mistakes please let me know, you'll help me improve my English. Thanks in advance.
Theme for KDE 3.5:
Apparently someone filed a bug for KDE 4.2 so one can disable the text for icons on the panel.
Last edited by mips; February 3rd, 2009 at 09:04 PM.


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LARAMIE, Wyo. -
Wyo WBB notes vs. Fresno State | Gameday Central
The Wyoming women's basketball team returns home to host the league-leading Fresno State Bulldogs on Saturday. The game is scheduled for 2 p.m. MT in the Arena-Auditorium. Live stats, audio and video can be found on the women's basketball Gameday Central page located on GoWyo.com.
The Cowgirls enter this week's match-up with a 7-8 mark and 2-3 in conference action a tough 57-54 loss against San Diego State Aztecs on Wednesday night. Senior forward Kayla Woodward finished with a game-high 20 points while shooting 7-17 from the field and 4-11 from beyond the arc. Junior guard Marquelle Dent followed with 17 points, seven rebounds, five assists and five steals. Junior guard Jordan Kelley led the way with a team-high eight rebounds. The Cowgirls were 20-of-53 (.377) from the field and 8-of-28 (.286) from beyond the arc.
Dent leads the way averaging 17.0 points, 5.6 assists and 2.1 steals. Woodward follows with a team-high 7.6 rebounds plus 15.4 points. Kelley is adding 6.3 points, 6.0 rebounds and 3.3 assists in her 15 contests this season. As a team, the Cowgirls are shooting 361-of-922 (.392) from the field and 110-of-333 (.330) from the beyond the arc.
The Bulldogs are 13-3 overall and 5-0 in league play. Senior forward Alex Sheedy leads the way with 17.3 points and 7.3 rebounds per contest. Center Bego Faz Davalos is averaging a team-high 7.8 rebounds plus 7.9 points. The Bulldogs average 66.1 points compared to 59.6 points for their opponents. This will be the 22nd meeting between the two schools. Fresno State leads the series 11-10. The last time the two teams met was Feb. 19, 2014. The Bulldogs earned a 69-60 victory in San Diego. Fresno State is coached by Jaime White who is in her first season with the program.


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Enter your name and e-mail below to receive updates about conference registration, program, and posters.You can unsubscribe at anytime. Please e-mail us if you have questions about your subscription.
The 27th annual Rotman Research Institute conference will present cutting-edge research on basic neural mechanisms informed by structural and functional neuroimaging. This year's broad theme discusses healthy and impaired brain function across the lifespan and features research on several disorders that affect the lives and well-being of millions of people within Canada and worldwide.
This conference provides a unique opportunity to bring together researchers with basic and translational scientific expertise to discuss their research programs' latest findings that ultimately aim to enhance clinical care for patients.
The Rotman Research Institute (RRI) at Baycrest Health Sciences is a premier international centre for the study of human brain function. The RRI's primary research focus is memory and the executive (frontal lobe) functions of the brain, both in normal aging and in the presence of diseases and conditions which affect the brain, such as stroke, traumatic brain injury, Alzheimer's disease and other dementias.


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Discovery and development of cephalosporins
Cephalosporins are a broad class of bactericidal antibiotics that include the β-lactam ring and share a structural similarity and mechanism of action with other β-lactam antibiotics (e.g. penicillins, carbapenems and monobactams).[1] The cephalosporins (and other β-lactams) have the ability to kill bacteria by inhibiting essential steps in the bacterial cell wall synthesis which in the end results in osmotic lysis and death of the bacterial cell.[2] Cephalosporins are widely used antibiotics because of their clinical efficiency and desirable safety profile.[3]
The cephalosporins are diverse in their antibacterial spectrum, water solubility, acid tolerability, oral bioavailability, biological half-life and other properties. Therefore, the cephalosporins can be further classified into generations depending on antibacterial activity, time of invention and structural basis.
- 1 Basic structure of cephalosporins
- 2 History
- 3 Mechanism of action
- 4 Drug design
- 5 Antimicrobial resistance
- 6 Drug development
- 7 Current status
- 8 See also
- 9 References
Basic structure of cephalosporins[edit]
The core of the basic cephalosporin molecule consists of a two ring system which includes a β-lactam ring condensed with dihydrothiazine ring. The core itself can also be referred to as 7-aminocephalosporanic acid which can be derived by hydrolysis from the natural compound cephalosporin C. Chemical compounds containing this core are relatively stable to acid hydrolysis and tolerance to β-lactamases. Cephalosporin C contains a side-chain which is derived from D-aminoadipic acid. Modification of side chains on the relevant positions has been used to create a whole new class of cephalosporin antibiotics. Modification of side-chains in position 7 of the lactam ring seems to affect the antibacterial activity while position 3 of the dihydrothiazine ring alters pharmacokinetic properties and receptor binding affinity.[4][5]
The first chemical compounds of the cephalosporin group were isolated from Cephalosporium acremonium, a cephalosporin-producing fungus first discovered by Giuseppe Brotzu in 1948 from a sewage outfall off the Sardinian coast.[1] From crude filtrates of the Cephalosporium acremonium culture scientists got new antibacterial activity. It was noted that the crude filtrate could inhibit the growth of Staphylococcus aureus.[3]
Further investigations by Sir Edward Abraham and Guy Newton were made in England and isolation of culture fluids from the Sardinian fungus yielded cephalosporin P, N and C. These natural compounds were not found to be potent enough to use as antimicrobial agents but with chemical methods and removal of the natural side chain it was possible to produce 7-aminocephalosporanic acid (7-ACA) which could be further fit with unnatural side chains. 7-ACA is analogous to 6-aminopenicillanic acid (6-APA), a starting block for making several derivatives of penicillins.[1]
In 1959 Abraham reported that his N-phenylacetyl derivative of cephalosporin C was much more potent against Staphylococcus aureus strains than the parent compound. This derivative was later named Cephaloram, a cephalosporin analogue of benzylpenicillin.
Eli Lilly developed a method for producing 7-ACA based on cleaving the α-aminoadipoyl side chain of cephalosporin C.[6] Further work by Robert Morin led to semisynthesis of 3-deacetoxy-7-ACA (7-ADCA) from penicillins which is convenient because penicillins can be fermented with more ease than cephalosporins. For example, 7-ADCA can be semisynthesized in seven chemical reaction steps from phenoxymethylpenicillin.[1]
Cephalothin, a first generation cephalosporin for parenteral use was the first cephalosporin to become available for patients in the US in 1964. It was chosen for clinical trials from series of 7-ACA derivatives prepared at Eli Lilly.[7] The second cephalosporin for parenteral use became available little later and was marketed in the US under the name Cephaloridine. The clinical successes of these two cephalosporins urged researchers to improve the pharmacological properties and develop more agents.[8][9] Today we are left with thousands of semisynthesized analogues of natural cephalosporin compounds based on the knowledge gained by intensive research on the chemistry of those two starting materials.[1]
Mechanism of action[edit]
The bactericidal effects of β-lactam antibiotics are achieved through inhibition of the bacterial cell wall synthesis. The cell wall of both gram-positive and gram-negative bacteria is a tight covalently bound and cross-linked peptidoglycan network and essential for bacterial growth, cell division and cellular structure. Therefore, bacteria need enzymes that can cleave the cell wall during bacterial growth and cell division. The cell wall of bacteria is built up in two steps from the outside of the cell. In the first step, molecules of disaccharide units linked with peptides on their ends are transported from the cytoplasm of the bacteria and joined together on the outside of the wall by a transglycolase. In the second step, a transpeptidase links together long polysaccharide chains which are linked together through peptide bonds. The amino acid sequence of D-alanyl-D-alanine is recognized by the transpeptidase at the end of the peptide chain. The enzyme cleaves off the alanine on the terminal end and joins the remainder to a peptide chain from an adjacent polysaccharide.[10] This transpeptidation reaction is inhibited by β-lactam antibiotics like cephalosporins. Because of this inhibition the antibiotics are most effective when the bacteria are in the logarithmic phase of growth, were then they are synthesizing the cell wall. If the bacteria are in the stationary phase of growth then there is no wall synthesizing in progress and the antibiotics have much lower effect.[3]
Although the mechanism of action for β-lactam antibiotics is not completely known they are believed to exert their mechanism of action by mimicking the structure of the transition state of the chemical reaction when the transpeptidase is bound to the D-alanyl-D-alanine sequence.[10] These proteins are often referred to as penicillin binding proteins (PBP). Opening of the β-lactam ring by a serine residue in the enzyme binding site leads to covalent binding of the antibiotic molecule with the active site of the enzyme. The result is an inactive irreversibly bound enzyme-complex which is incapable of further cell wall synthesis and the cell will die from osmotic-lysis.[2][10][11]
Drug design[edit]
Structure activity relationship[edit]
The molecular structure of cephalosporin can be altered in various ways to improve in vitro stability, anti-bacterial activity and resistance against β-lactamases. In the acidic conditions of the stomach, in vitro stability can be enhanced by the addition of an amino and a hydrogen to positions α1 and α2 of the cephalosporin structure. This results in a basic compound, an ammonium ion that is protonated in said conditions, giving us a more stable β-lactam which leads to an orally active drug. Anti-bacterial activity can be enhanced if A2 is an alkoxy group instead of a hydrogen. The 7-amino group is crucial for anti-bacterial activity. In some cases, adding a methoxy group in position A2, cephalosporin stability is enhanced toward β-lactamases. In position A1, sulfur and oxygen can be placed in the ring. Sulfur shows better anti-bacterial activity, but oxygen shows better stability towards β-lactamases. In position C6, hydrogen is crucial for biological activity. In position A3, anti-bacterial activity is greater when A3 is a 5-membered heterocycle instead of a 6-membered one. In position α1 and α2, the L-isomer is 30–40 times more stable towards β-lactamase than the D-isomer. Stability toward β-lactamase can be increased around 100-fold with the addition of methoxyoxime. Z-oxime is nearly 20,000-fold more stable than the E-oxime.[1]
Binding site[edit]
Advances in the field of recombinant protein engineering and expression, protein purification, NMR, X-ray crystallography and computational chemistry have improved the skills of drug designers to use data that have been gathered on the three-dimensional structures of protein ligand complexes.[12]
Most bacterial species have various types of PBP which differ in various ways such as enzymatic function, molecular weight and the affinity for β-lactam antibiotics. There are two types of enzymes there are particularly interesting with regard to the binding site of β-lactams, PBP and β-lactamases. Target alterations in the binding site of PBP have led to high-level resistance of β-lactams among bacterias like staphylococci, enterococci and pneumococci.[13] For example, the binding site of PBP2 in Neisseria gonorrhoeae has been structurally determined and has three sequence motifs that can be seen in nearly all β-lactam interacting enzymes.
- SXXK motif located at the N-terminal end of α2 helix and includes two residues that are important for the enzyme function.
- Ser-310 : Includes a serine nucleophile that is acylated by both peptide substrate and β-lactam antibiotics.
- Lys-313 : Plays an important role in providing the dense hydrogen bound network at the active site and is in distance of Ser 310, ASN-364 and the carbonyl backbone of Ser-362.
- SXN motif that includes Ser-362, Ser-363 and Asn-364
- KTG motif that includes Lys-497, Thr-498 and Gly-499
Research also implies that adjacent regions to the active site which differ between different PBP have significant influence on the rate of β-lactam acylation rate.[14]
Antimicrobial resistance[edit]
Bacterial resistance to the cephalosporin compounds can take place by three mechanisms.
- Modifications in target PBP
- Drug inactivation by bacterial β-lactamases
- Drug not being able to reach target PBP in the bacterial cell
Cephalosporins must get through the bacterial cell wall in order to reach the target PBP. In comparison, it is easier to penetrate the cell wall of gram-positive bacteria than the cell wall of gram-negative bacteria. The cell wall structure of gram-positive bacteria is made routinely up by peptidoglycan which allows the passage of cephalosporin-sized molecules. The cell wall structure of gram-negative bacteria is more complex, composed of polysaccharides, lipids and proteins, and is harder to penetrate. Particles get through the outer membrane through water-filled channels, or porins, which are trans membrane proteins.[15] During exposure to cephalosporins the bacteria can form resistance by itself or as selection of the next generation of bacteria after reproducing itself, by mutation.[16] Bacteria species such as pneumococci and meningococci can acquire exogenous genetic material, and incorporate it into their own chromosomes which leads to antimicrobial resistance.[17] In that manner the target PBP can be altered to have their attraction for cephalosporins and other β-lactam antibiotics lowered.[18][19] The bacteria can also replace the PBP that is vulnerable to Beta-lactam antibiotics with PBP that is less vulnerable.[20] β-lactam antibiotics can be inactivated by many types of β-lactamases, which are produced by bacteria. The enzymes hydrolyze the bond between the carbon and nitrogen atom of the β-lactam ring. There are many beta lactamases which vary in substrate specificity and host range.[21][22] The enzymes active site is easily regenerated hydrolytically so it is re-usable many times, in that way can a comparatively small amount of beta-lactamases destroy a large amount of drug. Gram-positive bacteria, such as a staphylococci, have a high release of beta-lactamases into their extracellular space, where they meet the drug outside the cell wall. Gram-negative bacteria on the other hand follow a more conservative course. They secrete their beta-lactamases into the periplasmic space between the inner and outer membrane so they can't easily escape into the extracellular space, and don't have to be biosynthesized in high quantities.[1]
Drug development[edit]
This section will review the drug development from one generation to the next with emphasis on the structural differences between the generations. The generation classification system relies on dividing the cephalosporins by their chemical properties and their relative activity against gram-negative versus gram-positive bacteria.[5] [14]. From the first generation cephalosporins to the third generation there is a development from being more effective against gram-positive bacteria to being more effective against gram-negative bacteria and less effective against gram-positive bacteria respectively. However the activity returns to a balanced effectiveness against gram-negative and gram-positive bacteria in the fourth generation.[23]
Classification of cephalosporins[edit]
The cephalosporin class is very extensive so a good classification system is necessary to distinguish different cephalosporins from each other. There are few chemical and activity features that could be used for classification, for example chemical structure, side chain properties, pharmacokinetic, spectrum of activity or clinical properties. Despite these variable features the most common classification system for cephalosporins is to divide them into generations. The generation system is based on different antimicrobial activity shown by different cephalosporins.[3][4][24]
1st generation cephalosporins[edit]
First generation cephalosporins were the first cephalosporins on the market. They have good antimicrobial activity against gram-positive bacteria but limited activity against gram-negative species.[25] The chemical structures of the first generation cephalosporins are fairly simple. As an example three drugs from this class (Cephalexin, Cephradine and Cefadroxil) all have a single methyl group at position C-3. The common side groups at C-3 for first class cephalosporins are small uncharged groups like methyl.[5] The methyl group at position C-3 gives low affinity for common PBP which can in part explain the relatively low activity of these first drugs. Cefaclor however has a Cl group at position C-3 which gives it better binding to PBP and thus better antimicrobial activity. There is not an agreement on classifying Cefaclor as a first generation cephalosporin because of the Cl group at the C-3 position and therefore its improved activity, but it is often classified as such because of its C-7 side chain which is more related to the first generation than the second. All of the first generation cephalosporins have an α-amino group at position C-7. This structure makes them vulnerable to hydrolysis by β-lactamases.[5][9]
2nd generation cephalosporins[edit]
Early second generation cephalosporins are very similar in basic structure to the first generation. Loracarbef however does not have the normal dihydrothiazin ring but is a carbacephem that has a carbon atom in the ring instead of a sulfur atom making it a tetrahydropyridine ring. This chemical property gives Loracarbef better stability in plasma while retaining oral absorption characteristics and affinity for binding to PBP. The 7-phenyl-glycine makes it orally available and the chlorine at position C-3 makes it as active as Cefaclor. An important structural change in the development of second generation cephalosporins was the introduction of an α-iminomethoxy group to the C-7 side chain. This gave an increased resistance to β-lactamases due to stereochemical blocking of the beta-lactam ring. Cefuroxime was the first cephalosporin to incorporate this side chain. Another very important group in the second generation is the aminothiazole ring to the C-3 side chain. This development drastically increased binding affinity to PBP and increased antimicrobial activity. The aminothiazole ring can be seen in the structure of Cefotiam.[5][9]
3rd generation cephalosporins[edit]
The majority of third generation cephalosporins have the aminothiazole group at position C-7. Different groups are found at the 7-α-position like 7-α-iminohydroxy and 7-α-iminomethoxy. Ceftibuten however possesses a 7-α-ethylidene group. This group gives ceftibuten higher resistance to enhanced spectrum β-lactamases. Many of the oral third generation cephalosporins are esters of parenteral forms and are hydrolysed by esterases in the digestive tract (Cefteram-pivoxil). Some of the third generation drugs can be absorbed orally without the need of esterification. This is for example done with Cefixime and Cefdinir by putting a vinyl group in the C-3 position.[5][9]
4th generation cephalosporins[edit]
The fourth generation cephalosporins have greater activity against gram-negative bacteria than the second and third generation. This difference is attributed to them being dipolar ionic zwitterion compounds. The C-7 side chain is similar to third generation cephalosporins usually containing iminomethoxy-aminothiazole group or in the case of Cefclidine an aminothiadiazole. Because of the positively charged quaternary nitrogen in the C-3 side chain fourth generation cephalosporins can diffuse through the gram-negative bacterial membrane more readily than earlier cephalosporins. It is thought that the positive charge orients the drug molecule to the entrance of the porin channel.[26]
5th generation cephalosporins[edit]
Currently there are only two drugs in this category, Ceftobiprole and Ceftaroline. These new drugs are also the only β-lactam antibiotics that are effective against methicillin-resistant-Staphylococcus-aureus (MRSA). Ceftobiprole is a pyrrolidinone-3-ylidenemethyl cephem. The C-3 side chain was specifically designed to have a strong binding affinity to PBP2a and PBP2x. PBP2a is known to give staphylococci resistance to other β-lactam drugs and PBPx does the same for pneumococci. Ceftobiprole also has an aminothiazoylhydroxyimino side chain at the C-7 position which is known to give good resistance to β-lactamase from S. aureus. Together these active groups make Ceftobiprole bactericidal to MRSA. Ceftobiprole has poor water solubility and is therefore administered intravenously as an ester prodrug called Ceftobiprole medocaril. It is rapidly broken down into active Ceftobiprole by plasma esterases.[27] Ceftaroline was developed from the fourth generation cephalosporin Cefozopran. It retains the alkoxyimino group at position C-7 from earlier generations so it is fairly stable in the presence of many β-lactamases. Since MRSA and penicillin resistant Streptococcus pneumoniae have resistance dedicated to new types of PBP, PBP2a and PBP2x respectively, both Ceftaroline and Ceftobiprole have C-3 side chains specially engineered to bind these new PBP. In the case of Ceftaroline this side chain contains a 2-thioazolythio spacer linkage optimised for its anti-MRSA activity. Ceftaroline has low water solubility but this problem was overcome by attaching a N-phosphonoamino group to the molecule making the intravenous prodrug Ceftaroline fosamil. The prodrug is dephosphorylated in plasma to form active Ceftaroline.[28]
Current status[edit]
Antimicrobial resistance is the driving force for the development of new antimicrobial agents. The complexity and diversity of resistance mechanisms has defined the need for new and improved β-lactam antibiotics.[29] With their broad spectrum the cephalosporins have come to dominate β-lactam chemotherapy although they often lack oral bioavailability.[9]
On 29 October 2010, a new cephalosporin agent - Ceftarolin - was approved by the food and drug administration (FDA). Teflaro (ceftaroline fosamil) is an injectable antibiotic prodrug to treat adults with acute bacterial skin and skin structure infections (ABSSI) and community acquired bacterial pneumonia (CABP).
Ceftobiprole has been approved for the treatment of adult patients with hospital acquired pneumonia (excluding VAP) and community acquired pneumonia in 12 European countries, Canada and Switzerland.[30][31]
See also[edit]
- ^ a b c d e f g Lemke, Thomas (2008). Foye's principles of medicinal chemistry. Philadelphia: Lippincott Williams & Wilkins. pp. 1028–1082. ISBN 978-0-7817-6879-5.
- ^ a b Klein, Lansing M. Prescott, John P. Harley, Donald A. (2005). Microbiology (6. ed.). Boston, Mass.: McGraw-Hill Higher Education. ISBN 0-07-111217-0.
- ^ a b c d Singh, Jasjit; Arrieta (January 1999). "New Cephalosporins". Seminars in Pediatric Infectious Diseases. 10 (1): 14–22. doi:10.1016/S1045-1870(99)80005-3. Retrieved 7 September 2011.
- ^ a b Goodman & Gilman's The pharmacological basis of therapeutics. (12th ed.). New York: McGraw-Hill Medical. ISBN 0-07-162442-2.
- ^ a b c d e f García-Rodríguez, J.A.; Muñoz Bellido, J.L.; García Sánchez, J.E. (1995). "Oral cephalosporins: current perspectives". International Journal of Antimicrobial Agents. 5 (4): 231–243. ISSN 0924-8579. PMID 18611674. doi:10.1016/0924-8579(95)00015-Z.
- ^ Hamilton-Miller, J.M.T. (1 March 2008). "Development of the semi-synthetic penicillins and cephalosporins". International Journal of Antimicrobial Agents. 31 (3): 189–192. PMID 18248798. doi:10.1016/j.ijantimicag.2007.11.010.
- ^ David Greenwood (21 February 2008). Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. OUP Oxford. pp. 128–. ISBN 978-0-19-953484-5.
- ^ Hara, Takuji (2003). Innovation in the pharmaceutical industry : the process of drug discovery and development. Cheltenham [u.a.]: Elgar. ISBN 1-84376-050-9.
- ^ a b c d e Sader, H (1 December 1992). "Historical overview of the cephalosporin spectrum: Four generations of structural evolution". Antimicrobic Newsletter. 8 (12): 75–82. doi:10.1016/0738-1751(92)90022-3.
- ^ a b c Bohlin, Gunnar Samuelsson, Lars (2009). Drugs of natural origin : a treatise of pharmacognosy (6., rev. ed.). Stockholm: Apotekarsocieteten. ISBN 978-91-976510-5-9.
- ^ Miguet, Laurence; Zervosen, Astrid; Gerards, Thomas; Pasha, Farhan A.; Luxen, André; Distèche-Nguyen, Martine; Thomas, Aline (2009). "Discovery of New Inhibitors of ResistantStreptococcus pneumoniaePenicillin Binding Protein (PBP) 2x by Structure-Based Virtual Screening". Journal of Medicinal Chemistry. 52 (19): 5926–5936. ISSN 0022-2623. PMID 19746934. doi:10.1021/jm900625q.
- ^ King, ed. by Frank D. (2002). Medicinal chemistry : principles and practice (2. ed.). Cambridge: Royal Soc. of Chemistry. ISBN 0-85404-631-3.
- ^ Malouin, F.; Blais, J.; Chamberland, S.; Hoang, M.; Park, C.; Chan, C.; Mathias, K.; Hakem, S.; Dupree, K.; Liu, E.; Nguyen, T.; Dudley, M. N. (1 February 2003). "RWJ-54428 (MC-02,479), a new cephalosporin with High Affinity for Penicillin-Binding Proteins, Including PBP 2a, and Stability to Staphylococcal Beta-Lactamases". Antimicrobial Agents and Chemotherapy. 47 (2): 658–664. PMC 151748 . PMID 12543674. doi:10.1128/Aac.47.2.658-664.2003.
- ^ Powell, A. J.; Tomberg, J.; Deacon, A. M.; Nicholas, R. A.; Davies, C. (28 October 2008). "Crystal Structures of Penicillin-binding Protein 2 from Penicillin-susceptible and -resistant Strains of Neisseria gonorrhoeae Reveal an Unexpectedly Subtle Mechanism for Antibiotic Resistance". Journal of Biological Chemistry. 284 (2): 1202–1212. PMC 2613624 . PMID 18986991. doi:10.1074/jbc.M805761200.
- ^ Gutmann, L; Williamson, R; Collatz, E (October 1984). "The possible role of porins in bacterial antibiotic resistance". Annals of Internal Medicine. 101 (4): 554–7. PMID 6089637. doi:10.7326/0003-4819-101-4-554.
- ^ Sanders, CC; Sanders WE, Jr (March 1985). "Microbial resistance to newer generation β-lactam antibiotics: clinical and laboratory implications". The Journal of Infectious Diseases. 151 (3): 399–406. PMID 2982957. doi:10.1093/infdis/151.3.399.
- ^ Spratt, Brian G. (10 March 1988). "Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae". Nature. 332 (6160): 173–176. PMID 3126399. doi:10.1038/332173a0.
- ^ Fontana, R; Grossato, A; Rossi, L; Cheng, YR; Satta, G (November 1985). "Transition from resistance to hypersusceptibility to β-lactam antibiotics associated with loss of a low-affinity penicillin-binding protein in a Streptococcus faecium mutant highly resistant to penicillin". Antimicrobial Agents and Chemotherapy. 28 (5): 678–83. PMC 176356 . PMID 3853962. doi:10.1128/aac.28.5.678.
- ^ Hartman, BJ; Tomasz, A (May 1984). "Low-affinity penicillin-binding protein associated with β-lactam resistance in Staphylococcus aureus". Journal of Bacteriology. 158 (2): 513–6. PMC 215458 . PMID 6563036.
- ^ Handwerger, S; Tomasz, A (January 1986). "Alterations in penicillin-binding proteins of clinical and laboratory isolates of pathogenic Streptococcus pneumoniae with low levels of penicillin resistance". The Journal of Infectious Diseases. 153 (1): 83–9. PMID 3941290. doi:10.1093/infdis/153.1.83.
- ^ Bush, K; Jacoby, GA; Medeiros, AA (June 1995). "A functional classification scheme for beta-lactamases and its correlation with molecular structure". Antimicrobial Agents and Chemotherapy. 39 (6): 1211–33. PMC 162717 . PMID 7574506. doi:10.1128/AAC.39.6.1211.
- ^ Livermore, DM (October 1995). "beta-Lactamases in laboratory and clinical resistance". Clinical Microbiology Reviews. 8 (4): 557–84. PMC 172876 . PMID 8665470.
- ^ Harrison, C. J.; Bratcher, D. (1 August 2008). "Cephalosporins: A Review". Pediatrics in Review. 29 (8): 264–273. doi:10.1542/pir.29-8-264.
- ^ Perez-Inestrosa, E; Suau, R; Montañez, MI; Rodriguez, R; Mayorga, C; Torres, MJ; Blanca, M (August 2005). "Cephalosporin chemical reactivity and its immunological implications". Current Opinion in Allergy and Clinical Immunology. 5 (4): 323–30. PMID 15985814. doi:10.1097/01.all.0000173788.73401.69.
- ^ Kalman, D; Barriere, SL (1990). "Review of the pharmacology, pharmacokinetics, and clinical use of cephalosporins". Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 17 (3): 203–15. PMC 324918 . PMID 15227172.
- ^ FUNGTOMC, J (1 August 1997). "Fourth-generation cephalosporins". Clinical Microbiology Newsletter. 19 (17): 129–136. doi:10.1016/S0196-4399(97)82485-3.
- ^ Chahine, Elias B.; Nornoo, Adwoa O. (1 February 2011). "Ceftobiprole: The First Broad-Spectrum Anti–methicillin-resistant Staphylococcus aureus Beta-Lactam". Journal of Experimental & Clinical Medicine. 3 (1): 9–16. doi:10.1016/j.jecm.2010.12.007.
- ^ Kaushik, Darpan; Rathi, Sudeep; Jain, Ankit (1 May 2011). "Ceftaroline: a comprehensive update". International Journal of Antimicrobial Agents. 37 (5): 389–395. PMID 21420284. doi:10.1016/j.ijantimicag.2011.01.017.
- ^ Theuretzbacher, Ursula (1 October 2011). "Resistance drives antibacterial drug development". Current Opinion in Pharmacology. 11 (5): 433–438. PMID 21862408. doi:10.1016/j.coph.2011.07.008.
- ^ Basilea Medical Ltd. Summary of Product Characteristics: Zevtera 500 mg powder for concentrate for solution for infusion. Medicines and Healthcare Products Regulatory Agency. http://www.mhra.gov.uk/spc
- ^ "Public Assesment Report" (PDF). mhra.gov.uk.