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Bought this beautiful blue jay for a gift for my uncle in Ontario. It looks beautiful in their garden. He loves his gift. Highly recommend Medalbird.
Great gift for nature lovers or bird watchers!
The blue jay made an awesome Christmas gift for my parents. I was a little surprised by how thin the metal was but it seems to be holding up, nearly 2 years later!
Love the Blue Jay and receive so many compliments about it! Definitely want to add a few more!
Birthday Blue Jay
I bought this as a gift for my wife, an avid gardener. It makes for a beautiful and conversation-generating piece of garden art and we have received many compliments. The real Blue Jays who fly past on their way to the feeder seem to like it too!
I gave this guy as a Xmas present to a dear friend, who couldn't wait for spring to place him in his new home.
Bought as a gift and it was very well received!
This is my 3rd Metal Bird. I love my Blue Jay! Great craftsmanship!
Also bought owl and both will be installed at cottage when weather appropriate looking forward to finding them a special tree.
the same comment has Hummingbird.
I bought these for my parents for their birthdays in June. So they haven't been outside yet. I did open them up and they are beautiful. The detail of the birds is great and the metal is good and solid! The quality looks awesome!
I have a number of metal birds myself but the most fun is giving them to unexpected friends. When you present the package they haven't a clue what's inside but when they open it the say WOW, pick it up and read what it's all about. And they are a surprise to see in trees and posts at friends and relatives. Very unique indeed.
They were all beautiful
Metal Bird Blue Jay
I am always so pleased with my Metal Bird purchase. The Blue Jay was a first and it did not disappoint.
This Blue Jay was a gift that will reside on the west coast of Vancouver Island when it gets to its home. Thank you!
My Lover loves it
Bought this for the girlfriend and she loved it. Durable, sleek, stylish. Good indoors or out
Metal bird Blue Jay
Ordered as a gift and the recipient was very happy with it!


Today Google opens access to Search Generative Experience and initiated the process of inviting the initial users to participate in the innovative Search Generative Experience. If you have previously joined the waitlist, you may receive an email notification granting you access.
Google Opens Access to Search Generative Experience
According to Google, "Today, we are commencing the availability of Search Labs, a novel program that provides early access to Google's experiments. If you have registered on the waitlist, you will get an email notifying you when you can begin testing Labs experiments."
Here are how twitter users are reacting to SGE experience:
Chat GPT and SEO: How Chat GPT is going to Impact SeO
To know if you have been accepted, you can participate in these experiments by selecting the Labs icon in the most recent version of the Google app on Android and iOS or through Chrome desktop to sign up. Alternatively, you can visit the Lab's website to check your waitlist status.
Visit your email account to see if you have been granted access, as email notifications are being sent Today. Google provides further details on this matter.
Once you gain access, the new Search experience powered by generative AI will assist you in simplifying the search process. It enables you to grasp a topic more quickly, discover new perspectives and insights, and accomplish tasks more efficiently.
Instead of posing multiple questions and assembling the information yourself, Search can now handle some of the heavy liftings for you, as stated by Google.
The value of this comes from the fact that it's a test run for Google Search. Exploring this opportunity can be enjoyable, educational, and thrilling. Although we do not know what Google will launch, this direction illustrates their current thinking.
Fix Error: “Twitter Something Went Wrong Try Reloading Chrome”
How to Signup?
Are you interested in joining the waitlist? Please note that it is currently limited to searchers based in the United States and only supports English.
Checkout: Cleverbot vs. ChatGPT: Exploring the Battle of Conversational AI
Do you wish to be of the first individuals to experience the new Google Search Generative Experience previewed at Google I/O Today? Google has opened a waitlist for you to register.
To register, visit the Google Search Labs website and join the "Experiment with Search Labs."
Please note that this opportunity is currently limited to searchers based in the United States and is only available in English, according to Google.
Additionally, Google Workspace users are not eligible for this feature. Please sign up using your personal Gmail account.
Also, Read: How to Make Money with Chat GPT
Google plans to gradually release the new Google Search Generative Experience, inviting users in waves over the next few weeks. Although the public has yet to be invited to try out this new Google Search, those who registered for the waiting list will be among the first to be invited in the upcoming weeks.
Google hopes early-release participants will provide valuable feedback to enhance this new Google Search experience.
The significance of this opportunity lies in the imminent transformation of Search. This is your chance to understand how it may impact your business and websites.


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NILES, Ohio (WKBN) — Infant mortality rates are high according to a spokesperson with Mercy Health in Mahoning and Trumbull counties.
A lot of that is because of a lack of education, support and resources. To counteract that, an infant health fair was held at Eastwood Mall.
From 11 a.m. to 3 p.m. they provided information to reduce infant sleep-related deaths and also educate parents about safe sleep practices.
Those there said there’s a lot of resources in the Valley. All of them wanted to come together to bring awareness about them.
“”We have safe sleep kits that come with a sleep sack as well as a refrigerated sack to put your breast milk in. A lot information about safe sleep, about pet safety. We are having raffles for free car seats as well as pack-and-plays,” said Jennifer Manning with Akron Children’s Hospital Mahoning Valley.
“We provide pre-natal care. We have midwives and physicians who work with our patients. We provide them with a health-nutritious meal at their pre-natal appointment in addition to pack-and-plays, diapers, car seats, childbirth education doula support,” said April Young with Mercy Health.
Manning and Young said the event was beneficial because they could refer people to each other based on what they needed help with.

domain: sociology


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1V SCOUTS MEET AND GREET ROYALTY
1V Scouts met with Royalty last week when the group was invited by the Scouts Association to showcase its work with children in an early years pilot.
HRH the Duchess of Cambridge was also given a guided tour of the Scouts headquarters by a 1V Scout Explorer.
The Scouts early years provision pilot programme for four and five year olds was announced in November 2018. The pilots are about exploring how younger children can benefit from the Scout programme to improve their confidence, problem solving skills, emotional resilience and communication skills. The pilot scheme also encourages active participation from parents, helping them to support their child’s early development.
The 1V Scouts is one of six who are currently involved in the pilot.
The Duchess of Cambridge attended the event and was firstly greeted by 1V Beavers and Cubs and then went to meet all the young people involved.
The 1V Scouts had several young people in attendance from hedgehogs, to a scout and two explorers. One of the explorers Tahseen Patel was tasked with showing the Duchess around Gilwell Park in Essex, which is celebrating its 100th birthday in 2019.
Tahseen said: “The Duchess was really interested in the kinds of activities scouting offers that children can’t always learn or have access to in schools.”
Duchess was able experience first-hand our pilot programme for four and five year olds and the work being done to help them prepare for their futures.
Iram Shoaib is a parent of one of the young people taking part in the early years pilot said ‘It’s been such a fantastic opportunity for all the young people to meet the Duchess of Cambridge,’ she said.
“They have already got so much out of the early years pilot at 1V Scouts. Each week I see them learning new skills, becoming more confident and resilient.”
1V Scout Group Leader, Nisbah Hussain said,
“It was an absolute privilege to meet HRS the Duchess of Cambridge, and an even greater privilege that a member of our Scouts team showed the Duchess the work of the groups running the Hedgehogs project. We started our scouting movement in 2014, and little did we know that within five years it would be making such an impact on a national level. It was a very proud and humbling moment for all involved.”

domain: news


Is Everything Deleted from Computer? – Know Data Recovery Methods and Techniques
No matter if users are using Windows 10, Windows 8, Windows 7, or any below versions, at least once they face the data loss issue. While scanning forums, we found so many Windows users are bothered with everything deleted from computer desktop problems. After this, you need data recovery methods and techniques to avoid data loss. Here is a typical case we have extracted from a forum website:
“Yesterday when I turned on my computer, I noticed that the background of my computer is gone and it is solid black. All the shortcuts, documents, files, folders, and images are also gone. I use a little desktop icon in the toolbar pretty often to minimize everything automatically from my desktop and it is gone as well. I had tried to restore my system and realized that my PC has not been making the checkpoints so that, I have no resource in that area. Well, this is very horrible for me and I do not know to whom I should ask PC manufacturer or Windows for help. I am afraid that if I will restart my computer, other files will be gone. Someone help me.”
Today, everything deleted from the computer has become an annoying issue but, the main question is how it happens and what are the possible techniques to get lost data back. In order to answer all such questions of users, here we are with this write-up. So, let’s get started with data recovery methods?
Methods to Recover Deleted Files from Desktop?
Below are some simple techniques to fix everything deleted from computer issues, and it is recommended to follow the guidelines sequentially. In the below section you will find two manual data recovery methods and one automated data recovery technique solution. Perform the techniques listed below:
Method 1: – Recover Desktop Deleted Files from Backup
In order to restore computer deleted files from backup, make sure the drive is available where your backup is saved. Then, follow the steps mentioned below and get a safe data recovery technique to fix everything deleted from computer issue:
- Click on Start >> Control Panel
- Select System and maintenance >> Backup and Restore
- Now, click on Restore my files and go with instructions of the wizard
Method 2: – Restore Computer Deleted Files from Previous Versions
One can fix everything deleted from desktop and recover computer desktop deleted files as well as folders to a previous state. In order to restore a deleted file/ folder from the desktop, perform data recovery steps listed below:
- Click Start >> Computer
- Go to the folder that is used to store files/ folder and hit a right-click on it
- Select Restore previous versions option (Note: If the folder was situated at the top level of the drive, for instance, C:\, then hit a right-click on the drive and click Restore previous versions.)
- After this, you will get a list of all available previous versions of the file/ folder. The list will show files stored on a backup and restore points (if both are available).
- Choose the previous version and click Open to ensure that you want to restore (Note: You cannot copy or open previous versions of files that were generated by Windows Backup, however, you can restore them.)
- At last, click on the Restore button.
Limitations of Manual Method
There are multiple limitations of using check disk command and few of them are listed below:
The manual method primarily scans the integrity of the file system and disk metadata. In case of any logical file system errors, it fixes them.
Chkdsk command is used to recover minor corruptions from your drive and also used for checking the health of your driver. But, it does not ensure the complete recovery of permanently deleted data from computer.
It optionally scan every sector on a disk and looking for the bad sector.
Method 3: – Recover Deleted Data from Computer Desktop (100% Safe)
If you are finding manual methods lengthy and tricky or if no manual solution works for you to deal with everything was deleted from my computer. Then, use Hard Drive Data Recovery Software. This is an eminent data recovery technique to recover and restore desktop deleted files in Windows 10, 8, 7, and all below versions.
It allows to recover normal as well as permanent (Shift+Delete) deleted data from computer desktop and recovers deleted data even after formatting. The tool supports data recovery from FAT/ NTFS file system and recovers video, audio, docs, PPT, images, etc. The tool is compatible with all versions of Windows OS. Use this tool, because it is the best data recovery technique.
What Could Be the Reason of Deleted Desktop Files?
Data loss from the desktop is a major inconvenience, that interrupts the workflow of any user or information-based business. There might be several reasons for data deleted from desktop issues and some most probable causes are mentioned below. In the above section, we have explained different data recovery techniques.
- Damaged Hard Drive: If the hard drive of Windows computer is crashed frequently, facing issues while booting up, or the files stored in it gets corrupted then, it might cause data loss from the desktop. You have to adopt a trusted data recovery technique to fix this issue.
- Reinstall or Upgrade Windows: Reinstalling Windows OS, formats the drive where the Windows is installed and mostly it is the drive where desktop files are stored. Hence, it removes the original files after re-installation. In this situation, the data recovery methods will not help you. Because it is the case of overwritten data.
- Sudden Power Outage: Shutting down the system without warning, abrupt power loss or computer shut down can result in everything deleted from desktop issue. In this, you can perform the data recovery methods.
- Human Errors: Intentional or accidental deletion of crucial files, liquid spill, hard drive formatting, and improper installation of Windows OS or any program can result in loss of desktop files. In this situation perform the above-mentioned data recovery methods and techniques.
- Software Corruption: Improper or unexpected software closing may seem fine on the surface however, it can cause some serious issues like deletion of data from the desktop. In this case, use the above-explained data recovery techniques and get all files back.
Everything deleted from computer is a serious disaster and most of the computer users undergo accidental deletion of necessary files. In this article, we have disclosed some simple and actually working data recovery methods and techniques to resolve everything deleted from desktop issues. So, from now recovering lost data from computer will be no more a difficult task.


[Fosc] Who makes decisions about your favorite parks and trails?
Stan Dodson via Fosc
fosc at lists.sausalcreek.org
Wed Oct 5 09:42:36 PDT 2016
While national and state officials make important decisions that affect our
lives, it's our local representatives, the ones who represent the streets
and sidewalks in front of our homes and businesses (and our favorite
trails!), that have the most impact on our everyday lives.
Do you enjoy the East Bay Regional Park system? Do you recognize and
appreciate the impact it has on our culture, our health, and our property
This November, we will elect a new East Bay Regional Park District Ward 2
board member. After almost 20 years, John Sutter will retire, leaving the
Ward 2 seat open to four new candidates.
Get to know the candidates tonight, Wed., Oct. 5, from 6:30pm–8:30pm at the
Trudeau Center, 11500 Skyline Blvd, Oakland. Co-hosted by OaklandTrails.org
and the League of Women Voters of Oakland, tonight's forum will help you
make an informed decision in the next election.
For all the details, visit:
Please forward this invitation.
The East Bay Regional Park District is governed by a seven-member board of
directors, who are publicly elected to serve four-year terms. Each Board
Member represents a specific geographic area of the Park District. The
District itself comprises all of Alameda and Contra Costa counties.
Ward 2 represents: most of Oakland, Piedmont, Canyon, Moraga, Orinda,
Orinda Village, Rheem Valley, Lafayette, Rossmoor, and part of Walnut Creek.
Parks in Ward 2 include: portion of Briones, Anthony Chabot (north of
Keller Ave. if extended east), Claremont Canyon, Huckleberry, Leona Open
Space, a small portion of Las Trampas, Redwood, Roberts, Sibley, and
See you on the trails,
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King. Warrior. Hero. Enough said – The Black Panther is one of the most recognizable faces in the world, and that’s saying a lot considering he is a superhero behind a mask!
Black Panther as an entity himself has garnished over a billion dollars since his inception in 1977. T’Challa is not only the wealthiest hero in the marvel universe, but he also has fought with the Fantastic Four, captured time traveling golden frogs, and tussled with the KKK. This dynamic hero is one and all, and that’s why this comic book spotlight will focus on our powerful feline Black Panther!
Origin: T’Challa didn’t make his first appearance until a Fantastic Four issue in which he initially attacks the group. He reveals that Ulysses Klaw sought to use vibranium as a way to power his incredible sound weapon. When T’Challa’s father tried to stop him Ulysses had him killed when T’Challa was a boy. This is what set T’Challa on the path to revenge, and reclaim the throne of Wakanda.
Powers: It’s a well known fact T’Challa gets the bulk of his power from vibranium including being able to teleport, become invisible, etc. But, T’Challa also has quite a few surprising powers through his comic book run. For one T’Challa use to be able to see into the future as this was granted to him through a vampire Kiber the cruel. However, when T’Challa tracks Kiber down and destroys his energy source – his sightseeing goes away.
Thanks to the genius Shuri – T’Challa’s suit can allow him to absorb energy, a massive amount of pain, and…walk on water! Because, the vibranium in his suit absorbs whatever surface T’Challa pounces on it makes him extremely flexible, and water is no different. While he isn’t able to walk on water in a straight line (more like a trampoline) he still has a large amount of leniency than any hero out there. You know what they say, all cats land on their feet!
Interesting Facts: #1 Black Panther and the Lazarus Effect: T’Challa has been called many things but King of the Dead is a new one entirely. Apparently, T’Challa has been known to converse with the dead many times, even leading an army of zombies to defeat Emperor Doom in a Secret Wars Issue #7. Another point in time, T’Challa channels the spirit of Necropolis to defeat another powerful enemy. So he can harness the most powerful metal on earth, and he can also raise the dead…sounds like a certain somebody (starts with an Kil ends with a B. Jordan) may make an appearance in Black Panther 2?!
#2: T’Challa the Space Case! During his time with the Fantastic Four, T’Challa and Storm took to the cosmos on a mission to discover who stole Gravity’s body. apparently he fought one of their greatest enemies The Silver Surfer. It is there T’Challa has a show down with the Silver Surfer in which the only way he took the Surfer down… was a good ol’ fashioned arm lock. However, it wasn’t T’Challa’s invincible strength that helped him master Galactus, but a machine designed to weaken any being with special abilities. It’s a good thing the Silver Surfer didn’t turn the weapon on T’Challa – that battle could have gone a different way!
#3: Illuminati, Illuminati, Illuminati – That’s right – T’Challa, yours truly, is apart of the exclusive secret group the Illuminati. The same one with Beyonce, Jay, and Madonna?! Not quite – this Illuminati is composed of some of the greatest mental beings in the Marvel Universe. Their members are Doctor Strange, Professor X (…no surprise there), Reed Richards, Iron Man (…also no surprise there) and a few others. Their mission is to manipulate their world from behind the scenes to protect humanity at all costs. So like our illuminati…but not like our illuminati?
#4: Panther vs. Mufasa! When T’Challa took the bulk of his missions in the U.S. due to his work with the Avengers, he wasnt able to attend to Wakanda as much. A random reporter decides to go all Pulitzer prize on him, and calls him to the carpet to go back home. As they journeyed back home T’Challa uses his keen senses to sniff out the reporter was Lion God! Lion God had a bone to pick with Panther God and lured T’Challa to help him trap the panther. The Lion God imprisoned T’Challa, and took his chances against the A -team in New York. Thor being the awesome Thunder God he is pretty much capped him with a lighting bolt, and freed T’Challa. That would be epic to see on screen!
T’Challa has so many interesting journey’s, powers, and traits that could make up an entire book. Our hero has faced down a plethora of enemies, and friends, took over the persona of Daredevil, gets his P.H.D. – the list goes on. T’Challa has all the great qualities of a King, hero, and human being, and it can’t get much sweeter than that. Well it can, but we’ll leave that up to Ryan Coogler. The only match to bad ass hero like Black Panther is a bad ass Black female hero to match him – that why we’re rounding out Juneteenth’s Comic Book Spotlight with –
What's Your Reaction?
Hi! Asia Minor here - I enjoy anything history, fantasy, and sci fi...its even better when its all combined. I am working on acquiring beautiful huskies for my pets, constantly watching movies (and plan on making them), and reading/writing. My musical choices limit to Disney, Lin-Manuel Miranda, and Lamar - enough said.

domain: entertainment


text:
Doctor insights on:
Feeling Bloated After Ovulation
Some thoughts...: It can be common for people to get a bloated feeling after eating- especially with spicy, acidic or heavy foods, caffeine, and alcohol. Dairy products can do it as well (many of us get a little lactose intolerant as we age). Try to see if there's any relationship with the foods you eat, and if not, try to check in with your doctor about it! ...Read more
Unprotected sex 4 days before ovulation, yes he came inside,6 days past ovulation and feeling immediately nauseated and bloated.
Period is 2.5 weeks late. i feel dizzy,nauseous, headaches,increased appetite. 2neg HPTs. bloated, full stomach, constipated. never had unprotectedsex?
Abdominal cramping 5 days after ovulation, very sore nipples and 8 days after ovulation painful sex. Pregnancy symptoms?
Had an unprotected sex, burning sensation when i pee before, irregular menstrual cycle, 4 days late, stomach ache not abdominal cramps?
Two Issues: You have a bladder or other urinary tract infection. Why are you not getting this treated? Second if you worry you could be pregnant then you go get a pregnancy test and complete it in the privacy of your home. You had exposure to sperm. And, your period is late. Don't you think it is time for a test? ...Read moreSee 2 more doctor answers
Feeling nauseous before after period, about 2 weeks(ish) only after eating/drinking headache pee a lot pelvic/back cramps not pregnant on mirena (levonorgestrel)?
Peroid01/07ovulated14/07.Had sex bfore nd after ovulation. Bn feeling nausea, bloated, cramping.Y/day had pain lke periodpain. Pregnant? When can test?
Pelvic cramping, nausea, frequent urination, feeling a little dizzy at times, mild headaches. Had unprotected sex days after my period.Can i be pregnan
There is always a : chance yesGet a more detailed answer ›
Pooping frequently, indigestion, stomach aches at times, heavy feeling abdomen, recently had full period and protected intercourse. Weird cramps too.
Needs to be checked: You probably have a viral gastroenteritis causing your symptoms .Consilt your doctor to confirm if you have it . Meanwhile make sure you drink plenty fluids to prevent dehydration . But if also vomiting and not able to retain fluids go to ER with your parents as you are a minor ...Read more
Unprotected sex on 21 period n 4days been feeling nausea after meals, headace, tiredness, sharp stomach pains culd i b pregnant?
Brown discharge and cramping, 4 days after ovulation, really sore nipples, bloated, is 4 days after ovulation implantation bleeding too soon?
Probably not: Implantation occurs 6-7 days after conception, implantation bleeding usually doesn't happen at all. I'd look for another explanation. ...Read more
- Talk to a doctor live online for free
- Feeling bloated during ovulation
- Arch the bak and feeling bloated five days after ovulation
- A bloated feeling after eating
- Ask a doctor a question free online
- Feeling bloated after surgery
- Feeling bloated after period
- Feeling full and bloated after eating
- Feeling bloated after eating bread
- Talk to a gynecologist online for free

domain: medical


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Sunday, 35 women activists from 15 countries will march across the Korean DMZ to call for a final peace treaty 62 years after the end of the conflict. The US has continued to oppose a political/diplomatic solution to the "Korean War."
Even though South Korea keeps trying to discourage the march by changing the rules, the activists plan to march tomorrow.
Please sign Code Pink’s petition below calling for a Korean Peace Conference.
Dear United Nations Secretary General Ban Ki-Moon,
On this 70th anniversary of Korea’s division, we urge the United Nations to broker a Political Peace Conference, as called for in Article 4 Paragraph 60 of the Korean War Armistice Agreement, to bring together all parties that took part in the Korean War to reach a peaceful settlement. As an international conflict that continues to hamper peaceful relations in East Asia and across the Pacific, it is time to finally end the state of war by replacing the Korean War Armistice with a more permanent Peace Accord.
The Korean War Armistice, the temporary military cease-fire agreement that has lasted for 62 years, has not led to peace. North Korea’s nuclear weapons program, the annual U.S.-South Korea military exercises, the rampant arms race in Northeast Asia, and the continued separation of families are proof of that. It is time for a Peace Treaty to end the hostilities and move forward on reconciliation.
In hopes of peace,


The Massachusetts Gaming Commission Releases March 2023 Casino and Sports Wagering Revenue
BOSTON, Massachusetts (April 18, 2023) — The Massachusetts Gaming Commission reported today that the month of March 2023 at Plainridge Park Casino (PPC), MGM Springfield (MGM) and Encore Boston Harbor (EBH) generated approximately $105 million in Gross Gaming Revenue (GGR).
Additionally, March saw the launch of online and mobile sports wagering at six Category 3 licensees on March 10, 2023. Approximately $47.06 million in taxable sports wagering revenue (TSWR) was generated across the six mobile/online licensees and the three in-person licensees for the month of March.
Gross Gaming Revenue (casino gaming) PPC, a category 2 slots facility, is taxed on 49% of GGR. Of that total taxed amount, 82% is paid to Local Aid and 18% is allotted to the Race Horse Development Fund. MGM Springfield and Encore Boston Harbor, category 1 resort casinos, are taxed on 25% of GGR; those monies are allocated to several specific state funds as determined by the gaming statute.
To date, the Commonwealth has collected approximately $1.374 billion in total taxes and assessments from the casino operations of PPC, MGM and Encore since the respective openings of each gaming facility.
View comprehensive revenue reports for each gaming licensee here. MGC issues monthly revenue reports on
the 15th of each month or the next business day.
Sports Wagering Revenue
EBH, MGM, and PPC are licensed as Category 1 Sports Wagering Operators, which allows them to operate a retail sportsbook at their respective property. Category 1 operators are taxed on 15% of TSWR.
Barstool Sportsbook, BetMGM, Caesars Sportsbook, DraftKings, FanDuel, and WynnBet are licensed as Category 3 Sports Wagering Operators, which allows them to operate a mobile or online sportsbook. Category 3 operators are taxed on 20% of TWSR.
Of the total taxed amount for all operators, 45% is allotted to the General Fund, 17.5% to the Workforce Investment Trust Fund, 27.5% to the Gaming Local Aid Fund, 1% to the Youth Development and Achievement Fund, and 9% to the Public Health Trust Fund. To date, the Commonwealth has collected approximately $9.65 million in total taxes and assessments from the sports wagering operations of licensed operators since sports wagering began in person on January 31, 2023 and online on March 10, 2023.
View comprehensive revenue reports for each sports wagering operator here.
SOURCE: Massachusetts Gaming Commission.Tags: Massachusetts Gaming Commission, March 2023, Casino and Sports Wagering Revenue


'Let Yourself Go' is a harder rock song that many Green Day fans are used to -- a song led by an energetic Billy Joe Armstrong. It is more punk than the album's first single, 'Oh Love,' which continues to top the rock charts, and is angrier than the fun, dance-influenced 'Kill the DJ.' Although Green Day's music continues to evolve, this song is as hard as 'American Idiot,' has a killer guitar solo and bass track, and may even remind some of their mid-'90s music. Armstrong sings angrily about someone, proclaiming, "You're getting on my every last nerve / everything you've said I've already heard."
'Let Yourself Go,' was performed last week at the MTV Video Music Awards to an enthusiastic crowd, many of whom joined the band on stage. 'Uno,' will be released on September 25, but the band continues to share more music, making the video for the opening track of the album 'Nuclear Family,' available on Yahoo! '¡Dos!' and '¡Tré!' are supposed to be released over the next few months. For now, you can enjoy their latest single on AOL Radio's New Alternative First.


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Atlanta Mayor Kasim Reed this week established the Welcoming Atlanta Working Group. The 21-person committee is tasked with developing ways to help immigrants integrate into the Atlanta community.
Monica Fuentes, who is heading the mayor’s initiative, says several factors led to the Reed’s decision.
“Metro Atlanta is actually the second-fastest growing foreign-born population in the United States right now,” she says. “So, the demographics are changing. People are here, people want to go to work, people want to go to school.”


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Could this be the oldest house you can stay at in Suffolk?
- Credit: The Landmark Trust
Bearing the date 1473, this medieval timber-framed building is one of the oldest places you can holiday at in Suffolk.
Managed by conservation charity the Landmark Trust, the Ancient House in Clare is available to hire as a holiday let.
Offering fantastic views of the St Peter and St Paul's churchyard, the first thing you notice about the house is the elaborate pargetting, a distinctive form of raised plaster decoration common in East Anglia.
Images on the building include the arms of the Hamelden family and two wild men of the woods carved into the oak window frame, as well as the arms of the de Clare family.
Because of the nature of lime plaster decaying over time, these designs are unlikely to be original.
The house was probably built by Hamelden Family, ether to house a chantry priest, or to live in themselves. No one is sure about the houses original form, but it seems likely that a 14th century building stood on the site.
This was likely expanded at the end of the 15th century, when an architectural showpiece was added behind the cross wing, and the houses orientation was changed to face the church.
- 1 Historic former pub with permission to convert into homes set for auction
- 2 Ipswich Town installed as early League One title favourites
- 3 GALLERY: 'Stunning' turnout as Hadleigh Show returns after enforced break
- 4 5 new places to eat and drink in Woodbridge this year
- 5 Excitement builds as Suffolk Show venue wakes up
- 6 Man dies after being found unresponsive in Sudbury river
- 7 Mike Bacon: Luke Woolfenden.... going nowhere, going everywhere
- 8 Homes destroyed after blaze breaks out in terraced housing
- 9 'We're blown away' - Classic car show visits care home after roadworks setback
- 10 'I keep selling out' - Mum-of-two dreams of fudge shop as business thrives
In the 1920s, an American tried to buy the Ancient House with the intention of shipping it across the Atlantic, but he was pipped to the property by a Charles Byford – who bought the house and gave it to Clare Parish Council.
In the modern day, the house is split between a holiday let managed by the Landmark Trust and the Clare Ancient House Museum.
Split over two stories, downstairs the holiday let has a comfortable and well lit modern kitchen with an oven and fridge.
The living room is furnished in a traditional style, with exposed wooden beams visible in both the walls and ceilings, adding to the character of the space.
Upstairs the bedroom, which has an ensuite bathroom, continues the theme of the living room, with its high vaulted ceiling and leaded oriel window giving it the feel of something from a period fiction book.
Find out more about the Ancient House in Clare at landmarktrust.org.uk/search-and-book/properties/ancient-house-4525.

domain: history


text:
The Queen: a Biography of Queen Elizabeth IIA biography of the woman who has, for more than 40 years, been the British Head of State. The author looks at the Queen from the standpoint of the justly curious citizen, and from that of the historian, sociologist and constitutional lawyer.
by Ben Pimlott
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The Queen: a Biography of Queen Elizabeth II Summary
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Research Paper Volume 12, Issue 15 pp 15581—15602
hsa_circRNA6448-14 promotes carcinogenesis in esophageal squamous cell carcinoma
- 1 Department of Radiation Oncology, Anyang Cancer Hospital, Anyang 455000, China
- 2 Department of Radiation Oncology, Henan Key Laboratory for Cancer Research, The first Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
- 3 Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471000, China
- 4 Department of Radiation Oncology, Rutgers - Cancer Institute of New Jersey, Rutgers - Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA
Received: March 24, 2020 Accepted: June 19, 2020 Published: August 15, 2020https://doi.org/10.18632/aging.103650
How to Cite
Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Circular RNAs (circRNAs) play important roles in cancer progression. hsa_circRNA6448-14 originates from exon 5 to exon 11 of the TGFBI gene. We investigated the roles of hsa_circRNA6448-14 in esophageal squamous cell carcinoma (ESCC) with microarrays and quantitative real-time polymerase chain reaction (qRT-PCR), Kaplan-Meier analysis, loss-of-function and gain-of-function assays, and pull-down assays for miRNA binding. The hsa_circRNA6448-14-miRNA-mRNA network was drawn using Circos. hsa_circRNA6448-14 was significantly upregulated in ESCC tissues and cell lines. As a diagnostic biomarker, hsa_circRNA6448-14 had an area under the curve (AUC), sensitivity, and specificity of 0.906, 82.9%, and 85.5%, respectively. hsa_circRNA6448-14 upregulation was correlated with poor differentiation, advanced pTNM stage, poor disease-free survival (DFS), and poor overall survival (OS). Elevated hsa_circRNA6448-14 promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro. hsa_circRNA6448-14 functioned as a miRNA sponge to competitively bind miR-455-3p, and hsa_circRNA6448-14 expression negatively correlated with that of miR-455-3p. hsa_circRNA6448-14 promoted carcinogenesis in ESCC, suggesting that hsa_circRNA6448-14 could serve as a diagnostic and prognostic biomarker for ESCC.
Esophageal cancer (EC) is one of the most frequently occurring malignant neoplasms worldwide, with high incidence and mortality [1, 2]. It is characterized by international differences in incidence and pathology [3, 4]. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of all EC in China. The highest incidence in China is found in the Taihang mountain region, Henan province . Due to local recurrence and distant metastasis, ESCC has a poor prognosis, with a 5-year survival rate of less than 15-20% . Since early detection plays a key role in controlling the mortality of ESCC, it is urgent to identify novel sensitive and effective biomarkers for ESCC.
Circular RNAs (circRNAs) are a novel class of non-coding RNAs with a covalently closed circular structure, formed by back-splicing, different from canonical splicing of linear RNAs. In 1976, Sanger et al.  discovered the first circRNA in a plant RNA virus. In 1979, circRNA was observed in the cytoplasm of eukaryotes . In 1991, Nigro et al.  confirmed that circRNA existed in human cells. However, circRNAs were initially considered junk generated in aberrant splicing events . More recently, with deep RNA sequencing and bioinformatics, thousands of circRNAs have been identified in eukaryotes. They can be evolutionarily conserved  and show tissue-specific expression and roles in pathological conditions . They are regulated by specific cis-elements and trans-factors , indicating they are functional . circRNAs have been implicated in several human disorders including cancer [15–20].
Previous studies demonstrated that circRNAs have diverse biological functions, including acting as miRNA or protein sponges [13, 21]. circRNAs may act as oncogenes or tumor-suppressors [22, 23]. circRNAs may be more stable than linear RNAs  as biomarkers. Previous studies confirmed circRNAs are biomarkers for cancers including prostate , liver , gastric , and lung . However, the function of circRNAs in ESCC was unclear.
Using circRNA microarray profiling, we identified hsa_circRNA6448-14 as a circRNA that was significantly up-regulated in ESCC tissues and cell lines. High expression of hsa_circRNA6448-14 was associated with poor differentiation, higher pTNM stage, and poor prognosis in ESCC patients. In vitro studies suggested that hsa_circRNA6448-14 promoted cell proliferation, migration, and invasion, and acted as a miR-455-3p sponge. Our study indicated that hsa_circRNA6448-14 promotes the progression of ESCC.
circRNA expression profiles in ESCC and adjacent normal tissues by microarray analysis
Six pairs of ESCC and adjacent normal tissues were randomly selected for circRNA microarray analysis. A total of 149789 circRNAs were detected. Cluster analysis indicated that a large number were expressed in two groups; correlation analysis indicated a high correlation of samples; box plot analysis showed that samples had comparable intensities; and a three-dimensional principal component analysis (PCA 3D) indicated high similarity between samples (Figure 1). A total of 15908 circRNAs were significantly dysregulated between ESCC and matched normal tissues after filtering. Among them, 7161 circRNAs (45.01%) were upregulated and 8747 (54.98%) were downregulated. Hierarchical clustering analysis, scatter plot, volcano plot, and Circos plot clearly showed differential circRNA expression between cancer and non-cancer groups (Figure 2A-2D). The chromosomal distribution of differentially expressed circRNAs showed that most were transcribed from chr1, chr2, chr3, chr5, chr7, and chr17, with a few transcribed from chr21, chr22, chrX, or chrY (Figure 2E). Most differentially expressed circRNAs (84.02%) originated from exons (Figure 2F).
Figure 1. CircRNAs expression profiles in ESCC and adjacent normal tissues. (A) Hierarchical clustering showed that a large number of circRNAs were expressed in two groups. (B) Correlation analysis showed a high correlation of samples. (C) Box plots showed that samples had comparable intensities. (D) Three-dimensional principal component analysis (PCA 3D) indicated high similarity of samples.
Figure 2. circRNA expression profile differences between ESCC and paired adjacent normal tissues. (A) Hierarchical clustering of circRNA expression profiles across samples. Each column is a tissue sample, and each row is a circRNA. (B) Scatter plot of differences in circRNA expression in ESCC and normal tissues. (C) Volcano plot showing dysregulated circRNAs. (D) Circos plot indicating differentially expressed circRNAs. Column width represents the number of differentially expressed circRNAs, and the column length the degree of differential expression. (E) Chromosomal distributions of differentially expressed circRNAs. Blue, green, and yellow represent upregulated, downregulated, and total circRNAs, respectively. (F) CircRNA source: 84.02% of dysregulated circRNAs originated from exons. Ca=ESCC tissues; Con=adjacent normal tissues. Red and green indicate upregulated and downregulated circRNAs, respectively.
qRT-PCR validation of circRNA expression profiles
Candidate clinically relevant biomarkers from the microarray results were selected from upregulated and downregulated circRNAs according to the following criteria: 1) fold change, p value, and moderate microarray signal value; 2) more than two miRNA binding sites; 3) predicted target miRNAs associated with ESCC. Based on these criteria, five circRNAs were selected for further validation (Table 1). They were validated using qRT-PCR in 26 pairs of ESCC and adjacent normal tissues. The dissolution curve showed that all the five circRNAs had single peaks and the peak values were high, indicating that the specificity of PCR amplification primers were good (Supplementary Figure 1). hsa_circRNA6448-14 was significantly up-regulated in ESCC tissues compared to adjacent normal tissues (p < 0.05), hsa_circRNA15930-8 was significantly down-regulated (p < 0.05), and hsa_circ_0110255, hsa_circ_0064369, and hsa_circ_0024108 showed no significant differences (p > 0.05) (Figure 3).
Figure 3. Relative expression of 5 circRNAs verified by qRT-PCR in 26 pairs of ESCC and adjacent normal samples. (A) hsa-circRNA6448-14. (B) hsa-circRNA15930-8. (C) hsa_circ_0110255. (D) hsa_circ_0064369. (E) hsa_circ_0024108. * p < 0.05, ** p < 0.01.
Table 1. Five candidate circRNAs selected for qRT-PCR validation.
|*p < 0.001. FC=fold change.|
hsa_circRNA6448-14 as a diagnostic biomarker in ESCC
ROC curve analysis was performed to determine the diagnostic values of hsa_circRNA6448-14 and hsa_circRNA15930-8 for ESCC. The area under the curve (AUC), sensitivity, and specificity of hsa_circRNA6448-14 were 0.846 (95% CI: 0.738-0.954, p = 0.045), 80.8%, and 77%; for hsa_circRNA15930-8 the values were 0.673 (95% CI: 0.519-0.828, p = 0.032), 73.1%, and 50.0%, respectively, for the diagnosis of ESCC. Because hsa_circRNA6448-14 showed a greater AUC and lower p value than hsa_circRNA15930-8, the former was chosen for validation in more samples and we expanded the sample size to 50 pairs. hsa_circRNA6448-14 displayed significant upregulation in ESCC tissues compared with adjacent normal tissues (p < 0.05), confirming the microarray analysis and the first qRT-PCR validation set and indicating the reliability of these results (Figure 4). ROC curves on the additional 50 samples gave an AUC of 0.941 (95% CI: 0.893-0.990, p = 0.023), with sensitivity and specificity of 84.6% and 86.0%, respectively. The 76 patients were pooled and analyzed, which confirmed that hsa_circRNA6448-14 was significantly up-regulated in ESCC, and ROC curves showed AUC, sensitivity, and specificity of 0.906 (95% CI: 0.899-0.903, p = 0.021), 82.9%, and 85.5%.
hsa_circRNA6448-14 as a prognostic biomarker in ESCC
The median hsa_circRNA6448-14 expression of all cases was chosen as the cutoff for dividing the dataset into high and low expression groups. Analysis of clinical pathological data showed high expression of hsa_circRNA6448-14 was positively associated with differentiation and pTNM stage (Table 2). All patients were followed-up until December 25, 2019. The follow-up time was 4 - 45 months (median: 37 months), and the follow-up rate was 100%. The 1, 2 and 3 year OS was 85%, 65%, and 55%, and the DFS was 57%, 47%, 45% for the 76 patients. Kaplan-Meier analysis revealed that ESCC patients with hsa_circRNA6448-14 high expression had shorter OS and DFS than those with hsa_circRNA6448-14 low expression. Univariate and Cox multivariate analysis indicated that pT stage and hsa_circRNA6448-14 expression were independent prognostic factors for postoperative DFS in ESCC (p = 0.031, p = 0.014), with HR values of 1.755 (95% CI = 1.054-2.921) and 0.376 (95% CI = 0.173-0.819), respectively. Family history of ESCC, pT stage, and hsa_circRNA6448-14 expression were independent prognostic factors for postoperative OS in ESCC (p = 0.033, p = 0.007, p = 0.003), with HR values of 2.149 (95% CI = 1.062 - 4.347), 2.516 (95% CI = 1.280 - 4.947) and 0.199 (95% CI = 0.069 - 0.573), respectively. hsa_circRNA6448-14 was identified as a potential prognostic biomarker in ESCC (Figure 5, Table 3).
Figure 5. Prognostic significance of hsa-circRNA6448-14 in 76 case of ESS by Kaplan-Meier analyses. (A) OS (B) DFS (C) OS based on family history of ESCC. (D) OS based on pT stage. (E) DFS based on pT stage.
Table 2. Correlation between hsa_circRNA6448-14 expression and clinical/pathological characteristics in ESCC.
|Age (years)||> 65||33||24||9||1.247||0.332|
|Tumor size||> 4 cm||28||19||9||0.084||0.772|
|≤ 4 cm||48||31||17|
|Total lymph node dissection (n)||≥15||45||26||19||3.146||0.076|
Table 3. Univariate and multivariate analysis for postoperative OS and DFS in 76 cases of ESCC.
|χ2||P value||P value||Exp(B)||95%CI|
hsa_circRNA6448-14 promotes ESCC cell progression
Functional assays were conducted to validate the role of hsa_circRNA6448-14 in ESCC progression. hsa_circRNA6448-14 expression was detected in four ESCC cell lines and one normal human esophageal epithelial cell line (HEEC) by qRT-PCR. hsa_circRNA6448-14 was elevated in ESCC cell lines compared to HEEC (Figure 6A). hsa_circRNA6448-14 expression was highest in KYSE150 cells and lowest in TE7 cells, so these two cell lines were respectively selected for hsa_circRNA6448-14 knockdown and overexpression. Expression of hsa_circRNA6448-14 was effectively silenced by si-circRNA6448-1 (si-circ) in KYSE150 cells, and significantly up-regulated by overexpression (over-circ) in TE7 cells (Figure 6B). A CCK-8 assay revealed that si-circ significantly suppressed cell growth, and over-circ promoted cell viability (Figure 6C). A colony formation assay confirmed that si-circ inhibited proliferation, while over-circ promoted it (Figure 6D). Apoptosis, measured by flow cytometry, was significantly promoted by si-circ, and decreased by over-circ (Figure 6E). Wound healing and Transwell assays revealed that si-circ significantly decreased migration; over-circ increased migration (Figure 6F, Figure 6G). Invasion, as measured by Transwell assays with Matrigel, showed si-circ reduced and over-circ enhanced invasion (Figure 6G).
Figure 6. hsa-circRNA6448-14 promotes ESCC progression in cell lines. (A) Relative expression of hsa-circRNA6448-14 in ESCC lines and normal cell line by qRT-PCR. (B) hsa-circRNA6448-14 expression detected after transfection in KYSE-150 and TE-7 cells. (C) CCK-8 assays to determine viability of KYSE150 and TE7 cells. (D) Colony-formation assays to measure proliferation after hsa_circRNA6448-14 knockdown in KYSE-150 cells or overexpression in TE7cells. (E) Flow cytometry to detect apoptosis of KYSE150 and TE7 cells after transfection. (F) Wound healing assays to detect cell migration capacities of KYSE150 and TE7 cells after transfection. (G) Transwell assays to detect cell migration and invasion capacities of KYSE150 and TE7 cells after transfection. *p < 0.05, **p <0.01.
hsa_circRNA6448-14 targeted a miRNA-mRNA network and served as a sponge for miR-455-3p
Recent evidence shows that many circRNAs may function as miRNA sponges . The genomic locus of hsa_circRNA6448-14 is on chromosome 5, and the predicted gene sequence of its transcript is ENST00000442011. We identified and ranked the putative target miRNAs of hsa_circRNA6448-14 based on mirSVR scoring. Five miRNAs were found with overlapping results. We hypothesized that hsa_circRNA6448-14 acted as a miRNA sponge to regulate this circRNA-miRNA-mRNA network, and that the interactions could be predicted by TargetScan and miRanda. A total of five miRNAs and 138 mRNAs were predicted to interact with hsa_circRNA6448-14. The possible miRNA binding sites of hsa_circRNA6448-14 were predicted to be miR-503-5p, miR-455-3p, miR-4646-5p, miR-382-5p and miR-204-5p, and the hsa_circRNA6448-14-miRNA-mRNA network was constructed (Figure 7). GO and KEGG pathway analysis was performed. GO annotation analysis involved three major categories: biological processes, cell component, and molecular function. hsa_circRNA6448-14 showed a strong relationship with biological processes including cell processes, single-organism processes, and metabolic processes. The cell, cell part, and organelle were identified as the cell components. In the molecular function classification, binding was the most prominent category, followed by catalytic activity and nucleic acid binding transcription factor activity (Supplementary Figure 2A). KEGG pathway analysis showed that hsa_circRNA6448-14 may participate in the regulation of axonal guidance, catalytic activity, adhesion plaques, and tumor proteoglycan pathways (Supplementary Figure 2B). Analysis using publicly available algorithms (Target Scan, miRWalk, and miRanda) showed that a number of negative regulators, including RICTOR, SKI, NDP, SMAD7, IGF1R, CCND1, RAD9A, TIMP3, FN1, XOH, PTPN9, ABCB1, ADCY1, CUL3, SUV39H1, ITGA5, and EZR were associated with ESCC.
To validate binding of the miRNAs to hsa_circRNA6448-14, we conducted RNA pull down assays using biotin-labeled probes targeting the hsa_circRNA6448-14 junction site (Supplementary Figure 3). Based on the hsa_circRNA6448-14-miRNA-mRNA network, we selected two miRNAs, miR-455-3p and miR-204-5p for pulldown assays. The results showed that hsa_circRNA6448-14 could bind to miR-455-3p, but not miR-204-5p (Figure 8A). Furthermore, we analyzed the expression of miR-455-3p in 76 pairs of ESCC tissues, and determined that the expression of miR-455-3p was significantly down-regulated in ESCC tissues compared to adjacent normal tissues (Figure 8B). The expression of miR-455-3p was negatively correlated with that of hsa_circRNA6448-14 in 76 pairs of ESCC tissues (r = -0.701, p < 0.001, Figure 8C).
Figure 8. miR-455-3p in ESCC tissues. (A) RNA pull-down array to detect the enrichment of hsa_circRNA6448-14 and miR-455-3p in ESCC tissues. (B) Expression of miR-455-3p in 76 cases of ESCC tissues and adjacent normal tissues (** p < 0.01). (C) Correlation analysis of expression between hsa_circRNA6448-14 and miR-455-3p in 76 cases of ESCC (* p < 0.05).
Recently, circRNAs have been implicated in cancer occurrence and development. circRNA expression profiling is a prerequisite to identify novel tumor suppressors and oncogenic circRNAs, and to elucidate their mechanisms and functions . In this study, we selected ESCC patients from a high incidence area and compared the circRNA profiles of ESCC and adjacent normal tissues by RNA-seq. Through hierarchical clustering analysis of differentially expressed circRNAs, samples separated into cancer and non-cancer groups, confirming differential expression patterns of circRNAs in ESCC and adjacent normal tissues. These data strongly suggested that circRNAs were involved in the pathogenesis of ESCC.
A total of 15908 significantly dysregulated circRNAs in ESCC were identified, predominantly transcribed from chr1 and chr2, suggesting that the expression patterns may be related to certain biological processes. circRNA sequences largely determine their binding targets. circRNAs can be exonic, intronic, or exonic-intronic, although more than 80% are derived from exons [29, 30]. In our study, the majority of differentially expressed circRNAs were exonic (84.02%). The proportion of up-regulated and down-regulated circRNAs was 88.41% and 80.43%, respectively, consistent with previous reports [30, 31].
Based on RNA-seq and qRT-PCR validation, we identified a circRNA up-regulated in ESCC that was identified in the authoritative database DeepBase as hsa_circRNA6448-14. hsa_circRNA6448-14 had not been previously reported in ESCC, and so was identified as a candidate oncogene in ESCC for the first time. Most circRNAs are expressed from known protein-coding genes and consist of a single or multiple exons . hsa_circRNA6448-14 originates from exon 5 to exon 11 of the TGFBI gene located on chr5, and information is available about it (Supplementary Table 3).
The expression and characteristics of circRNAs, including tissue/cell specificity and stability, make them ideal biomarkers. Several circRNAs have been reported as biomarkers in ESCC. hsa_circ_0001946 is downregulated in ESCC; its overexpression can reduce cell proliferation, migration, and invasion, and predict recurrence, OS, and DFS in ESCC . hsa_circ_0006948 is overexpressed in ESCC; high hsa_circ_0006948 was positively correlated with lymph node metastasis and poor prognosis . cirs-7 is significantly up-regulated in ESCC tissues compared to normal; ESCC patients with cirs-7 overexpression had poor OS . We found that hsa_circRNA6448-14 was more abundant in ESCC, and distinguished ESCC from normal tissues as a diagnostic biomarker. hsa_circRNA6448-14 was positively correlated with differentiation and pTNM stage. Patients with high hsa_circRNA6448-14 expression had poor DFS and OS. These results suggest that hsa_circRNA6448-14 expression could provide diagnostic and prognostic value for ESCC patients.
Loss-of-function and gain-of-function experiments in vitro demonstrated that hsa_circRNA6448-14 was associated with proliferation, migration, invasion, and apoptosis. These results strongly suggest that hsa_circRNA6448-14 plays a role in the progression of ESCC.
Emerging evidence confirms that circRNA acts to competitively bind with miRNAs . For instance, circCDR1as harbors over 70 conserved binding sites and acts as a sponge for miR-7, regulating the expression of human epidermal growth factor receptor and others .
We constructed a hsa_circRNA6448-14-miRNA-mRNA network with predicted functions and mechanisms by GO and Pathway analysis. RNA pulldown experiments confirmed that hsa_circRNA6448-14 targeted miR-455-3p in ESCC. miR-455-3p has been demonstrated to play a role in tumorigenesis and be associated with HCC [36, 37]. miR-455-3p, STK17B, and the AKT/GSK-3β/Snail pathway may operate in combination to regulate epithelial-mesenchymal transition (EMT) and metastasis in HCC . miR-455-3p mediates GATA3 tumor suppression in mammary epithelial cells by inhibiting TGF-ß signaling . Downregulation of miRNA-455-3p links proliferation and drug resistance of pancreatic cancer cells by targeting TAZ . These results indicate a pro-oncogenic role of miR-455-3p in tumor progression. miR-455-3p acts as a prognostic marker and inhibits the proliferation and invasion of ESCC by targeting FAM83F . We found downregulated miR455-3p in ESCC tissues, and a negative correlation between miR-455-3p and hsa_circRNA6448-14 expression, suggesting that hsa_circRNA6448-14 affects ESCC progression by negatively regulating miR-455-3p. miRNAs bind to the 3’UTR of mRNA and inhibit gene functions . We predicted potential mRNA binding sites for miR-455-3p, and will study their regulatory mechanisms in depth.
In conclusion, this study identified a profile of dysregulated circRNAs in ESCC in patients from a high incidence area of China. We found that hsa_circRNA6448-14 was upregulated in ESCC tissues and cell lines, and may predict diagnosis and clinical outcomes. hsa_circRNA6448-14 may promote ESCC carcinogenesis by decreasing miR-455-3p. Additional rigorous clinical and fundamental studies are needed to confirm the present results.
Materials and Methods
Patients and cell lines
The 82 pairs of freshly frozen ESCC and adjacent normal tissues were obtained from patients who underwent operations at the Anyang Cancer Hospital (Henan, China) between June 2015 and April 2016. All patients were from high incidence areas in the Taihang Mountain of China, and received no radiotherapy, chemotherapy, or targeted therapy before surgery. The patients included 49 males and 33 females; ages ranged from 45 to 77 years, with a median of 61 years. Tumor stages were determined according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging criteria . Six pairs of samples were used for microarray profiling, and the remaining 76 pairs of samples were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). The study was approved by the Ethics Committee of the Anyang Cancer Hospital, and all patients provided written informed consent.
ESCC cell lines including TE1, TE7, Eca109, KYSE150, and human normal esophageal epithelial cells HEEC were obtained from Cell Bank of the Chinese Academy of Sciences (Shanghai).
Microarrays (Capitalbiotech, human circRNA Array v2., Beijing, China) were performed in six pairs of ESCC and adjacent normal tissues. RNA digestion, amplification, and labeling were performed according to the protocol provided. A total RNA extraction kit (Capitalbiotech, Beijing, China) was used. RNA was resuspended in RNase-free water. RNA integrity was assessed using standard denaturing agarose gel electrophoresis. RNA purity and concentration were determined by OD260/280 readings using a ND1000 spectrophotometer (NanoDrop, Wilmington, DE, United States). RNA was stored at -80°C until use. The circRNA array data were summarized, normalized, and subjected to quality control using GeneSpring software V13.0 (Agilent). The differentially expressed circRNAs were selected according to threshold values of ≥ 2 and ≤ −2 -fold change (FC) and p value of < 0.05.
Total RNA samples were reverse-transcribed (RT) into complementary DNA (cDNA) with a random primer using a PrimeScript RT reagent kit with gRNA Eraser according to the manufacturer’s protocols (Takara Bio, Nojihigashi, Kusatsu, Japan). qRT-PCR was performed using SYBR-Green Premix Ex Taq (Takara Bio, Nojihigashi, Kusatsu, Japan) and monitored on an ABI PRISM 7500 Sequence Detection System (Applied Biosystems, Life Technologies, Waltham, MA, USA). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference gene. The primer sequences are listed in Supplementary Table 1. The appearance of a single peak in the melting curve analysis indicated primer specificity. All of the experiments were performed in triplicate and data were analyzed using the 2-ΔΔCT method to establish the relative expression levels of circRNAs.
Cell culture and cell transfection
Vectors for overexpression of hsa_circRNA6448-14 and si-hsa_circRNA6448-14 and their corresponding controls were commercially obtained from Gene Company (Shanghai, China). Scrambled sequences and empty vector were used as negative controls. The hsa_circRNA6448-14 siRNA and overexpression plasmid were transfected into KYSE150 cells and TE7 cells respectively using Lipofectamine 2000 (Invitrogen), according to the instructions, and harvested for experiment after 48 hours. The transfection efficiency was detected by qRT-PCR.
Cell proliferation assays
Details of cell counting Kit-8 (CCK-8) and colony formation assays are available in previous studies .
Wound healing assay
Cells transfected for 24 hours were seeded in 6-well plates at a 3×105 cells per well and cultured at 37°C for 12 hours. A 10 μL pipette tip was used to draw a linear wound in the middle of each well, and the cells were further cultured for 24 hours after washing. Photos were taken at zero and 24 hours after scrapping.
Cell invasion and migration assays were carried out using Transwell chambers (8-mm pore size, Corning) pre-coated with (for invasion assay) or without Matrigel (for migration assay) (BD Pharmingen, USA). Cells were serum starved for 24 hours, then seeded in the upper chamber with 200 ml of FBS-free medium, while 600 ml complete medium with 10% FBS was added to the lower chamber as a chemoattractant. After incubation for 24 hours, non-migrating or non-invading cells were removed from the upper chamber. Cells that passed through the membrane were fixed with 4% paraformaldehyde for 30 minutes and stained with 0.1% crystal violet solution (Sigma, St. Louis, USA) for 30 minutes. Cells were counted under a light microscope (Leica, German). All experiments were performed in triplicate.
Transfected cells were collected and washed with PBS and analyzed with Annexin V: PI apoptosis detection kit (BD Bioscience, USA). Cells were resuspended in the provided 1× binding buffer. After coincubating with 5 μL Annexin V-FITC and 5 μL PI for 15 minutes, apoptosis was detected by flow cytometry (FACSCaliber BD, USA).
Biotin-labeled hsa_circRNA6448-14 probes and control probes were synthesized by Sangon Biotech (Shanghai, China). The lysis buffer included 1 mM PMSF, 100 U RI (RNase Inhibitor, ThermoFisher, EO0384) and 1×PIC (Protease Inhibitor Cocktail, Roche, 04 693 116 001). The cell lysis buffer was incubated with Streptavidin beads (Invitrogen, 65801D, USA) at 25°C for 30 minutes, and the pre-hybridized cell lysates were collected and divided into three groups: beads, antisense, and sense. Beads were washed 5 times with RNA binding buffer, and incubated with miRNA. Finally, TRIzol reagent was added to the beads mixture for RNA extraction, followed by qRT-PCR. The probe sequences are shown in Supplementary Table 2.
Statistical analyses were performed using SPSS 26.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism v8.0 (GraphPad Software Inc., San Diego, CA, USA). Data are presented as mean ± standard deviation (SD). The differences between groups were tested using one-way ANOVA, Student’s t-test, or chi-square. Receiver operating characteristic (ROC) curves were applied to analyze the diagnostic values of circRNAs. OS and DFS were analyzed with the Kaplan-Meier method and compared by the log rank test. The univariate and multivariate analyses were analyzed by Cox proportional hazards model. Correlations were determined using Pearson’s correlation coefficients. All p values were based on two-sided testing, and p < 0.05 was considered significant.
We thank all patients for their participation in the study and their doctors for their willingness to refer patients.
Conflicts of Interest
The authors have no conflicts of interest to disclose.
This study was supported by National Natural Science Foundation of China(U1504814), Major projects of Science and Technology Department in Henan Province (16110311200, 161100311300) and Anyang Science Foundation of Henan Province (2016).
This corresponding author has a verified history of publications using the personal email addresses for correspondence.
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domain: biology


text:
Mikaela Shiffrin's first World Cup win came in Austria in December 2011
American Mikaela Shiffrin claimed the 70th World Cup race win of her career with victory in the giant slalom in Soelden, Austria.
The reigning Olympic champion was 0.02 seconds behind Switzerland's Lara Gut-Behrami after the first run of the season opener.
But she was the fastest on the second run to triumph by 0.14secs overall.
Shiffrin is hoping to compete in five events at the Winter Olympics, which start in Beijing on 4 February 2022.
The 26-year-old has two golds and a silver from her two previous Games appearances.
Saturday's win was her first giant slalom victory since December 2020 in Courchevel, France.
"Starting off the season strong is important, so I'm super happy," said Shiffrin, who missed last year's opener with a back injury.
"It's early to start already racing in October and you're like 'Oh my gosh, here we go'. So sometimes I think people are not pushing so hard, they're just trying to almost use it like training.
"But you have to really attack this hill and I've learned that the hard way. Today was a good one."
Overall World Cup giant slalom champion Petra Vlhova of Slovakia was third but Italy's Marta Bassino, who won last year's opener, skied out on the first run while compatriot Federica Brignone, the 2020 World Cup overall champion, missed a gate on the second.
Britain's Alex Tilley was 13th, 2.47secs down on Shiffrin.
1. Mikaela Shiffrin (USA) two minutes 07.22seconds
2. Lara Gut-Behrami (Swi) +0.14secs
3. Petra Vlhova (Svk) +1.30
4. Katharina Liensberger (Aut) +1.39
5. Maria Therese Tviberg (Nor) +1.45
6. Meta Hrovat (Slo) +1.59
7. Valerie Grenier (Can) +1.85
8. Tessa Worley (Fra) +2.06
9. Nina O'Brien (USA) +2.31
10. Ramona Siebenhofer (Aut) +2.38


text:
And the service is worse. There is no service. They start by making you pay for your dinner in full... before you even enter the restaurant. the food is served under heat lamps and there were a number of trays that looked hours old.
Own or manage this property? Claim your listing for free to respond to reviews, update your profile and much more.

domain: food


text:
Treasury Bill Yield for 91 days decreased by 11.8% whilst treasury bill for 182 days and 364 days have increased
Importance of Outsourcing in Banking Industry Nowadays outsourcing is well practiced in banking industry. The concept of outsourcing is as
Import of gold by Nepal reached to NPR 20.6 Billion in first seven months of FY 2018/19 from NPR 17.7
Net import of electricity from India by Nepal reduced significantly in first seven months of current fiscal year compared to
The rupee continues to depreciate against all other major currencies this week compared to previous week except Yen. Yuan created
M1 increased by 5.1% whilst M2 increased by 13.8% this month compared to corresponding month of previous year.
The rupee continues to depreciate against all other major currencies this week. Pound Sterling bounced back this week with appreciation


text:
PROVIDENCE, R.I. — Vermont farmer Brian Kemp is used to seeing the pastures at Mountain Meadows Farm grow slower in the hot, late summer, but this year the grass is at a standstill.
That’s “very nerve-wracking” when you’re grazing 600 to 700 cattle, said Kemp, who manages an organic beef farm in Sudbury. Kemp attributes the changing climate to his inconsistency and unpredictable weather.
” “I don’t believe there is any normal anymore,” Kemp stated.
The impacts of climate change have been felt throughout the Northeastern U.S. with rising sea levels, heavy precipitation and storm surges causing flooding and coastal erosion. But this summer has brought another extreme: a severe drought that is making lawns crispy and has farmers begging for steady rain. Heavy, brief rainfall from the odd thunderstorm can tend to evaporate rather than soak into the soil.
Water supplies are low or dry, and many communities are restricting nonessential outdoor water use. Fire departments are combatting more brush fires and crops are growing poorly.
Providence, Rhode Island had less than half an inch of rainfall in the third driest July on record, and Boston had six-tenths of an inch in the fourth driest July on record, according to the National Weather Service office in Norton, Massachusetts. The governor of Rhode Island issued Tuesday a drought advisory for the state, with suggestions to decrease water consumption. There are water restrictions in place for the Hoppin Hill Reservoir at its north end, Massachusetts.
Officials in Maine said drought conditions really began there in 2020, with occasional improvements in areas since. In Auburn, Maine, local firefighters helped a dairy farmer fill a water tank for his cows when his well went too low in late July and temperatures hit 90. About 50 dry wells have been reported to the state since 2021, according to the state’s dry well survey.
The continuing trend toward drier summers in the Northeast can certainly be attributed to the impact of climate change, since warmer temperatures lead to greater evaporation and drying of soils, climate scientist Michael Mann said. But, he said, the dry weather can be punctuated by extreme rainfall events since a warmer atmosphere holds more moisture — when conditions are conducive to rainfall, there’s more of it in short bursts.
Mann stated that there is evidence from Penn State University showing climate change has created a stuck jet stream pattern. This means that the jet stream’s meanders, also known as the air current, can get trapped in one place. It could lead to extreme weather events such as extreme heat or drought at one spot and severe rainfall at another. Mann explained that this pattern has been evident in recent summers with heat and drought in Northeastern and Midwest.
The majority of New England are in drought. A new map was released by the U.S. Drought Monitor on Thursday. It shows parts of Eastern Massachusetts that are not in Cape Cod, and most of Rhode Island and southern Rhode Island, which is now experiencing severe drought.
New England has experienced severe summer droughts before, but experts say it is unusual to have droughts in fairly quick succession since 2016. According to Vandana Rao (director of water policy Massachusetts), Massachusetts was subjected to droughts in 2016, , and 2022,. This is likely because climate change.
“We hope this is maybe one period of peaking of drought and we get back to many more years of normal precipitation,” she said. “But it could just be the beginning of a longer trend.”
Rao and other water experts in New England expect the current drought to last for several more months.
“I think we’re probably going to be in this for a while and it’s going to take a lot,” said Ted Diers, assistant director of the New Hampshire Department of Environmental Services water division. “What we really are hoping for is a wet fall followed by a very snowy winter to really recharge the aquifers and the groundwater.”
Rhode Island’s principal forest ranger, Ben Arnold, is worried about the drought extending into the fall. This is when more people tend to burn wood, do yard work, and use fireplaces. It also increases the likelihood of forest fires. The fires this summer have been relatively small, but it takes a lot of time and effort to extinguish them because they are burning into the dry ground, Arnold said.
Hay farmer Milan Adams said one of the fields he’s tilling in Exeter, Rhode Island, is powder a foot down. In prior years it rained in the spring. He said that the dryness began in March and April, which was so dry, made him nervous about cutting his first hay.
“The height of the hay was there, but there was no volume to it. From there, we got a little bit of rain in the beginning of May that kind of shot it up,” he said. “We haven’t seen anything since.”
Farmers are fighting more than the drought — inflation is driving up the cost of everything, from diesel and equipment parts to fertilizer and pesticides, Adams added.
“It’s all through the roof right now,” he said. “This is just throwing salt on a wound.”
The yield and quality of hay is down in Vermont too, which means there won’t be as much for cows in the winter, said Vermont Agriculture Secretary Anson Tebbetts. The state has roughly 600 dairy farms, a $2 billion per year industry. Like Adams, Tebbetts said inflation is driving up prices, which will hurt the farmers who will have to buy feed.
Kemp, the president of the Champlain Valley Farmer Coalition, is thankful to have supplemental feed from last year, but he knows other farmers who don’t have land to put together a reserve and aren’t well-stocked. The coalition is trying to help farmers evolve and learn new practices. They added “climate-smart farming” to their mission statement in the spring.
“Farming is challenging,” Kemp said, “and it’s becoming even more challenging as climate change takes place.”
The post Northeastern farmers face new challenges with severe drought appeared first on Associated Press.


text:
This is a lot of two J. Ferrar silk ties made in Italy.
The ties are:
1. Blue and gray with an elongated oval and stripe type design, measuring 61.5" long and 4" wide at the bottom.
2. Black and green with a rhombus type pattern with beige and white spots on one side. This tie measures 65" long and 4" wide at the bottom.
These ties are in very good pre-owned condition.

domain: artistic


Kantara has set the box office on fire. Unlike KGF, Baahubali, and the recent Ponniyin Selvan, which were marketed and promoted as pan-Indian films, Rishab Shetty’s Kantara was promoted as a Kannada film. However, the game changed after it premiered in multiple cities outside Karnataka.The film has now been dubbed in Telugu, Tamil, and Hindi, Tulu, and more.
Rishab Shetty, director, and the lead actor in Kantara and Hombale Films Chaluve Gowda speak to financialexpress.com about the success of the film, how regional cinema is a way forward, the Kannada industry, and more.
Watch interview here:
Kantara was released in the Kannada version and Hindi versions on September 30 and October 14 respectively. The film is written and directed by Rishab Shetty. Produced by Vijay Kiragandur and Chaluve Gowda, under Hombale Films, the film features Rishab Shetty, Sapthami Gowda, and Kishore Kumar G in pivotal roles.


text:
There is some debate over whether succulents prefer acidic or alkaline soil. Most growers seem to think that succulents do better in slightly acidic soil, but there are exceptions. Some succulents, like sedums and sempervivums, actually prefer alkaline soil. If your soil is too acidic or too alkaline for your succulents, you can amend the soil by adding organic matter or limestone, respectively.
But if you’re growing succulents specifically for the beauty of their foliage, it’s best to make sure your soil is at least slightly acidic. In fact, most of them grow well in soil with around pH6.
Can Succulents Survive in any Soil?
Succulents are plants that have evolved to store water in their leaves, stems, or roots. This makes them very drought tolerant and able to survive in many types of soil. However, not all succulents will thrive in every type of soil. Sandy soils, for example, can be difficult for succulents to grow in because they do not hold water well. If you’re planting succulents in sandy soil, try to amend it with compost or garden lime. Clay soils can also be challenging for succulents because they don’t hold enough water for them to survive.
Ingredients For a Succulent Soil
When caring for succulents, it is important to use a potting mix that drains well. A succulent soil mix can be made with ingredients that are readily available at most garden centers. The mix should consist of one part potting soil, one part sand, and one part perlite or vermiculite. If desired, a small amount of compost can be added to the mix to help improve drainage and provide nutrients to the plants.
What are the signs of a pH imbalance in succulents?
If you are new to succulents, or just looking to be more knowledgeable about their care, it’s important to learn about pH levels and how they can impact your plants. Most succulents prefer a soil pH of 6.0-7.5, but there are a few that can tolerate a pH as low as 5.0 or as high as 8.0. Soil pH is measured on a scale of 1-14, with 7 being neutral. A reading below 7 means the soil is acidic, while a reading above 7 means the soil is alkaline.
Soil pH can be easily tested using a soil test kit from your local garden center or home improvement store. The test kit will come with instructions on how to take a soil sample and how to read the results.
How to Make Soil Acidic for Succulents
If you’re not sure which of these additives will work best for your plants, start with a small amount and then increase the dosage if needed. Be careful not to add too much, as this can damage your plants. Also, you should test your soil for pH before adding any chemicals. You can also use a fertilizer that contains an acid-forming element.
There are a few ways to lower (acidify) or raise (alkalinize) the pH of soil. One common way to lower the pH of soil is to add sulfur. Sulfur reacts with water in the soil to form sulfuric acid, which lowers the pH. Another way to lower the pH is to add aluminum sulfate. Aluminum sulfate also reacts with water in the soil to form a weak acid that lowers the pH. To raise (alkalinize) the soil, lime can be added. Lime contains calcium carbonate, which reacts with water in the soil to form calcium hydroxide, a base that raises the pH.
Are Coffee Grounds Good for Succulents?
Many gardeners have succulents and are always looking for ways to help them thrive. One question that comes up often is whether coffee grounds can be used as a soil amendment for succulents. The answer is yes - coffee grounds can be beneficial for succulents.
Coffee grounds are acidic, which makes them a good choice for amending soil with a high pH level. They are also rich in nitrogen, potassium, and magnesium, all of which are nutrients that succulents need. Additionally, coffee grounds help to improve soil drainage and aeration.
If you’re looking to add coffee grounds to your succulent’s soil, it’s best to do so sparingly. A little goes a long way - too much can make the soil too acidic and could potentially harm your plants.
Is Alkaline Water Good for Succulents
There are many opinions on whether or not alkaline water is good for succulents. Some people say that the higher pH level in alkaline water is beneficial to succulents because it helps to prevent root rot and other diseases. Others say that the opposite is true and that alkaline water actually harms succulents by leaching nutrients from their roots. The truth is, there is no definitive answer when it comes to whether or not alkaline water is good for succulents.
In case you are preferring a video about succulents and the soil they like you should see the below video:
The best way to find out if your succulents prefer alkaline or regular water is to test it out. Start by watering your plants with regular tap water and then watering them with alkaline water a few days later. Observe how they look and feel, and take note of any differences.

domain: agronomy


Hearts will vote in favour of proposals to change Scotland's league structure in time for next season.
SPL clubs are due to vote on the 12-12-18 proposal at Hampden on Monday, with an 11-1 majority needed to carry the plan.
St Mirren plan to vote against the proposal and BBC Scotland understands Ross County are also opposed.
"While by no means perfect, (the proposal) delivers a series of important improvements," Hearts said.
The set-up would involve the top two divisions splitting into three leagues of eight midway through the season.
Other features of the proposals include a revised financial distribution model and the merging of the SPL and SFL, with the Scottish Football Association having also been heavily involved in the protracted discussions.
But, if SPL clubs do not vote it through, it is likely the current make-up of 12-10-10-10 will continue for next season.
Explaining the club's stance, Hearts said the proposal for 12-12-18 would increase competition for the top 24 clubs, "with almost every game at every stage in the season having value for spectators, broadcasters and sponsors".
"Hearts believes, as one of the most established and largest clubs in Scottish football, that it has a responsibility to the game in this country and that the new proposed 12-12-18 structure, while by no means perfect, delivers a series of important improvements," the statement continued.
"These are improvements we, along with many other clubs and their supporters, have lobbied for in recent years.
"It is incumbent on us to deliver change for the game as a whole and in turn improve the longer term prospects of all clubs, at all levels, within the game."
Meanwhile, Aberdeen chairman Stuart Milne feels Scottish football "is on its knees financially" and that 12-12-18 is a viable alternative.
Motherwell, both Dundee clubs and Inverness CT have all publically stated they are in favour of the proposal.


When we design an operating system or equipment platform for foodservice employees to use, oftentimes our zeal to provide the most complete solution results in our creating something that is impractical or even impossible to use. And as we all know, what’s easy is what gets done in any foodservice environment.
That’s why I am firm believer that less is often more when it comes to foodservice design. Simply put, for any foodservice design to create a competitive advantage it needs to facilitate the work for the employees in order to enable flawless execution. The so-called bells and whistles any solution may have become irrelevant if they don’t make execution easier.
This is why I believe that less is more very often and perhaps our primary design principle to use is KISS: Keep it Simple Stupid.
Last month the world saw a perfect example of how keeping it simple can produce remarkable results as we watched the rescue of the miners in Chile. I don’t know about you, but I found myself starting at the TV quite often as each of the 33 miners emerged from below ground. Looking closely at the how the miners were freed you can see it was a combination of significant teamwork and an application of existing technology. Using a less is more mentality the rescuers took available tools and technology and developed a new application that got the job done.
At the heart of the operation was a giant drill, with a capsule device, both of which have been around quite some time and both of which had to go into the earth for one-third of a mile. Perhaps we may think that the technology was revolutionary, since most of us are not familiar with it. But if you think about it, what is so new about a drill and a capsule? Let’s not forget that before these devices were put to use, the rescuers had to find the trapped miners. Guess what technology they used? Maps and drawings of the area – neither of which were very revolutionary.
The focus of the operation was more around how to use existing technologies to engineer the rescue. This was accomplished by applying sheer brain power and a huge level of teamwork. Clearly this rescue was a tremendous feat and we can all learn from it as we go about our jobs as foodservice professionals.
When it comes to foodservice design, generally speaking, we are not in the business of rescuing people. Still, there is much we can learn from the approach taken to rescue these miners as we go about our business each day. Whether we are running a foodservice establishment, designing an operating system or creating technologies and equipment applications, we may want to consider applying the KISS principle, focusing on the capabilities of the end user, be they an employee or customer.
When tackling a project, look at the available resources at your disposal to see which ones might work. Grouping existing knowledge and technology in the right combination may work better than creating designs that are much more complex and glorious (sophisticated), and may not be as easy for employees or customers to use.
In reading this, some of you might be inclined to recall the old adage that insanity is doing the same thing twice and expecting a different result. While occasionally appropriate, matching the appropriate level of technology with the end users’ capabilities could produce a different result. We have to recognize that many of these ideas, as simplistic as they seem, may not have had the right combination of other variables to be successful. I believe that you can actually take an idea that did not work in the past, for whatever reasons, bring it back and it would work now with a few, in some cases minor, adjustments. Perhaps technology has advanced. Perhaps different technologies were applied individually instead of collectively or in the wrong combination. The most subtle of changes can make the biggest of differences.
One interesting fact to consider is that as the individual players within the foodservice arena become more homogenized, meaning in the eyes of the customer they have similar menus and value propositions, ideas that were previously only appropriate for one category of service, can work well in the other. That’s why today we see practices that were strictly for QSRs being put into play within the fast casual arena, for example.
As a result, we must always be on the lookout for applications or ideas that were successful in other foodservice segments and evaluate whether they will be beneficial to our projects. Just remember that you may want to keep the application simple, and that less may facilitate more impact when it comes to real execution and application at the unit level. KISS.