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Patriots Vs. Eagles Final Score: New England Falls To Philadelphia, 27-17
By Gethin Coolbaugh Aug 20, 2012, 11:31pm EDT
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Tom Brady's absence certainly didn't help the New England Patriots in their 27-17 loss to the Philadelphia Eagles in a Week 2 preseason battle on Monday night at Gillette Stadium in Foxboro, MA. Nevertheless, the Pats were in the mix and were almost able to overcome.
Then again, it's only a meaningless preseason game, so it really doesn't matter, right?
Brady was held out of the Patriots second preseason game, likely due to the fact that New England has two games on the schedule this week. Following Monday's game, the Pats are scheduled to take on the Tampa Bay Buccaneers on Friday night in Tampa, Florida.
Ryan Mallett started for Brady and completed 10-of-20 passes for 105 yards and one score. Brian Hoyer also saw time under center, throwing for 55 yards on 5-of-17 passing.
New England put the first points on the board when Stephen Gostkowski kicked a 51-yard field goal with 6:15 left in the first quarter. Mallett then found Alex Silvestro for a seven-yard touchdown with 13:48 to go before halftime, and the Pats went for two and succeeded.
Philadelphia scored back-to-back touchdowns -- a one-yard run from Lesean McCoy at 10:11 and a one-yard pass from quarterback Nick Foles (18-for-28, 217 yards, two touchdowns, one interception) to Clay Harbor at 9:11 -- to go ahead 14-11. A 35-yard field goal from Gostkowski with 3:13 to go tied the game at 14-14 heading into halftime.
Harbor caught his second and final touchdown pass -- a three-yard strike from Foles -- at the 11:06 mark of the third quarter, putting the Eagles on top for good. Gostkowski hit a preseason-best 55-yard field goal at 4:17 in the third to bring the Pats a little closer, but that was cancelled out by a 42-yard field goal from Alex Henery of the Eagles with 38 ticks left.
Henery kicked a 21-yard field goal with 2:03 left in the fourth to put the nail in the coffin.
Deion Branch had three catches for 51 yards to lead the Pats' receiver. Stevan Ridley rushed for 25 yards on 10 carries and Shane Vereen had 20 rushing yards on 10 carries. Will Allen, Niko Koutouvides and Sterling Moore each had five tackles for the Pats.
Michael Vick started the game under center for Philly, but left in the first quarter after being hit hard by Jermaine Cunningham. Vick had an X-Ray on his ribs in the locker room, which was negative. He finished with five yards on 1-of-3 passing. DeSean Jackson had four catches for 82 yards and Bryce Brown rushed for 51 yards on nine rushes for the Eagles.
New England and Tampa Bay will kick off in Tampa at 7:30 p.m. ET on Friday evening.
Patriots Vs. Eagles Score Update: New England Down, 24-17, After Three


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Aussonce ist eine französische Gemeinde mit  Einwohnern (Stand: ) im Département Ardennes in der Region Grand Est (bis 2015 Champagne-Ardenne). Sie gehört zum Arrondissement Rethel, zum Kanton Château-Porcien sowie zum Gemeindeverband Pays Rethélois. Die Einwohner werden Alsontains genannt.

Geographie
Die Gemeinde Aussonce liegt in der Trockenen Champagne, etwa 25 Kilometer nordöstlich von Reims. Umgeben wird Aussonce von den Nachbargemeinden Ménil-Lépinois im Norden, Juniville im Nordosten, La Neuville-en-Tourne-à-Fuy im Osten, Bétheniville im Südosten, Pontfaverger-Moronvilliers im Süden, Heutrégiville im Südwesten sowie Warmeriville im Westen.

Bevölkerungsentwicklung

Sehenswürdigkeiten
 Kirche Saint-Sindulphe
 Kommanderie von Merlan
 deutscher Militärfriedhof

Weblinks

Ort in Grand Est
Träger des Croix de guerre 1914–1918 (Ort in Frankreich)

redpajama_set_name: RedPajamaWikipedia


This week, my mom Joanie passed a milestone birthday–85 years on the planet. Jumpin' Jive, Joanie's 85! With the exception of some minor aches and pains, she is blessed with good health and a sharp mind. She and my dad (a robust 88!) live on their own, and go about their day-to-day with enthusiasm and gratitude.
Five years ago, she celebrated her 80th with a big hullabaloo. This anniversary, however, she decided to observe on the down-low.
From me, she requested an afternoon of my cooking and company, with time reserved to solve the Sunday NYTimes crossword. Preparing a special meal, dining together, and then escaping with our erasable ink pens into the world of cleverly constructed words: That's a gift I am happy to provide.
For our lunch, I made three dishes–puree of cauliflower soup, grilled strip steak smothered in sherried mushrooms, and chocolate pudding parfaits. All three were delicious, but it's the soup I want to tell you about today.
It is lush and creamy, without a speck of cream. No roux or other thickening agents either. A couple of potatoes, an onion, a parsnip or heirloom yellow carrot work together with the cauliflower to give the soup its silken body.
Simply put, it is vegetables and broth, simmered and pureed.
And, with a modicum of embellishments, it elevates to a soup for celebrations.
I reserve a handful of cauliflower curds, which I oven roast to crispness and drop into the soup, like croutons. Then I sprinkle in crumbles of gorgonzola–or any blue, which slightly melt into the soup where they fall, supplying little knobs of pungency in select spoonfuls.
Joanie and I loved the soup. I was happy, because it was beautiful to serve, delectable to eat and easy to make. The fact that it is gluten free, vegetarian, (and if you omit the gorgonzola, vegan and dairy-free) makes it one that I'll keep in my repertoire, knowing that I can serve any guest with any dietary preference with confidence.
Place a large pot over medium heat. Add the olive oil.
Add onions, carrot or parsnip, and potatoes. Saute for five minutes, stirring occasionally.
Add the chopped cauliflower and continue sauteeing for another five minutes.
Pour in the broth. Stir well. Cover and simmer until the vegetables are tender–12 minutes.
Blend until smooth—I use an immersion blender to puree the soup, but you may use a food processor or regular blender if that's what you have.
Garnish with roasted cauliflower "croutons," crumbled gorgonzola, green onion, and chili oil, if desired.
For more tips on roasting cauliflower, with corresponding recipes, visit Cooking Light's healthy makeovers here.
Toss the cauliflower in a tablespoon of olive oil.
Spread over a baking sheet and place into the oven.
Roast until golden brown and slightly crispy, about 15 minutes.
My friend Heather had overbought produce for an event, and found her fridge bursting with 12 bunches of assorted winter greens–curly kale, lacinato kale, and great fronds of Swiss chard. She called me, wondering, what could she do? They were becoming limp, and it would be a shame for them to be fodder for the compost.
Later that day, she arrived at my door, arms laden with grocery bags, a jumble of green leaves, bright and dark, veined and rumpled, some sturdy and sweeping, some starting to look a bit weary.
Great greens, girl. Gotta get to work.
Before I could figure out their destiny, I had to assess their condition. I trimmed their stems, and plunged them in tubs of fresh water to rehydrate. Within an hour, most of the greens had perked up. The chard plumped and straightened, out of the tub. The rumpled kale regained its bounce.
The thing with greens—any sort really—is that what starts out as monumental quickly cooks down to manageable. Nonetheless, I had enough chard to make a great pot of stewy-soup, and plenty of lacinato kale to make this beguiling recipe I'd just discovered on Food 52.
Both are simple wintertime recipes, hearty and delicious. Most of work is in prepping the greens–cleaning, deribbing, tearing, chopping.
You begin this soup the way you do most soups: You build a foundation. Saute hunks of portabello mushrooms with diced onions and carrots to get a meaty base before adding vegetable broth and tomato paste. The mushrooms and tomato are the powerhouse duo, making the sienna-colored broth in which the chard simmers a veritable umami-bomb of flavor.
And this kale gratin? Ridiculously easy. Only 6 ingredients, 3 of them being salt, pepper, and nutmeg. Everything gets tossed into a baking dish and then placed into the oven. That's it!
The original recipe calls for 3 cups of Cream. I know. So rich, so luxurious, so over-the-top—but I couldn't bring myself to go there. And, I already had a quart of half-and-half in the fridge. I dialed it back a bit–and substituted the half and half for cream. Instead of placing slabs of sharp cheddar over the top of the casserole, I shredded the cheese–4 ounces each of New York yellow and Vermont white—to generously sprinkle over the mass, the pieces nestling in and around the greens.
Don't worry about the tower of kale in your baking dish–it cooks down in that hot oven. Some of the leaves get dry and crispy on the top—and boy, is that ever a boon. (Kale chips!) The cheese, as it bubbles and melts, forms a savory caramel crust too. Scoop through that layer of crunch into this compelling press of green, cooked to tenderness, the kale absorbing the nutmeg-scented dairy in the process–a perfect balance of bitter and sweet.
I cannot overstate the absolute wonder and earthy delectability of this dish. If it's this marvelous with half-and-half, the cream version must be Heaven. I just want to be a little mindful of my heart, and not get there too soon.
Place a 6 quart pot over medium heat. When warm, add the olive oil. Then add the onions, sauteing them until translucent, about 3 minutes. Add the carrots and continue to stir and saute for another three minutes. Increase the heat to medium high, and add the mushrooms.
Season with salt, black pepper, and thyme. Stir. The mushrooms may stick to the bottom, but don't worry–that will add to the flavor of the base.
Pour in the vegetable stock. Add the tomato paste and a cup of water. Stir well.
Add the Swiss chard, folding into the broth. It will collapse as it cooks. Cover and reduce the heat to low. Simmer for 20 minutes. Taste for seasonings.
Preheat oven to 350 convection or 375 conventional.
Remove the kale ribs and tear the leaves into pieces. Place into a large bowl. Sprinkle the leaves with salt, black pepper and nutmeg and toss. Heap the seasoned kale into a 9 inch by 13 inch baking dish. Pour the half-and-half over the kale, taking care that it doesn't spill over the sides. Top with shredded cheddar, tucking some of the shreds underneath some leaves.
As a first time author of a cookbook, having just passed a milestone birthday, I have found myself in a reflective mood. I've been thinking about my culinary evolution, how I got here today, how I've grown up and grown in the world of food. It had a shaky beginning: a girl, born in New York, who didn't care for most foods at all.
Moving to The South made a big impact. It took time, but I came to embrace its culinary ways. There's a real focus on vegetables that we never experienced up North.
The climate supports a greater variety, that alone surprised me. I had never seen or tasted okra, crookneck squash, pole beans, yellow wax beans, collards, turnip and mustard greens, October beans, or purple hull peas.
Have you heard of purple hull peas? These are tender pulses belonging to the family of Cowpeas, Vigna unguiculata, whose relatives include black-eyed peas, crowders, lady peas, and field peas. High in protein (24%) and easy to grow: they actually thrive in poor soil, and hot, dry conditions.
Their history in the South has dark roots in slave trade. Their seeds were brought on ships, along with enslaved West Africans to the Caribbean and eastern Atlantic seaboard. Rejected by the Europeans as poor man's fodder, fit only for cattle, they acquired the name "cowpeas." Little did the Landed Gentry realize all the good they were rejecting.
As a picky child, I did enjoy corn on the cob–what self-respecting kid doesn't? Once you got through the task of shucking (and avoiding any green worms!) the prospect of eating it was as fast as a plunge in the kettle of boiling, lightly salted water.
There's nothing as blissful as sitting on a back porch stoop, chomping on an ear in the summer, hands and face sloppy with kernels, spurted "corn milk" and butter .
But until I came to Nashville, I had never eaten fresh fried corn–cut from the cob, scraped and skillet-simmered in butter and water. More a technique than a recipe–this is not "creamed corn." No cream, milk, or flour.
I learned about the pure pleasure of this dish at my first restaurant job in the late '70's at a Southern style "Meat-and-Three" called "Second Generation" run by Anna Marie Arnold. Anna grew up cooking with her mother, first generation founder of The White Cottage, a tiny yet legendary eatery that vanished–closed and bulldozed in the '90's, when a city bridge had to be widened.
Silver Queen was the favored corn of the day–a small kerneled white corn that had candied sweetness.
Stir—stir—stir. It can be a meditative process. You might find yourself reflecting on your own life in food!
As the rice becomes plump and savory, releasing its starch into the broth, a seductive creaminess results. Fold in the corn and its scrapings, and finally the purple hull peas, along with the "pot likker" in which they were cooked.
Garnish with fresh thyme, if you like, or a few curls of pecorino romano.
But it is not necessary–the risotto is rich with flavor, and wonderful texture. Enjoy it with spoon, to capture every luscious bite.
Cut the corn from the cobs, scraping the cobs for extra "corn milk," into a bowl and set aside.
Shell the purple hull peas, rinse, drain, and place into a bowl. Set aside.
Place olive oil into a 2 quart sized saucepan on medium heat. Add 2 cloves slivered garlic and 1/2 onion, diced, into the saucepan to saute for 2 minutes. Add chili pepper, purple hull peas and enough water to cover the peas by 2 inches. Season with a little salt and black pepper. Increase the heat to bring it to a boil. Simmer for 15 minutes, until peas are tender, yet still firm. Let the peas cool.
Place tomato-vegetable broth into a saucepan and warm.
In a large heavy duty pot, (such as an enameled cast iron Le Creuset) melt the butter over medium heat. Add remaining diced onion and minced garlic. Saute for a minute, then add the rice. Stir until the grains are well coated.
Begin adding the broth, a cupful at a time, stirring the rice, watching it plump up from the savory liquid, monitoring its creaminess from the released starch.
At the 20 minute mark, fold in the corn. Stir stir stir.
At the 25 minute mark, fold in the cooked purple hull peas. Stir Stir Stir.
On fleet and chilly foot, this year is surely making its exit. I trust that your holidays have been full of joy and camaraderie, and good food shared with those you love. Ours have been exceptional, heralded by the birth of my first grandchild, Zachary James. He was due to arrive on the first of December, but he chose—wisely, no doubt– to wait until the 12th to make his wondrous entrance. For parents who married on 10-10-10, his 12-12-12 birthdate is all the more auspicious.
I was privileged to be a part of the birth team, and witness his entry. I was thrilled to be one of the first to caress his pink cheeks and welcome him into this strange new world.
A week after his arrival, I returned to my own home after a month-long absence to put Christmas together. A hectic pace, but the tree got trimmed, presents got wrapped, the beef got roasted, and the chocolate mousse trifle got mounded high in the bowl.
But what I'd like to share with you today veers away from the indulgences of the season.
It is a healthy, hearty dish using Escarole.
This great green bouquet resembles lettuce in appearance, but belongs to the Endive family. (The sprawling head made me think of the old wives tale imparted to children about where babies come from…) Also known as broadleaf endive, Bavarian endive, or scarola, it is one of its less bitter members. Escarole can be eaten raw in salads, but it is really luscious when braised into soups or stews.
I've never prepared these greens in any form before now. But the forces aligned. Friend and farmer Tally May of Fresh Harvest Coop had grown splendid rows of escarole, market ready on my return. A vivid description of this recipe from my cousin Cathy and her husband John (given as they drove me to the airport!) left no doubt that a pot of escarole with fusilli and cannellinis would be simmering on my stovetop soon.
It is a traditional Italian dish, which, depending on the amount of liquid that you choose to add, becomes either a stewy pasta or a robust soup. Either way, you'll want to serve it in a bowl, with a spoon and hunk of bread to sop up all the sumptuous broth.
It's a garlic-friendly dish, too. Don't be timid with those cloves!
Highly seasoned cannellini beans are also key. I used Rancho Gordos mega-meaty, super creamy beans, which I prepared the day before. If you use canned beans, be sure to drain and rinse them before simmering them in good olive oil, garlic, and bay leaf.
Cathy also insists–and rightfully so–on using DeCecco brand fusilli. It's an excellent pasta: full-flavored, with terrific texture. Those tight curls capture the broth while remaining resilient in the sauce.
Here's a trick I used to add more body to the broth. I reserved a cup of cooked beans and pureed them before stirring them into the pot. The sauce becomes almost silken. And the greens themselves maintain integrity in the braise–toothsome, juicy, with a pleasant hint of bitterness.
In the waning days of 2012, we've been enjoying our bowls of beans, pasta, and escarole. Bill calls this peasant food, and he means it in the best possible way. Simple. Soothing. Nutritious. Satisfying. You really couldn't want for anything more.
Many thanks for your continued visits to Good Food Matters.
In a large stockpot set on medium heat, warm olive oil and saute garlic and onions until translucent.
Add chopped escarole and stir well to coat the leaves.
Season with salt, black pepper, and red pepper flakes.
Stir, allowing the heat to collapse the leaves.
Pour vegetable broth over the escarole. Simmer for 15 minutes, stirring occasionally.
Boil fusilli in lightly salted water until al dente–about 9 minutes. Drain.
Combine pasta and beans (whole, pureed, and liquid) with the braised escarole. Toss well.
Ladle into bowls and sprinkle grated cheese over the top.
Heat olive oil in a 3 quart saucepan set on medium. Stir in garlic and onions. Add salt and black pepper, and saute until translucent.
Add cannellinis, stirring well so that the beans are coated with oil.
Pour water over the beans–enough to cover them by two inches.
Stir in bay leaves and red pepper flakes.
Bring to a rolling boil, then reduce heat to a simmer.
Skim off any scum that may accumulate as the beans cook.
Cook, partially covered for about 2 hours, stirring occasionally and adding more liquid if needed.
Cannellinis will retain their structure, but will creamy to the bite. Discard bay leaves.
Sungolds, Black Cherokees, Sweet Millions: these three varieties of cherry tomatoes showed up unannounced in my garden. Volunteers!
Make no mistake, I've been thrilled with their appearance, and their profusion of tangy-sweet yellow, orange, and dark red-green fruit.
When we haven't been popping them into our mouths for snacks, I've been finding other ways to use them.
Easy–I've cut them in half and strewn them over salad greens.
The best thing, I decided, would be to toss them into a big pot and turn them into soup.
I know–tomato soup. How mundane is that?
But, wait. Let me tell you, this one surprised me. The taste is so pure, so bright and intensely tomato.
It reveals what a true summer tomato soup can be.
There are so few ingredients that it is barely a recipe. More of a technique, really.
The first part is laissez-faire.
Once you toss your little truckload into the soup pot, let it simmer, covered, for thirty minutes, or so. You can practically forget the pot while you tend to other things.
Meanwhile, all the little globes collapse and release their juices.
The second part is where the magic happens: with the food mill.
I discovered that milling twice—once with the coarse grinding disc, once with the fine sieve—is the key to making silken full-bodied soup.
The first pass really crushes the pulp, and removes some of the peel, and few of the seeds.
It's the second pass through the mill that extracts all the remaining juices, and that intense flavor. I've read that the most acidic part of the tomato (which gives its sweetness dimension) is in the gel that surrounds the seeds. In this second pass, you get that essence, and leave the seeds behind.
There's no added water. There's no cream, and yet it seems creamy.
Dress it up, like I have here, with a scoop of arborio rice and diced roasted veggies–a late summer meal in a bowl.
Or with a grilled cheese?
Place all the ingredients into a large heavy duty soup pot on medium heat.
Cover and simmer for about 30 minutes. Occasionally stir, mashing the tomatoes to release their juices.
Set food mill fitted with coarse grinder over a 4 qt. bowl. Run all of cooked tomatoes and juices through it. The mixture will contain a fair amount of seeds and peels. Discard peels and seeds that remain in the mill.
Rinse off the food mill and fit it with a fine grinder. Place it back over the soup pot and churn the tomato mixture through the it.
This time, the soup will be velvet smooth, with scant seeds.
Warm the soup, tasting and adjusting for salt. Makes 4-6 servings.
I credit this humble tribe for waking me up, turning me around, and nudging me in the right culinary direction, oh-so many years ago. Once an affirmed picky eater, I had disliked 'most everything. I had heaped onions and their ilk into my big pile of things never-ever to eat.
It wasn't until I lived in Holland that I became enlightened to their beneficent ways.
I was an exchange student, just out of high school. Gert, my Dutch mother, was a kind and patient woman who allowed me to accompany her on her daily round of shopping for the meals. Together we'd choose vegetables, a bit of meat, potatoes–of course!–and a hearty loaf of bread. I would help her wash and cut carrots, peel the spuds, trim the white endive.
She understood that I was picky, and that I was trying to push past the barriers I'd long entrenched for myself. Working together on the meals not only helped me to better learn the language and culture, indeed it forged a loving bond, easing me into the fold of her family.
Maybe she sensed that, deep inside me, there was a burgeoning chef, the anti-picky eater.
I had come home from a class late one afternoon, and Gert had already done most of the dinner preparations. I don't remember what the skillet of caramelized onions was for–could have been a base for a soup or stew. It doesn't–and didn't– matter. What mattered was the smell. It filled the kitchen with a pungency that was heady and earthy and sweet and compelling. It touched on something–a memory? a desire?
I wasn't sure. It was nothing I would ever have attributed to onions. I had to have a taste, pickyness be damned!
I grabbed a spoon and dug in. Mercy, what had I been missing?
It's funny how change occurs. Often it is slow, almost imperceptible in its unfolding. And then there are those Great A-Ha's! A dramatic turn, where nothing is the same as before. After my indulgent spoonful of sweet sauteed onions, I opened my senses to the world of food.
In no time, the disdained became the embraced.
This simple hearty soup is a celebration of that first skillet of Genus Allium. I've put in most of the family—I love 'em all—each contributing a lush layer of savory-sweet bite. It's vegetarian, although you could make it with chicken or beef stock, if you like. I prefer the straightforward vegetable. Delete the butter, and it becomes vegan.
Farro, that wonderful nutritious and nutlike grain, cooks up beautifully in the soup. It adds body, and a pleasant chewiness. Serve the soup with crusty bread—or try this easy, airy spoonbread. Essentially, it's a cornmeal mush souffle—and it is divine.
Heat a stockpot and add olive oil and butter. Add your cut onions, leeks, shallots, and garlic. Stir well to coat the pieces. Sprinkle with salt and black pepper. Cook on medium heat, stirring occasionally. After 15 minutes (or so), the onions will begin to release their natural sugars and caramelize.
Pour in vegetable stock and stir well, scraping any browned bits on the bottom and sides of the pot. Add the farro. Cover and simmer for 30-40 minutes.
If the soup get too thick, add water–2 cups–to thin. You will not sacrifice flavor. Check seasoning—add some red pepper flakes, and fresh thyme at the end of the cooking cycle, if you like.
Spoon into bowls. Garnish with chives and serve.
Have you ever eaten spoonbread?
It is a Southern delicacy, light–airy—so like a souffle.
Some recipes call for separating the eggs, beating the whites and yolks separately, and folding into the mix, just as you would for a souffle. This recipe, based on the famous one served at Boone Tavern in Berea, Kentucky, calls for whole eggs, beaten into the cornmeal mush for a long time.
It, too, results in a Grand Puff.
You'll enjoy dipping your spoon into this special treat–a bit elegant, but rustic at its roots.
In a saucepan, heat milk. Stir in cornmeal and salt. Cook on medium heat, stirring continuously, until mixture thickens, but becomes smooth—corn meal mush. Stir in butter until it is melted. Remove from heat.
Place eggs into a stand mixing bowl. Add baking powder. Begin beating. Gradually add cornmeal mush. Keep beating—up to 15 minutes total. This seems long—but it beats sufficient air into the batter, which will make a delectably light spoonbread.
Pour batter into buttered baking dish or casserole.
Bake for 25-30 minutes, until spoonbread has risen, with a browned top, and a toothpick, once insert, removes clean.
Living with a vegetarian restricts my intake of red meat. This is not a complaint–trust me. I consider it a benefit. I'm an omnivore who is happy–and better off– not consuming the vast quantity of beef that many Americans do. And, with just two in our household, it doesn't make sense for me to buy those great hunks needed for pot roast, meat loaf, and the like.
But, cooking for our Third Thursday Community Potluck is a different matter. No restrictions! Here I get the chance to Go Big and Meaty, should I choose. From time to time, I splurge, and cook up a cauldron of something wonderful and stew-ish. Because it's so infrequent, I enjoy the process, lengthy as it can be, and really savor the results.
For our most recent potluck gathering–a week before T-Day–I indulged in stewy-splurge. I made a supa-sized batch of Shepherd's Pie, fancy-pants style. Onions, carrots and parsnips, oven-roasted to a caramel sweet, were folded in with tender chunks of beef, browned and simmered in an enamel cast-iron pot.
Not so fancy, you say?
Potatoes seasoned with chives and paprika were whipped light and buttery—then piped in a mound of pretty rosettes, sealing in the stew. The whole she-bang went into the oven for a final blast, emerging puffed and golden and utterly irresistible.
Another fancy note, regarding the green you see flecked in the pot. This is "Par-Cel" a parsley-celery hybrid that one of our local farmers was selling last week. Have you ever seen–or used it before? I couldn't resist something so new. I was surprised at how it tasted: Indeed a true hybrid–possessing both fresh parsley and celery leaf flavors. It was a nice addition, plunged into the pot at the end of cooking time.
Place cubed meat into a mixing bowl. Stir in minced garlic, olive oil, and balsamic vinegar. Sprinkle salt and pepper. Strip the sprigs of thyme and rosemary and stir into the meat. The meat should be well coated. Add bay leaves. Allow to marinate for at least 4 hours, or overnight.
Heat the stew pot on medium. Add olive oil. Add meat, a few pieces at a time. Do not crowd. Brown the meat on all sides, and remove–putting into a separate bowl. Continue the browning process. When all the meat is browned, toss with 2 T. flour.
Return to the flour-coated meat to the pot and cook gently–toasting the flour. Stir in water to cover, scraping up browned bits from the bottom and sides of the pot. Cover and simmer for at least an hour. Meat should be fork tender.
Spread out vegetables on a baking sheet and lightly coat with olive oil. Season with sea salt and black pepper.
Roast in a preheated 400 degree oven for 20 minutes, until pieces are softened and caramelized. Remove from heat.
When the beef is tender, add the vegetable to the pot. Stir in chopped Par-cel (or parsley, or celery leaves) Taste for seasoning.
Place potatoes into a large pot of lightly salted water and bring to a boil. Reduce to a simmer, and cook until potatoes are tender when pierced with a knife tip.
Pour cooked potatoes into a colander. Drain well and return to the pot. Under low heat, toss the potatoes in the pot to cook off any remaining water.
Place warm potatoes into a big mixing bowl. Using a stand or hand-held mixer, beat the potatoes until the lumps are broken down. Beat in the butter. Season to taste with salt, black pepper. Beat in chives. Slowly add milk, continuing to whip the potatoes until they become creamy and somewhat fluffy.
Spoon whipped potatoes into a large pastry bag fitted with a star tip. Pipe rosettes allover the top of the beef stew. Continue to mound the potato rosettes.
Sprinkle with paprika and bake in a 350 degree oven for 30 minutes—until stew is bubbly and potato topping is puffed and golden.
Third Thursday Potluck friends surround the feasting table.


If you expect the whacky, weird and magical from a Madame Zingara franchise, you won't be disappointed after a visit to Bombay Bicycle Club. The dimly lit restaurant, crammed from head to toe in paraphernalia – from ceramics, golden picture frames, gilded mirrors, dusty books and collectibles, right to a flying tiger and a floating bed (YOLO!) it's a feast for the senses from start to finish.
Housed at the top of Kloof Street in Gardens, it's a parade of the eccentric. Walk the red carpet through the curtained doorway, before being escorted to your seat by the friendly (and equally eccentric) staff. Booking is recommended, and mandatory for weekends – everyone wants a taste of The Bombay. It's Cape Town's wonderfully wacky bohemian love den and you're encouraged – with a complimentary shot of tequila – to let your hair down and relax in the eclectic ensemble.
The menu is a compendium of well-loved favourites, accompanied by seasonal specials to keep things fresh and interesting. We kicked things off with a cocktail and glass of red wine at the bar, before succumbing to the temptation that is cheeeeese from the baked camembert after finding our seats. This oozing, cheesy goodness was followed by the irresistibly tempting beef carpaccio; light, fresh and a great balance if you suffer from the fate of being 'not so hungry'.
Bombay Bicycle Club is unlike any restaurant you've experienced before, and it's a sensory overload that makes dining between its walls festive, romantic and comedic all at once. Never was the saying more apt: never a dull moment.
PS. Don't forget the 2 for 1 drinks between 4–6 pm daily, and happy hour from 10 pm on select items.


We love indulging in a luxurious & invigorating bath, and these sweet bath cakes from SÖK are perfect for adding a special touch to any bath. They are a wonderful blend of moisturising oils & Pure Essential Oils.
Utterly moisturising, these Bath Cakes include scents of Lavender, Sweet Orange, Chamomile and Geranium for a completely relaxing experience.


NFL quarterback Colt McCoy, a former standout with the Texas Longhorns, will speak at an event Saturday, May 4, 2019, at San Angelo Stadium.
SAN ANGELO — Former Texas Longhorns quarterback Colt McCoy is going to be in San Angelo in May.
McCoy, who currently plays in the NFL for the Washington Redskins, will speak at the Clarion Call for 14K Christians meeting, which will be held from 6 p.m. to 10 p.m. Saturday, May 4, 2019, at San Angelo Stadium,1621 University Ave.
McCoy played at UT from 2006-2009, where he was the runner-up for the Heisman Trophy, awarded to the best player in college football.
He graduated from Jim Ned High School in nearby Tuscola.
Clarion Call for 14K was created by pastor Ronnie and Maria Hawkins, who wanted to bring Christians and nonbelievers together to celebrate Psalm 133, which reads, "Behold, how good and how pleasant it is for brethren to dwell together in unity."
The meeting will have four speakers, including San Angelo Diocese Bishop Michael Sis, Bishop Joseph L. Garlington, Sr., PhD, senior pastor at Covenant Church of Pittsburgh, and minister Gloria Pope.
Where: San Angelo Stadium,1621 University Ave.


text:
[![Build Status](https://travis-ci.org/shonny-ua/gulp-rev-collector.svg)](https://travis-ci.org/shonny-ua/gulp-rev-collector)
[![Dependencies](https://david-dm.org/shonny-ua/gulp-rev-collector.svg)](https://david-dm.org/shonny-ua/gulp-rev-collector)
[![devDependencies](https://david-dm.org/shonny-ua/gulp-rev-collector/dev-status.svg)](https://david-dm.org/shonny-ua/gulp-rev-collector#info=devDependencies&view=table)
[![NPM version](https://badge.fury.io/js/gulp-rev-collector.svg)](http://badge.fury.io/js/gulp-rev-collector)

# [gulp](https://github.com/wearefractal/gulp)-rev-collector

[![NPM](https://nodei.co/npm/gulp-rev-collector.png?downloads=true&stars=true)](https://nodei.co/npm/gulp-rev-collector/)

> Static asset revision data collector from manifests, generated from different streams, and replace their links in html template.

## Install

```sh
$ npm install --save gulp-rev-collector
```

## Usage

We can use [gulp-rev](https://github.com/sindresorhus/gulp-rev) to cache-bust several assets and generate manifest files for them. Then using gulp-rev-collector we can collect data from several manifest files and replace lincks to assets in html templates.

```js
var gulp         = require('gulp');
var rev = require('gulp-rev');

gulp.task('css', function () {
    return gulp.src('src/css/*.css')
        .pipe(rev())
        .pipe(gulp.dest('dist/css'))
        .pipe( rev.manifest() )
        .pipe( gulp.dest( 'rev/css' ) );
});

gulp.task('scripts', function () {
    return gulp.src('src/js/*.js')
        .pipe(rev())
        .pipe(gulp.dest('dist/js'))
        .pipe( rev.manifest() )
        .pipe( gulp.dest( 'rev/js' ) );
});

...

var revCollector = require('gulp-rev-collector');
var minifyHTML   = require('gulp-minify-html');

gulp.task('rev', function () {
    return gulp.src(['rev/**/*.json', 'templates/**/*.html'])
        .pipe( revCollector({
            replaceReved: true,
            dirReplacements: {
                'css': '/dist/css',
                '/js/': '/dist/js/',
                'cdn/': function(manifest_value) {
                    return '//cdn' + (Math.floor(Math.random() * 9) + 1) + '.' + 'exsample.dot' + '/img/' + manifest_value;
                }
            }
        }) )
        .pipe( minifyHTML({
                empty:true,
                spare:true
            }) )
        .pipe( gulp.dest('dist') );
});
```

### Options

#### replaceReved

Type : `Boolean`

You set a flag, replaceReved, which will replace alredy replaced links in template's files. Default value is `false`.

#### dirReplacements

Specifies a directories replacement set. [gulp-rev](https://github.com/sindresorhus/gulp-rev) creates manifest files without any info about directories. E.c. if you use dirReplacements param from [Usage](#usage) example, you get next replacement:

```
"/css/style.css" => "/dist/css/style-1d87bebe.css"
"/js/script1.js" => "/dist/script1-61e0be79.js"
"cdn/image.gif"  => "//cdn8.example.dot/img/image-35c3af8134.gif"
```

#### revSuffix

Type : `String`

It is pattern for define reved files suffixes. Default value is '-[0-9a-f]{8,10}-?'. This is necessary in case of e.c. [gulp-rename](https://github.com/hparra/gulp-rename) usage. If reved filenames had different from default mask.

### Works with gulp-rev-collector

- [gulp-rev](https://github.com/sindresorhus/gulp-rev)

## License

[MIT](http://opensource.org/licenses/MIT) © [Oleksandr Ovcharenko](mailto:shonny.ua@gmail.com)

redpajama_set_name: RedPajamaGithub


text:
Guterres to ask for a global vaccination plan against covid-19
Home » News » Guterres to ask for a global vaccination plan against covid-19
The UN secretary general, António Guterres, travels this week to the United Kingdom to participate in the G7 summit, where he intends to ask the leaders for a global plan for the production and distribution of vaccines against covid-19.
Another of the requests is for more funds for the fight against climate change, according to the announcement made by the spokesperson, Stéphane Dujarric, who assured that Guterres will demand a "great leap" from the G7 in response to the great global challenges, especially the pandemic and the global warming.
The UN head will participate in several working sessions and press the leaders for a "global vaccination plan" against covid-19 that will allow to double the production of doses and guarantee an equitable distribution so that everyone has access to them.
The diplomat and former Portuguese prime minister will also defend ambitious and concrete commitments from the G7 in financing against climate change, indicated Dujarric.
Specifically, it will demand that the joint financial commitment of these countries be doubled to meet the target of having 100,000 million dollars (82 billion euros) annually, said the spokesman.
The G7 summit (comprised of the seven most developed economies: United Kingdom, United States, Canada, Italy, France, Germany and Japan, in addition to the European Union as a partner) will take place from Friday to Sunday in Cornwall, in southwest England.
This meeting will be the first in which the leaders of the seven countries celebrate in person in two years and is expected to address, among other issues, post-pandemic recovery, the climate crisis and job creation.
Tags: covid-19, HIM-HER-IT, international, TVI24, vaccination, vaccines
Previous PostProfile of the child vulnerable to Covid: with type 1 diabetes and obesity, but also with anxiety or trauma
Next PostUN calls for urgent measures to eradicate AIDS by 2030

redpajama_set_name: RedPajamaCommonCrawl


I'm just going to highlight quickly.
If we go through this, it's the same setup.
I'm just going to evaluate everything for the sake of time.
But this is the step.
I'm using equal weight, so my weight matrix just becomes a diagonal of ones.
If there was unequal, you'd have blocks of ones and twos and threes and so forth.
Then I do the differences that I needed, I join up, I get the sums.
This gives me my, here I have two observation.
So I have a set that's six dimensional and here I have a three by six.
And then I can dissolve this minimum norm inverse which gives me [INAUDIBLE] Q bar.
Now if you compare this to the truth, I happen to get 1.68.
You can see it's slightly different than Davenport's Q method.
It's very good, it's very close.
But statistically speaking, we are not solving Wapo's problem.
optimization problem, making this the least square kind of formulation.
any methods that do Wamba's it's a statistical difference.
they're both solving some different type of optimality.
at the beginning is what is the optimality we're actually solving?
If they're the same QUEST q method, I should get the same answer.
answer, but it will be a slightly different one and which one is better?
analyze different, how airs impact the solution and so forth, like that.
the high level concepts is what I expect you to be able to do.
And the homeworks have you run through some of them.
you might want to come back with your questions next Tuesday.
Okay, we'll talk it over.
Good. So, see you on Thursday.


text:
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Glucuronidation of Thyroxine in Human Liver, Jejunum, and Kidney Microsomes
Hiroyuki Yamanaka, Miki Nakajima, Miki Katoh and Tsuyoshi Yokoi
Drug Metabolism and Disposition September 2007, 35 (9) 1642-1648; DOI: https://doi.org/10.1124/dmd.107.016097
Hiroyuki Yamanaka
Miki Nakajima
Miki Katoh
Tsuyoshi Yokoi
Glucuronidation of thyroxine is a major metabolic pathway facilitating its excretion. In this study, we characterized the glucuronidation of thyroxine in human liver, jejunum, and kidney microsomes, and identified human UDP-glucuronosyltransferase (UGT) isoforms involved in the activity. Human jejunum microsomes showed a lower Km value (24.2 μM) than human liver (85.9 μM) and kidney (53.3 μM) microsomes did. Human kidney microsomes showed a lower Vmax value (22.6 pmol/min/mg) than human liver (133.4 pmol/min/mg) and jejunum (184.6 pmol/min/mg) microsomes did. By scaling-up, the in vivo clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 μl/min/kg body weight, respectively. Recombinant human UGT1A8 (108.7 pmol/min/unit), UGT1A3 (91.6 pmol/min/unit), and UGT1A10 (47.3 pmol/min/unit) showed high, and UGT1A1 (26.0 pmol/min/unit) showed moderate thyroxine glucuronosyltransferase activity. The thyroxine glucuronosyltransferase activity in microsomes from 12 human livers was significantly correlated with bilirubin O-glucuronosyltransferase (r = 0.855, p < 0.001) and estradiol 3-O-glucuronosyltransferase (r = 0.827, p < 0.0001) activities catalyzed by UGT1A1, indicating that the activity in human liver is mainly catalyzed by UGT1A1. Kinetic and inhibition analyses suggested that the thyroxine glucuronidation in human jejunum microsomes was mainly catalyzed by UGT1A8 and UGT1A10 and to a lesser extent by UGT1A1, and the activity in human kidney microsomes was mainly catalyzed by UGT1A7, UGT1A9, and UGT1A10. The changes of activities of these UGT1A isoforms via inhibition and induction by administered drugs as well as genetic polymorphisms may be a causal factor of interindividual differences in the plasma thyroxine concentration.
Thyroid hormones mediate many physiological processes including embryonic development, cellular differentiation, metabolism, and the regulation of cell proliferation (Hulbert, 2000; Wu and Koenig, 2000; Zhang and Lazar, 2000). The plasma concentrations of thyroid hormones are strictly controlled by thyroid-stimulating hormone, which is subjected to negative feedback regulation by thyroid hormones. The major form of thyroid hormone secreted from thyroid gland is thyroxine. In hypothyroidism, thyroxine is orally administered to keep the plasma thyroid hormone level normal. Thyroxine has little biological activity and is converted to the active form, triiodothyronine (T3) mainly in human liver and kidney (Leonard and Koehrle, 1996). In human, approximately 80% of the total plasma T3 is produced by thyroxine via outer ring deiodination (Fig. 1). In addition to deiodination, thyroxine is metabolized to sulfate and glucuronide by sulfo-transferases and UDP-glucuronosyltransferases (UGTs), respectively (Fig. 1). The thyroxine sulfate hardly appears in bile, urine, or serum, because it is rapidly degraded by inner ring deiodination in the liver. In contrast to the sulfate, thyroxine glucuronide is readily excreted into bile and subsequently hydrolyzed by β-glucuronidases in the intestine, and may affect the enterohepatic circulation of thyroxine (Visser, 1994). It has been reported that administration of UGT inducers such as phenytoin, carbamazepine (Isojarvi et al., 1992), and rifampicin (Ohnhaus and Studer, 1983) markedly decreased serum thyroxine levels in patients. Thus, glucuronidation is a major metabolic pathway to control the serum thyroxine level.
In humans, UGTs are divided into two families: UGT1 and UGT2 (Mackenzie et al., 2005). The UGT1 and UGT2 genes appear to be structurally different in that the UGT1 proteins result from alternate splicing of the unique first exon with four common exons encoded by the UGT1 gene complex, whereas UGT2 proteins appear to be encoded by unique genes. In humans, there are nine functional UGT1A and seven UGT2B proteins (Mackenzie et al., 2005). Among them, human UGT1A1 and UGT1A9 have been reported to catalyze thyroxine glucuronidation (Findlay et al., 2000). However, a limitation of the study was that only two UGT isoforms were investigated. The first purpose of the present study is to investigate the catalytic activity of thyroxine glucuronidation by all human UGT isoforms for which recombinant proteins are currently available.
Human UGTs are expressed in a tissue-specific manner. Table 1 summarizes the UGT isoforms expressed in human liver, intestine, and kidney (King et al., 2000; Tukey and Strassburg, 2000; Fisher et al., 2001; Levesque et al., 2001; Basu et al., 2004, Finel et al., 2005). In general, liver plays an important role in the glucuronidation of most drugs, but extrahepatic tissues also contribute significantly to the glucuronidation of certain drugs in human (Krishna and Klotz, 1994). It is conceivable that the glucuronidation of thyroxine occurs not only in liver but also in intestine and kidney. The second purpose of the present study is to characterize thyroxine glucuronidation in human liver, jejunum, and kidney microsomes, and to identify the UGT isoforms involved in the glucuronidation in each tissue.
Tissue distribution of human UGT mRNAs
Data are from King et al. (2000), Tukey and Strassburg (2000), Fisher et al. (2001), Levesque et al. (2001), Basu et al. (2004), and Finel et al. (2005).
Major metabolic pathways of thyroxine in human.
Materials. Thyroxine, UDP-glucuronic acid (UDPGA), and alamethicin were purchased from Sigma-Aldrich (St. Louis, MO). Bilirubin, chenodeoxycholic acid, serotonin, imipramine hydrochloride, and propofol were purchased from Wako Pure Chemicals (Osaka, Japan). Morphine hydrochloride was from Takeda Chemical Industries (Osaka, Japan). Pooled human liver microsomes (lot H161), microsomes from 12 individual human livers (H003, H023, H030, H043, H056, H064, H066, H070, H089, H093, H112, and HK23), recombinant human UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17 expressed in baculovirus-infected insect cells (Supersomes), and UGT control Supersomes were purchased from BD Gentest (Woburn, MA). The human jejunum (lot HJM0023) or kidney (lot 045290170002) microsomes from an individual donor were purchased from KAC (Kyoto Japan). All other chemicals and solvents were of analytical or the highest grade commercially available.
Thyroxine Glucuronidation Assay. A typical incubation mixture (100 μl total volume) contained 100 mM Tris-HCl buffer (pH 7.4), 5 mM MgCl2, 5 mM UDPGA, 25 μg/ml alamethicin, 0.4 mg/ml human liver, jejunum, or kidney microsomes or recombinant UGTs, and 50 μM thyroxine. Thyroxine was dissolved in dimethyl sulfoxide/0.05 M sodium hydroxide (50:50). The final concentration of the organic solvents in the incubation mixture was 1% (v/v). The reaction was initiated by the addition of UDPGA. After incubation at 37°C for 90 min, the reaction was terminated by adding 100 μl of ice-cold 94% acetnitrile/6% formic acid. After the centrifugation at 12,000 rpm for 5 min, the supernatant was filtered with a 0.22-μm filter (Ultrafree-MC centrifugal filter unit; Millipore, Eschborn, Germany). Aliquots of 10 μl were injected into the LC-MS/MS system.
LC-MS/MS Analysis for Thyroxine Glucuronides. LC was performed using an HP1100 system including a binary pump, an automatic sampler, and a column oven (Agilent Technologies, Waldbronn, Germany), which was equipped with a Mightysil RP-18 GP (4.6 × 150 mm; 5 μm) column (Kanto Chemical, Tokyo, Japan). The column temperature was 35°C. The mobile phase was 0.1% formic acid (A) and acetonitrile including 0.1% formic acid (B). The conditions for elution were as follows: 25% B (0-1 min); 25 to 70% B (1-4 min); 70% B (4-10 min); 70 to 25% B (10-11 min). Linear gradients were used for all solvent changes. The flow rate was 0.5 ml/min. The LC apparatus was connected to a PE Sciex API2000 tandem mass spectrometer (Applied Biosystems, Langen, Germany) operated in the positive electrospray ionization mode. The turbo gas was maintained at 450°C. Nitrogen was used as the nebulizing, turbo, and curtain gas at 50, 80, and 20 psi, respectively. Parent and/or fragment ions were filtered in the first quadrupole and dissociated in the collision cell using nitrogen as the collision gas. The collision energy was 20 V and 26 V for thyroxine and thyroxine glucuronides, respectively. Two mass/charge (m/z) ion transitions were recorded in the multiple reaction monitoring mode: m/z 778 and 778 for thyroxine, and m/z 954 and 778 for thyroxine glucuronide. The retention times of thyroxine glucuronide and thyroxine were 7.1 min and 8.9 min, respectively. For the quantification of thyroxine glucuronide, the eluate of the HPLC from the incubation mixture including thyroxine glucuronide was collected, referring to the retention time. A part of the eluate was incubated with 800 U/ml β-glucuronidase at 37°C for 24 h. The produced thyroxine was quantified by LC-MS/MS. Once we determined the peak area per known content of thyroxine glucuronide, the ratio was applied to the calculation of the thyroxine glucuronide formed in the incubation mixtures.
Kinetic Analyses of Thyroxine Glucuronidation in Human Liver, Jejunum, and Kidney Microsomes or Recombinant UGTs. Thyroxine glucuronosyltransferase activities were determined as described above with substrate concentrations from 2 μM to 100 μM. Kinetic parameters were estimated from the fitted curve using a computer program (KaleidaGraph; Synergy Software, Reading, PA) designed for nonlinear regression analysis. The following equations were applied for Michaelis-Menten kinetics (eq. 1) or substrate inhibition kinetics (eq. 2) (Houston and Kenworthy, 2000):
where V is the velocity of the reaction, S is the substrate concentration, Km is Michaelis-Menten constant, Vmax is the maximum velocity, and Ksi is the substrate inhibition constant. Data are expressed as mean ± S.D. of three independent determinations.
Kinetic analyses of thyroxine glucuronosyltransferase activities in human liver, jejunum, or kidney microsomes. Michaelis-Menten plots (A) or Eadie-Hofstee plots (B) are shown. Microsomes were incubated with 2 to 100 μM thyroxine and 5 mM UDPGA at 37°C for 90 min. Each data point represents the mean of triplicate determinations. HLM, human liver microsomes; HJM, human jejunum microsomes; HKM, human kidney microsomes.
Estimation of Tissue Clearances from in Vitro Data. In vivo clearance was scaled-up by an equation (Obach et al., 1997; Soars et al., 2002):
According to a previous study (Soars et al., 2002), 45, 3, and 45 mg/g tissue were used as the contents of the microsomal protein in liver, intestine, and kidney, respectively. For the weights of liver, intestine, and kidney, 20, 30, and 4.4 g/kg body weight, respectively, were used.
Immunoblot Analysis of Recombinant Human UGT1A Isoforms. SDS-polyacrylamide gel electrophoresis and immunoblot analysis of recombinant UGT1A isoforms were performed according to the method of Laemmli (1970). The microsomes from baculovirus-infected insect cells (0.5 μg) were separated on 10% polyacrylamide gel and transferred electrophoretically to a polyvinylidene difluoride membrane Immobilon-P (Millipore, Bedford, MA). Rabbit anti-human UGT1A polyclonal antibodies (BD Gentest) react with all human UGT1A isoforms, since the antibodies recognize the conserved C-terminal region of UGT1A isoforms (Malfatti and Felton, 2004). Biotinylated anti-rabbit IgG and a VECTASTAIN ABC kit (Vector Laboratories, Burlingame, CA) were used for diaminobenzidine staining. The densities of the bands were determined using an ImageQuant (GE Healthcare Bio-Sciences Corp., Piscataway, NJ). For each isoform, the densities of multiple bands, possibly owing to variability in glycosylation (Malfatti and Felton, 2004), were summed for the quantification. The expression level of UGT1A was defined based on a standard curve using recombinant UGT1A1 (1 unit per 1 mg protein).
Other Glucuronidation Assays. Bilirubin O-glucuronosyltransferase (Katoh et al., 2007), imipramine N-glucuronosyltransferase (Nakajima et al., 2002), and serotonin O-glucuronosyltransferase (Fujiwara et al., 2007) activities in microsomes from 12 human livers were determined according to methods established in our laboratory. Chenodeoxycholic acid 24-O-glucuronosyltransferase activities in these human liver microsomes were determined according to the method of Trottier et al. (2006) with slight modifications. Estradiol 3-O-, propofol O-, and morphine 3-O-glucuronosyltransferase activities in these human liver microsomes were provided by the manufacturer.
Correlation Analyses. Correlation between thyroxine glucuronidation and the other glucuronosyltransferase activities was determined by unpaired Student's t test. A p value of less than 0.05 was considered statistically significant.
Inhibition Analysis of Thyroxine Glucuronosyltransferase Activities in Human Liver, Jejunum, and Kidney Microsomes or Recombinant UGTs. Bilirubin is a typical substrate of UGT1A1 (King et al., 2000). Imipramine is a substrate of UGT1A3 and UGT1A4 (Green and Tephly, 1998). Emodin is a substrate of UGT1A1, UGT1A3, UGT1A8, and UGT1A9 (King et al., 2000). Propofol is a substrate of UGT1A8 and UGT1A9 (King et al., 2000). Troglitazone is a substrate of UGT1A1, UGT1A8, and UGT1A10 (Watanabe et al., 2002). Bilirubin was dissolved in 0.1 M sodium hydroxide. Imipramine hydrochloride was dissolved in water. Emodin and troglitazone were dissolved in dimethyl sulfoxide. Propofol was dissolved in methanol. These compounds were added to the incubation mixtures described above to investigate their inhibitory effects on the thyroxine glucuronosyltransferase activities in human liver, jejunum, and kidney microsomes or recombinant UGTs. The final concentration of the organic solvents in the incubation mixture was <2% (v/v). The substrate concentration was 20 μM.
Thyroxine Glucuronosyltransferase Activities in Human Liver, Jejunum, or Kidney Microsomes. The formation of thyroxine glucuronide increased in a microsomal protein concentration- and time-dependent manner. The formations were linear at least for 0.5 mg/ml microsomal protein and 120 min incubation (data not shown). Unless specified, the typical incubation mixture containing 0.4 mg/ml microsomal protein was incubated at 37°C for 90 min. The kinetics of thyroxine glucuronosyltransferase activities in human liver, jejunum, and kidney microsomes were fitted to the Michaelis-Menten equation (Fig. 2A). The Eadie-Hofstee plots were monophasic (Fig. 2B). The apparent Km and Vmax values are summarized in Table 2. Human jejunum microsomes showed a lower Km value (24.2 μM) than did human liver (85.9 μM) and kidney (53.3 μM) microsomes. Human kidney microsomes showed a lower Vmax (22.6 pmol/min/mg) value than did human liver (133.4 pmol/min/mg) and jejunum (184.6 pmol/min/mg) microsomes. The in vitro intrinsic clearances (Vmax/Km) of thyroxine glucuronidation in human liver, jejunum, and kidney microsomes were 1.6, 7.8, and 0.4 μl/min/mg, respectively. By scaling-up, the in vivo clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 μl/min/kg body weight, respectively.
Kinetic parameters of thyroxine glucuronosyltransferase activities in human liver, jejunum, and kidney microsomes, and by recombinant UGTs
Thyroxine Glucuronosyltransferase Activities by Recombinant UGT Isoforms. Eleven recombinant UGT isoforms expressed in baculovirus-infected insect cells were used to determine their thyroxine glucuronosyltransferase activities. As shown in Fig. 3A, UGT1A8 exhibited the highest thyroxine glucuronosyltransferase activity (87 pmol/min/mg), followed by UGT1A1 (26 pmol/min/mg), UGT1A10 (20 pmol/min/mg), UGT1A3 (18 pmol/min/mg), UGT1A9 (5 pmol/min/mg), and UGT1A7 (5 pmol/min/mg). To quantify the expression level of UGT1A in each expression system, immunoblot analysis was performed (Fig. 3B). In accordance with previous studies (Malfatti and Felton, 2004; Fujiwara et al., 2007), the recombinant UGT1A isoforms showed multiple bands, possibly owing to variability in the glycosylation. Based on a UGT1A1 level of 1.00 unit/mg, the expression levels of the other isoforms were determined as follows: UGT1A3, 0.20 unit/mg; UGT1A4, 0.38 unit/mg; UGT1A6, 0.95 unit/mg; UGT1A7, 0.60 unit/mg; UGT1A8, 0.80 unit/mg; UGT1A9, 0.68 unit/mg; and UGT1A10, 0.42 unit/mg. By normalization with the UGT expression levels (Fig. 3C), UGT1A8 (108.7 pmol/min/unit) and UGT1A3 (91.6 pmol/min/unit) exhibited the highest thyroxine glucuronosyltransferase activities, followed by UGT1A10 (47.3 pmol/min/unit) and UGT1A1 (26.0 pmol/min/unit). The activities by UGT1A7 (7.6 pmol/min/unit) and UGT1A9 (7.1 pmol/min/unit) were low.
Thyroxine glucuronosyltransferase activities by recombinant human UGTs expressed in baculovirus-infected insect cells. The substrate concentration was 50 μM. Each column represents the mean of duplicate determinations. The activities are expressed as pmol/min/mg (A) or pmol/min/unit (C) normalized with the UGT1A expression levels determined by immunoblot analysis (B). Immunoblot analysis of the recombinant UGT1A isoforms (0.5 μg) was performed using rabbit anti-human UGT1A antibodies. Control represents the UGT control Supersomes (0.5 μg). The expression levels were defined assuming that UGT1A1 was 1.00 unit/mg. ND, not detected.
Kinetics of Thyroxine Glucuronosyltransferase Activities by Recombinant UGT1A Isoforms. For six UGT isoforms showing thyroxine glucuronosyltransferase activity, kinetic analyses were performed. The kinetics of thyroxine glucuronosyltransferase activities by recombinant UGT1A1, UGT1A7, and UGT1A9 fitted to the Michaelis-Menten kinetics (Fig. 4A). The activities by recombinant UGT1A3, UGT1A8, and UGT1A10 fitted to the substrate inhibition kinetics (Fig. 4B). The apparent Km and corrected Vmax values are summarized in Table 2. The Km values varied from 24.1 μM to 104.9 μM. UGT1A8 (6.6 μl/min/unit) exhibited the highest clearance, followed by UGT1A3 (6.2 μl/min/unit) and by UGT1A10 (3.7 μl/min/unit). UGT1A1 (0.7 μl/min/unit), UGT1A9 (0.4 μl/min/unit), and UGT1A7 (0.4 μl/min/unit) exhibited low intrinsic clearance.
Interindividual Variability of Thyroxine Glucuronosyltransferase Activities in Microsomes from 12 Human Livers and Correlation Analyses. The thyroxine glucuronosyltransferase activity in microsomes from 12 human livers ranged from 23.7 to 84.8 pmol/min/mg protein, representing 3.6-fold variability. Correlation analyses were performed between the thyroxine glucuronosyltransferase activity and typical activities including bilirubin O-glucuronidation catalyzed by UGT1A1, estradiol 3-O-glucuronidation catalyzed by UGT1A1 and UGT1A8 (Lepine et al., 2004), chenodeoxycholic acid 24-O-glucuronidation catalyzed by UGT1A3 (Trottier et al., 2006), imipramine N-glucuronidation catalyzed by UGT1A3 and UGT1A4, serotonin O-glucuronidation catalyzed by UGT1A6, propofol O-glucuronidation catalyzed by UGT1A8 and UGT1A9, or morphine 3-O- glucuronidation catalyzed by UGT2B7 (Table 3). Since UGT1A8 is not expressed in human liver, the estradiol 3-O- and propofol O-glucuronosyltransferase activities represented are the UGT1A1 and UGT1A9 activities, respectively. The thyroxine glucuronosyltransferase activities in 12 human liver microsomes were significantly correlated with bilirubin (r = 0.855, p < 0.001), estradiol (r = 0.827, p < 0.0001), and serotonin (r = 0.522, p < 0.05) glucuronidation.
Correlation coefficients between thyroxine glucuronidation and other glucuronidations in microsomes from 12 human livers
Inhibitory Effects of Typical Substrates for UGT Isoforms on Thyroxine Glucuronosyltransferase Activities in Human Liver, Jejunum, and Kidney Microsomes or Recombinant UGTs. The inhibitory effects of bilirubin, imipramine, emodin, propofol, and troglitazone on thyroxine glucuronosyltransferase activity were investigated. These inhibitors were used at effective concentrations according to previous studies (Watanabe et al., 2002; Kuehl et al., 2005; Yamanaka et al., 2005). The thyroxine glucuronosyltransferase activity in human liver microsomes was strongly inhibited by bilirubin (29% of control) and emodin (15% of control), and was moderately inhibited by troglitazone (51% of control), but was activated by propofol (121% of control) (Fig. 5A). The thyroxine glucuronosyltransferase activity in human jejunum microsomes was strongly inhibited by emodin (45% of control) and was moderately inhibited by bilirubin (68% of control). The thyroxine glucuronosyltransferase activity in human kidney microsomes was strongly inhibited by troglitazone (46% of control), and was moderately inhibited by emodin (55% of control). Thus, the effects of these compounds on the activity were different between the tissues. The inhibitory effects on thyroxine glucuronidation were also investigated for recombinant UGT1A isoforms (Fig. 5B). Bilirubin strongly inhibited the activity by UGT1A1 (16% of control) and moderately inhibited the activities by UGT1A7 (68% of control). Imipramine moderately inhibited the activity by UGT1A3 (68% of control) and UGT1A10 (64% of control). Emodin strongly inhibited the activities by all UGT1A isoforms. Propofol moderately inhibited the activities by UGT1A9 (63% of control) and UGT1A10 (66% of control), and activated the activities by UGT1A1 (349% of control) and UGT1A3 (324% of control). Troglitazone strongly inhibited the activities by the five UGT1A isoforms other than UGT1A3.
Kinetic analyses of thyroxine glucuronosyltransferase activities by recombinant UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. Recombinant UGT1As were incubated with 2 to 100 μM thyroxine and 5 mM UDPGA at 37°C for 90 min. The activities by recombinant UGT1A1, UGT1A7, and UGT1A9 fitted to the Michaelis-Menten kinetics (A). The activities by recombinant UGT1A3, UGT1A8, and UGT1A10 fitted to the substrate inhibition kinetics (B). Each data point represents the mean of triplicate determinations.
In this study, we extensively investigated thyroxine glucuronidation in human liver, jejunum, and kidney microsomes and recombinant UGTs. The tissue clearances in liver, intestine, and kidney were estimated to be 1440, 702, and 79 μl/min/kg body weight, respectively. Although the UGT activities are not the same in the region of intestine (Strassburg et al., 2000), it was first demonstrated that intestine exhibited approximately one half the clearance of liver for thyroxine glucuronidation. The glucuronidation in intestine may affect the enterohepatic circulation of thyroxine. In kidney, thyroxine is highly converted to T3 with Km = 3.0 μM, Vmax = 26.1 pmol/min/mg, and Vmax/Km = 8.7 μl/min/mg (Boye, 1986). In addition to the outer ring deiodination, this study demonstrated that thyroxine is glucuronidated in kidney.
This is the first study demonstrating that human UGT1A8, UGT1A10, and UGT1A3 have high, and UGT1A1 has moderate catalytic activity toward thyroxine glucuronidation. Since UGT isoforms are expressed differently in human liver, jejunum, and kidney, it was conceivable that UGT isoform(s) responsible for the thyroxine glucuronidation might be different between these tissues. If the absolute protein levels of each UGT isoform in human tissues are available, quantitative estimation of the contribution of each isoform to the concerned activity can be accomplished as for cytochrome P450 (Becquemont et al., 1998). Unfortunately, for UGT, a methodology of quantification is lacking. In addition, specific antibodies against each UGT1A isoform are limited. In the present study, we qualitatively identified the UGT isoforms that are responsible for the thyroxine glucuronidation in human tissues by kinetic, correlation, and inhibition analyses as well as tissue distribution of each UGT isoform.
The Eadie-Hofstee plots of thyroxine glucuronosyltransferase activities in human liver, jejunum, and kidney microsomes were monophasic, suggesting that one or more UGT isoforms would be involved in the activities. In human liver microsomes, the apparent Km value was similar to that of recombinant UGT1A1. The activity in a panel of human liver microsomes was significantly correlated with the bilirubin O- and estradiol 3-O-glucuronosyltransferase activities catalyzed by UGT1A1. Although the thyroxine glucuronosyltransferase activity was also correlated with the serotonin O-glucuronosyltransferase activity catalyzed by UGT1A6, it might be a fortuitous result, because the serotonin O-glucuronosyltransferase activity was significantly (r = 0.627, p < 0.005) correlated with the estradiol 3-O-glucuronosyltransferase activity in the panel of human liver microsomes. These results suggested that a major UGT isoform responsible for the thyroxine glucuronidation in human liver microsomes would be UGT1A1. We could not exclude the possibility that UGT1A9 might also contribute to the thyroxine glucuronosyltransferase activity in human liver microsomes. Interestingly, propofol activated the thyroxine glucuronosyltransferase activity in human liver microsomes. It has been reported that propofol activated 4-methylunbelliferone glucuronidation by recombinant UGT1A1 (Mano et al., 2004). Thus, the result supported the finding that a major isoform responsible for thyroxine glucuronidation in human liver microsomes would be UGT1A1. We used propofol as an inhibitor of UGT1A8 and UGT1A9. However, our previous study found that propofol can activate trans-3′-hydroxicotinine O-glucuronidation by recombinant UGT1A9 (Yamanaka et al., 2005). Propofol might not be an appropriate inhibitor. The contribution of UGT1A3 to the thyroxine glucuronidation in human liver microsomes would be negligible, because the thyroxine glucuronosyltransferase activity in the panel of human liver microsomes was not correlated with the chenodeoxycholic acid 24-O-glucuronosyltransferase activity catalyzed by UGT1A3 (Table 3), and imipramine did not inhibit the thyroxine glucuronosyltransferase activity (Fig. 5) although it inhibited the chenodeoxycholic acid 24-O-glucuronosyltransferase activity by 48% of control (data not shown).
Effects of typical substrates for UGTs on thyroxine glucuronosyltransferase activities in human liver, jejunum, and kidney microsomes (A) or recombinant UGTs (B). Bilirubin (UGT1A1), imipramine (UGT1A3 and UGT1A4), emodin (UGT1A1, UGT1A3, UGT1A8, and UGT1A9), propofol (UGT1A8 and UGT1A9), and troglitazone (UGT1A1, UGT1A8, and UGT1A10) were used as inhibitors. A, control activities in human liver microsomes (HLM), human jejunum microsomes (HJM), and human kidney microsomes (HKM) at 20 μM thyroxine were 26.7 pmol/min/mg, 90.9 pmol/min/mg, and 6.2 pmol/min/mg, respectively. B, control activities for 20 μM thyroxine by recombinant UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 were 11.1 pmol/min/unit, 69.2 pmol/min/unit, 4.7 pmol/min/unit, 81.5 pmol/min/unit, 4.7 pmol/min/unit, and 42.6 pmol/min/unit, respectively. Each data point represents the mean ± S.D. of triplicate determinations.
In human jejunum microsomes, the apparent Km value was similar to that of recombinant UGT1A8. The thyroxine glucuronidation in human jejunum microsomes was inhibited by emodin, and was moderately inhibited by bilirubin. These results suggested that the thyroxine glucuronidation in human jejunum microsomes might be catalyzed mainly by UGT1A8 and UGT1A10, and to a minor extent by UGT1A1. In human kidney microsomes, the apparent Km value was similar to that of recombinant UGT1A7. The thyroxine glucuronidation in human kidney microsomes was inhibited by troglitazone and emodin. It was suggested that the thyroxine glucuronidation in human kidney microsomes might be catalyzed by UGT1A7, UGT1A9, and UGT1A10. In summary, the contribution of each UGT1A isoform would vary between human tissues, depending on the relative abundance of each isoform.
In conclusion, we characterized the thyroxine glucuronidation in human liver, intestine, and kidney microsomes and found that UGT1A1 in the liver, UGT1A8 and UGT1A10 in the intestine, and UGT1A7, UGT1A9, and UGT1A10 in the kidney mainly contribute to the activity. The change of activities of these UGTs via inhibition and induction by administered drugs (Kiang et al., 2005) as well as genetic polymorphisms (Miners et al., 2002) may be a causal factor of interindividual differences in the plasma thyroxine concentration.
We acknowledge Brent Bell for reviewing the manuscript.
H.Y. was supported as a Research Fellow of the Japan Society for the Promotion of Science.
doi:10.1124/dmd.107.016097.
ABBREVIATIONS: T3, triiodothyronine; LC-MS/MS, liquid chromatography-mass/mass spectrometry; UGT, UDP-glucuronosyltransferase; UDPGA, UDP-glucuronic acid.
Received April 3, 2007.
Accepted June 19, 2007.
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Drug Metabolism and Disposition September 1, 2007, 35 (9) 1642-1648; DOI: https://doi.org/10.1124/dmd.107.016097
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text:
Síť linek autobusové dopravy se v Olomouci vedle tramvají podílí na zajišťování městské hromadné dopravy. Dopravní podnik města Olomouce (DPMO) provozuje celkem 25 autobusových linek (z toho 3 noční) o celkové délce 273 km, které obsluhují nejen samotné město, ale i některé okolní obce. K datu 1. prosince 2018 disponoval DPMO 78 autobusovými vozy.

Příměstské autobusové linky byly do MHD v Olomouci zaintegrovány postupně od 1. ledna 1997 v rámci IDOS Olomoucka, od 3. dubna 2004 v rámci IDSOK – oblast Olomoucko. Pro olomouckou MHD mají význam především příměstské linky Arriva Morava a.s. a Vojtila Trans s.r.o. Doplňkovou linku 725 a bezplatnou nákupní linku 61 ze zastávky Náměstí Hrdinů ve dvou větvích k obchodnímu centru Olympia provozuje společnost Arriva Morava a.s. Předtím od 10. února 2014 provozoval obdobnou linku pro Olympii pod číslem 60 (895060) dopravce Mgr. Jan Žváček.

Historie provozu
Před zahájením oficiální městské linkové dopravy provozovali městští hoteliéři již od roku 1845 vlastní omnibusy, které jezdily z centra města k relativně vzdálenému hlavnímu vlakovému nádraží.

Provoz městské autobusové dopravy v Olomouci oficiálně zahájil 7. února 1927 podnikatel Rudolf Synovec na třech linkách, označených písmeny A, B, C. Vozový park čítal celkem 4 vozy, a to typu Praga AN a Škoda 505.

Roku 1933 městskou autobusovou dopravu převzaly Elektrické podniky hlavního města Olomouce. Roku 1952 byly autobusové linky přeznačeny z písmen na čísla. Roku 1994 bylo zavedeno elektronické odbavování cestujících. 1. ledna 1997 byl zaveden Integrovaný dopravní systém Olomoucka, který představoval především přenechání obsluhy některých okrajových částí Olomouce a přilehlých obcí souběžným příměstským linkám. 3. dubna 2004 byl nahrazen Integrovaným dopravním systémem Olomouckého kraje. V rámci nového rozdělení výkonů mezi příměstskými linkami a MHD od 1. ledna 2018 začaly být linkami MHD opět obsluhovány některé městské části (např. Nedvězí).

Linky

Vozový park
 1959 – zakoupeny první autobusy Škoda 706 RTO
 1969 – zakoupeny první vozy Karosa ŠM 11
 1996 – zakoupeny 2 vozy SOR B 7,5 s plošinou pro vozíčkáře
 2003 – 1. květen byl prvním dnem provozu nízkopodlažních autobusů Solaris Urbino 12 v Olomouci
 2005 – v lednu byl zahájen provoz prvního kloubového nízkopodlažního autobusu Solaris Urbino 18
 2005 – 7. června byl ukončen provoz kloubových autobusů maďarské výroby Ikarus 280
 2009 – jako náhrada za vůz SOR B 7,5 pořízen nízkopodlažní minibus Mave CiBus ENA 3X
 2011 – vyřazeny poslední vozy typu Karosa B 731
 2013 – vyřazen poslední autobus Karosa B 732, služební vůz č. 754
 2013 – zahájení provozu midibusu Solaris Alpino 8,6 a vyřazení zbylého vozu SOR B 7,5
 2014 – 30. září byl vyřazen poslední autobus Karosa B 741, vůz č. 306
 2016 – 22. prosince vyjely na linky první autobusy Solaris Urbino IV. generace
 2017 – od 26. května jsou vypravovány pouze nízkopodlažní autobusy
 2018 – od října zařazen do provozu první elektrobus SOR NS 12
Současný vozový park se skládá z autobusů typu:

Většina linek je obsluhována krátkými (standardními) autobusy. Linky 16 a 19 jsou v pracovní dny obsluhovány výhradně kloubovými autobusy Solaris Urbino 18 (mimo večerních spojů), dále se kloubové autobusy vyskytují i na linkách 10, 12 a 17. V období turistické sezóny jsou od roku 2016 vypravovány také na spoje posilové expresní linky 111, vedoucí na Svatý Kopeček. Na linky 24, 25, 42 a ve dnech pracovního klidu i na linku 13 jsou nasazovány midibusy Solaris. Elektrobus SOR je nasazován na dělené směny linky 14 s přejezdy na linku 31, vůz se v období sedla nabíjí na odstavné ploše.

DPMO k 1. prosinci 2018 vlastnil 78 autobusů, z toho 23 kloubových autobusů Solaris Urbino 18 a 52 krátkých autobusů Solaris Urbino 12. Všechny autobusy ve vozovém parku DPMO jsou nízkopodlažní. K vyřazení posledních vysokopodlažních vozů Karosa B 961 a Karosa B 952 došlo v průběhu června 2017. V létě 2018 došlo též k vyřazení prvních devíti nízkopodlažních autobusů Solaris Urbino 12.

Odstavná plocha

Odstavná plocha autobusů je umístěna na Dolní hejčínské ulici v Hejčíně, nedaleko centra města. Polohově je sice umístěna ideálně, ale počet autobusů výrazně přesahuje maximální kapacitu. Odstavná plocha je doplněna o objekty mycí linky, STK, diagnostiky, dílny lehké údržby apod. Problém ovšem představuje těžká údržba, jejíž pracoviště se nachází v objektu tramvajové vozovny na Koželužské ulici a limituje tak opravárenské možnosti obou trakcí. V současnosti se reálně uvažuje o přesunu autobusových garáží do areálu, kde by byla současně tramvajová vozovna. Umístění tohoto areálu je vytipováno, návrhy na realizaci jsou již zkompletovány, pro stavbu se však nedostává finančních prostředků.

Odkazy

Související články
 Integrovaný dopravní systém Olomouckého kraje
 Tramvajová doprava v Olomouci
 Dopravní podnik města Olomouce

Reference

Externí odkazy

 Dopravní podnik města Olomouce
 Stránky o olomoucké MHD, neoficiální nezávislé stránky
 MHD na Hané, neoficiální nezávislé stránky, rozsáhlá fotogalerie MHD Olomouc
 Olomoucké autobusy, Společnost pro veřejnou dopravu, Michal Lošťák, Lukáš Vrobel, březen 2008, aktualizace 6. 4. 2008
 Olomouc 26. 7. 2004,
 11. 7. 2005, web MHD zastávka, Filip Drápal

Doprava v Olomouci
Olomouc


text:
Netflix Is Starting To Change Its Mind About Theatrical Releases
Published: Nov. 1. 2018 3:42 PM
Netflix may soon join the ranks of having Oscar-winning films under its belt. 2018 marked the year that the streaming service tied with HBO in Emmy wins after years of highly-acclaimed original series releases. Now the company has made a case for film recognition by backing the projects of masterful directors, including Alfonso Cuarón and the Coen Brothers. The studio is now also officially giving three of their releases exclusive runs in theaters before placing them on its streaming service.
Netflix initially planned on simultaneously releasing its award hopefuls in theaters and for streaming, but theaters were understandably concerned. Why would Netflix users pay admission for a ticket to see a movie when it's already waiting for them in their queue at home? Of course, giving one's full attention to a film on the big screen and an at-home watch are completely different experiences, but convenience would sway most in favor of streaming the titles. According to The New York Times, Netflix is cooperating with these concerns and will give its movies Roma, The Ballad of Buster Scruggs and Bird Box some time in theaters before moving them to the streaming platform.
The films will get a limited release period of one to three weeks in theaters to give them each a chance to make box office numbers and garner the attention of the Academy and Hollywood talent to work with them on future projects. Depending on how well the movies do commercially, Netflix expects the select theaters to keep them in their line-up once they hit the streaming platform as well. This compromise hasn't fared well with big theater chains such as AMC and Regal, which still insist upon a 90-day exclusivity period, but maybe the releases could still end up on their rosters.
Gravity's Alfonso Cuarón both penned and directed his Mexico-set passion project inspired by his childhood. Critics who have seen it along the festival circuit have been calling it a masterpiece not to be missed on the big screen. The film is a deeply-emotional chronicle of a year in the life of a family living in Mexico City in the '70s. The film is set to come to theaters on November 21 before hitting Netflix on December 14.
The Ballad of Buster Scruggs is a six-part western anthology from the Coen Brothers starring the likes of James Franco and Liam Neeson. For fans of the filmmakers behind cult hits including Fargo, The Big Lebowski and O Brother, Where Art Thou?, it has certainly earned a shot at the big screen. Bird Box similarly has a star-studded cast as it stars Sandra Bullock, Sarah Paulson, John Malkovich and Lil Rel Howery. The Quiet Place-esque thriller has Bullock hiding and protecting her family and fellow survivors from an unseen threat that can manifest itself into one's darkest fears if seen.
Unlike Roma's near-month theater exclusivity, Buster Scruggs will have theatrical engagements starting on November 8 before it hits Netflix on November 16 and Bird Box will premiere in select theaters on December 13 before its December 21 Netflix debut.
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Matt Haney has become the most visible SF supervisor. Is he eyeing the mayor's office?
Dominic Fracassa, Trisha Thadani
Feb. 12, 2020 Updated: Feb. 12, 2020 8:55 a.m.
1of4Buy PhotoSan Francisco District 6 Supervisor Matt Haney poses for a portrait at Boeddeker Park, located at 246 Eddy Street, in San Francisco, Calif., on Friday, February 7, 2020. Since entering City Hall last year, Haney has quickly emerged as one of the most visible and active supervisors.Yalonda M. James / The ChronicleShow MoreShow Less
2of4Matt Haney, District Supervisor for the Tenderloin, speaks at a protest organized by the Tenderloin People's Congress at Golden Gate and Leavenworth on Friday afternoon, three days after a 12-year-old boy was struck by a man driving without a license and driving under the influence in San Francisco, Calif., on September 13, 2019.Kate Munsch / Special to The ChronicleShow MoreShow Less
3of4Buy PhotoSan Francisco District 6 Supervisor Matt Haney poses for a portrait at the corner of Eddy and Hyde streets in San Francisco, Calif., on Friday, February 7, 2020. Since entering City Hall last year, Haney has quickly emerged as one of the most visible and active supervisors.Yalonda M. James / The ChronicleShow MoreShow Less
4of4San Francisco Supervisor Matt Haney is arrested while protesting with UNITE HERE Local 2 airline catering workers who were demonstrating at SFO calling on American Airlines, which contracts with catering companies, to take urgent and necessary steps to raise wages and offer better healthcare in San Francisco, Calif. on Tuesday, November 26, 2019.Nick Otto / Special to The ChronicleShow MoreShow Less
Ever since winning a spot on the Board of Supervisors by a landslide just over a year ago, Supervisor Matt Haney has quickly established himself as one of the most visible and outspoken public officials in San Francisco.
As the District Six supervisor for such neighborhoods as the Tenderloin, South of Market and Civic Center, Haney oversees one of the most troubled swaths of San Francisco. In the past year, he has approached the job with boundless energy and a laser-like focus on the city's most pressing issues: homelessness, mental health and drug addiction.
While his supporters applaud his stamina, his critics say he has stoked division in City Hall by constantly dressing down city leaders, claiming they are ineffective. His criticisms of mayoral departments are often perceived as a rebuke of the mayor herself.
And as his name recognition grows, a chorus of San Francisco political observers are pondering another question: Does Matt Haney have his eyes on the mayor's office?
In an interview with The Chronicle, Haney objected to speculation of his political ambitions: "I'm not thinking about that at all," he said. "I'm doing the job that I have right now and working to keep the promises that I made to to the residents of District Six."
For years, District Six has been the epicenter of San Francisco's homelessness, mental health and drug crises. Haney says his constituents expect him to focus on one job at a time.
"I don't think I was elected to come in here and be nice to city bureaucrats and the department heads," he said. "I was elected to come in here and get them to do their jobs."
Jim Ross, a longtime political consultant, said it makes sense that Haney is focused on the city's most pressing issues.
"His district is really ground zero for a lot of issues," he said. "His work on that is going to put him out in front, naturally."
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Still, his first year on the Board of Supervisors — filled with a stream of legislation and a spirited presence on social media — suggests his aspirations may stretch far beyond the district's borders.
"That's not even a question," said Del Seymour, a longtime Tenderloin activist, when asked whether Haney seemed like he was seeking higher office.
With Breed barely a month into her first full term as mayor, some political observers said it was too soon to guess who might take her on in the next election. But the mayor and her staff appear to be sizing Haney up as a potential rival.
"The mayor was just sworn in for a four-year term a month ago, and we are focused on addressing the very real challenges facing our city, especially around housing and homelessness," said Jeff Cretan, a spokesman for the mayor's office.
"We will continue to work with the members of the board to advance solutions to address these issues," he said.
Randy Shaw, director of the Tenderloin Housing Clinic, and a reliable Breed supporter, said the mayor's staff members think Haney is readying for a run.
San Francisco District 6 Supervisor Matt Haney converses with Dawn Starr, of Tenderloin Safe Passage, on Ellis Street in San Francisco, Calif., on Friday, February 7, 2020. Since entering City Hall last year, Haney has quickly emerged as one of the most visible and active supervisors.Yalonda M. James / The Chronicle
Before becoming a supervisor, Haney was a longtime school board member who'd worked at a social justice nonprofit and taught law and sociology.
During his tenure, Haney and other board members have been deeply critical of the Department of Public Health, the Juvenile Justice Department and Public Works.
"Everything that I'm doing is to make changes happen up against a bureaucracy that is continuing to fail my district," Haney said.
Over just the past few months, Haney has pushed forward legislation to overhaul the city's mental health care system and is readying a November ballot measure to break up Public Works into two departments.
But in following his political instincts to seize the spotlight, Haney has stumbled at times. After sparring for months with Public Works over street cleaning, Haney called for the ouster of its powerful director, Mohammed Nuru, after Nuru was charged with fraud this month.
Supervisor Matt Haney during a board meeting on Tuesday, June 4, 2019, in San Francisco, Calif. The Board of Supervisors voted to shut down juvenile hall by the end of 2021.Santiago Mejia / The Chronicle
But Haney had to walk back his remarks after an organization that represents government managers said he may have been flirting with official misconduct. The city's Charter forbids supervisors from influencing hiring and firing decisions. Haney later tweeted that "so much time and energy" had been expended "trying to prevent me from speaking out" about Nuru.
Privately, members of Breed's staff fumed at Haney's outspokenness on the issue.
"It's great that Matt is pushing on a lot of fronts. But since the Nuru thing, he's been a little more combative than strategic," said Shaw. "The notion has been that 'Nuru did all this and it connects to London Breed and her administration's culture.' It's perceived by her people as 'Matt's running for mayor.'"
Breed's public response to Haney's criticisms has been generally muted. And while both Haney and Breed's office say they're always willing to work together, the friction is clear.
City employees, non-profit providers, doctors, nurses, social workers, and countless others are working every single day to address the public health crisis brought on by drug addiction.
Let's do more, but let's not pretend that nothing's being done. https://t.co/vSV9C7LzuG
— Mayor London Breed's Press Office (@MyrPressOffice) January 10, 2020
Last week, Haney said he received "no heads-up" before Breed announced a plan to open a sobering center for methamphetamine users in his district. Shaw said keeping Haney in the dark about the proposal meant Tenderloin residents also weren't informed about an important development in their community.
"We're in an unfortunate dynamic where the mayor thinks getting back at him requires the disenfranchisement of the Tenderloin," he added.
Meanwhile, some legislation sponsored by Haney has made a splash in City Hall, but also rankled the mayor.
Perhaps the most notable was Mental Health SF, a sweeping plan to overhaul the city's behavioral health care system. He spearheaded the proposal with Supervisor Hillary Ronen.
The plan rankled Breed and the Department of Public Health, who say they weren't consulted in the plan's creation. Breed and the department then came up with their own competing plan, which they said was more realistic.
Yes! The pressure is working. I hope to see more Navigation Centers proposed and announced even before our legislation is passed the Board. https://t.co/FoSkPQSPIg
— Matt Haney (@MattHaneySF) December 19, 2019
In the end, they compromised, but Ronen and Haney argued the overhaul wouldn't have happened without their leadership.
Ronen praised Haney's work ethic. "I get texts from him early in the morning and late at night with ideas and worries and frustrations about what is going on. We've shared similar struggles to get departments to be responsive," she said.
Among his colleagues, Haney was behind only Supervisor Aaron Peskin in the number of pieces of legislation sponsored in 2019.
Some of the proposals called out the executive branch for what he sees as ineffective leadership. For example, he tried — and failed — to get a measure on the November ballot to create an oversight commission for the Department of Homelessness and Supportive Housing. The proposal frustrated Breed, who argued it would increase bureaucracy.
Now Haney is fighting to get a homeless shelter in every district that doesn't have one — a response to the majority of homeless resources landing in his district. But some of his board colleagues are not thrilled.
San Francisco District 6 Supervisor Matt Haney checks his phone while standing in Boeddeker Park, located at 246 Eddy Street, in San Francisco, Calif., on Friday, February 7, 2020. Since entering City Hall last year, Haney has quickly emerged as one of the most visible and active supervisors.Yalonda M. James / The Chronicle
Haney's supporters say he is genuinely fighting for the needs of his district. Seymour, the Tenderloin activist, said over his 37 years working in the neighborhood, he has never seen a supervisor out on the streets as much as Haney.
"We see him in the Tenderloin daily, which I have never seen with a supervisor," he said.
Privately, Haney's critics claim he offers a lot of empty bluster — hearings and task forces — that have yielded few tangible results.
Haney rebukes the criticism that he is too active, but doesn't deliver change.
"I could write legislation to basically micromanage everything that every department is doing. Nobody wants me to do that. Instead I'm trying to force them to actually be responsible and accountable, and wherever I have the opportunity, I will legislate," Haney said.
Jason McDaniel, a political scientist at San Francisco State University, said Haney's status as a newcomer in San Francisco politics has given him the freedom to call out the so-called establishment.
"He is active," McDaniel said. "But I've been wondering if it's because I'm on Twitter a lot and so is he — or if it's something else."
Dominic Fracassa and Trisha Thadani are San Francisco Chronicle staff writers. Email: dfracassa@sfchronicle.com, tthadani@sfchronicle.com Twitter: @dominicfracassa, @TrishaThadani
Dominic Fracassa
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Dominic Fracassa is an assistant metro editor overseeing breaking news and criminal justice in San Francisco. He previously covered San Francisco City Hall as a staff writer.
Trisha Thadani
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Trisha Thadani is a City Hall reporter for The San Francisco Chronicle. She previously covered work-based immigration and local startups for the paper's business section.
Thadani graduated from Boston University with a degree in journalism. Before joining The Chronicle, she held internships at The Boston Globe, USA Today, The Wall Street Journal, and was a Statehouse correspondent for the Worcester Telegram & Gazette.