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Seventy years ago, Hiroshima and Nagasaki. Let us remember.
For the 70th anniversary of the bombings that in some short moments left over 200 000 dead and countless thousands wounded, various ceremonies commemorate these tragical events all around the world, of course at first in the two targeted cities. Seventy years later, the danger remains great of other cities and other populations being annihilated, including by accident, at a much larger scale. The very survival of humanity is at stake.
For its part, ACDN (Action des Citoyens pour le Désarmement Nucléaire) is organising with the Town Council of Saintes two Public Ceremonies at the Monument to the Fallen (Saintes, Cours national, in front of the Palais de Justice). One is on 6 August 2015 at 11am, the other on 9 August at 10 45am.
On 6 August the Nuclear Disarmament Flame, first lit in May 2001 by Mme Schmitt, Mayor of Saintes, will be lit again, as it regularly has been, in memory of the victims of Hiroshima. On 9 August it will be extinguished in memory of the victims of Nagasaki, at 11.02am (the time of the explosion). Between those two dates, it will burn to call for the abolition of nuclear weapons.
Saintes is, with Saint Pierre d'Oléron, one of only two French towns that belong to both the international network « Abolition 2000 » and to the « Mayors for Peace» network, both of which call for the abolition of nuclear weapons in conformity with the UN Charter and with International Law. « Abolition 2000 » groups over 2000 NGOs and municipalities around the world, and "Mayors for Peace" groups over 6700 towns in 160 countries, including over 150 French towns.
In 2004 Saintes received the visit of the Hiroshima Mission for World Peace, during which two hibakusha (nuclear bomb survivors) lit the Nuclear Disarmament Flame near the Monument to the Fallen and carried it through the city. In 2004, 2006 and 2008 Saintes hosted the RID-NBC rallies (International Rallies for Disarmament - nuclear, biological and chemical) during which the Hiroshima and Nagasaki trees were planted — two gingko biloba. In 2009 Saintes welcomed the World March for Peace and Nonviolence, accompanied by the Hiroshima Flame.
Now, on the 70th anniversary of the bombings that plunged humankind into the permanent anguish of a nuclear apocalypse — which is very possible since the current 16000 atom bombs are much more powerful than those of Hiroshima and Nagasaki — we say with the hibakusha : « Never Again! »
We know that the hibakusha are working for peace in the world and that they condemn militarism in all its forms, starting with Japanese militarism. As the Mayor of Hiroshima has reminded us (in his letter which will be read in French on 6 August), we know that they are not acting in a spirit of revenge but on the contrary with a desire to see their painful story serve all humanity.
It is in this spirit of solidarity and peace that we invite all you — and all citizens aware of the gravity of the stakes — to take part in these two ceremonies or in any similar event taking place nearer to their home.
More on this: Hiroshima, Nagasaki - an unknown story
See also: In Saintes they are fasting for the end of nuclear weapons
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Roubaix (French: Roubaix, pronoonced French pronunciation: [ʀu.bɛ]; Dutch: Robaais, pronoonced Dutch pronunciation: [roʊˈbeɪ]) is an auld industrial ceety in northren Fraunce, at the sooth o the umwhile province o French Flanders, naur tae the mairch wi Belgium. It is an aw a commune in the Nord depairtment. Roubaix is crosst bi the canaul o the same name, wi the ceety o Tourcoing tae its north, an the toun o Leers tae its east.
Wi ower ninety-five thoosand indwallers, Roubaix wis the third-maist populatit ceety o the Hauts-de-France region efter Lille an Amiens in 2013. Thegither wi the ceeties o Lille, Tourcoing, Villeneuve-d'Ascq an aichty-sax ither communes, Roubaix forms the European Metropolis o Lille conurbation aurie populatit bi mair nor 1.1 million fowk.
The ceety o Roubaix is maist weil-kent as the steid o the feenish o the Clessic Paris–Roubaix.
The steid wis first documentit in 863. It remainit a smaa mercat toun till the nineteent yeirhunder, whan the Industrial Revolution led tae the growthe o the entire aurie. Waxin factories an warkshaps becam employers o monie fowk in Roubaix an the local airt. In 1800, 8,091 indwallers livit in Roubaix; in 1896 the population haed eikit tae 124,661. Durin this stound, the ceety gainit an internaitional staundin for oo an claith production, an becam kent as the "Toun o a thoosand lums" or unner the eik-name o "French Mahnchestur".
Internaitional competeetion in textile gart a dwyne in tradeetional hamelt industries atween the nineteen-seventies an nineteen-aichties. In order tae kemp economic, social an environmental difficulties associatit wi deindustrialisation, maist ceety govrenments hae wirkit tae impruive infrastructur, diversify acteevities, an invest in the airts iver syne.
Roubaix haes a multicultural identity stemmin frae its sindry fowk's oreegins. Bytimes kent bi thair name in the hamelt variant o the Picard leid, Roubégnos, the ceety's indwallers are referrt tae as Roubaisiens in French an Roubaisians in Inglis.
Acause its historical an cultural backgrund, the ceety haes been clesst frae its designation as a Ville d'art et d'histoire[note 1] syne December 2000. The Museum o airt an industrie foondit in 2001 unner the name o La Piscine – Musée d'art et d'industrie André Diligent an ither important cultural venues are locatit in Roubaix.
↑ Neveu, Clarisse (December 15, 2016). "Métropole Européenne de Lille : les vice-présidents et conseillers métropolitains délégués élus" [European Metropolis o Lille : electit vice-presidents an metropolitan delegate-councilors]. MEL. Communiqué de presse (in French). Lille, F: Métropole Européenne de Lille. Retrieved 2016-12-18. La fusion, effective au 1er janvier 2017, acte un élargissement historique du territoire de la Métropole Européenne de Lille, passant de 85 à 90 communes pour près d'1.2 million d'habitants.
↑ "Skopje - Twin towns & Sister cities". Official portal of City of Skopje. © Grad Skopje - 2006 - 2013, www.skopje.gov.mk. Archived frae the oreeginal on 2013-10-24. Retrieved 2013-11-04.
This page wis last eeditit on 17 Mairch 2018, at 07:37.


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Kevin Hart's Birthday Bash At The Essence Music Festival [PHOTOS]
Danielle Young, Associate Editor
"I'm doing a lot of happy sh*t these days," boasts funnyman Kevin Hart during his performance at this year's Essence Music Festival. The comedic genius was given a chance to perform on the same stage as icons like Aretha Franklin, Mary J. Blige and Chaka Khan at the 18th annual Essence Music Fest.
Must Read: Top 4 Travel Apps You Need This Summer
During Hart's performance, the audience was urged to put away cell phones and all other recording devices, or risk being kicked out. However, Hart–ever the open book–mentioned during the show that he's not sad or bitter because of his recent divorce from wife, Torrei. "She's happy, she's moved on. I'm happy, I've moved on. I'm happier than she is though," Hart joked.
As this marked Hart's first time headlining a show like this, his 33rd birthday was celebrating more than just another year of life. Kevin seemed to be celebrating his own happiness and success alongside Hollywood heavyweights like Denzel Washington, LisaRaye and Kevin Liles to name drop a few.
Check out some of the hot shots from Kevin Hart's star-studded birthday bash in New Orleans!
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Listen To This Hilarious Playlist!
Kevin Hart's Birthday Bash At The Essence Music Festival [PHOTOS] was originally published on hellobeautiful.com
Kevin Hart's Birthday Bash At The Essence Music…

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Isis Naija Gaston (born January1, 2000), known professionally as Ice Spice, is an American rapper. She grew up in the Bronx, New York City, and began her career in 2021 after meeting record producer RiotUSA while attending State University of New York at Purchase. She rose to prominence in late 2022 with her song "Munch (Feelin' U)".

The release of her singles "Bikini Bottom" and "In Ha Mood", preceded her debut extended play Like..? (2023). In 2023, she achieved her first Billboard Hot 100 chart entry with the Lil Tjay collaboration "Gangsta Boo", and her remix single "Boy's a Liar Pt. 2" with PinkPantheress reached the top three.

Ice Spice was hailed by Jon Caramanica of The New York Times as "rap's new princess", and was named a "breakout star" by Time magazine.

Early life
Isis Gaston was born on January 1, 2000, in the Bronx, New York City, where she was raised in the Fordham Road neighborhood. She is the oldest of five siblings. Her father, a former underground rapper, is African-American, while her mother, who gave birth to Gaston at age 17, is Dominican. The two first met at a McDonald's and divorced when Gaston was two years old. Because her parents were frequently busy working, she spent much of her time with her grandparents and cousins growing up. She went to school in the Bronx until she was sent to Sacred Heart High School, a Catholic high school in Yonkers. At age seven, she took a liking to hip hop after listening to rappers like  Lil' Kim, Nicki Minaj, and others and wrote poetry and freestyle raps from elementary school to high school. She would type out lyrics in the notes section of her iPhone, listening to hip-hop instrumentals and rapping out loud to them. "When I saw Nicki [Minaj], I was so mesmerized," Ice Spice explained. "She's the first female rapper that I seen. And ever since then, I was kinda set on what I wanted to be." She chose Ice Spice as her soubriquet while she was a freshman in high school.

Ice Spice attended State University of New York at Purchase, where she played back row on the school's volleyball team and studied communications. Ice Spice dropped out of SUNY Purchase around her sophomore year. "I left because I felt like I was in the wrong place." Ice Spice also attributed her "strenuous commute" for leaving college.

Ice Spice is the eldest sister to five siblings, and told The Cut she was their self-appointed protector. She supported herself as a cashier at Wendy's and The Gap.

Career
Ice Spice started rapping in 2021 after meeting with a record producer, RiotUSA, while they were attending State University of New York at Purchase. He produced her debut song, "Bully Freestyle", released in March 2021 after a video of Ice Spice doing the "Buss It" challenge went viral on Twitter. Her song "Name of Love" gained traction on SoundCloud, which led to her becoming popular on Instagram. Her song "Munch (Feelin' U)", released on August 10, 2022, with a video, and also produced by RiotUSA and distributed by WorldStarHipHop, gained popularity after getting support from Drake, who played the song on his Sirius XM radio station, Sound 42. It subsequently went viral on Twitter and TikTok, and charted on Billboards Hot R&B/Hip-Hop Songs and Bubbling Under Hot 100 charts. In September 2022, Ice Spice appeared as a featured artist on the song "One Time" by B-Lovee. Later that month, she signed a record deal with 10K Projects and Capitol Records. On October 28, she released the single "Bikini Bottom". Ice Spice's debut EP, Like..?, was released on January 20, 2023, and included the singles "Munch (Feelin' U)", "Bikini Bottom", and "In Ha Mood".

In February 2023, Ice Spice collaborated with Lil Tjay on the tribute single "Gangsta Boo" to the late rapper of the same name, which became her first song on the Billboard Hot 100 at No. 82. On February 3, 2023, the remix of singer PinkPantheress's song, "Boy's a Liar Pt. 2" featuring Ice Spice and the corresponding music video were released. The song peaked at No. 3 on the Billboard Hot 100, the highest charting position for either artist at the time.

Musical style
Ice Spice's music is primarily Bronx drill. Her name came from a "finsta" (secret Instagram account) she made at age 14. She has said she writes all her own lyrics. She was first inspired to start rapping by Sheff G and Pop Smoke, and has listed Lil' Kim, Nicki Minaj, Cardi B, Foxy Brown, and Remy Ma as musical influences due to their New York roots. She has also called Erykah Badu and Lauryn Hill inspirations because of their "graceful angelic vibe of timeless beauty".

Discography

Extended plays

Singles

Other charted songs

Music videos

Notes

References

External links

2000 births
Living people
21st-century American rappers
21st-century African-American musicians
21st-century LGBT people
21st-century women rappers
African-American women rappers
American LGBT songwriters
American rappers of Dominican Republic descent
Drill musicians
East Coast hip hop musicians
Hispanic and Latino American rappers
LGBT people from New York (state)
LGBT rappers
Pansexual musicians
Queer songwriters
Rappers from the Bronx
State University of New York at Purchase alumni

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Canal Park - 300 S. Main Street, Akron OH 44308
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HomeMEMBERSPatrick Obrien
Year Inducted – 2018
Patrick was born in Chicago, IL but was raised and grew up in Akron, OH. After attending Revere schools through 8th grade, he went to high school at Walsh Jesuit where he played baseball and basketball.
After Walsh Jesuit, he was drafted and played in the Pittsburgh Pirates organization while attending the University of Notre Dame during the fall semesters. After his baseball career ended and upon graduating from Notre Dame, he began his professional career which landed him back in Akron. He started working at The Goodyear Tire & Rubber Company as a finance executive.
Outside of work, he enjoys spending most of his free time with his wife of 11 years – Katie – and their 4 girls: Ashlyn, Avery, Madison, and Maren.
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At least your children really do know what Christmas is all about and happily celebrate it. GLad that it wasn't a sad ending to the fun.
I loved it! That reminded me of when mine were little. Out of the mouths of babes. They are so innocent and make you sit back and think about how fast time goes. Not to many children know the "true" meaning of Christmas anymore. It's the little things that count.
Your husband Scott is so smart! I'm glad it worked!


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Q: Convergence of series involving the prime numbers
Given the series $A=\sum\limits_{n=1}^{+\infty}\frac{p_n}{p_{n+1}}$ and $B=\sum\limits_{n=1}^{+\infty}\frac{p_{2n}}{p_{2n+1}}$, where $p_n$ is the sequence where the nth number are the nth prime number, is it possible to determine whether they are converging or diverging?

I think there are some ways using the fact that $\sum\limits_{p\in\mathbb{P}}\frac{1}{p}$ diverges, but I'm not sure of how I can use it.

A: Hint: Bertrand says $p_{n+1}/p_n < 2$.

A: For the first one, suppose $A<\infty.$ Then $p_n/p_{n+1} \to 0.$ By the ratio test, that implies $\sum_{n=1}^{\infty}1/p_n < \infty,$ contradiction.

A: \begin{align}
\frac{p_1}{p_2} + \frac{p_3}{p_4} + \cdots \ge \frac 1 {p_2} + \frac 1 {p_4} + \cdots & = \frac 1 2 \left( \frac 2 {p_2} + \frac 2 {p_4} + \cdots \right) \\[10pt]
& \ge \frac 1 2 \left( \left( \frac 1 {p_2} + \frac 1 {p_3} \right) + \left( \frac 1 {p_4} + \frac 1 {p_5} \right) + \cdots \right) \\[10pt]
& = \infty.
\end{align}

A: You can consider the bounds, if $n$
  sufficiently large, say for some $k>0
 $ $$n\log\left(n\right)<p_{n}<n\log\left(n\right)+n\log\left(\log\left(n\right)\right)
 $$ then $$\sum_{n\geq k}\frac{p_{n}}{p_{n+1}}>\sum_{n\geq k}\frac{n\log\left(n\right)}{\left(n+1\right)\log\left(n+1\right)+\left(n+1\right)\log\left(\log\left(n+1\right)\right)}>\frac{1}{2}\sum_{n\geq k}\frac{1}{\left(n+1\right)\log\left(n+1\right)}=\infty
 $$ and the same holds for $\sum_{n\geq k}\frac{p_{2n}}{p_{2n+1}}
 $.

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Large bag with pictures of Bob Marley on the both sides. You can use either handstrap or shoulderstrap for carrying the bag. The main pocket has a zipper and two smaller, separate pockets of which one has a zipper.


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The South Maui Wetlands Restoration Hui has the following mission:
Identify critical wetlands in need of restoration:
The Hawai`i" Island Land Trust (HILT) and the South Maui Save the Wetlands Hui are working collaboratively to assess the current ecological conditions and propose strategies to restore the health of select wetlands in the Kēōkea-Waiohuli corridor. The assessment will consider a variety of factors, including the degree of wetlands degradation, the likelihood of restoration success, and the potential benefits such restoration work will bring (measured against such goals as sediment attenuation, habitat provisioning, and restoration of cultural significance), and will lay the foundation for future wetlands restoration priorities.
Map and monitor the hydrological flow and habitat conditions of critical remaining wetlands:
The South Maui Save the Wetlands Hui has identified the critical long-term need for a comprehensive wetlands inventory of South Maui/Kula Kai, and the development of a wetlands program and management plan to be used as a guide for future conservation, development, and land-use changes within the region. The project will begin with collecting the hydrological flow data and habitat conditions of wetlands, assessing the feasibility of purchasing critical wetland sites or securing conservation easements, and collecting baseline data to quantify habitat improvements over time. Then data gathered will inform a future wetlands management plan and guide restoration priorities moving forward.
Conduct ecological wetland restoration work:
Ecological restoration work will be focused on repairing the structure, function, and composition of the pre-disturbance wetlands ecosystem in order to achieve greater productivity, biodiversity, and ecosystem resilience. Among the most important first steps is the identification of the sources of degradation, selection of appropriate plant species to promote restoration (the structure and composition elements of the restoration work identified above), and the restoration best management practices (BMPs) needed to ensure that the work has a lasting beneficial impact on the wetlands in question. The work is following these general steps:
Survey of various wetlands to determine their present condition, and assess their potential for restoration.
GIS mapping and drone surveying of these areas.
Educational outreach to the public to raise awareness about the importance of wetlands conservation, restoration, and protection:
To achieve our restoration goals, we are working closely with individuals, community groups, and landowners to encourage their participation in the process of wetlands restoration. Community outreach remains one of the most crucial elements in this process, both to involve the community in restoration, and to offer educational outreach programs to the community which will highlight the important task of wetlands protection and restoration.
Outreach includes presentations to community groups and various community associations across Maui as well as volunteer planting days or workdays involving the public. Our hope is that our work will lead to tangible benefits in the South Maui/Kula Kai area, as well as inspiration for future generations, groups, and other communities to take on the important task of wetlands restoration and protection island-wide.
Wetlands role in protecting beaches:
Coastal wetlands in Maui play a critical role in protecting beaches and other valuable near-shore natural resources by providing a number of important ecosystem services, including regulating and attenuating sediment flow in nearshore waters, creating a nutrient sink that prevents nitrogen and phosphorous pollution from entering the ocean and harming coral reefs, provisioning of habitat for indigenous and endemic Hawaiian waterbirds, providing for groundwater aquifer recharge, and flood mitigation. Additionally, wetlands play a significant role in the lives of the Hawaiian people (Kanaka Maoli), as both the domain of ʻaumakua (particularly Kihawahine in the South Maui area), and the establishment of landscapes that serve important economic, social, and ritual purposes, such as loʻi kalo (taro patches), and loko iʻa (fishponds). In the face of climate change and sea-level rise the wetlands provide important protection f land and water. These realities make the protection and restoration of coastal wetlands important to improving the resilience and durability of the entire Maui community. Wetland protection and restoration represent the cornerstone of the Hui's goals, and long-term vision. Unfortunately, for well over a century in South Maui, wetlands have been filled in, cut up, and disconnected resulting in these vital ecosystem services being lost to development. It is estimated that over 75%-80% of the wetlands along the Kēōkea-Waiohuli corridor have been lost in the past 50 years.
Saving the remaining Wetlands:
The importance of protecting, restoring, and expanding, the remaining South Maui/Kula Kai wetland ecosystems cannot be overemphasized. A long-term goal of this project is to develop a comprehensive wetlands program for South Maui/Kula Kai, and Maui County as a whole. The program has begun the process of assessing, identifying, and prioritizing the remaining wetlands for restoration, work with landowners to protect wetlands on their property, and seek to link wetlands into a corridor that functions as an interconnected ecological system for the mutual benefit of the County. This project represents Phase 1 of this multi-year goal, and we are beginning the process of protecting wetlands in the South Maui/Kula Kai region because the wetlands in this area are currently under intense pressure from development and are being lost or marginalized at an alarming rate. If we do not act now, there will be few ecologically viable wetlands left within the coming decade.
Hawaiian Cultural Considerations: Hawaiian cultural sites include culturally important natural features like Puʻuone (sand dunes,) muliwai (estuary), and kahawai (stream and gulches) as well as Hawaiian burial sites in shoreline areas and sand dunes. (Quote from Lucienne de Naie). In addition to the ecological and watershed functions of wetlands and riparian areas, special care and consideration should always be given to the historical and cultural aspects. Many ancient and sacred sites are based in and around these areas, and careful consideration of cultural practices and sacredness should always be of primary concern.
Economic Impacts:
Based on the known ecosystem services provided by wetlands globally, South Maui/Kula Kai wetlands clearly represent a significant economic value to Maui County. This value comes in the form of:
Flood Mitigation: Wetlands provide floodplain storage of excessive stormwater, reducing flood damage. Wetlands slow runoff, increase water infiltration and attenuate floodwaters (Goldberg & Watkins, 2021).
Attenuating sediment flow in near shore waters: Due to trapping of sediment and depth of water (Li & Yang, 2009).
Carbon sequestration and pollution filtration: Wetland ecosystems by their nature are extremely biologically productive and sequester carbon and filter sewage and other potentially harmful pollutants from the environment (Macreadie, et al., 2017).
Creating a nutrient sink that prevents nitrogen and phosphorous pollution from entering the ocean and harming coral reefs (Kaldec, 2012).
Groundwater Aquifer recharge: Wetlands allow surface water to infiltrate safely into aquifers where it can be later utilized for drinking water or irrigation needs. (Hayashi & Rosenberry, 2002).
Shoreline protection: Coastal wetlands provide a buffer for sea-level rise and can absorb the energy of ocean waves and storms; they act as natural run-up areas in their interplay between beach dune ecosystems and estuaries, giving rising seawater a place to go.
Natural value and greenspace: Wetlands provide urban greenspace that increases surrounding property values and provides recreation opportunities for residents and visitors alike.
Goldberg, Nisse, and Russell L Watkins. "Spatial Comparisons in Wetland Loss, Mitigation, and Flood Hazards Among Watersheds in the Lower St. Johns River Basin, Northeastern Florida, USA." Natural hazards (Dordrecht) (2021): n. page. Web.
Hayashi, Masaki, and Donald O Rosenberry. "Effects of Ground Water Exchange on the Hydrology and Ecology of Surface Water." Ground water 40.3 (2002): 309-316. Web.
Kadlec, Robert H. "Constructed Marshes for Nitrate Removal." Critical reviews in environmental science and technology 42.9 (2012): 934-1005. Web.
Li, H., & Yang, S. (2009). Trapping Effect of Tidal Marsh Vegetation on Suspended Sediment, Yangtze Delta. Journal of Coastal Research, 25(4), 915-930. Retrieved July 9, 2021, from http://www.jstor.org/stable/27698386
Macreadie, Peter I et al. "Carbon Sequestration by Australian Tidal Marshes." Scientific reports 7.1 (2017): 44071-44071. Web.
Qualls, Robert G, and Alan C Heyvaert. "Accretion of Nutrients and Sediment by a Constructed Stormwater Treatment Wetland in the Lake Tahoe Basin." Journal of the American Water Resources Association 53.6 (2017): 1495-1512. Web.
Hawai`i" Island Land Trust (HILT)
Maui Tomorrow
Kihei Community Association (KCA)
Maui Nui Marine Resource Council


Joy grew up enveloped in the culinary world. Her father was the founder of the illustrious Pinausukan Seafood House which was synonymous to Filipino culinary perfection. She remembers, as a child, watching her father create the best Filipino dishes in their kitchen. This gave Joy first hand insight into the culinary business and it was when the start of her love affair with food began. Joy is a foodie at heart and an educator by profession.
Joy grew up enveloped in the culinary world. Her father was the founder of the illustrious Pinausukan Seafood House which was synonymous to Filipino culinary perfection. She remembers, as a child, watching her father create the best Filipino dishes in their kitchen. This gave Joy first hand insight into the culinary business and it was when the start of her love affair with food began. Joy is a foodie at heart and an educator by profession. She was one of the very first Filipino teacher representatives sent to the United States for practice teaching. She also took a course at Alliant International University in California to further her training in K-12 teaching and was awarded by U.S navy commander, Shanti Sethi, a gold medallion for Bold and Daring Youth of the New Generation. She eventually took a course in baking and pastries at First Gourmet Academy. Since then, Joy has been cooking and baking her way around the kitchen bringing joy to all of her family gatherings. Her background in food and education keeps her motivated, guided and focused on this new career path she was born to walk. Similar to a verse in the Bible, Joy believes that "if you give a man a home cooked meal, you will feed him for a day, but if you teach a man how to cook, you will feed him for a lifetime."
The culinary business runs in her blood. At a young age, interior design graduate turned chef, Chef Regine, established a Filipino - Chinese restaurant with a colleague. Her love for food and travel developed an appreciation for varied cuisines from restaurants in Paris to exploring different corners in Binondo in search of the best siopao and dumplings. She pursued and conquered her dream of entering the culinary world.
The culinary business runs in her blood. At a young age, interior design graduate turned chef, Chef Regine, established a Filipino - Chinese restaurant with a colleague. Her love for food and travel developed an appreciation for varied cuisines from restaurants in Paris to exploring different corners in Binondo in search of the best siopao and dumplings. Because of Chef Regine's passion for food, she pursued and conquered her dream of entering the culinary world. She acquired her education in Culinary Arts at Enderun Colleges and became the president of the Alain Ducasse Formation-International Society Organization. She also worked as a part of the team who pioneered the luxurious, six star hotel, Solaire Resort & Casino. Her extensive experience includes working at two signature, fine dining restaurants: Yakumi Japanese Restaurant and Strip Steakhouse. At present, she has her own catering service, Cucina Express, and joined the Red Apron Cooking Academy to share her love for cooking. Her goal is to ensure that the culinary principles, philosophies and techniques she learned along the way are shared with the students of the Red Apron Cooking Academy.
Being born into a multi-cultural, foodie family, Chef Adrienne's culinary education started early. Her mother's knowledge of Persian cooking and her grandmother's culinary skills in authentic Filipino and Spanish food gave her the foundation for the career that was to be her future. She spent her summers in California learning and procuring a wide variety of fresh ingredients to elevate her palate from the diverse flavors found there.
Being born into a multi-cultural, foodie family, Chef Adrienne's culinary education started early. Her mother's knowledge of Persian cooking and her grandmother's culinary skills in authentic Filipino and Spanish food gave her the foundation for the career that was to be her future. Her father's love for exploring different cuisines and travelling, fuelled her passion at a very young age. She spent her summers in California learning and procuring a wide variety of fresh ingredients to elevate her palate from the diverse flavors found there. Her desire for Epicureanism and panache soared after the birth of her first child. She studied culinary arts at Enderun and has been a member of the Alain Ducasse Foundation since 2011. She further developed her skills at the world-renowned international buffet, Spiral at Sofitel Manila. Soon after, she worked at the 6-star Solaire Resort & Casino under the award-winning Malaysian chef, Hisham Johari. Chef Adrienne is currently an instructor at the Red Apron Cooking Academy and a devoted mother of two beautiful little boys, spending her free time exploring fairs and farmer's markets, and cooking for family and friends.
From a very young age, Chef Erick knew his calling would be in the culinary arts. In 2006, he graduated with 2nd honors from the International School of Culinary Arts and Hotel Management. In the years that followed, he honed his talent by training with some of the best chefs in the local and international food and service industry.
From a very young age, Chef Erick knew his calling would be in the culinary arts. In 2006, he graduated with 2nd honors from the International School of Culinary Arts and Hotel Management. In the years that followed, he honed his talent by training with some of the best chefs in the local and international food and service industry. In pursuit of culinary excellence, he attended the Kitchen and Personal Hygiene (HACCP) Training in Doha, Quatar and acquired the Alain Ducasse Formation: Basic Culinary Arts and Regional French Cuisine Certification. Currently, he is an instructor at the Red Apron Cooking Academy, a Sous Chef at Restaurant 101 by Alain Ducasse Formation and, the resident expert in modern French cooking.
Chef Jenine's journey did not begin on a culinary path. Her initial educational background began with a bachelor's degree in Consular and Diplomatic Affairs. She found herself drawn to cooking and ultimately discovered that this was her true calling in life. She believes that becoming part of the culinary world was the best decision she ever made.
Chef Jenine's journey did not begin on a culinary path. Her initial educational background began with a bachelor's degree in Consular and Diplomatic Affairs. In pursuit of the perfect job, she found herself drawn to cooking and ultimately discovered that this was her true calling in life. Chef Jenine's insatiable quest to refine her skills prompted her to enroll at Enderun Colleges, mastering the art of French cuisine. But her desire for learning did not stop there. She continued with a local internship at the Shangri-La Boracay where she worked as a line cook at Cielo restaurant and in the pastry department of the hotel. Her international career began when she received an internship at one of the largest ski resorts in Steamboat Springs, Colorado. She was given the opportunity to work at three of their casual and fine dining restaurants as a line cook. Her career continued to blossom when she became part of the luxurious Ritz Carlton Hotel in Florida. She worked as a line cook at their restaurant, Ocean Bar and Grill, and eventually was promoted to work for Salt , a multi-award winning restaurant. It was here where she earned the AAA- Diamond award as a gardemanger line cook making her the first ever female intern to be join their prestigous team. Chef Jenine is an instructor at Red Apron Cooking Academy and also works as the Pastry Demi-Chef de Partie at Enderun where she handles both the Restaurant 101 and the banquets department. She believes that becoming part of the culinary world was the best decision she ever made. It is through this wonderful journey that she learned it is never too late to pursue something you really love and make your dreams a reality.
A graduate of De La Salle-College of Saint Benilde, and has taken courses in international cuisine, baking and pastry and advance cake decorating. Owner and chief baker at Tickle Tongue Cakes and Pastries. Has has also worked in several top hotels such as Solaire Resort and Casino. A Bronze awardee at the recently held World Food Expo's 5th Philippine Culinary Cup, wedding cake category.


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Two PA communities honored by EPA for protecting vital sources of drinking water
The EPA honored two Lancaster County, Pa. communities for protecting sources of drinking water used by more than 20,000 people.
PHILADELPHIA, PA, Dec. 18, 2012 -- The U.S. Environmental Protection Agency today honored two Lancaster County, Pa. communities for protecting sources of drinking water used by more than 20,000 people. EPA Regional Administrator Shawn M. Garvin presented the agency's 2012 regional Source Water Protection Award to the Warwick Township Municipal Authority and the Borough of Lititz at a ceremony at the Warwick Municipal Office.
"Protecting the sources of our drinking water benefits public health, our environment and our economic well-being as well as our quality of life," said Garvin. "Warwick and Lititz have shown the way for more than a decade of working with farmers and others in taking responsible steps protecting drinking water supplies."
The Source Water Protection Award recognizes organizations and communities that take extraordinary steps to protect drinking water sources in EPA's mid-Atlantic region.
Warwick and Lititz were recognized for their joint Wellhead Protection Program to protect groundwater sources from contamination. The communities were nominated for the award by the Pennsylvania Department of Environmental Protection.
"DEP is proud to nominate Warwick Township and Lititz Borough for their approach of working with local farmers," DEP South-central Regional Director Lynn Langer said. "They have set the bar high for protecting drinking water, and hopefully other communities will follow their example."
"We know that in order to protect our sensitive water supply we need to use many different approaches," said Dan Zimmerman, Warwick Township Manager.
Sue Barry, Lititz Borough Manager explained, "We appreciate the willingness of our partners in the community and state, local and county governments who have helped to make this program successful."
The communities created a steering committee of local stakeholders to guide their steps, supported state-of-the-art farming techniques and plans, sponsored public education activities, completed watershed improvement projects, and developed protective land use planning strategies and emergency water supply plans.
These steps are designed to deal with high levels of nutrient pollution in the heavily-agricultural area. More than 30 percent of the public water systems in Lancaster County have nitrate removal systems installed to assure that water provided to customers meets health-based standards.
The communities reported a steady decline in raw water nitrate concentrations for their drinking water sources, reducing treatment requirements and expenses.
The upgrade of the Lititz Sewer Authority's wastewater treatment plant is helping to protect local waters and the Chesapeake Bay by significantly reducing nitrogen and phosphorus discharges to Lititz Run. The plant's technology is also producing dried biosolids that are being used by local farmers as a slow release fertilizer as part of their nutrient management program.
Warwick and Lititz are the first Source Water Protection Award winners in Pennsylvania since 2009.
The federal Safe Drinking Water Act requires that states develop EPA-approved programs to assess all drinking waters sources in the state. These assessments define land areas contributing water to each public water supply system, identify potential sources of contamination, and determine how susceptible the water supply is to pollution. Utilities and citizens can then use the information to create protection programs.
For more information on source water protection, visit: http://www.epa.gov/reg3wapd/drinkingwater/swp/.
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Yes, we now accept dogs! Exciting, isn't it.
We want to ensure that your dogs have as much of a luxurious break as you do! We are truly dog friendly, having 7 (yes you read that right, 6) of our own, many of which we have taken in as hopeless cases from various animal charities. We know how much they enjoy running around, and experiencing new sights and smells in the glorious Devon countryside and coast. So, by all means, bring your dogs, and enjoy the wondrous walks that Devon has to offer – some of them even start straight from our doorstep! So that this works for everyone, we do have a Doggy Do's and Don'ts Guide, which you can find below (coming soon).
Your Dog will need be checked in at the booking stage, just like their owners, so we need to know about them from the very start. There will be a dedicated little area on the booking form, to book your furry friends in by name!
There is even a fully fenced field directly behind The Burrow, which you are free to use to play ball, if it is empty. We do always have livestock on most of our fields, so they cannot be entered, but there is always the wonderful East Hill plantation that starts within 500 metres of the property, for your both to roam in, and so many walks, that it is impossible to list them all.
Outside tap for the really muddy characters.
Throws provided for covering the furniture.
(Coming soon) – A guide to dog friendly attractions, beaches, walks (including al ong the South West coastal path and The East Devon Way).
We do make a small charge of £30 per dog, per stay, with a 2 dog maximum rule (1 dog for giant breeds).
Also, as part of your booking, you are required to sign the terms and conditions, these include you agreeing to adhere to our "Doggy Do's and Don'ts", which is essential in keeping The Burrow in pristine, clean condition for all our guests.
We do not allow dogs to be left alone in The Burrow.
But where can we go?
You will probably we surprised how many places in Devon are dog friendly.
All the beaches in this area accept dogs from October to the end of April, and some have a restricted dog area throughout the year. See HERE for a link for more information for beaches in the East Devon area, or HERE for further afield.
Sidmouth beach: Dogs are welcome all year on part of the beach and from October to the end of April on the main beach. Dog bins are provided.
Branscome Beach: There is a dog exercise area.
Seaton beach: Dog bins provided and dogs are welcome all year on the second beach zone.
Beer beach: dogs are not allowed on the West side of the beach from 1st May – 30th September.
Many of Devon's visitor attractions welcome dogs on leads, including Escot and the Donkey Sanctuary, and you can even take your furry friend on a boat trip with Stuart Line Cruises or tram ride with Seaton Tramway! Bicton Botanical Gardens also accepts dogs on leads.
Devon also has lots of beautiful National Trust properties and places, such as Killerton House near Exeter, and Castle Drogo, which are well-known for welcoming dogs when at all possible.
Also, the children's theme parks Crealy, Pennywell Farm and Woodlands Family Theme Park all offer day kennels and exercise areas.
Don't forget, there is the incredible Dartmoor National Park where dogs can run free without the worry of traffic, not to mention the truly magnificent walks locally, such as the South West Coast Path and the East Devon Way, which runs exceptionally close to us.
There are also wide areas of heathland stretching from East Budleigh to Aylesbeare Common, including Woodbury Common, Colaton Raleigh Common, Mutters Moor and Bicton Common.


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Takeshi Faupula rushes for over 600 yards and scores eight touchdowns during eight games with Lehi in Utah this year. Faupula recently committed to the Navy on a football scholarship.
Yuba City High's Takeshi Faupula runs for some yards against River Valley during a game in 2019 at Honker Stadium in Yuba City.
Chris Kaufman/Appeal file
Navy bound: Former Honker football player gets recruited following transfer out of state
By Jeff Larson jlarson@appealdemocrat.com
Nov 27, 2020 Updated Nov 27, 2020
Is Takeshi Faupula an opportunist, a pioneer or just an athlete who simply did not want to give up on a chance at playing college football?
The most appropriate label for the former Yuba City High football player may well be Navy commit and soon to be midshipman running back, after Faupula recently committed to the Navy in Annapolis following a senior prep season playing football for Lehi High in Utah.
Faupula plans to sign with the Navy on Dec. 20 at an invite-only ceremony with limited family and friends in attendance. COVID protocols will remain in place, according to his trainer and uncle, Michio Takahashi.
For Faupula, the road to the Navy was complex due to the ongoing COVID-19 pandemic that hit back in March of 2020. With the prolonged shutdown of youth sports in California, Faupula had to make a decision early on about his senior prep football season.
As the pandemic continued to drag on and the likelihood that it would get worse in the fall with the so-called twindemic of flu and COVID season combining, time was running out on Faupula and his family.
He needed to act fast and decide whether he would wait it out and finish at Yuba City where he called the football extremely high quality, or find a different team.
A decision was finally made based on the fact that the state leaders were not going to give in on permitting the California Interscholastic Federation to move forward with high school sports until it was absolutely safe to do so.
"None of us believe that there would be a season," said Takahashi, who trains many Yuba-Sutter-Colusa athletes at a local gym on Sunsweet Boulevard. "In the winter with flu and COVID it was going to be difficult, so we decided to go."
Of course there were guidelines in place, including a transfer sit-out period of three games once he enrolled at Lehi. His first reported carry didn't come until Sept. 4 when he rushed it five times for 50 yards against Mountain Ridge.
However, it wouldn't be too long before he'd leave his mark, combining to run for over 600 yards on 78 carries and score eight touchdowns in eight games. Faupula earned all-region and helped Lehi finish 6-5 on the year.
It was a relatively safe experience in terms of the play on the field, Takahashi said.
"I have not heard of one case passed through playing the games," he said. "In the state of Utah not one case of COVID was traced back to playing high school football."
Faupula's time in Utah was almost completely centered around football. Beginning with the weight room where Takahashi said he had built himself up to be bigger than some of Lehi's linemen.
"He is a beast in the weight room and it shows," he said.
While it was difficult to be away from his immediate family for a prolonged time, Faupula said everything eventually fell into place.
"(At first) I was like, 'No way I would move to another state,'" Faupula said. "It was my second transfer in my career."
He also was concerned with coming in as a senior and learning a brand new offense.
"It turned out for the best," Faupula said. "I feel blessed to be able to play my senior year."
On why he chose Navy over reported offers from the College of Idaho, Eastern New Mexico and Air Force, Faupula said it came down to the connections he made during the recruitment process and the style of football that he wanted to play.
The Navy possesses a triple-option attack and runs the ball a lot under head coach Ken Niumatalolo.
"I like how they pound the rock and out physical teams," Faupula said.
Faupula also said that he was promised that he would be able to go on his two-year Mormon mission before starting his football eligibility.
Faupula said he won't suit up for the Navy until 2023 – at that point he will have four years eligibility and a five-year commitment to serve.
Overall, he's excited about his next venture in life and owes a lot of it to the decision he made to transfer out of state early on during the pandemic.
As for whether or not he is a pioneer time will tell.
In the meantime he will welcome any communication from other athletes as to how to approach their athletic futures during COVID restrictions.
"I would ask how serious they are and if they are really about it," he said.
But for the serious and committed athlete, Faupula says transferring is a viable option.
"That's what I would say because it worked out for me," he said.
Takeshi Faupula
Michio Takahashi
Mostly sunny. High 72F. Winds light and variable..


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The Lost Carousel of Provence (Compact Disc)
By Juliet Blackwell, Xe Sands (Narrated by)
An artist lost to history, a family abandoned to its secrets, and the woman whose search for meaning unearths it all in a sweeping and expressive story from the New York Times bestselling author of Letters from Paris. Long, lonely years have passed for the crumbling Ch�teau Clement, nestled well beyond the rolling lavender fields and popular tourist attractions of Provence. Once a bustling and dignified ancestral estate, now all that remains is the ch�teau's gruff, elderly owner and the softly whispered secrets of generations buried and forgotten. But time has a way of exposing history's dark stains, and when American photographer Cady Drake finds herself drawn to the ch�teau and its antique carousel, she longs to explore the relic's shadowy origins beyond the small scope of her freelance assignment. As Cady digs deeper into the past, unearthing century-old photographs of the Clement carousel and its creators, she might be the one person who can bring the past to light and reunite a family torn apart.
Historical - General
Kobo eBook (September 17th, 2018): $9.99
MP3 CD (September 18th, 2018): $29.99
Paperback (September 18th, 2018): $15.00
Library Binding, Large Print (January 1st, 2019): $38.95


A Model Life™ Giftset features a doll in lingerie and fashions in one complete package. Barbie® comes wearing a delicate pale pink brassier with black lace and half-slip accented by thigh high black stockings. For her meetings with fashion executives, she wears the first-ever pantsuit introduced to the Barbie® Fashion Model Collection. Her exquisite black and white 'tweed' suit is lined with pink 'taffeta' to complement a chiffon wrap blouse with ruffles. A beautiful faux pearl brooch and matching earrings complete her ensemble. For evenings out on the town, Barbie® has a sleek black skirt. Stylish accessories include black slingbacks, pink sunglasses, five photographs from Barbie® doll's fashion shoot, a black portfolio, and matching portfolio case to hold her photographs.


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Yellow Bikes Recycled To Dress Festival Route
A yellow cycling festival bike on the outskirts of Bourne
Yellow painted bikes are appearing along the race routes of next month's Bourne CiCLE Festival to raise awareness of the event.
They include a classic bike from the 1940s donated by Grantham man John Baldwin, re-painted and placed in Billingborough to commemorate his late father.
John, of Cedarwood Avenue, donated three bikes to the festival. He made a special request that his father's bike was displayed in the village where the family used to live.
"I liked the idea of his bike going on show back in our village as part of the festival," he said. "I couldn't bring myself to scrap it."
South Kesteven District Council is organising the festival, along with the Discover South Kesteven visitor team at InvestSK, the council's economic growth and regeneration company.
Andrew Norman, Head of Visitor Economy for InvestSK said "We wanted to recreate the look and feel of the Tour of Yorkshire with these colourful bikes. We are looking to establish South Kesteven as a cycling destination and want to make a splash with our first festival.
"We put out an appeal for unwanted cycles to paint yellow and place along the routes and more than 50 have now been handed over, many of which are now in place."
All the bikes are being painted yellow to brighten both the men's and women's races in the district's first cycling festival. One of the first was put in place on the outskirts of Bourne.
Others will appear along the men's 175-kilometre road race route and the 115-kilometre women's route, with both races expected to attract the UK's top professional teams.
Both start and finish in Bourne, going through the town twice before final dashes to the finish.
The men's race takes in Billingborough, Folkingham and Old Somerby and the women's race includes Ingoldsby, Bitchfield and Castle Bytham.
The festival also stages an amateur riders' Sportive on Saturday morning and a women's team time trial on Sunday morning.
For all routes, timings and festival details; www.bourneciclefestival.com
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New luxury student accommodation is coming to Lincoln in the form of The Dog House Living, which aims to create a 'home from home' for students which is expertly interior
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Tailor-made teddies are taking off with charity supporters around the world to help raise money for a major medical facility which is close to completion at Castle Hill Hospital. In
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Unlocking children's imaginations, inspiring creativity and connecting them to nature Family arts organisation Birdhouse will be hosting a week-long programme of cultural activities for children over October half term. Life's
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Ferroptosis inhibitor alleviates cytotoxicity induced by cobalt nanoparticles through reactive oxygen species attenuation
Chen Wang, Weinan Zhang, Fan Liu, Yake Liu
https://doi.org/10.21203/rs.3.rs-619496/v1
Background Currently, tissue damage induced by cobalt nanoparticles (CoNPs) are the most noticeable adverse effect in the patients with metal-on-metal (MOM) hip prostheses. Therefore, effective therapeutic strategy is needed to limit the toxicity of CoNPs. In this study, we aimed to investigate the protective effect of ferroptosis inhibitor on CoNPs-induced cytotoxicity.
Methods To evaluate the detoxification effect of ferroptosis inhibitor, MG-63 cells were treated with CoNPs and ferroptosis inhibitor for 24 h. The cell viabilities were measured by CCK-8 assay. The expressions of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) were examined by western blot. Reactive oxygen species (ROS) and the GSH level were measured by the relevant kits. The cell apoptosis was detected by flow cytometry. The serum levels of inflammatory cytokines were measured with Elisa.
Results The cytotoxic effects of CoNPs were time- and dose-dependent. In addition, CoNPs elicited a significant (p <0.05) reduction in cell viability and the glutathione (GSH) level with a concomitant increase in ROS generation and inflammatory cytokines such as tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) after 24 hours of exposure. Deferiprone (DFP) provided significant protection for cells after treatment with CoNPs. Western blot analysis demonstrated that CoNPs decreased the expression of GPX4 and SLC7A11, and treatment with DFP inhibited the decrease.
Conclusions CoNPs were highly cytotoxic and ferroptosis inhibitor DFP has a detoxification effect on cytotoxicity induced by CoNPs. Ferroptosis plays an important role in the process that CoNPs induced the cytotoxicity. The effectiveness of ferroptosis inhibition on MG-63 cells may initiate the development of novel strategies for reducing the adverse effects associated with metal implants in future.
Trial registration: no human participant.
total hip arthroplasty
cobalt nanoparticles
ferroptosis
ferroptosis inhibitor
Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are among the most effective orthopedic surgeries that can significantly restore joint function, relieve pain, and improve the patient's standard of living [1]. After total hip replacement, many different reasons lead to the production of metal particles, mainly due to mechanical wear and biological environmental erosion, such as erosion of the prosthesis by fluid and tissues around the hip joint. Cobalt-containing metal alloys release a large number of metal debris particles and metal ions[2]. Due to various of metal particles generated by wear, CoNPs may spread throughout the body, causing toxic effects around the implants. Horev-Azaria et al. believe that the toxicity of CoNPs is caused by the dissolution of Co2+ in the nanoparticles. However, previous researches have confirmed that the toxicity of nanoparticles themselves is greater than that of ionic forms [3, 4]. Many studies have shown that exposure to CoNPs can cause oxidative stress, lung inflammation and cell proliferation, which in turn leads to DNA damage and DNA mutations [5]. In vitro studies have indicated that CoNPs result in cellular oxidative stress [6] and genotoxicity [7]. Nanoparticles is known to enter human cells and induce the production of reactive oxygen species, thereby leading to cytotoxicity and genotoxicity [8]. In the cytoplasm, CoNPs can affect the mitochondrial redox reaction, generate a large number of ROS, and consume intracellular antioxidants such as GSH, in turn, induce redox stress and cause damage to the cell structure [9]. Excessive ROS production leads to the damage of mitochondria, lysosomes and nuclei, and ultimately activates the apoptosis pathway [10]. In addition, pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were found in the tissues surrounding the necrotic implants [11, 12]. Therefore, it is important to determine how to protect tissues from oxidative stress and inflammation.
The term ferroptosis was proposed by Dixon et al. in 2012 to describe the form of cell death induced by small molecules such as erastin [13]. Ferroptosis is dependent upon intracellular iron, accumulation of lipid ROS, and loss of activity of the lipid repair enzyme GPX4. Ferroptosis is a recently recognized form of regulated cell death, involving iron accumulation and lipid peroxidation, and its death phenotype is different from other types of cell death (such as apoptosis and necrosis) [14]. The depletion of GPX4, the down-regulation of SLC7A11 activity and the increase of lipid peroxidation products are common features of ferroptosis [15, 16]. At the same time, GPX4 is also an important regulator of ferroptosis [17]. The expression of SLC7A11 can potentially improve the survival rate of cells by regulating iron metabolism[18]. In addition, SLC7A11 is not only an essential component of the amino acid antiporter system Xc−, but also plays a crucial protective role in GSH synthesis. Since its recognition, ferroptosis has been involved in degenerative diseases such as the kidney and brain, and plays an important role in a variety of cancers [19]. The accumulation of reactive oxygen species plays a key role in causing ferroptosis [20], which is also the main trigger for the toxicity of CoNPs. In addition, ferroptosis inhibitors have been shown to have anti-inflammatory effects by inhibiting the expression of inflammatory cytokines including TNF-α[21], and the inflammatory response is also one of the toxic factors of CoNPs. Therefore, we speculate that ferroptosis inhibitors can reduce the toxicity of CoNPs based on inhibition of inflammation and ROS.
As far as we know, there is no previous study on ferroptosis inhibitors to antagonize the toxicity of cobalt nanoparticles. In this study, we explored the iron chelator DFP as an ferroptosis inhibitor to antagonize the toxicity of cobalt nanoparticles by depletion of ROS. This experiment aims to explore the possible protective effects of ferroptosis inhibitors on the toxicity of cobalt nanoparticles. Finally, we suggest that DFP, as an ferroptosis inhibitor, can be used as a therapeutic agent to prevent toxicity after MOM artificial joint replacement.
Reagent and chemicals
CoNPs (30nm,99.9%) were produced by Shanghai Chaowei Nano Technology Company. Dulbecco's Modified Eagle's medium (DMEM), 2', 7'-dichlorofluorescin diacetate (DCFH-DA),fetal bovine serum (FBS), trypsin-eDtA and penicillin/streptomycin were purchased from Gibco (Life Technologies, Paisley, UK).Tissue culture dishes were obtained from corning Inc. (New York, New York). Cell counting kit-8 (CCK-8), ROS detection kit, were purchased from Beyotime Company (Jiangsu, China). Mouse TNF-α, IL-1β, and IL-6 enzyme-linked immunosorbent assay (ELISA) kits were purchased from R&D Systems (Minneapolis, MN). Annexin V-FITC was purchased from Multi Sciences (Hanzhou, China). All antibodies were purchased from Abcam (Cambridge, UK).10% polyacrylamide gel premix (NCM FastPAGE) was purchased from New Cell&Molecular Biotech Co.,Ltd (Suzhou, China). Deferiprone was gotten from MCE (New Jersey, USA).
Preparation of Cobalt nanoparticles
CoNPs samples were sterilized at 180℃ for 4 h, suspended in ultrapure water to achieve the initial concentration of 40 mM. The Freshly prepared stock solution was ultrasonicated at room temperature at 40 W for 30 min in order to minimize particle aggregates and diluted to achieve the required concentrations (25µM, 50µM, 100µM, 200µM, 400µM, 800µM) with complete culture medium.
Preparation of DFP
DFP (1mM) was irradiated and sterilized under ultraviolet light for 2h, and then diluted to 25µM with basal medium for subsequent experiments. Store the processed DFP at -20°C.
Cell culture and sample treatment
The MG-63 cell line was bought from the cell repository of Chinese Academy of Sciences. Briefly, cells were cultured in DMEM supplemented with 10% FBS, penicillin and streptomycin. The medium was replaced every 3 days. All cells were grown at 37℃ in a humidified incubator containing 5% CO2. For the dose-related experiments, the cells were exposed to CoNPs for 4, 24 and 48 h. To examine the protective effects of DFP on the viability of cells, the cells were treated with varying concentrations of DFP and exposed to target concentration of CoNPs for 24 h.
According to the manufacturer's protocol, MG-63 cells were incubated in 96-well plates and then treated with different concentrations of DFP and 400 µM CoNPs for 4, 24 or 48 h. After that, 10 µL CCK-8 was added to each well and incubated at 37 ℃ for another 4 h. The absorbance was measured by the microplate reader at 450 nm. The Cell viability ratio was expressed as percent control. From this, the 50 % inhibitory concentration (IC50 value)[22] was calculated.
Detection of Cytokines
Cells were plated at a density of 1×105 cells/well in six-well plates and incubated for 24 h at 37℃. Then the cells were exposed to CoNPs (400µM) with or without the treatment of DFP (25µM) for 24 h. After treatment, cytokines levels of the supernatants collected from cell cultures were measured. The concentrations of TNF-α、IL-1β、IL-6 in the culture media were determined using ELISA kits according to the manufacturer's instructions. Each sample was analyzed in triplicate.
ROS measurement
Spectrofluorometry analysis and fluorescence microscopy imaging were used to assess ROS generation in cells exposed to target concentrations of CoNPs and the protective effects of DFP treatment. For the spectrofluorometry analysis, cells (1×105/well) were seeded in 96-well plates. MG-63 cells were exposed to CoNPs and ferroptosis inhibitor for 24 h. Following completion of the DCFH-DA reaction, the reaction mixture was washed thrice by 200 ml of PBS in each well. The fluorescence intensity of the suspension was measured on a multi-well microplate reader using excitation and emission of 485 nm and 525 nm, respectively. Values were expressed as the percentage of fluorescence intensity relative to the control wells.
GSH Measurement
The cells were treated with 25µM DFP and exposed to 400 µM CoNPs for 24 h. After the exposure, the cells were washed with PBS twice, scraped off, suspended in PBS, and centrifuged at 1000×g. The cell pellet was then homogenized in 5% 5-sulfosalicylic acid. Next, the suspension was lysed by freezing and thawing twice after 5 min centrifuged at 10,000×g for 10 min. The amount of GSH were measured according to the manufacturer's protocol.
Quantitative assessment of cell apoptosis detected by flow cytometry
For measurement of cell apoptosis, the AnnexinV-FITC assay kit was conducted according to manufacturer's protocol. Briefly, cells were washed with PBS solution and harvested. Next, the cells were suspended in binding buffer at 1×106 cells/ml. A 100 ml cell suspension was withdrawn supplemented with 5 ml AnnexinV-FITC and 10 ml of PI and subsequently incubated for 15 min at room temperature in the dark. A Becton Dickinson flow cytometer was employed for the measurement within 1 h of staining.
The cells were treated with 25µM DFP and exposed to target concentrations of CoNPs for 24 h. Cells were washed in cold PBS and lysed in RIPA with 1 mM phenylsulfonyl fluoride (PMSF, beyotime, Nantong, China). The supernatants were harvested and protein concentrations were measured with the bicinchoninic acid (BCA) assay kit. The concentrated samples were subjected to 15% SDS-polyacrylamide gel electrophoresis and transferred to a poly-vinylidene diflouride filter (PVDF) membrane by a transfer apparatus at 300 mA for 1 h. The membranes were blocked for 1 h and then incubated with primary antibodies at 4℃ overnight. After washing with TBST, the membranes were incubated with secondary antibodies for 2 h at room temperature. The PVDF membranes were washed four times with TBST according to the manufacturer's protocol.
All statistical analyses were performed using GraphPad Prism software 7 (GraphPad Software Inc., La Jolla, CA, USA) using one-way analysis of variance (ANOVA) followed by Dunnett's test to evaluate significance relative to control. Results shown summarise data from three independent experiments and were represented as the mean ± standard deviation (SD). Differences between groups were considered significant if p-values < 0.05.
Ferroptosis inhibitor protected against cytotoxicity induced by CoNPs in MG-63 cells
Cells were treated with different concentrations of CoNPs for 4h, 24h or 48h and the effect of CoNPs on MG-63 cell survival was determined by CCK-8 assay. The percentage of survived cells strikingly decreased with the increase of CoNPs concentration (Fig. 1a). The IC50 value was 400 µM 24 h later, respectively. Cells cultured in the medium with varying concentrations of DFP, which showed a dose-dependent survival rate. When the concentration of DFP increased, the viability of MG-63 cells increased. When cells were cultured in 400 µM CoNPs and different concentrations of DFP, the viability of cells was significantly higher compared with the cells treated with CoNPs (Fig. 1b).
Ferroptosis inhibitor reduced inflammatory cytokines in MG-63 cells
The results are shown in the Fig. 2. The levels of TNF-α, IL-1β and IL-6 in the CoNPs group were noticeably higher than those in the control group. Compared with the CoNPs group, DFP treatment had a significant protective effect, and significantly reduced TNF-α (p < 0.05), IL-1β (p < 0.05) and IL-6 (p < 0.05) induced by cobalt nanoparticles expression.
ROS formation in MG-63 cells
The oxidative damage induced by ROS is considered to be an important cause of the toxicity of cobalt nanoparticles. ROS is also the main incentive of ferroptosis. In this study, as shown in the Fig. 3, after 400 µM CoNPs were treated for 24 h, the ROS level of MG-63 cells increased significantly (p < 0.05), while DFP (25µM) could significantly inhibit this increase (p < 0.05), and the difference was statistically significant (p < 0.05).
GSH is the key cellular endogenous antioxidant that can scavenge toxic free radicals, and depletion of GSH appears to promote intracellular ROS accumulation, leading to apoptosis. Altered GSH levels represent increased cellular response to oxidative stress. The results suggested that CoNPs treatment decreased GSH levels (p < 0.05) and DFP inhibited this decrease (p < 0.05) as measured by the GSH assay kit (Fig. 3c).
Apoptosis assay in MG-63 cells
To investigate the apoptosis rate of cells treated with 400 µM CoNPs and 25 µM DFP, the AnnexinV-FITC assay kit was used. Incubation with 400 µM CoNPs for 24 h mildly increased the cell apoptosis rate compared with the control group. When DFP was added as a treatment before exposure to CoNPs, the apoptosis was slightly alleviated (Fig. 4a, b).
Ferroptosis inhibitor exerted the positive regulation on GPX4 in MG-63 cells
GPX4 is the central regulator of ferroptosis, and the decline of GPX4 is often used as a marker of ferroptosis[23–25]. SLC7A11 is a unit of the glutamate-cystine antiporter Xc−, resulting in enhanced lipid oxidation and ferroptosis. Western blot showed that CoNPs noticeably decreased the protein amount of GPX4 and SLC7A11. However, the decrease in GPX4 and SLC7A11 levels was inhibited when cells were treated with 25 µM DFP and 400 µM CoNPs for 24 h. These results suggest that CoNPs might induce ferroptosis and the ferroptosis inhibitor DFP exerts therapeutic action against CoNPs.
With the gradual popularity of artificial joint replacement, the materials of artificial joint prostheses have also attracted much attention. Due to the low dislocation and wear rate of MOM implants, their use in prostheses has gradually become widespread. It is crucial to elucidate the adverse biological consequences of metal nanoparticles released from implants, and provide a potential method for reducing the adverse effects associated with these metal particles. The main adverse effects come from cobalt nanoparticles produced under long-term wear and tear. So far, the mechanism of CoNPs-induced toxicity has not been fully understood, and the current mainstream is still the ROS theory and the inflammation caused by ROS[26, 27]. The excessive accumulation of ROS and the production of a large number of inflammatory cytokines such as TNF-α play an important role in the toxicity mechanism induced by cobalt nanoparticles, leading to inflammation, cell damage and proliferation, which in turn leads to DNA damage and DNA mutations, as well as damage to mitochondria, lysosomes and the nucleus, eventually leading to cell death. Past studies have found that although the apoptosis rate of treatment is significantly higher than that of the control group, it is still much lower than the cell death rate[28]. Therefore, it could be possible that there are still other types of cell death besides apoptosis in MG-63 cells exposed to CoNPs. Ferroptosis is a newly identified form of cell death that is characterized by the accumulation of intracellular iron and the need for lipid peroxidation[14]. In this process, a variety of inducers disrupt the cell redox balance and produce a large amount of lipid peroxidation products, which ultimately trigger cell death. Generally speaking, ferroptosis is a form of ROS-dependent regulatory necrosis that occurs through multiple signals and pathways[29]. In this study, we focused on the role of ferroptosis in toxicity induced by cobalt nanoparticles and evaluate the protective effects of ferroptosis inhibitors on MG-63 cells.
In current study, the CCK8 was used to assess the viability of MG-63 cells exposed to CoNPs. The results showed that the cytotoxic effect of CoNPs on MG-63 cells was time- and dose-dependent. On this basis, the IC50 value was calculated, and 400µM CoNPs was used as a positive control for subsequent experiments. In addition, 25µM DFP was selected to evaluate its effect on CoNPs-induced cell damage. Our results suggest that DFP treatment can reduce the decline in cell viability induced by CoNPs. The cell viability of the experimental group treated with the ferroptosis inhibitor was much higher than that of the control group, which indicated that the ferroptosis inhibitor had a certain protective effect on MG-63 cells.
Studies have shown that cobalt-chromium wear particles can induce the release of a variety of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6[30–32]. In this study, we confirmed the pro-inflammatory effect of CoNPs through the increase of TNF-α, IL-1β and IL-6, and determined whether ferroptosis inhibitors can reduce the increase in the levels of inflammatory cytokines induced by CoNPs. The treatment of ferroptosis inhibitor significantly reduced the inflammatory cytokines induced by CoNPs after 24 hours of exposure, and the difference was statistically significant compared with the control group (P < 0.05). DFP treatment can significantly reduce the expression of TNF-α, IL-1β and IL-6 in MG-63 cells induced by 400µM CoNPs, suggesting that ferroptosis inhibitors have a protective effect on inflammatory cytokines in MG-63 cells induced by 400µM CoNPs.
CoNPs induced a noticeable increase in ROS. ROS is considered to be the main cause of ferroptosis, which can cause DNA damage, oxidative stress and activate other cellular processes. On the one hand, ROS acts as a dynamic balance signal molecule that regulates cell growth, and on the other hand, it acts as an adaptive response at physiological concentrations. However, the production of ROS at higher concentrations can cause cell damage and death. GSH is an important antioxidant substance that plays an important role in protecting against apoptosis. The depletion of GSH promotes the accumulation of ROS in cells and cell apoptosis. In current study, compared with CoNPs group, the addition of ferroptosis inhibitors significantly reduced the production of ROS in MG-63 cells(Fig. 3a, b). In addition, our results shows that CoNPs treatment decreased GSH levels and DFP reversed this decrease (p < 0.05) as measured by the GSH assay kit (Figure.3c).
Flow cytometry results exhibited that CoNPs induced mild cellular apoptosis, which could be further alleviated by the exposure of DFP. Although the apoptosis rate of MG-63 cells for the CoNPs treatment group was significantly increased as compared to the control group (Fig. 4), it was still much lower than that of control group, as shown by CCK-8 under the same conditions (Fig. 1). These results indicate that non-apoptotic mechanisms are involved in CoNPs-mediated cell death.
GPX4 and SLC7A11 are recognized as important endogenous regulators of ferroptosis and the decline of GPX4 and SLC7A11 is always regarded as a marker of ferroptosis[33, 34]. A previous study has indicated that SLC7A11 protects cells from ferroptosis by increasing GSH production. In this study, we found that after exposure to CoNPs, the protein levels of GPX4 and SLC7A11 were significantly decreased, while DFP up-regulated the levels of GPX4 and SLC7A11, reducing the damage of ROS. Our results strongly support the idea that ferroptosis inhibitors can upregulate the expression of GPX4 and SLC7A11 to inhibit the cytotoxicity caused by CoNPs.
In summary, all these results strongly supported the idea that the ferroptosis inhibitor counteracts cytotoxicity and inflammation induced by CoNPs and ferroptosis plays an important role in the occurrence of CoNPs-induced toxicity. In addition, we are supposed to compare the results of different ferroptosis inhibitors on cell detoxification, and further screen out the most suitable drugs to relieve the CoNPs-induced toxicity produced in MOM artificial joints. The research provides a new perspective for antagonizing CoNPs-induced cytotoxicity, and provides a potential method to reduce adverse reactions related to MOM joint implants.
CoNPs: cobalt nanoparticles; MOM: metal-on-metal; GPX4: glutathione peroxidase 4; SLC7A11: solute carrier family 7 member 11; ROS: Reactive oxygen species; GSH: glutathione; TNF-α: tumour necrosis factor α; IL-1β: interleukin-1β; IL-6: interleukin-6; DFP: Deferiprone; TKA: Total knee arthroplasty; THA: total hip arthroplasty; DCFH-DA: 2', 7'-dichlorofluorescin diacetate; DMEM: Dulbecco's Modified Eagle's medium;FBS: fetal bovine serum; CCK-8: Cell counting kit-8; PMSF: phenylsulfonyl fluoride; PVDF: poly-vinylidene diflouride filter;SD: standard deviation
Competing interests: The authors declare that they have no conflicting interests.
Funding: This work was supported by Postgraduate Research & Practice Innovation Program of Jiangsu Province [grant number SJCX20_1167].
Author details: 1Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China 226001
Authors' contributions: CW and WZ researched literature and conceived the study. YL was involved in protocol development and data analysis. CW wrote the first draft of the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript
Acknowledgements: Not applicable
Availability of data and materials: The datasets used and/or analyzed during the current study are not publicly available. Data are however available from the corresponding author on reasonable request.
1. O, E., et al., Health-related quality of life in total hip and total knee arthroplasty. A qualitative and systematic review of the literature. 2004. 86(5): p. 963-74.
2. Jacobs, J., et al., Metal degradation products: a cause for concern in metal-metal bearings? 2003(417): p. 139-47.
3. Sabbioni, E., et al., Cytotoxicity and morphological transforming potential of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse fibroblasts: an in vitro model. Nanotoxicology, 2014. 8(4): p. 455-464.
4. Papageorgiou, I., et al., The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. Biomaterials, 2007. 28(19): p. 2946-2958.
5. Wan, R., et al., Cobalt nanoparticles induce lung injury, DNA damage and mutations in mice. Part Fibre Toxicol, 2017. 14(1): p. 38.
6. C, M., et al., The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area. 2007. 64(9): p. 609-15.
7. R, C., et al., Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro. 2008. 23(5): p. 377-82.
8. S, R., et al., Comparative cytotoxicity and genotoxicity of cobalt (II, III) oxide, iron (III) oxide, silicon dioxide, and aluminum oxide nanoparticles on human lymphocytes in vitro. 2016. 35(2): p. 170-83.
9. Horev-Azaria, L., et al., Predictive toxicology of cobalt nanoparticles and ions: comparative in vitro study of different cellular models using methods of knowledge discovery from data. Toxicological sciences : an official journal of the Society of Toxicology, 2011. 122(2): p. 489-501.
10. M, O., et al., Mitochondria, oxidative stress and cell death. 2007. 12(5): p. 913-22.
11. Masui, T., et al., Expression of inflammatory cytokines, RANKL and OPG induced by titanium, cobalt-chromium and polyethylene particles. Biomaterials, 2005. 26(14): p. 1695-1702.
12. Goodman, S.B., et al., Cellular profile and cytokine production at prosthetic interfaces. Study of tissues retrieved from revised hip and knee replacements. The Journal of bone and joint surgery. British volume, 1998. 80(3): p. 531-539.
13. Dixon, S.J., et al., Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012. 149(5): p. 1060-72.
14. Dixon, S.J., et al., Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 2012. 149(5): p. 1060-1072.
15. Han, C., et al., Ferroptosis and Its Potential Role in Human Diseases. Front Pharmacol, 2020. 11: p. 239.
16. Xie, Y., et al., Ferroptosis: process and function. 2016. 23(3): p. 369-79.
17. Yang, W.S., et al., Regulation of ferroptotic cancer cell death by GPX4. Cell, 2014. 156(1-2): p. 317-331.
18. Jiang, L., et al., Ferroptosis as a p53-mediated activity during tumour suppression. 2015. 520(7545): p. 57-62.
19. Zou, Y. and S.L. Schreiber, Progress in Understanding Ferroptosis and Challenges in Its Targeting for Therapeutic Benefit. Cell Chem Biol, 2020. 27(4): p. 463-471.
20. Imai, H., et al., Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis. Current topics in microbiology and immunology, 2017. 403: p. 143-170.
21. Zhang, Y., et al., Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury. Brain research, 2019. 1706: p. 48-57.
22. Jiang, H., et al., Effects of cobalt nanoparticles on human T cells in vitro. Biol Trace Elem Res, 2012. 146(1): p. 23-9.
23. Dixon, S., et al., Ferroptosis: an iron-dependent form of nonapoptotic cell death. 2012. 149(5): p. 1060-72.
24. Yang, W., et al., Regulation of ferroptotic cancer cell death by GPX4. 2014. 156: p. 317-331.
25. Friedmann Angeli, J., et al., Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. 2014. 16(12): p. 1180-91.
26. Sabbioni, E., et al., Cytotoxicity and morphological transforming potential of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse fibroblasts: an in vitro model. 2014. 8(4): p. 455-64.
27. Yan, X., et al., alpha-Tocopherol protected against cobalt nanoparticles and cocl2 induced cytotoxicity and inflammation in Balb/3T3 cells. Immunopharmacol Immunotoxicol, 2018. 40(2): p. 179-185.
28. Liu, Y., et al., Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death. J Nanobiotechnology, 2020. 18(1): p. 141.
29. Lu, L.-Q., et al., Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury. Cellular and molecular life sciences : CMLS, 2021. 78(1): p. 63-78.
30. Thomas, V., et al., In vitro studies on the effect of particle size on macrophage responses to nanodiamond wear debris. 2012. 8(5): p. 1939-47.
31. Hallab, N.J.S., Biologic Responses to Orthopedic Implants: Innate and Adaptive Immune Responses to Implant Debris. 2016: p. S30-1.
32. Kaufman, A., et al., Human macrophage response to UHMWPE, TiAlV, CoCr, and alumina particles: analysis of multiple cytokines using protein arrays. 2008. 84(2): p. 464-74.
33. Imai, H., et al., Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis. 2017. 403: p. 143-170.
34. Chen, D., et al., ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner. 2017. 36(40): p. 5593-5608.


The Jardin Anglais is a beautiful public garden behind the Basilica St Saveur.
At the end of the garden is a part of the medieval town walls with a breathtaking view over the viaduct and the old port of Dinan. The house looks out on the garden and the Basilica (which is lit up at night).
There are two double bedrooms, both with en-suite and the house has every mod-con including satellite TV, DVD and stereo with iPod dock.


text:
package org.wildfly.extras.creaper.commands.web;

import org.wildfly.extras.creaper.commands.foundation.offline.xml.GroovyXmlTransform;
import org.wildfly.extras.creaper.commands.foundation.offline.xml.Subtree;
import org.wildfly.extras.creaper.core.CommandFailedException;
import org.wildfly.extras.creaper.core.offline.OfflineCommand;
import org.wildfly.extras.creaper.core.offline.OfflineCommandContext;
import org.wildfly.extras.creaper.core.online.OnlineCommand;
import org.wildfly.extras.creaper.core.online.OnlineCommandContext;
import org.wildfly.extras.creaper.core.online.operations.Address;
import org.wildfly.extras.creaper.core.online.operations.OperationException;
import org.wildfly.extras.creaper.core.online.operations.Operations;
import org.wildfly.extras.creaper.core.online.operations.Values;

import java.io.IOException;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.List;

/**
 * Command which creates connector with specified parameters
 */
public final class AddConnector implements OnlineCommand, OfflineCommand {
    private final String connectorName;

    private final Boolean enableLookups;
    private final Boolean enabled;
    private final String executor;
    private final Integer maxConnections;
    private final Integer maxPostSize;
    private final Integer maxSavePostSize;
    private final String protocol;
    private final String proxyBinding;
    private final String proxyName;
    private final Integer proxyPort;
    private final String redirectBinding;
    private final Integer redirectPort;
    private final Boolean secure;
    private final String scheme;
    private final String socketBinding;
    private final List<String> virtualServers;
    private final boolean replaceExisting;

    private AddConnector(Builder builder) {
        this.connectorName = builder.connectorName;
        this.enableLookups = builder.enableLookups;
        this.enabled = builder.enabled;
        this.executor = builder.executor;
        this.maxConnections = builder.maxConnections;
        this.maxPostSize = builder.maxPostSize;
        this.maxSavePostSize = builder.maxSavePostSize;
        this.protocol = builder.protocol;
        this.proxyBinding = builder.proxyBinding;
        this.proxyName = builder.proxyName;
        this.proxyPort = builder.proxyPort;
        this.redirectBinding = builder.redirectBinding;
        this.redirectPort = builder.redirectPort;
        this.secure = builder.secure;
        this.scheme = builder.scheme;
        this.socketBinding = builder.socketBinding;
        this.virtualServers = builder.virtualServers;
        this.replaceExisting = builder.replaceExisting;
    }

    @Override
    public void apply(OnlineCommandContext ctx) throws IOException {
        Operations ops = new Operations(ctx.client);
        Address connectorAddress = Address.subsystem("web").and("connector", connectorName);
        if (replaceExisting) {
            try {
                ops.removeIfExists(connectorAddress);
            } catch (OperationException e) {
                throw new IOException("Failed to remove existing datasource " + connectorName, e);
            }
        }
        ops.add(connectorAddress, Values.empty()
                .andOptional("name", connectorName)
                .andOptional("enable-lookups", enableLookups)
                .andOptional("enabled", enabled)
                .andOptional("executor", executor)
                .andOptional("max-connections", maxConnections)
                .andOptional("max-post-size", maxPostSize)
                .andOptional("max-save-post-size", maxSavePostSize)
                .andOptional("protocol", protocol)
                .andOptional("proxy-binding", proxyBinding)
                .andOptional("proxy-name", proxyName)
                .andOptional("proxy-port", proxyPort)
                .andOptional("redirect-binding", redirectBinding)
                .andOptional("redirect-port", redirectPort)
                .andOptional("secure", secure)
                .andOptional("scheme", scheme)
                .andOptional("socket-binding", socketBinding)
                .andListOptional(String.class, "virtual-server", virtualServers));
    }

    @Override
    public void apply(OfflineCommandContext ctx) throws CommandFailedException, IOException {
        GroovyXmlTransform connector = GroovyXmlTransform
                .of(AddConnector.class)
                .subtree("web", Subtree.subsystem("web"))
                .parameter("connectorName", connectorName)
                .parameter("enableLookups", enableLookups)
                .parameter("enabled", enabled)
                .parameter("executor", executor)
                .parameter("maxConnections", maxConnections)
                .parameter("maxPostSize", maxPostSize)
                .parameter("maxSavePostSize", maxSavePostSize)
                .parameter("protocol", protocol)
                .parameter("proxyBinding", proxyBinding)
                .parameter("proxyName", proxyName)
                .parameter("proxyPort", proxyPort)
                .parameter("redirectBinding", redirectBinding)
                .parameter("redirectPort", redirectPort)
                .parameter("secure", secure)
                .parameter("scheme", scheme)
                .parameter("socketBinding", socketBinding)
                .parameter("virtualServers", virtualServers)
                .parameter("replaceExisting", replaceExisting)
                .build();
        ctx.client.apply(connector);
    }

    @Override
    public String toString() {
        return "AddConnector " + connectorName;
    }

    /**
     * Some details about the attributes can be found at http://wildscribe.github.io/JBoss%20EAP/6.2.0/subsystem/web/connector/index.html
     */
    public static final class Builder {
        private final String connectorName;

        private Boolean enableLookups;
        private Boolean enabled;
        private String executor;
        private Integer maxConnections;
        private Integer maxPostSize;
        private Integer maxSavePostSize;
        private String protocol;
        private String proxyBinding;
        private String proxyName;
        private Integer proxyPort;
        private String redirectBinding;
        private Integer redirectPort;
        private Boolean secure;
        private String scheme;
        private String socketBinding;
        private List<String> virtualServers;
        private boolean replaceExisting = false;

        public Builder(String connectorName) {
            if (connectorName == null) {
                throw new IllegalArgumentException("Name of the connector must be specified as non null value");
            }
            this.connectorName = connectorName;
        }

        /**
         * Specify whether to replace the existing connector based on its name.
         * By default existing connector is not replaced and exception is thrown.
         */
        public Builder replaceExisting() {
            this.replaceExisting = true;
            return this;
        }

        /**
         * Enable/disable DNS lookups for Servlet API.
         */
        public Builder enableLookups(Boolean enableLookups) {
            this.enableLookups = enableLookups;
            return this;
        }

        /**
         * Defines whether the connector should be started on startup.
         */
        public Builder enabled(Boolean enable) {
            this.enabled = enable;
            return this;
        }

        /**
         * Sets the name of the executor that should be used for the processing threads of this connector. If undefined,
         * it defaults to using an internal pool.
         */
        public Builder executor(String executor) {
            this.executor = executor;
            return this;
        }

        /**
         * Sets amount of concurrent connections that can be processed by the connector with optimum performance.
         * The default value depends on the connector used.
         */
        public Builder maxConnections(Integer maxConnections) {
            this.maxConnections = maxConnections;
            return this;
        }

        /**
         * Sets maximum size in bytes of a POST request that can be parsed by the container.
         */
        public Builder maxPostSize(Integer maxPostSize) {
            this.maxPostSize = maxPostSize;
            return this;
        }

        /**
         * Sets maximum size in bytes of a POST request that will be saved during certain authentication schemes.
         */
        public Builder maxSavePostSize(Integer maxSavePostSize) {
            this.maxSavePostSize = maxSavePostSize;
            return this;
        }

        /**
         * Sets the web connector protocol.
         */
        public Builder protocol(String protocol) {
            this.protocol = protocol;
            return this;
        }

        /**
         * Sets the socket binding to define the host and port that will be used when sending a redirect.
         */
        public Builder proxyBinding(String proxyBinding) {
            this.proxyBinding = proxyBinding;
            return this;
        }

        /**
         * Sets the host name that will be used when sending a redirect.
         */
        public Builder proxyName(String proxyName) {
            this.proxyName = proxyName;
            return this;
        }

        /**
         * Sets the port that will be used when sending a redirect.
         */
        public Builder proxyPort(Integer proxyPort) {
            this.proxyPort = proxyPort;
            return this;
        }

        /**
         * Sets the socket binding to define the port for redirection to a secure connector.
         */
        public Builder redirectBinding(String redirectBinding) {
            this.redirectBinding = redirectBinding;
            return this;
        }

        /**
         * Sets the port for redirection to a secure connector.
         */
        public Builder redirectPort(Integer redirectPort) {
            this.redirectPort = redirectPort;
            return this;
        }

        /**
         * Defines whether content sent or received by the connector is secured from the user perspective.
         */
        public Builder secure(Boolean secure) {
            this.secure = secure;
            return this;
        }

        /**
         * Sets the web connector scheme.
         */
        public Builder scheme(String scheme) {
            this.scheme = scheme;
            return this;
        }

        /**
         * Sets the web connector socket-binding reference, this connector should be bound to.
         */
        public Builder socketBinding(String socketBinding) {
            this.socketBinding = socketBinding;
            return this;
        }

        /**
         * Adds virtual servers to list of virtual servers that can be accessed through this connector. If none are
         * defined, the default is to allow all virtual servers.
         */
        public Builder virtualServer(String... virtualServers) {
            if (this.virtualServers == null && virtualServers != null) {
                this.virtualServers = new ArrayList<String>();
            }
            if (virtualServers != null) {
                this.virtualServers.addAll(Arrays.asList(virtualServers));
            }
            return this;
        }

        public AddConnector build() {
            return new AddConnector(this);
        }
    }
}

redpajama_set_name: RedPajamaGithub