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Kraft Kitchens Tips Heat oven to 375°F. Prepare stuffing as directed. Place chicken in 13x9-inch baking dish or 2-qt. casserole. Mix soup and sour cream; pour over chicken. Top with stuffing. Bake 35 min. or until chicken is done. Awesome recipe! I couldn't believe how fast this was to make, and I loved how creamy the soup mixture made the stuffing. I used low fat cream of chicken soup and fat free sour cream and it didn't taste low fat at all. I only used three pieces of chicken (just my fiancee and I) so we had a lot of yummy leftovers for our lunches today! Scamp9393 posted: 1/14/2007 This meal is perfect for busy people. I was able to make the meal and clean up while making it. Flavorful and looks like it took a while to make. kpeace05 posted: 1/5/2007 me and my husband really enjoy this recipe we have made it a few times and last time we cut up the chicken and it was great that way. Smaller pieces. CaroleJeanne123 posted: 12/14/2006 An excellent one-dish meal. I sauteed some sliced 'baby bello' mushrooms & red peppers with the chicken breasts and liked the additional flavor they provided. Sonoma Gal posted: 11/16/2006 We love this!! We added broccoli & fresh mushrooms to make it a one-dish meal! tbengineer posted: 10/20/2006 My daughter and I found the recipe on the back of a 6oz box of Stovetop stuffing mix. We thought the recipe seemed to be a bit dry and we decided to go on-line to check. Thanks for having this web site. The back of the box left out ONE IMPORTANT STEP. It neglected to have us add 1 1/2 cups of water and 1/4 cup of butter. Dinner was saved by the aid of your wonderful web site thank-you a cook posted: 9/26/2006 This is a good and easy recipe. My kids loved it and had a second helping. I used cornbread stuffing and a can of mushrooms too. carolynlf1 posted: 9/1/2006 It was an easy and fast meal. Next time I make this, I will dilute the sauce with a little bit of milk and put the stuffing on the side.
No Scrub Method for cleaning stove burner grates: Seal in a plastic bag with a little ammonia (doesn't need to cover grates). Let sit overnight and the ammonia fumes will break down burnt on grease, etc. Next day, wipe clean with sponge. How to Refill your Swiffer How to Refill your Swiffer I love my Swiffer Wet Jet. I can not afford the… More ideas Swiffer Wet Jet Refills - How To Save Money By Making Your Own Homemade Cleaning Solution How to make your own Swiffer Wet Jet solution refills - plus how to get off that top that's so hard to remove! This saves SO much money because those refill bottles are crazy expensive! If you’re a home or pet owner, you’ve probably become very acquainted with a household appliance called the Swiffer. You know, the modern looking sweeper that picks up unwanted dirt and debris around your household. Well, if you are familiar with this cleaning device then you’re prob.. How to Clean Grease From Kitchen Cabinet Doors No more greasy cabinets! Here are a few different solutions that can help you get your kitchen cabinets squeaky clean: www.ehow.com/... How To Clean A Microwave With Vinegar & Steam; No Scrubbing! Microwave cleaning tip... My microwave has never looked like this, but I really want to try this out to see if it really works! This could be the fastest way to clean your blinds Everyone who owns a gas stove, pin this!! It works! Mine were absolutely disgusting and I tried everything to clean them. It was so gross how much came off! Definitely the best stove grate cleaner ever. Do-It-Yourself Swiffer Pad Refills Make your own Swiffer Cloth refills. Now to find a natural alternative to the Swiffer cleaning solution... Keep Home Simple: How to Clean Dirty Blinds (with an old sock and vinegar+water or rubbing alcohol). Heavy Duty Floor Cleaner DIY Get those grimy floors clean with this heavy duty floor cleaner! It is perfect for getting rid of the "boy bathroom" smell! How to: Clean Window Tracks How to Clean Window Tracks: white vinegar and baking soda (or hydrogen peroxide!) 30 Q-tips toothbrush hot water paper towels Sprinkle baking soda into the corners, then pour in some vinegar. The baking soda will begin to bubble and loosen up the cruddy stuff. When the bubbling calms down, begin to make circle motions with a Q-tip, then go back into the corners and sweep the muck towards the middle. Pour warm water from the corner to the center. Use your paper towels to wipe everything dry.
Working water pump as used by the fire brigade. Was originally hand carried by two persons and hand pull start (hard work) now converted to battery start and wheels for easy movement. Petrol hillman imp engine. 3 lengths of flexible hose, 3 wat...
The unsung heroes MASERU-As businesspeople heaved a sigh of relief following the lifting of the lockdown last Tuesday, for midwife, Mamello Makhele, the action had a much bigger meaning – saving mothers from pregnancy-related deaths.For the duration of the lockdown, imposed to prevent the spread of coronavirus at the beginning of April, Makhele, a midwife at Katse Health Centre, had been in anguish. Due to lack of reliable public transport as a result of the lockdown, many of her patients could not access much-needed lifesaving medical services.Her work is her passion and seeing women go without the services that could save their lives and that of their babies left her with a feeling of desperation. Child deliveries became dangerous during the lockdown, as some women were forced to give birth in unsafe home deliveries.“It wasn’t because there were soldiers but because they travel long distances to get to the clinic,” she said, adding that “there were no taxis”.Makhele told thepost in a telephone interview that she is happy because she can now resume her duties without hindrances. “Now the women have resumed their ante-natal visits,” Makhele said, adding that the situation got so desperate that at one time she had to assist a woman in one village deliver her baby at home during the lockdown.People who come to Katse Health Centre often travel long distances for services, with some travelling for up to 10 hours from places such as Senqunyane. It was not only pregnant women that got Makhele worried.In one of her catchment areas, family planning pills and services became unavailable.“This is because of the disturbed global chain supply,” she said.“Airports and border posts are closed. How are we going to get FP (family planning)’s from India to Lesotho?” she said. “This is just an assumption that there will be a decline in FP intake.” Makhele foresees an influx of teenage pregnancies because young people are more exposed to sexual activities when they are idle.“During the lockdown there is really not much to do as a form of entertainment especially when schools are closed,” she said. “They get married young too because they are in a cultural setting that has normalised getting married young. Our teenage corner is closed because of the Covid-19 and this has also contributed to the challenges they face,” she said. Statistics also show that gender-based violence was on the rise during the lockdown and this may translate into a rise in unplanned pregnancies, Makhele said.She said amidst the turmoil, the country should celebrate the unsung heroes of health during this lockdown because they have made “mighty strides to put the health system in the position it is today”. She said service delivery is better than during the past years. “More people are accessing health services and there is more mobilisation of information for people who have stayed uninformed.”Midwives are the cornerstone of Sexual Reproductive Health Rights (SRHR) of women. “We have done well to save a lot of lives and bring lives into the world,” Makhele said.“Midwives play an essential role and they go beyond the call of duty in ensuring a safe delivery of a baby and its mother,” she said.“Not only to ensure safe delivery but you take a mother through the stages of pregnancy, labour stage and post-partum and until the baby is five years old.” She said in the rural areas, midwives help young mothers as young as 13 years old who go through a lot of emotions.“Midwives ease the journey of these young mothers, encouraging them through the journey, advising them. Some of them were forced into child marriages.” “Midwives in the rural areas are the pillars of the health system. They offer services against all odds and go beyond the call of duty”.Makhele’s passion for her job brings to mind the words of Robin Lim, a US midwife and founder of Yayasan Bumi Sehat (Healthy Mother Earth Foundation) health clinics, which offer free prenatal care, birthing services and medical aid to anyone who needs it. Robin Lim’s famous quote says: “After disasters, reproductive healthcare falls by the wayside. Yet babies continue to be born. When all infrastructure falls apart, when the hospitals and all their technological equipment are destroyed, midwives come in handy. They can help a woman give birth with or without electricity, running water, equipment- even shelter is optional. When babies are ready, they come.” This quote depicts the realities of midwives in Lesotho.Most endure tough conditions in rural areas where women deliver in the absence of essential basics such as adequate shelter, electricity and running water. On Tuesday last week, the world celebrated International Day of the Midwife during the Covid-19 epidemic that has killed over 290 000 while infecting another 4.8 million people worldwide.Lesotho has one confirmed case of the Covid-19 disease.In February the Ministry of Health, in collaboration with nursing institutions and associations in the country, launched the 2020 international year of the nurse and midwives. According to the United Nations Populations Fund (UNFPA)’s Lesotho suppliers’ coordinator, Tšeliso Masilo, the trends of women on contraceptives, antenatal clinic visits by skilled labour, skilled birth attendance, institutional delivery and post natal care has changed over the years. Different statistics from Lesotho Demographic Health Survey (LDHS) of 2004, 2009, 2014 and Multiple Indicator Cluster Survey (MIC’s) reports demonstrate a health shift and positive growth in health accessibility.The reports show that contraceptive intake among married women has increased from 35 percent in 2004 to 64.9 percent in 2018. They also show that ante-natal skilled provider increased from 90 percent in 2004 to 91.3 percent in 2014, skilled birth attendance between 2004 and 2018 has increased from 55 percent to 86 percent while institutional delivery from 52 percent to 89.4 percent and post natal care from 39 percent to 84 percent. All of this work and more is done by a nurse midwife in Lesotho.Unlike in the past years when nurses and midwives would gather to celebrate the day, the outbreak of coronavirus has made this year different.Covid-19 has disrupted the usual celebratory gatherings due to demands of social distancing and avoiding closed congested spaces. In a statement marking the day, the UNFPA Executive Director Dr Natalia Kanem said in countries hard hit by the Covid-19 crisis, midwives are dying due to lack of personal protective equipment (PPE) and overall lack of support. She said midwives are redeployed to respond to the crisis and this leaves women without access to life saving, time critical services.
My sickness has been going on for a few days now, but it only really kicked in yesterday. Basically i have a sore throat, with a stuffy nose. Last night I was able to sleep fine thanks to some sleeping pills I took. But tonight I didn't take any, and now I am having trouble staying asleep. I was advised by my mother to call our family doctor for medicine and to have a prescription filled but it's been icing and snowing so bad I wouldn't be able to leave campus even if my car started in this cold. I've tried praying and reading scripture, I suppose even if I cannot sleep it would be better if I did something since suffering is always an important time to turn towards God. (seeing as I haven't been as faithful recently) I may try and see if we have anything to help with my throat, but since we are kind of isolated on campus atm, there isn't much I can do to be able to run to a grocery store or a pharmacy (or even the hospital 2 blocks away)... Please, I need prayers right now, I don't believe this is just a passing sickness, it may indeed be something a bit more reflective of my soul at the current time. Through your prayers and the prayers of the Saints, I am confident I will become well in soul and body. "O Cross of Christ, all-holy, thrice-blessed, and life-giving, instrument of the mystical rites of Zion, the holy Altar for the service of our Great Archpriest, the blessing - the weapon - the strength of priests, our pride, our consolation, the light in our hearts, our mind, and our steps"Met. Meletios of Nikopolis & Preveza, from his ordination. As a result of a thousand million years of evolution, the universe is becoming conscious of itself, able to understand something of its past history and its possible future.-- Sir Julian Sorell Huxley FRS Thank you all very much for your prayers,I finally fell asleep and finally stayed asleep. I'm feeling better than I felt yesterday. After talking to my mother (who has been working in the medical field for longer than i've been alive, about 21 years), I think we'eve detirmined the prescription i had taken (Phenavent or Pseudovent) had possibly kept me awake because I had taken it way too late. (midnight) Hopefully I can keep getting better and keep praying, Lord knows I certainly need to get back on track spiritually. I am also confident with your prayers and the prayers of my Patron Saint (well not officially, but I am named after him) Luke, I can be healed. Feeling a bit better, I may be near the end of my illness. The fluid from my sinus infection has been going down my throat causing a lot of throat pain (I was unable to sleep very much last night).I'm still taking medicine, but it only helps during the daytime. My parents will be sending me some nighttime medicine soon. Hopefully this is almost over, I have a full day of classes tomorrow and it was hard to just get through the one I had today.
The Lipscomb Bisons golf team finished fifth in the 2006 Comfort Inn and Suites Belmont Intercollegiate held at Old Natchez Trace Country Club. The Bisons shot 875 (219-292-292) as a team in the 54-hole tournament Monday and Tuesday in the 11-team tournament. Lipscomb's Taylor Lewis finished eighth overall with a three-round total of 214 (69-73-72). Dustin Lynch tied for 12th place with a score of 217 (72-74-71). Cody Hale tied for 16th with a score of 220 (74-70-76). Parker Beck tied for 29th with a 224 (76-75-73). Paul Warren finished 64th with a 243 (81-85-77).
Palais Galliera The Palais Galliera, also formally known as the Musée de la Mode de la Ville de Paris (City of Paris Fashion Museum), and formerly known as Musée Galliera, is a museum of fashion and fashion history located at 10, avenue Pierre 1er de Serbie, in the 16th arrondissement of Paris, France. The museum has no permanent displays due to conservation issues. When exhibitions are on it is open daily except Mondays and public holidays; an admission fee is charged and varies depending on the exhibition programmed. The museum opened its doors again 28 September 2013 after being closed for major renovation. Palais Galliera is one of the 14 City of Paris museums that have been incorporated since 1 January 2013 in the public institution Paris Musées. History The Duke of Galliera was a partner in the urban planning firm Thome & Cie, and owned a large parcel of land in one of the finest neighborhoods in Paris. Upon his death in 1876, his wife, Marie Brignole-Sale de Ferrari, the Duchesse de Galliera, became heir to his immense fortune. The duchess decided that she wanted to use the land to build a museum, at her expense, to hold their works of arts. According to her wishes, a notary prepared a deed of gift to give the land parcel to the French state. However, after the gift was registered and accepted by presidential decree on 30 August 1879, it was discovered that the notary had made a serious error. Rather than donating the parcel to France, the deed was written as a gift to the City of Paris. Unable to change the deed at this point, the gift remained as written. Construction of the museum began in 1879 on an opulent design by architect Léon Ginain, who also supervised its construction. In 1884, the Duchess gave 6.5 million francs to the City of Paris for work already done as well as funds necessary to complete it. On 22 June 1886, Jules Grévy and Georges Clemenceau convened the Chamber of Deputies of the French Third Republic and adopted a law expelling any person who was a direct heir of a royalist dynasty that had reigned in France. The Duchess Galliera, who had descended from the House of Orléans, was outraged by the law, no less because she had already donated the Hôtel Matignon to France. Unable to revoke her gift of the new museum, she abandoned the rest of her planned legacy to Paris. Thus, her collection of paintings and fine art were given to Genoa, Italy, where they are now displayed at the Palazzo Rosso and Palazzo Bianco. The Duchess died in December 1888, before the museum was completed, but in May 1889, her heirs gave the City of Paris 1.3 million francs to finish its construction. Léon Ginain completed the museum in February 1894, which was officially received by the city a few months later, in July. In the absence of the Galliera art collection, for which it was designed, the City of Paris used the museum for temporary displays. The first exhibition, devoted to portraits of women and lace, was inaugurated by President Félix Faure on 1 March 1895. It became a museum of industrial arts in 1902, and later, it served as space for temporary shows of modern art. The city also rented it to auctioneers for prestigious sales. The building The Palais Galliera faces Brignole Galliera Square, immediately north of the Palais de Tokyo and one block east of the Musée Guimet. The architect Léon Ginain based his design on a palace that the Duchess Galliera owned in Genoa. The building is faced in cut stone in the Italian Renaissance style supported by an underframe of steel, constructed by the Eiffel Company. The mosaic floors and domes are the work of Giandomenico Facchina (1826–1904). The statues on the façade that fronts Avenue du President Wilson represent "Painting" by Henri Chapu, "Architecture" by Jules Thomas, and "Sculpture" by Peter Cavelier. In 1916, a fountain was built in front of the museum. Fashion Museum Since 1977, the City of Paris has operated the Palais Galliera as the Musée de la Mode de la Ville de Paris, a permanent museum devoted to fashion. It displays exhibits of French fashion design and costume from the eighteenth century to the present day. The museum is closed in between exhibitions. The museum's holdings contain about 70,000 items, and are organized as follows: Costumes - from the 18th century to the present, including clothes owned by Marie-Antoinette, Louis XVII, and the Empress Josephine, the dress worn by Audrey Hepburn in Breakfast at Tiffany's (1961), and displays of fashions by the leading 19th and 20th century designers including Balenciaga, Pierre Balmain, Anne-Marie Beretta, Louise Chéruit, Sonia Delaunay, Christian Dior, Jacques Fath, Mariano Fortuny, Jean Paul Gaultier, Givenchy, Paul Poiret, Paco Rabanne, Yves Saint Laurent, and Elsa Schiaparelli. Undergarments - an excellent collection of slips, corsets, crinolines, etc. Accessories - including jewelry, canes, hats, fans, purses, scarves, gloves (including a pair owned by Sarah Bernhardt), parasols, and umbrellas. Graphic arts and photography - stamps, drawings, photography, advertisements, etc. See also List of museums in Paris References Hubert Demory, Auteuil et Passy : De l'Annexion à la Grande Guerre, Paris:L'Harmattan, Béatrice de Andia, Le 16e : Chaillot - Passy - Auteuil : Métamorphose des trois villages, Paris:Délégation à l'Action Artistique de la Ville de Paris, External links Official Palais Galliera site Galliera Museum page on Paris Musées' website Paris Musées official website ParisInfo entry Category:Museums in Paris Category:Buildings and structures in the 16th arrondissement of Paris Category:Fashion museums in France Category:Museums established in 1895 Category:1895 establishments in France
#!/bin/bash onion compile \ --lib src \ --lib vendor/corneltek/cliframework/src \ --lib vendor/corneltek/getoptionkit/src \ --lib vendor/corneltek/universal/src \ --classloader \ --bootstrap scripts/pux-emb.php \ --executable \ --output pux.phar mv pux.phar pux chmod +x pux
/* * Hibernate Validator, declare and validate application constraints * * License: Apache License, Version 2.0 * See the license.txt file in the root directory or <http://www.apache.org/licenses/LICENSE-2.0>. / package org.hibernate.validator.ap.testmodel; import org.hibernate.validator.constraints.ISBN; /* * @author Marko Bekhta */ public class ModelWithISBNConstraints { @ISBN private String string; @ISBN private CharSequence charSequence; @ISBN private Integer integer; }
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Bill Gates and Richard Branson Back Startup That Grows Clean Meat Cargill Inc., one of the largest global agricultural companies, has joined Bill Gates and other business giants to invest in a nascent technology to make meat from self-producing animal cells amid rising consumer demand for protein that’s less reliant on feed, land and water. Memphis Meats, which produces beef, chicken and duck directly from animal cells without raising and slaughtering livestock or poultry, raised $17 million from investors including Cargill, Gates and billionaire Richard Branson, according to a statement Tuesday on the San Francisco-based startup’s website. The fundraising round was led by venture-capital firm DFJ, which has previously backed several social-minded retail startups. "I’m thrilled to have invested in Memphis Meats,” Branson said in an email in response to questions from Bloomberg News. “I believe that in 30 years or so we will no longer need to kill any animals and that all meat will either be clean or plant-based, taste the same and also be much healthier for everyone.” This is the latest move by an agricultural giant to respond to consumers, especially Millennials, who are rapidly leaving their mark on the U.S. food world. That’s happening through surging demand for organic products, increasing focus on food that’s considered sustainable and greater attention on animal treatment. Big poultry and livestock processors have started to take up alternatives to traditional meat. “The world loves to eat meat, and it is core to many of our cultures and traditions,” Uma Valeti, co-founder and chief executive officer of Memphis Meats, said in the statement. “The way conventional meat is produced today creates challenges for the environment, animal welfare and human health. These are problems that everyone wants to solve.” ‘Clean Meat’ To date, Memphis Meats has raised $22 million, signaling a commitment to the “clean-meat movement,” the company said. Cargill has “taken an equity position in Memphis Meats’ first series of funding,” Sonya Roberts, the president of growth ventures at Cargill Protein, said in an email, without disclosing the investment amount. “Our equity position with Memphis Meats gives Cargill entry into the cultured protein market and allows us to work together to further innovate and commercialize,” Roberts said. “We believe that consumers will continue to crave meat, and we aim to bring it to the table, as sustainably and cost-effectively as we can. Cultured meats and conventionally produced meats will both play a role in meeting that demand.” The investment is just the most recent by traditional meat companies. Tyson Foods Inc., the largest U.S. meat producer, has created a venture capital fund focused on investing in companies “to sustainably feed” the world’s growing population and in December announced a stake in plant-based protein producer Beyond Meat, which counts Gates among its early funders.
Q: Update totals in another table when changes made to the current table I have this table ID Name Price 1 John 12 € 2 John 35 € 3 Alex 15 € 4 Alex 12 € 5 James 10 € I need a query that update a field in another table, summing up all the values in price field that have the same name. For example the results of the query in this case would be: ID Name Price 1 John 47 € 2 Alex 27 € 3 James 10 € A: With Access 2010 and later we can use Data Macros to accomplish this:
Q: Can a flying predator have slit-like pupils? In an alien world, much alike earth, exists a theropod-like aerial predator, slightly larger than a lion, which also hunts on land. The creature's eyes occupy around 30% of its face, for hunting both during the day and at night. Now as far as I am aware of, slit shaped pupils are great for hunting at both day and night and provide good depth perception, being common in ambush predators, but it's not as common in animals "far" from the ground, as we see in cats having slit pupils but most panthers having round ones. Would it be possible to have something akin to a slit shape on a flying creature (maybe something like a target shape?) or should I just stick with a round one? A: Skimmers, which are real-life birds, have slit pupils. Given their rarity, the evolutionary advantage of slit pupils seems pretty minor. The good news is that you can give your flying predator whatever eye type you like. Having an aerial predator bigger than a lion may be more of an issue, don't sweat the small stuff...!
William Bundey William Bundey may refer to: William Bundey (mayor) (1826–1889), mayor of Adelaide, South Australia 1883 to 1886 William Henry Bundey (1838–1909), Australian politician and judge, Attorney-General of South Australia 1878 to 1881
Spatial regulation of actin dynamics: a tropomyosin-free, actin-rich compartment at the leading edge. Rapid polymerization of a network of short, branched actin filaments takes place at the leading edge of migrating cells, a compartment enriched in activators of actin polymerization such as the Arp2/3 complex and cofilin. Actin filaments elsewhere in the cell are long and unbranched. Results reported here show that the presence or absence of tropomyosin in these different actin-containing regions helps establish functionally distinct actin-containing compartments in the cell. Tropomyosin, an inhibitor of the Arp2/3 complex and cofilin function, was localized in relation to actin filaments, the Arp2/3 complex, and free barbed ends of actin filaments in MTLn3 cells, which rapidly extend flat lamellipodia following EGF stimulation. All tropomyosin isoforms examined using indirect immunofluorescence were relatively absent from the dynamic leading edge compartment, but did colocalize with actin structures deeper in the lamellipodium and in stress fibers. An in vitro light microscopy assay revealed that tropomyosin protects actin filaments from cofilin severing. The results suggest that tropomyosin-free actin filaments under the membrane can participate in rapid, dynamic processes that depend on interactions between the activities of the Arp2/3 complex and ADF/cofilin that tropomyosin inhibits elsewhere in the cell.
FILED Pursuant to Ind.Appellate Rule 65(D), this Memorandum Decision shall not be regarded as precedent or cited before May 21 2012, 9:10 am any court except for the purpose of establishing the defense of res judicata, collateral estoppel, or the law of the CLERK of the supreme court, court of appeals and case. tax court ATTORNEY FOR APPELLANT: ATTORNEYS FOR APPELLEE: DAVID M. PAYNE GREGORY F. ZOELLER Ryan & Payne Attorney General of Indiana Marion, Indiana J.T. WHITEHEAD Deputy Attorney General Indianapolis, Indiana IN THE COURT OF APPEALS OF INDIANA JOSEPH JESSE CLARK SMITH, ) ) Appellant-Defendant, ) ) vs. ) No. 27A05-1108-CR-415 ) STATE OF INDIANA, ) ) Appellee-Plaintiff. ) APPEAL FROM THE GRANT SUPERIOR COURT The Honorable Dana J. Kenworthy, Judge Cause No. 27D02-1104-FB-89 May 21, 2012 MEMORANDUM DECISION - NOT FOR PUBLICATION BROWN, Judge Joseph Jesse Clark Smith appeals his convictions and sentences for criminal trespass as a class A misdemeanor,1 intimidation as a class A misdemeanor,2 and two counts of theft as class D felonies.3 Smith raises three issues, which we revise and restate as: I. Whether the court abused its discretion in permitting the State to elicit certain testimony from a witness; II. Whether the evidence is sufficient to sustain Smith’s convictions; and III. Whether the court abused its discretion in sentencing Smith. We affirm. The relevant facts follow. In April 2011, Arlyn Wilson was eighty-two years old with Alzheimer’s Disease and suffered from short-term memory loss. Howard Mundt lived next door to Wilson since 1960, and Marilee Murphy lived across the street from Wilson since 1967. Wilson had an accountant who was responsible for writing checks for many of Wilson’s bills. In addition, Wilson was assisted by two caregivers, Frankie Fanning and Elicia Bockover, who worked for Fanning. Fanning or Bockover went to Wilson’s home two times each day to prepare food and medication for Wilson. Either Fanning or Bockover would stay with Wilson from approximately 7:00 a.m. to 10:00 a.m. and again from 4:00 p.m. to 7:00 p.m. Wilson’s yard was cared for by Ron Campbell, who was responsible for cutting the grass and trimming the trees on Wilson’s 1 Ind. Code § 35-43-2-2 (Supp. 2009). 2 Ind. Code § 35-45-2-1 (Supp. 2006). 3 Ind. Code § 35-43-4-2 (Supp. 2009). 2 property as well as on Murphy’s property. Also, Fanning would sometimes work in the yard with Wilson and pick up sticks and leaves. On one occasion in the summer of 2010, Murphy observed Smith walking around Wilson’s house and it caused her concern. Murphy walked over to Wilson’s house, and she and Wilson went into the yard to speak to Smith. Murphy observed a vehicle parked in front of the house with a woman and some children in it. Smith indicated he wanted to clean up the needles under Wilson’s large spruce trees. Smith did not have any tools with him at the time. Smith quoted a price of $150 to remove the needles, and Wilson stated she did not have the money to do that. Smith then offered to do the work for $100, and Wilson “still said no” and “did not want that done.” Transcript at 195. Smith was “quite persistent” and stated that Wilson knew who he was and that he had done work for her before. Id. Murphy asked for Smith’s name and repeated to Smith what Wilson had said by stating “No, she doesn’t want anything done with this now” and that “she’s declined and he ought to leave.” Id. Smith then entered the vehicle parked in front of Wilson’s house and drove away. Approximately twenty minutes later, Smith returned in a truck, and Murphy returned to Wilson’s house. Wilson and Murphy “reiterated the same thing and told him again” that Wilson did not desire that any work be performed. Id. at 197. Smith then entered the truck and drove away. On another occasion during the summer of 2010, Wilson’s caregiver Fanning arrived at Wilson’s house in the afternoon and observed Smith, Smith’s wife Christa, and a toddler in the backyard. Id. at 94. Fanning asked Wilson what Smith was doing and Wilson said she didn’t know. Smith told Fanning that “they were cleaning up something 3 in the backyard” and that “they had been hired to do a job and they were trying to complete it.” Id. However, Fanning “didn’t see any evidence of that” and noticed that “they weren’t doing anything but letting their toddler crawl all over the table on the back patio.” Id. Fanning then asked Smith to leave. On April 18, 2011, Smith visited Wilson’s house at about 1:00 p.m. Smith knocked on the front door, and Wilson let him inside. Wilson wrote a check payable to Smith in the amount of $140, and Smith cashed the check. The following day, on April 19, 2011, caregiver Bockover arrived at Wilson’s house at approximately 4:00 p.m. The interior front door to Wilson’s house was open, and the exterior glass storm door was closed. At some point a man named Floyd drove Smith to Wilson’s house and waited in his vehicle for Smith. At approximately 5:30 p.m., while Wilson was seated at the dinner table eating, Smith knocked on the front door of the house, and Bockover answered the door. Bockover opened the exterior storm door “[m]aybe six, 12 inches,” which was not “enough for an individual to slide in,” to speak to Smith and asked if she could help him. Id. at 141. Smith asked if Bockover’s grandmother was home, and Bockover replied that Wilson was not her grandmother but that she was home. Bockover “turned to [Wilson] from the door,” let the door “go shut,” and “went to tell [Wilson] that there was somebody at the door and when [she] turned back around to tell [Smith] that [Wilson] would be right there, he was walking past [her].” Id. at 141-142. Bockover stated to Smith: “Well, wait. Hold on. She’ll come to the door.” Id. at 142. Smith stated “Well, she knows who I am. . . . I worked here for years and done tree 4 work.” Id. Bockover responded and stated “that’s fine. She’ll come to the door. . . . [S]he’s eating dinner and she’ll just come to the door and speak to you.” Id. Smith then stated that he needed “his pay for the tree service.” Id. Bockover had not previously seen Smith, knew that Ron Campbell usually cared for Wilson’s yard, and called Fanning. After Bockover told Fanning about Smith’s visit, Fanning said “No, [Wilson] pays Ron Campbell and that’s the only person that was supposed to [be] doing yard work and anybody else should come with an appointment.” Id. at 144. Smith stated that he “had a lot of brush from the trees that he had trimmed and he had done yard work,” that “he had to pay to get rid of” the tree brush, and that “[t]hat’s why he needed his money that day to pay his crew.” Id. at 145. Smith stated that he had completed the work “the day before and earlier that day.” Id. Bockover had walked around the yard earlier in the day and did not notice anyone working, any work that had been done, or any “fresh cuts” in the yard. Id. at 147. Bockover told Smith to wait at the door and that Fanning “does [Wilson’s] finances so in order for [Smith] to get a check, [he] should come back tomorrow” when Fanning was present. Id. Smith told Bockover “no” and that he “needed his money now so he could pay his crew.” Id. at 148-149. Bockover told Smith that he “really need[ed] to come back when you don’t smell like alcohol and you’re sober,” and Smith said, “You don’t smell alcohol, you smell my cologne.” Id. at 149. Smith’s “face was turning red,” and Bockover believed he was becoming angry. Id. During this time Wilson was standing back and looked “intimidated and nervous.” Id. at 148. She retrieved her checkbook and asked Smith “how much can I give you 5 today . . . so you can come back with an appointment tomorrow,” and Smith “said something like $250” and “I’ll knock $40 off of it.” Id. at 151. Wilson then started to write a check. Bockover “picked up her cell phone and dialed 911 and [] didn’t say anything [be]cause [she] didn’t want [Smith] to know [she] was calling the cops.” Id. Smith “slammed his hand down on the piano” and said “Come on, [Wilson]. She’s calling the cops.” Id. Smith was telling Wilson “to hurry up because his ride was leaving him.” Id. at 152. Wilson finished writing a check for $150, handed it to Smith, and he returned to Floyd’s vehicle and told Floyd, “[j]ust go.” Id. at 104. Shortly thereafter Marion Police Captain Angela Haley arrived at Wilson’s house, spoke with Bockover, and obtained a description of Smith and of Floyd’s vehicle. Marion Police Officer Kenneth Allen learned of the descriptions given by Bockover by radio, noticed Floyd’s vehicle at a gas station, and followed the vehicle as it left the station. Smith told Floyd to “[g]o, go, go” and tried to grab the steering wheel. Id. at 107. Floyd told Smith to get out of his vehicle and pulled to the side of the road. Smith exited the vehicle and began to walk down the sidewalk and Floyd drove away. Officer Allen pulled up next to Smith and engaged him in conversation. Smith was initially evasive and gave Officer Allen a different name, but later admitted his identity. Officer Allen asked Smith about the check from Wilson, and Smith gave him the check. Captain Haley obtained a statement from Bockover and photographed the yard of Wilson’s house. On April 21, 2011, the State charged Smith with: Count I, burglary as a class B felony; Count II, intimidation as a class A misdemeanor; Count III, theft of $150 on April 19, 2011, as a class D felony; and Count IV, theft of $140 on April 18, 2011, as a class D 6 felony. At Smith’s trial, a jury heard the testimony of, among others, Dr. Dawn Lagerkvist, a family physician who had been treating Wilson since October 2010, Wilson’s accountant, Fanning, Floyd, Officer Allen, Bockover, Mundt, Murphy, Captain Haley, Christa, and Smith. Dr. Dawn Lagerkvist testified that Wilson “is very agreeable” and that “[w]hen she’s been in the office, if I ask her a question that she doesn’t recall, she’ll turn to who is with her which is very common for Alzheimer’s patients if they don’t recall.” Id. at 69- 70. Dr. Lagerkvist also indicated that Wilson’s short term memory loss was significant, that the memory loss causes confusion for Wilson regarding her surroundings and regarding events in her life, that it would be difficult for Wilson to adapt to new surroundings, and that it would be very confusing for Wilson to come into a courtroom.4 Dr. Lagerkvist testified that Wilson is “more agreeable and she is more ready to placate someone” and that “[e]ven when I ask nonthreatening questions in the office, that’s how she responds to stressful situations. She just becomes more agreeable.” Id. at 72-73. Dr. Lagerkvist indicated that Wilson would have a tendency to agree to someone’s demands or assertions that she owes them something. Floyd testified that Smith’s mother lived next door to him and that Smith asked for a ride because “a lady owed him money for tree work.” Id. at 100. Floyd testified that, when he dropped Smith off at Wilson’s house, he was “calm, collected, normal,” and that when Smith returned to the vehicle he said “Just go.” Id. at 101, 104. 4 Wilson did not testify at trial. 7 During his testimony, Mundt indicated that he lived “right next door” to Wilson, that Smith “did tree work for [him] some years ago,” and that he never observed Smith do any work for Wilson. Id. at 176. Mundt, Murphy, Fanning, and Bockover each testified that Ron Campbell was the person who did Wilson’s yard work. During her testimony, Murphy indicated that on the day Smith visited Wilson’s house in the summer of 2010 and Murphy told Smith that Wilson did not desire for him to do any work, she was direct with Smith, was clear and factual, and was “very definite in [her] tone of voice.” Id. at 198. Also at trial, after obtaining the court’s permission, the State elicited certain testimony from Christa related to a no contact order which had been issued in connection with Smith’s previous arrest for a battery against her. Smith testified that Wilson owed him $400 and that he accepted the $140 check from Wilson on April 18, 2011 as partial payment. He testified that he was “contracting for topping [a] maple tree and spraying the bug spray,” saying that he obtained bug spray and sprayed around the house and all of the trees and bushes on April 18, 2011. Id. at 387. His testimony was that after Bockover answered the door on April 19, 2011, Wilson also came to the door, that Bockover left the door, that he spoke with Wilson at the front door, that he asked Wilson if he could step inside, and that Wilson said yes. The jury found Smith guilty of criminal trespass as a class A misdemeanor as a lesser included offense of burglary under Count I; intimidation as a class A misdemeanor under Count II; theft as a class D felony under Count III; and theft as a class D felony under Count IV. The court sentenced Smith to one year for each of his convictions under 8 Counts I and II and three years for each of his convictions under Counts III and IV, with Counts I, II, and III to be served concurrently with each other and Count IV to be served consecutive to the sentences under Counts I, II, and III. I. The first issue is whether the trial court abused its discretion in permitting the State to elicit certain testimony from Christa. Outside the presence of the jury, the State questioned Christa regarding a no contact order issued against Smith in March or April of 2011 which stemmed from Smith’s arrest for domestic battery against Christa in March 2011. Christa indicated that there was a no contact order in place prohibiting Smith from being around her on April 18, 2011. The State asked Christa whether she told the police in March 2011 that she was fearful of Smith, and Christa responded affirmatively. The State asked the court for permission to question her on the issue of her fear of Smith given the recent report regarding the battery. Smith’s defense counsel argued that the testimony the State desired to elicit would have no probative value and would be prejudicial. The court later stated that it researched the issue of whether the State should be allowed to question Christa regarding reports she made to the police and events surrounding the report. The court found that the evidence was “not being offered to prove [Smith’s] character nor to show action in conformity with that character” but rather “to show [Christa’s] bias or motive to lie which is appropriate under Rule 616.” Transcript at 291. The court noted that Christa was the “only witness who has testified that she observed [] Smith performing work at [] Wilson’s home, so clearly any bias, 9 prejudice, or motive to lie she may have are highly relevant in this case” and that “[t]he events [] about which the State wishes to cross-examine [Christa] are recent and close in time to the events in this case . . . .” Id. The court further found that “[t]he evidence offered by the State bears heavily on [Christa’s] motive to lie for her husband” and “that the probative value of this testimony under Rule 403 is not substantially outweighed by the danger of unfair prejudice to [Smith] and the State may cross-examine [] Smith on these issues.” Id. at 292. The court stated that it had drafted a limiting instruction and that it would give the instruction to the jury if the defense so desired. The court then read its proposed instruction: Evidence has been introduced that the defendant was involved in wrongful conduct other than the offenses charged in this case. This evidence has been received solely on the issue of [Christa’s] credibility. This evidence should be considered by you only for that limited purpose. Id. Smith’s counsel indicated that it desired for the court to give the instruction to the jury. During its cross-examination of Christa before the jury, the State asked Christa if there was a no contact order in place on April 18, 2011, and whether Smith was prohibited from being in her presence or communicating with her, and Christa responded affirmatively. The State then asked “[a]nd that’s because he had battered you in March,” and Christa stated “Yeah.” Id. at 318-319. Christa indicated that she had reported the battery to police in March. The State asked Christa whether she reported to the police that she was “afraid of [her] husband,” and Christa stated “I ---- possibly, I don’t know if I said I was afraid of him” and “I don’t remember saying I was afraid of him. I don’t know. I may have.” Id. at 319. The State asked whether she told the police in March 10 “that he had threatened to kill you” and “that he was a controlling person,” and Christa testified that she did not “remember saying that.” Id. The State then asked if it was “in fact [] the case” that she was afraid of Smith either at the time she made the report to police or at trial, and Christa stated “No.” Id. at 320. During re-direct examination, Christa indicated that she received calls from Smith from jail and that Smith did not ask her to lie for him. The court gave its proposed instruction to the jury. Smith argues that the trial court erred by allowing the State to present evidence that Christa was testifying out of fear. Smith argues that “[t]here is very little evidence of probative value to show that Christa is testifying out of fear,” that “[o]n the contrary, there is enormous prejudicial value in presenting evidence to show that [Smith] is a wife beater,” that “[t]he defense never voir dired jurors on domestic abuse,” that “[t]he allegations were not even substantiated,” and that the questions the prosecutor asked “poison[ed] the well.” Appellant’s Brief at 13; Appellant’s Reply Brief at 4. Smith further argues that “[w]hen considering the probative value of her testimony, one would have to ask what exactly was it [Christa] lied about” and that “[s]he did not provide [Smith] with a slam dunk alibi.” Id. at 17. The State argues that the court properly admitted evidence of Christa’s potential bias and motive to lie, namely, her fear of reprisal by Smith, and that the jury instruction rendered any error harmless. The admission and exclusion of evidence falls within the sound discretion of the trial court, and we review the admission of evidence only for abuse of discretion. Wilson v. State, 765 N.E.2d 1265, 1272 (Ind. 2002). An abuse of discretion occurs “where the decision is clearly against the logic and effect of the facts and circumstances.” Smith v. 11 State, 754 N.E.2d 502, 504 (Ind. 2001). “Errors in the admission or exclusion of evidence are to be disregarded as harmless error unless they affect the substantial rights of a party.” Fleener v. State, 656 N.E.2d 1140, 1141 (Ind. 1995) (citations omitted). Ind. Evidence Rule 607 provides that the credibility of a witness may be attacked by any party. Ind. Evidence Rule 616 specifies: “For the purpose of attacking the credibility of a witness, evidence of bias, prejudice, or interest of the witness for or against any party to the case is admissible.” The Rule provides for the admission of evidence showing bias or prejudice of a witness without any qualifications. Ingram v. State, 715 N.E.2d 405, 407 (Ind. 1999). However, it “should be read in conjunction with Rule 403’s required balancing of probative value against the danger of unfair prejudice.” Id. Ind. Evidence Rule 403 provides that “[a]lthough relevant, evidence may be excluded if its probative value is substantially outweighed by the danger of unfair prejudice, confusion of the issues, or misleading the jury, or by considerations of undue delay, or needless presentation of cumulative evidence.” Further, on appeal we presume that the jury followed the instructions tendered by the trial court. Williams v. State, 782 N.E.2d 1039, 1047-1048 (Ind. Ct. App. 2003), trans. denied. Based upon our review of the record, including the trial court’s instruction to the jury, we cannot say the testimony elicited from Christa by the State was not evidence of bias, prejudice, or interest under Ind. Evidence Rule 616 or that the probative value of the evidence is substantially outweighed by the danger of unfair prejudice to Smith. The court did not abuse its discretion in admitting the testimony challenged by Smith. See Ingram, 715 N.E.2d at 408 (holding that the trial court did not abuse its discretion in 12 finding that the probative value of challenged evidence was not substantially outweighed by the danger of unfair prejudice). In addition, even if the challenged testimony was admitted in error, we conclude that such error does not warrant reversal. An error will be found harmless if its probable impact on the jury, in light of all of the evidence in the case, is sufficiently minor so as not to affect the substantial rights of the parties. Gault v. State, 878 N.E.2d 1260, 1267- 1268 (Ind. 2008). Smith does not demonstrate that the admission of the challenged portion of Christa’s testimony affected his substantial rights. The evidence before the jury included the testimony from Fanning, Floyd, Officer Allen, Bockover, Mundt, Murphy, and Captain Haley, as well as photographs of Wilson’s yard and the trees in the yard. This evidence supported the conclusion that Smith committed two counts of theft when on two occasions he demanded and took money from Wilson for work he never performed or intended to perform, and that he committed the trespass and intimidation offenses. Based upon our review of the record, we find that the probable impact of any erroneous admission of the challenged portion of Christa’s testimony did not affect Smith’s substantial rights, and any error in admitting the testimony must be disregarded as harmless. II. The next issue is whether the evidence was sufficient to sustain Smith’s convictions. When reviewing claims of insufficiency of the evidence, we do not reweigh the evidence or judge the credibility of witnesses. Jordan v. State, 656 N.E.2d 816, 817 (Ind. 1995), reh’g denied. Rather, we look to the evidence and the reasonable inferences 13 therefrom that support the verdict. Id. We will affirm the conviction if there exists evidence of probative value from which a reasonable trier of fact could find the defendant guilty beyond a reasonable doubt. Id. Smith argues that the evidence is insufficient to sustain his convictions for criminal trespass, intimidation, and two counts of theft. A. Criminal Trespass With respect to his conviction for criminal trespass, Smith argues that “[a]s a result of having stepped in the home, [he] was charged with burglary,” that “[t]he jury found him not guilty of burglary, but did convict him on the Class A criminal trespass charge,” and that “[t]here is no indication that he was asked to leave and the testimony is uncontroverted that he had been in the house the day before.” Appellant’s Brief at 23. Smith further argues that “[u]nder the circumstances, when [Bockover] opened the door, it was fair for [Smith] to assume that he was being invited in, based on the fact that he had been in the home the day before” and that he “had the implied consent of [Wilson] to step in the door and if [Wilson] did not want him in the home, someone should have asked [him] to leave.” Id. The State argues that “Bockover told Smith to ‘wait’ and ‘hold on’ but he did not” and that “Smith ignored her.” Appellee’s Brief at 17. The State argues that Bockover “even tried to close the door when she turned around to tell [Wilson] that Smith was at the door.” Id. The State argues that “Smith entered the home without [Wilson’s] consent, intentionally, when he had no proprietary interest in her home.” Id. 14 The offense of criminal trespass is governed by Ind. Code § 35-43-2-2, which provides in part that “[a] person who . . . not having a contractual interest in the property, knowingly or intentionally enters the dwelling of another person without the person’s consent . . . commits criminal trespass, a Class A misdemeanor.” The record reveals that, at approximately 5:30 p.m. on April 19, 2011, Smith knocked on the front door of Wilson’s house, and Bockover answered the door. The interior front door to Wilson’s house was open, and the exterior glass storm door was closed. During her testimony, Bockover indicated that, when Smith knocked on the front door of Wilson’s house on April 19, 2011, she opened the exterior storm door “[m]aybe six, 12 inches,” which was “[f]ar enough for [her] to [be] able to talk to [Smith] face to face” but not “enough for an individual to slide in.” Transcript at 141. Bockover testified that when she turned around to Wilson after speaking with Smith at the door, the door “was shut” and that she “had let it go shut when [she] turned to [Wilson].” Id. at 142. Bockover testified that Smith nevertheless entered Wilson’s house and “was walking past [her],” id. at 141, that she told Smith to “wait” and “[h]old on,” that Wilson would “come to the door,” id. at 142, and that she told Smith that he “really need[ed] to come back when you don’t smell like alcohol and you’re sober.” Id. at 149. Smith did not exit Wilson’s house until Wilson gave him a check and Bockover dialed 911. A reasonable trier of fact could have concluded from the testimony presented at trial that Smith knowingly or intentionally entered Wilson’s home without consent. Based upon the evidence most favorable to the conviction, we conclude that sufficient evidence exists from which the jury could find Smith guilty beyond a reasonable doubt of 15 criminal trespass as a class A misdemeanor. See Belcher v. State, 453 N.E.2d 214, 215- 216 (Ind. 1983) (affirming a conviction for criminal trespass where witnesses testified that the defendant entered the victim’s property, despite the defendant’s testimony to the contrary). B. Intimidation With respect to his conviction for intimidation, Smith argues that he “went to the home to receive partial payment for work he had contracted to perform,” that “[i]t’s unclear as to what threat he communicated,” and that Bockover “did call 911” but that Wilson “had nothing to fear--the police were not being called on her.” Appellant’s Brief at 24. Smith also argues that he “apparently, according to [Bockover], claimed the work had been completed and that he needed the money to pay his crew,” and that “[i]f he said that, it is a lie, but it is not a threat.” Id. The State argues that “[w]hether a particular communication constitutes a threat is a question for the trier of fact” and that “Smith communicated his threat to [Wilson] when he slammed his hand down on her piano, visibly angered, and said ‘Come on, [Wilson], she’s calling the cops.’” Appellee’s Brief at 17-18. The offense of intimidation as a class A misdemeanor is governed by Ind. Code § 35-45-2-1(a), which provides in part that “[a] person who communicates a threat to another person, with the intent . . . that the other person engage in conduct against the other person’s will . . . commits intimidation, a Class A misdemeanor.” A “threat” means an expression, by words or action, of an intention to . . . unlawfully injure the person 16 threatened or another person, or damage property; unlawfully subject a person to physical confinement or restraint; [or] commit a crime . . . .” Ind. Code § 35-45-2-1(c). The Indiana Supreme Court has stated that “whether a defendant intended that someone engage in conduct against his or her will depends on the facts and circumstances of each case” and that “we have adopted an objective view of whether a communication is a threat.” Owens v. State, 659 N.E.2d 466, 474 (Ind. 1995), reh’g denied. The Court then concluded that “[t]herefore, both whether [the defendant] intended that the three men engage in conduct against their will and whether his communications to the three men, objectively viewed, were threats were questions of fact for the jury to decide.” Id. Based upon the evidence most favorable to the conviction and observing that we cannot reweigh the evidence or judge the credibility of witnesses, we conclude that sufficient evidence exists from which the jury could find Smith guilty beyond a reasonable doubt of intimidation as a class A misdemeanor. See Owens, 659 N.E.2d at 474-475 (holding that substantial evidence of probative value was presented on each element of each alleged instance of intimidation and finding no basis to disturb the jury’s verdicts). C. Theft With respect to his two convictions for theft, Smith argues that he and Wilson had reached an agreement that he would be paid $400 for his work, that “[i]t took at least an hour to do the spraying,” that he “did not do any other work on” April 18, 2011, and that “[h]e asked if he could be paid part of his money and [Wilson] gave him a check for One Hundred Forty Dollars ($140.00) as partial payment.” Appellant’s Brief at 19. Smith 17 further argues that the evidence most favorable to the State would show that on April 19, 2011, he “demanded to be paid and indicated that he had finished the work,” and that “[a]t most, it appears [he] was demanding money when in fact he hadn’t finished the work.” Id. at 20-21. Smith argues that he did not exert unauthorized control over the property of another person, that Wilson gave him the checks, and that “[t]he evidence shows that [Wilson] had simply paid [Smith] for work that he had not yet completed.” Id. at 21. The State argues that it proved both counts of theft, that the “amounts charged – four hundred ($400.00) dollars for an hour of bug spraying and no tree work – also supports the reasonable conclusion that Smith’s sole purpose was to deprive [Wilson] of her money . . . .” Appellee’s Brief at 19. The State asserts that discrepancies in Smith’s testimony undermine his credibility, and that “the jury chose to believe that Smith took [Wilson’s] money, period, without working for it, and that was their province.” Id. at 19- 20. The State argues that it “sufficiently proved that Smith took money from [Wilson] on both dates, April 18, and April 19,” and that “it was money for no work, but was simply money that Smith scared out of his victim, or conned out of her, given her inability to function mentally or remember recent events.” Id. at 20. The offense of theft is governed by Ind. Code § 35-43-4-2, which provides in part that “[a] person who knowingly or intentionally exerts unauthorized control over property of another person, with intent to deprive the other person of any part of its value or use, commits theft, a Class D felony.” We have observed that “[i]ntent is a mental function, and without a confession, it must be determined from a consideration of the conduct and 18 the natural consequences of the conduct giving rise to the charge that the defendant committed theft.” Long v. State, 867 N.E.2d 606, 614 (Ind. Ct. App. 2007) (citations omitted), reh’g denied. “Accordingly, intent may be proven by circumstantial evidence, and it may be inferred from a defendant’s conduct and the natural and usual sequence to which such conduct logically and reasonably points.” Id. Based upon the evidence most favorable to the convictions as recited previously in this opinion, we conclude that sufficient evidence exists from which the jury could reasonably conclude that Smith knowingly or intentionally exerted unauthorized control over the property of Wilson with intent to deprive her of its value and find Smith guilty beyond a reasonable doubt of two counts of theft as class D felonies. See Long, 867 N.E.2d at 614 (holding that the evidence presented was sufficient to support defendant’s theft conviction where the victims made payments for items but the defendant never delivered the items and noting that intent may be inferred from a defendant’s conduct and that it is not our appellate role to reweigh the evidence and assess witness credibility); see also Wallace v. State, 896 N.E.2d 1249, 1252 (Ind. Ct. App. 2008) (holding that the evidence was sufficient to sustain the defendant’s conviction for theft as a class D felony), reh’g denied, trans. denied. III. The next issue is whether the trial court abused its discretion in sentencing Smith. We review the sentence for an abuse of discretion. Anglemyer v. State, 868 N.E.2d 482, 490 (Ind. 2007), clarified on reh’g, 875 N.E.2d 218 (Ind. 2007). A trial court abuses its discretion if it: (1) fails “to enter a sentencing statement at all;” (2) enters “a sentencing 19 statement that explains reasons for imposing a sentence—including a finding of aggravating and mitigating factors if any—but the record does not support the reasons;” (3) enters a sentencing statement that “omits reasons that are clearly supported by the record and advanced for consideration;” or (4) considers reasons that “are improper as a matter of law.” Id. at 490-491. However, the relative weight or value assignable to reasons properly found, or those which should have been found, is not subject to review for abuse of discretion. Id. at 491. Smith argues that the court erred in sentencing him to two consecutive three-year terms for theft. Smith argues that the two sentences for theft should have been merged as a single crime for sentencing purposes. Smith also asserts that theft is not a crime of violence under Ind. Code § 35-50-1-2(a), that his convictions for theft constitute a single episode of criminal conduct under Ind. Code § 35-50-1-2(b), and thus that his sentence may not exceed the advisory sentence of four years for a class C felony as set forth under Ind. Code § 35-50-1-2(c). The State argues that Smith was properly sentenced, that Smith’s two thefts “do not constitute a single episode of criminal conduct,” that they “are two separate thefts, or two separate acts,” and that “[t]he evidence even supports the conclusion that the success of the first theft inspired an altogether different, second theft of [] Wilson.” Appellee’s Brief at 21. Ind. Code § 35-50-1-2(c) provides in part: [E]xcept for crimes of violence, the total of the consecutive terms of imprisonment, exclusive of terms of imprisonment under IC 35-50-2-8 and IC 35-50-2-10, to which the defendant is sentenced for felony convictions arising out of an episode of criminal conduct shall not exceed the advisory sentence for a felony which is one (1) class of felony higher than the most serious of the felonies for which the person has been convicted. 20 Ind. Code § 35-50-1-2(b) provides: “As used in this section, ‘episode of criminal conduct’ means offenses or a connected series of offenses that are closely related in time, place, and circumstance.” “In making this determination, emphasis has been placed on the timing of the offenses and the simultaneous and contemporaneous nature, if any, of the crimes.” Gootee v. State, 942 N.E.2d 111, 114 (Ind. Ct. App. 2011) (citing Reed v. State, 856 N.E.2d 1189, 1200 (Ind. 2006)), trans. denied. “Additional guidance on whether multiple offenses constitute an episode of criminal conduct can be obtained by considering whether the conduct is so closely related in time, place, and circumstance that a complete account of one charge cannot be related without referring to details of the other charge.” Id. In this case, the trial court concluded that Smith’s two theft offenses did not constitute a single episode of criminal conduct. In its order of sentence, the court stated that it based its conclusion on the following specific factors: 1. The crimes in Counts 1-3 occurred on a different date (April 19, 2011) than the crime in Count 4 (April 18, 2011). 2. The Theft in Count 3 involved a different sum of money ($150) than the Theft in count 4 ($140). 3. The Thefts in Counts 3 and 4 involved two different checks. [Smith] cashed the first check on April 18, 2011; the second check was in [Smith’s] possession on April 19, 2011 at the time of his arrest. 4. The Thefts in Counts 3 and 4 involved two separate occasions on which [Smith] went to the victim’s home, and two separate interactions between [Smith] and [the] victim. 5. Although [Smith] testified at trial that the two occasions were related by a contract for work that he and [the] victim had reached, the Court does not find his testimony credible. Rather, the Court finds 21 based upon the totality of the evidence that [Smith] went to the victim’s home with the intention of conning her out of money with no intention of doing work for her. After his successful theft on the first date, he decided to go back and take advantage of the victim a second time. 6. [Smith] had more than adequate time and opportunity following the first crime[] to conform his behavior to the dictates of the law prior to the Theft in Count 4, and therefore avoid consecutive sentencing. He chose not to do so. Appellant’s Appendix at 88-89. Smith’s two theft offenses did not constitute an episode of criminal conduct. Although the two thefts occurred within a period of two days and at the same location, they were nevertheless separate incidents. Each theft can be recounted without referring to the other theft. Based upon the record and evidence, we cannot say that the trial court abused its discretion in finding that Smith’s two theft offenses did not constitute an episode of criminal conduct and ordering that Smith serve his sentences for his two theft convictions consecutive to each other. See Gootee, 942 N.E.2d at 114-115 (holding that the defendant’s offenses did not constitute an episode of criminal conduct and that although the forgery-fraud incidents all occurred within a period of two days, and two of the incidents occurred within minutes of each other at the same location, they were all, nevertheless, separate incidents). For the foregoing reasons, we affirm Smith’s convictions and sentence. Affirmed. KIRSCH, J., concurs. BAKER, J., concurs in part and dissents in part with separate opinion. 22 IN THE COURT OF APPEALS OF INDIANA JOSEPH JESSE CLARK SMITH, ) ) Appellant-defendant, ) ) vs. ) No. 27A05-1108-CR-415 ) STATE OF INDIANA, ) ) Appellee-plaintiff. ) BAKER, Judge, concurring in part and dissenting in part. While I agree that Christa was properly permitted to testify at trial and that Smith’s convictions for theft and criminal trespass should be affirmed, I respectfully dissent with the majority’s decision to affirm Smith’s conviction and sentence for intimidation. Indiana Code section 35-45-2-1(c) defines a threat as “an expression, by words or action, of an intention to . . . unlawfully injure the person threatened or another person, or damage property; unlawfully subject a person to physical confinement or restraint; [or] commit a crime.” In this case, Wilson began writing the check and asked what the date was. Given these circumstances, Smith’s subsequent act of hitting his hand on the piano, coupled 23 with the statement, “come on [Wilson], she’s calling the cops,” tr. p. 151, does not amount to a threat with the intent that Wilson engage in conduct against her will pursuant to Indiana Code 35-45-2-1(a)(2). In other words, I cannot agree that the State sufficiently proved that Smith’s words or actions intimidated Wilson into giving him money for work that he did not perform. In sum, I do not believe that the State proved that Smith committed the offense of intimidation. Thus, I vote to vacate the conviction and sentence on that offense. However, I would affirm the judgment in all other respects. 24
Observing the observation deck of Haneda Airport at night This is the story of a man marked by an image from his childhood. The violent scene, whose meaning he would not grasp until much later, took place on the great jetty at Orly, a few years before the start of the Third World War. On Sundays, parents bring their children to watch the planes... Of this Sunday, the child of this story would remember the frozen sun, the scene at the end of the jetty. Moments to remember are just like other moments. They are only made memorable by the scars they leave. The face he had seen was to be the only peacetime image to survive the war. Had he really seen it? Or had he invented the tender gesture to shield him from the madness to come? The sudden noise, the woman's gesture, the crumpling body, the cries of the crowd. Later, he knew he had seen a man die. I have never been to the observation deck of Haneda Airport before. So last night, before heading to the gates, I decided to take a look. When I was there, for some reason I cannot comprehend, the opening lines from Chris Marker's LA JETEE started playing in my mind. (I'm a huge fan of La Jetee) Of course, instead of a frozen sun, all I saw was a round luminous moon. The sky was dark, but there were numerous people on the deck. They were either hanging out, waiting, reading books, whispering sweet nothings to each other. I looked at the airplanes through the steel fences. The colourful lights of the airport that surrounded these planes somehow felt a little intoxicating. Behind me, behind the airport buildings, there was this mysterious orange glow that lit up the sky. I didn't know what was going on. My mind, often filled with inane references to movies, anime and video games, compared the scenery before me with imaginary cyberpunk locations. Maybe that is why I favour the night over the day, when everything is concealed in shadows, there is so much left for my imagination.
The Banff International Research Station will be receiving $12.5 million in funding over the next five years from agencies in Canada, Mexico and the United States. The station brings together scientists and mathematicians to study solutions to challenges in sectors such as energy, technology and health at the Banff Centre. "The station has been so successful. We started getting hundreds of applications for workshops from all over the world and we only had 50 weeks to assign, so we were declining many, many excellent proposals," said Nassif Ghoussoub, scientific director at the research station. Alberta's provincial government is putting in $4 million. The research station attracts international experts to Alberta, and will help universities attract and retain talented people, say provincial officials. "It is incredibly exciting to have one of the world's best mathematical institutes here in Alberta. Students and mathematicians come from across the globe in order to learn new methods and participate in ground-breaking discoveries," said Minister of Veterans Affairs Kent Hehr in a press release. Including the funding from Alberta, the research station will receive $12.5 million total from the province, the federal government, the Natural Science and Engineering Research Council, the U.S. National Science Foundation, and Mexico's Consejo Nacional de Ciencia y Tecnologia. MORE ALBERTA NEWS \| Entire Bow River watershed infected with whirling disease, CFIA says MORE ALBERTA NEWS \| Notley highlights strategies to improve Alberta-U.S. trade
Joe Biden Confronted Over Child Molesting Claims At CSPAN LIVE Event Former vice president confronted over child absuse claims © press Howard Caplan attended the event at Global Institute of Long Island University Ex-Vice President Joe Biden was confronted at an event in New York being streamed in Live TV over his infamous 'inappropriate behavior' with touching young girls. Howard Caplan attended the event at Global Institute of Long Island University, which featured speaker Joe Biden. Caplan took the opportunity to call out the former Vice President regarding the viral videos of him groping young girls. SCROLL DOWN FOR VIDEO “Why did you molest all those girls on CSPAN?” Caplan shouted as the audience goes silent. “It’s all on YouTube. "You know you did it, everybody’s seen it!” Carter vows to make decisions about sending troops into harm's way with greatest care pic.twitter.com/ygQVFUSbXS — Nedra Pickler (@nedrapickler) February 17, 2015 In the midst of his protest, security escorted Caplan out of the event as the crowd booed and shouted, “Get out of here.” The altercation has resembled one Trump supporter shouting “Bill Clinton is a rapist” during the 2016 election. But the mainstream media continues to turn Joe Biden into a presidential candidate for 2020, portraying him as a "soft uncle" type. However, the reality is the former Vice President is a sexual predator who openly preys on young children. Biden's reputation on D.C is that potent, other politicians keep their children and their families far away from him. Is Joe Biden is a prime example of the permissiveness that infests the inner circle of the D.C. Satanists and pedophiles? The pedophilia problem in government is the elephant in the room, and it used to keep politicians in check.
Dear Editor, {#sec1} ============ the publication on "Intrabiliary Ruptured Cyst Hydatid" is very interesting. In this case, Mermi et al. mentioned that "In geographical areas endemic for hydatid disease, cyst rapture into the bile ducts should be included in the differential diagnosis even in seronegative cases, although it is not typical for hydatid cyst to be found as a mass lesion in the liver on US in patients with right upper quadrant pain and jaundice. Detailed imaging by MRI/MRCP should be done" \[[@cit0001]\]. There are some points for discussion. First, the main question is whether the diagnostic imaging is sufficient for diagnosis of hydatid cyst. In fact, the parasitic cystic lesion at liver and biliary tract is not uncommon, but the hydatid cyst usually presents a classical big cystic lesion \[[@cit0002]\]. The main differential diagnosis, for tropical countries, is cysticercosis \[[@cit0002]\]. Second, a possible answer to the question of why there is a seronegative result in the present case might be due to the basic clinical pathology principle, namely the prozone effect \[[@cit0003],[@cit0004]\]. In immunodiagnosis or serodiagnosis, if there are excessive antigens, the false negative can be derived, and this might be the explanation for the present case. The way to resolve the problem and confirm diagnosis by serological test is by pre-analytical specimen dilution before repeated serological examination. Conflict of interest ==================== The authors report no conflict of interest.
The United States Government Is Completely Irrelevant The American Revolution is Inevitable Historically, America has been a model for Democracy and the Western way of life. But we’ve lost our national identity to enablers who gave corporations carte blanche at the Bank of American Dreams. That’s okay. It happens. That’s the end result of Capitalism. They got all our money. They’re not going to give it back. That is a fact we have to accept which can’t be changed. Further deterioration of our standard of living can be prevented, however, but it’s going to take “something bigger” than simply electing a new guy in 2012. To avoid total collapse of the American nation, Americans need to overthrow their government, which is now extensively corrupt, harmful and irrelevant. Capitalism is fine, but the United States Government is not. It must come down. The American Dream should not belong only to the elite, but high-ranking government officials created the conditions allowing corporate entities to absorb so much money, there is not enough left to run a business, much less turn a profit. Starting a small business is virtually impossible. Even as the Federal Reserve prints more money it can’t substantiate, that new cash finds its way not into the federal budget, not into your paychecks, not in the form of an economic stimulus package, but into the vacuum of corporate will, forcing inflation. America is in the exact same place as Egypt before Egypt’s revolution and will ultimately be forced to follow their model, military-based interim government and all. The media is not going to do it for you. There will be no reality TV show called “Protesters,” where the stars conspire to revolt all the while taking your emotional housewives on a spiritual journey into their own ugly centers. The TV news won’t even acknowledge a revolution until it’s right outside their doors, and God only knows the spin they’re going to put on it for you middle-aged couch-dwellers out there. So you are on your own with your decision to stay put or to act. But you can rest assured, that regardless of your choice, you will not be alone; and should you choose to act on the purest of impulses – to see justice brought to our corrupt leaders – you will be joined not by tens of thousands, but a half-million or more good, Democracy-loving Americans just like yourselves. Using the Egyptian model, change is within reach. The American military is comprised of our brothers, sisters, children, friends and parents who wish to see the best for America, not corrupt politicians; and like Egypt, will continue to protect the country, even if a murderous career liar happens to hold office. The only reason Egypt hasn’t yet fully come around is because they’re still trying to draft a Constitution. Americans love their Constitution, inasmuch as the Federal Government allows us to use it. Therefore, every 10,000 protesters on the streets will be matched by 100,000 who, from their PCs and recliners, may wish the revolutionaries well, and pray silently to God activism doesn’t shut down the Internet. If American leadership refuses to use the tools voted into their hands, then there is no other solution than to empty every seat in the House, Congress and Senate, and clear out the White House – and also their bank accounts – where at least a portion of your money sits, awaiting reclamation. We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness- That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed – That whenever any Form of Government becomes destructive of those ends, it is Right of the People to alter or to abolish it, and to institute new Government, laying its foundation on such principles and organizing its powers in such form, as to them shall seem most likely to effect their Safety and Happiness. Prudence, indeed, will dictate that Governments long established should not be changed for light and transient causes; and accordingly all experience hath shewn, that mankind are more disposed to suffer, while evils are sufferable, than to right themselves by abolishing the forms to which they are accustomed. But when a long train of abuses and usurpations, pursuing invariably the same Object evinces a design to reduce them under absolute Despotism, it is their right, it is their duty, to throw off such Government, and to provide new Guards for their future security. 8 comments to The United States Government Is Completely Irrelevant Mr. Trump is the best example we could dig up, of a sleazy, corrupt businessman (so he might have a chance), and is gaining unprecedented support from the Tea Party, the likes of which Michelle Bachmann and Sarah Palin haven’t seen. I’d just as well laugh it off, if Barack Obama hadn’t already proven the total impotence of the American Presidency. Make promises that appeal to what most Americans want Get in office Abandon promises Serve corporations The American Tea Party appeals to the xenophobia and racism of the 40+ voters to serve corporate interests, represented by the face of evil itself, Donald fucking Trump. Hillary Quittin’s no positive response. Nor would be anyone the Democrats could possibly stick in. The possibility of a Third Party candidate is zilch, because of election laws which prevent a Third Party candidate from winning, and even obstruct the viability of running. I never read an article wich was more selfish like this one. You (America) never have been a “model for Democracy and the Western way of life.” First you took a land wich was never yours ! Then you extinguished the native people there. Later on, you went to enslave africans for many years (wich was the base of your wealth you gained). The “American Way of Life” is simply (still) that you take what you want (doesn’t matter if you have to kill, destroy, occupy or suppress other nations, their people or their believes). Fact is that you care for nothing but your way ! Shame on you, and all of your followers. And as long as you go on, wasting more global resources than any other country, bringing “your way” to others who doesn’t want it, and show no respect to other ways of life, you are nothing more than a bunch of ignorant and selfish egoists ! And then you still wonder why people start to hate you ??? Listen here you pathetic excuse for a troll. We didn’t steal this land, we conquered it. As I recall, the “native American’s” only claim to the land they lived on was through conquest. Over the years, the United States has sent many of its fine young men and women into great peril to fight for freedom beyond our borders. The only amount of land we have ever asked for in return is enough to bury those that did not return. lol, we certainly did conquer it. i like how people act as though the native americans were the first people to be mistreated. should i blame history teachers, parents, or the kids themselves? either way, we won, the natives lost. it happened, it is happening, and it will always happen. i <3 war:) whether or not this land was stolen, the truth is that we are being ran by corporate pigs. it is futile to argue over whether this is conquered land or not, because now is now. and NOW we are sludging down the wrong tubes which are being led by evil, money hungry mongols. I grew up on a reservation in the southwest us.(I will not go into detail) I AGREE with the author of this article that it is time for a revolt! They want us to suffer and die in cancerous pools of waste while the corporate pigs have vacations on the Island of Cutter swimming pools of money. it is not too late for us to start over…. ha! the author is a pussy. he and the rest speak of revolt and revolution, yet all they succeed in is adding more bitching. they pretend to be revolutionaries and you all fall for it. it’s a game to them, and a weird pointless one at that
Newe House Newe House is a Grade II* listed Jacobean dower house in the village of Pakenham, Suffolk. Newe House was built in 1622 by Sir Robert Bright and today the façade of the house remains largely unmodified. Sir Robert had bought the land surrounding Pakenham from the Bacon family several years before. In the late 1640s it was sold to Sir William Spring, who had been a prominent Parliamentarian during the Civil War. The house remained in the Spring family until the mid-nineteenth century, being used as the family dower house. The Spring family coat-of-arms is still apparent above the main door to the manor. Newe House has been extensively restored by its current owners whose family have owned it since 1947. See also Spring family References Category:Grade II* listed buildings in Suffolk Category:Country houses in Suffolk **
Heretofore, a rechargeable secondary battery such as a lithium ion battery has been available for e.g. power supply to an in-vehicle equipment of a vehicle, a power source of a battery mounting device, etc. The secondary battery generally includes a power generating element constituted of a wound electrode body made by winding positive and negative electrode sheets and separator sheets in laminated relation and impregnating them with electrolyte. The secondary battery is normally configured such that the wound electrode body is hermetically sealed in a case. As a winding manner of the wound electrode body, there are flat winding, cylindrical winding, and others. The shape of the case depends on the winding manner. A case for a flat wound electrode body has a flat shape. In some cases, plural secondary batteries are assembled to provide a battery assembly in order to comply with the details of electric power required by a power supply destination. In the case of assembling the flat-type secondary batteries into a battery assembly, the secondary batteries are arranged in a direction of thickness of each battery and entirely bound into one unit by an appropriate binding member. In this bound state, each of the secondary batteries is pressed in the thickness direction. It has been known that appropriate application of the pressing load on the wound electrode bodies is important in power generation capability of the secondary batteries. An example of such secondary battery is disclosed in for example Patent Literature 1.
Pacemaker Implantation Surgery Pacemaker implantation is a surgical procedure where a small electrical device called a pacemaker is implanted on the chest or abdomen. The pacemaker sends regular electrical pulses that help keep your heart beating regularly.The pacemaker is a small metal box. It is attached to one or more wires, known as pacing leads, which run to the heart. The pacemaker contains: a battery, a pulse generator and a tiny computer circuit. Pacemakers can be programmed to adjust the discharge rate in response to one’s needs. Having a pacemaker implanted is a relatively straightforward process. It is usually carried out under local anaesthetic, which means the patient is awake during the procedure. The procedure usually takes about an hour and most people are well enough to leave hospital the day after surgery. Advantages: Having a pacemaker fitted can greatly improve your quality of life as the heart rate and rhythm is normalized. It is a life saving device for the patients. FAQs Can I go back to my normal activities after my implant? Very few activities will be off limits to you because you have a pacemaker. Your doctor may ask you to avoid strenuous activity just after surgery. Doing so helps ensure your lead(s) has time to attach firmly to your heart tissue. After that, you will probably be able to do most of the things you did before your implant. Is it safe for me to use electrical appliances? Your pacemaker is designed to work properly around most appliances and equipment, including microwaves, electric razors, and personal computers. Will my pacemaker ever need to be replaced? Eventually, yes. Your pacemaker runs on a battery. Like all batteries, the battery in your device will be used up over time. When the battery power reaches a certain point, your pacemaker needs to be replaced. Related Procedures Coronary Angioplasty Angioplasty is a specialised procedure performed in a Cath lab (cardiac catheterisation laboratory). Since the patients are awake and alert through the procedure, they are given medication before and during angioplasty procedure to help relax Coronary Angiography Coronary angiography is an imaging technique or a radiological test that helps visualize the insides of the coronary arteries. It shows the exact location and severity of any plaque formation and consequent narrowing of the coronary arteries. This helps the doctor to decide on what treatment is needed. Valvuloplasty Surgery Our heart is located in our chest cavity and is a pump made of special muscles known as myocardium. Our heart is divided into four chambers; two upper chambers known as auricles (atria) and two lower chambers are known as ventricles. They are interconnected by a passage and the opening and closing is controlled by valves. Vascular Surgery Arteries, veins and lymphatic vessels form the vascular system of our body and vascular surgery is a specialty dealing with diseases affecting the vascular system The diseases affecting our vascular system involve the obstruction in the blood flow due to blockages (aneurysms) in the vessels. Heart Valve Surgery Heart valve surgery is used to repair or replace diseased heart valves. Blood flows between different chambers of the heart must flow through a heart valve. Human heart has four valves namely Tricuspid, Pulmonary, Mitral and Aortic Valves. If a valve is not working correctly, blood flow is impaired either by leakage or by back flow. Cardiac Pacemaker Cardiac Electrophysiology (EP Study & Ablation) Electrophysiology is a branch of cardiology that deals with the diagnosis and treatment of heart rhythm disorders. Electrophysiologists are the cardiologists with special training in heart rhythms disorders and its management. Closed Heart Surgery Heart Surgery may be required to fix the problem with the functioning of the heart. Closed heart surgery does not require patients to be supported by a heart-lung bypass machine and the heart chambers are opened during the procedure. Some repairs are best performed using closed heart surgery. Paediatric Cardiac Surgery Heart surgery in children are indicated to repair heart defects a child is born with CHD (congenital heart defects) and heart diseases a child gets after birth. The surgery is needed for the child's wellbeing. There are many kinds of heart defects ranging from minor to serious. Double Valve Surgery Heart valve surgery fixes a damaged or faulty heart valve. There are two main types of heart valve surgeries: valve repair and valve replacement. Double valve surgery is a surgery where two valves are involved. Sometimes a faulty valve can be repaired by cutting away excess tissue in the cusps of the valve and sewing the edges together. VSD Closure Surgery A ventricular septal defect (VSD) is an opening or hole in the wall that separates the two lower chambers of the heart. This wall is the ventricular septum. The hole causes oxygen-rich blood to leak from the left side of the heart to the right side. ASD Closure Surgery The upper chambers of the heart are divided a wall called “interatrial septum”. The defect in this wall is known as Atrial septal defect (ASD). It is a form of a congenital heart defect, the defect the baby is born with.
WEBVTT WE BEGIN TONIGHT WITH A BREAKING NEWS UPDATE.. TWO BODIES FOUND IN A WEST OMAHA HOME. GOOD EVENING, I'M ROB McCARTNEY. I'M BRANDI PETERSEN. WE'VE CONFIRMED 18 YEAR OLD COOPER FLANAGAN - SEEN HERE IN A FACEBOOK 156TH AND BLONDO. HIS MOTHER,MAUREEN ALSO FOUND DEAD. INVESTIGATORS HAVE BEEN IN THE FARMINGTON WOODS NEIGHBORHOOD SINCE LATE THIS MORNING.. KETV NEWSWATCH 7'S DAVE ROBERTS IS THERE TOO.. HE'S LIVE AT SIX WITH WHAT WE'RE LEARNING ABOUT THE FAMILY. A VERY SAD DAY HERE..AFTER DEPUTIES DISCOVERY A MOTHER AND HER SON... DEAD INSIDE THIS DUPLEX.THEY FOUND MAUREEN AND COOPER FLANAGAN... AFTER A CONCERNED FRIEND CALLED POLICE AND REQUESTED A WELFARE CHECK. AROUND 10 THIS MORNING... DEPUTIES DISCOVERED 54 YEAR THE BASEMENT ... AND HER 18 YEAR OLD SON COOPER DEAD IN A CAR PARKED IN THE GARAGE.WHILE THE DOUGLAS COUNTY SHERIFF'S OFFICE WON'T CONFIRM HOW THEY DIED... IT APPEARS WHATEVER HAPPENED... HAPPENED BETWEEN THE MOTHER AND HER SON.is there any reason to believe the public is in danger? Lt. Mark Gentile: The public is not in danger. We're not looking for any suspects, nor suspects. We believe we know what happeedn, we're just waiting on the final results of the autopsies to be definiteNEIGHBORS SAY THE MAUREEN WAS ILL, BATTLE LUPUS... AND HER TEENAGE BOY A JOY TO BE AROUND.Jay Shattuck: meticulous in anything he did-- he really made a real impression on me when I saw him and talked to him.Tom McFadden: No never saw any activity in the house-- heard she was sick-- probably explains that-- but yeah, it's been a safe neighborhood so, INVESTIGATORS SAY THE DEATHS LIKELY OCCURED THREE DAYS AGO. FIRENDS AND RELATIVES HAVE HEARD FROM EITHER THE MOTHER OF SON SINCE JULY NINTH. PHOTOS WE'VE FOUND THIS AFTERNOON ON MAUREEN FLANAGAN'S FACEBOOK PAGE. WAS PROUD OF HER SON COOPER. POSING HERE ON A PHOTO DATED MARCH 30TH-- PROM NIGHT. AND HERE-- FROM LAST OCTOBER... WE KNOW FROM HIS POSTS COOPER FLANAGAN WAS ACTIVE IN PLAYING ALTO SAX. MAUREEN FLANAGAN WROTE SHE WAS 'VERY' PROUD OF HER SON-- AND IN ANOTHER POST-- HIS FATHER WROTE COOPER WAS A 'HANDSOME' YOUNG MAN. COURT RECO S SHOW ... TODAY A WARRANT WAS ISSUED FOR COOPER IN SEWARD COUNTY WHEN HE DIDN'T SHOW UP FOR COURT.HE WAS CHARGED WITH CARRYING A CONCEALED WEAPON AND MINOR IN POSSESSION... SPEEDING AND CARELESS DRIVING. IT APPAERS THOSE CITATIONS TOOK PLACE JUST DAYS AFTER THE DEATH OF MAUREEN'S FATHER-- COOPER'S GRANDFATHER-- IN MISSOURI. HOW ALL THAT UNRAVELED-- WHAT MAY HAVE HAPPENED INSIDE THIS HOUSE-- REMAINS THE BIG QUESTION. AUTOPSIES TOMORROW SHOULD REVEAL HOW THE FLANGANS DIED. IN NORTHWEST OMAHA-- DAVE ROBERTS, K-E-T-V NW7
Q: Break huge URLs so they don't overflow Is there a way to force huge urls such as http://www.google.de/search?q=65daysofstatic&hl=de&safe=off&prmd=ivnsl&source=lnms&tbm=isch&ei=P9NkToCRMorHsgaunaClCg&sa=X&oi=mode_link&ct=mode&cd=2&ved=0CBkQ_AUoAQ&biw=1697&bih=882 break when rendered in the website? I'd rather shorten it but where I'm working they've asked me to show the entire url but I only have a space of 320px to show it and it overflows. Overflow:hidden, isn't an option either and adding a style to the td where the url is contained is simply ignored. A: CSS3 has a new feature: word-wrap:break-word; You can see a live example here (you must have a browser compatible with that new feature). It's also the same tecnique adopted by StackOverflow, if you examine your long URL you will notice. Alternatively you can try Hyphenator. A: In Chrome, word-wrap does not work. You should use: word-break: break-all; If you want to apply it only on a tags, then you should use: a {word-break: break-all;} Note that break-all will even split words, so a word can start on one line and end on another, that's why it's a good idea to apply it only on a tags. If you know that your links always contain words (e.g. are not something like mylink/abcdefghijklmnopqrstuvwxyz1234567890abcdefghijklmnopqrstuvwxyzabcdefghijklmnopqrstuvwxyz1234567890abcdefghijklmnopqrstuvwxyz1234567890 ), then you can apply the following at the body tag level (this way a word is not split onto 2 lines): body {word-break: break-word;} A: -ms-word-break: break-all; word-break: break-all; // Non standard for webkit word-break: break-word; -webkit-hyphens: auto; -moz-hyphens: auto; hyphens: auto; The above works in Internet Explorer 8+, Firefox 6+, iOS 4.2, Safari 5.1+ and Chrome 13+.
Q: What is the process "python3 unattended upgrade shutdown"? I was looking at the process list on my Ubuntu 18.04 server and saw the following two processes: 930 ? Ssl 0:00 /usr/bin/python3 /usr/bin/networkd-dispatcher --run-startup-triggers 958 ? Ssl 0:00 /usr/bin/python3 /usr/share/unattended-upgrades/unattended-upgrade-shutdown --wait-for-signal I am sure I did not start them. What are they? Are they harmful? How do I stop them from reappearing? A: These processes are likely not harmful[1]. The "unattended upgrades" mechanism is responsible for automatically installing security updates. You can find more information in official documentation, e.g. here. The networkd-dispatcher allows triggering of scripts in response to a change of the network interface state. Again, if you are curious, check the official docs. There are plently of processes that the OS starts without the user's explicit knowledge or consent. This is perfectly OK and for the most part you should not interfere unless you know exactly what you are doing. Such processes might be crucial to OS operation and even beneficial for your OS security (such as the unattended upgrades system). [1] Of course, we can't truly know without having full access to your computer
Q: Return rows with both NA and a value at once I have a df ID <- c(101,102,103,104) Status <- c('P','F_Avg','F_Sig',NA) df <- data.frame(ID,Status) I am trying to filter the failed ones and return both Pass and NA but I am not able to do so. I know it's a basic question but please bear with me and help me out. I tried the following df1 <- sqldf("SELECT * FROM df WHERE Status NOT LIKE 'F%'") and it returns only one observation and that is row1 which is 'P' but I also need row4 'NA'. A: df1 <- sqldf("SELECT * FROM df WHERE (Status NOT LIKE 'F%' OR Status IS null)") Output: ID Status 1 101 P 2 104 <NA> Using dplyr: library(dplyr) filter(df, !grepl("^F", Status))
Cyanobacterial RNA thermometer The first cyanobacterial RNA thermometer (RNAT) Hsp17 was found in the 5'UTR of Synechocystis heat shock hsp17 mRNA. Further study demonstrated that cyanobacteria commonly use RNATs to control the translation of their heat shock genes. HspA is a homolog of Hsp17 in thermophilic Thermosynechococcus elongatus. Two more thermometers were found in the 5'UTRs of mesophilic cyanobacteria A. variabilis and Nostoc sp. The first RNAT called avashort was shown to regulate translation by masking the AUG translation start site. The second RNAT called avalong, as it has an extended initial hairpin, might involve tertiary interactions and has similarities to the ROSE element. References Category:Non-coding RNA Category:Cis-regulatory RNA elements
MaryAnn Lippert MaryAnn T. Lippert (born December 21, 1953) is a Wisconsin health educator, health administrator, and Republican politician who served one term as a member of the Wisconsin State Assembly. She is currently executive assistant to the Secretary of the Wisconsin Department of Children and Families. Background Born in Marshfield, Wisconsin, Lippert graduated from Pittsville High School. She received a B.S. from the University of Wisconsin–La Crosse in 1976 and an M.S. from the same university in 1980. She worked for many years as a health educator. Assembly In 1998, she challenged fellow Pittsville resident and Democratic incumbent Donald W. Hasenohrl for the 70th Assembly District (portions of Portage and Wood counties) seat, coming close to defeating him (8,906 for Hasenohrl to 8,386 for Lippert) with $38,708 in campaign expenditures. Hasenohrl chose not to run for re-election in 2000, and Lippert defeated Democrat Amy Sue Vruwink by 104 votes (12,068 [50.2%] to 11,964 [49.8%]) in the 2000 general election, after spending $114,563. Lippert served on the Assembly's Committees on Children and Families and Public Health (on both of which she served as Vice-Chair), as well as the Committees on Aging and Long-Term Care; Economic Development; Health; and Transportation. In 2002, she chose not to run for re-election due to the health of her husband, Jerry, who was suffering from chronic obstructive pulmonary disease, which he attributed to twenty years of smoking (he was a member of the state Tobacco Control Board). She was succeeded by Vruwink. After the legislature After leaving the Assembly, Lippert went back to work in the health field. In February 2011, she was appointed as executive assistant to Eloise Anderson, the new Secretary of the Wisconsin Department of Children and Families, as part of the administration of incoming governor Scott Walker. Personal life Lippert is a mother of three children and is a long-term resident of Pittsville, Wisconsin, where she is a member of the Pittsville School District board of education. References Category:American health educators Category:Members of the Wisconsin State Assembly Category:People from Marshfield, Wisconsin Category:People from Wood County, Wisconsin Category:University of Wisconsin–La Crosse alumni Category:Women state legislators in Wisconsin Category:Wisconsin Republicans Category:1953 births Category:Living people
--- title: "Backup Hooks" layout: docs --- Velero supports executing commands in containers in pods during a backup. ## Backup Hooks When performing a backup, you can specify one or more commands to execute in a container in a pod when that pod is being backed up. The commands can be configured to run before any custom action processing ("pre" hooks), or after all custom actions have been completed and any additional items specified by custom action have been backed up ("post" hooks). Note that hooks are _not_ executed within a shell on the containers. There are two ways to specify hooks: annotations on the pod itself, and in the Backup spec. ### Specifying Hooks As Pod Annotations You can use the following annotations on a pod to make Velero execute a hook when backing up the pod: #### Pre hooks * `pre.hook.backup.velero.io/container` * The container where the command should be executed. Defaults to the first container in the pod. Optional. * `pre.hook.backup.velero.io/command` * The command to execute. If you need multiple arguments, specify the command as a JSON array, such as `["/usr/bin/uname", "-a"]` * `pre.hook.backup.velero.io/on-error` * What to do if the command returns a non-zero exit code. Defaults to Fail. Valid values are Fail and Continue. Optional. * `pre.hook.backup.velero.io/timeout` * How long to wait for the command to execute. The hook is considered in error if the command exceeds the timeout. Defaults to 30s. Optional. #### Post hooks * `post.hook.backup.velero.io/container` * The container where the command should be executed. Defaults to the first container in the pod. Optional. * `post.hook.backup.velero.io/command` * The command to execute. If you need multiple arguments, specify the command as a JSON array, such as `["/usr/bin/uname", "-a"]` * `post.hook.backup.velero.io/on-error` * What to do if the command returns a non-zero exit code. Defaults to Fail. Valid values are Fail and Continue. Optional. * `post.hook.backup.velero.io/timeout` * How long to wait for the command to execute. The hook is considered in error if the command exceeds the timeout. Defaults to 30s. Optional. ### Specifying Hooks in the Backup Spec Please see the documentation on the [Backup API Type][1] for how to specify hooks in the Backup spec. ## Hook Example with fsfreeze This examples walks you through using both pre and post hooks for freezing a file system. Freezing the file system is useful to ensure that all pending disk I/O operations have completed prior to taking a snapshot. This example uses [examples/nginx-app/with-pv.yaml][2]. Follow the [steps for your provider][3] to setup this example. ### Annotations The Velero [example/nginx-app/with-pv.yaml][2] serves as an example of adding the pre and post hook annotations directly to your declarative deployment. Below is an example of what updating an object in place might look like. ```shell kubectl annotate pod -n nginx-example -l app=nginx \ pre.hook.backup.velero.io/command='["/sbin/fsfreeze", "--freeze", "/var/log/nginx"]' \ pre.hook.backup.velero.io/container=fsfreeze \ post.hook.backup.velero.io/command='["/sbin/fsfreeze", "--unfreeze", "/var/log/nginx"]' \ post.hook.backup.velero.io/container=fsfreeze ``` Now test the pre and post hooks by creating a backup. You can use the Velero logs to verify that the pre and post hooks are running and exiting without error. ```shell velero backup create nginx-hook-test velero backup get nginx-hook-test velero backup logs nginx-hook-test \| grep hookCommand ``` ## Using Multiple Commands To use multiple commands, wrap your target command in a shell and separate them with `;`, `&&`, or other shell conditional constructs. ```shell pre.hook.backup.velero.io/command='["/bin/bash", "-c", "echo hello > hello.txt && echo goodbye > goodbye.txt"]' ``` [1]: api-types/backup.md [2]: https://github.com/vmware-tanzu/velero/blob/main/examples/nginx-app/with-pv.yaml [3]: cloud-common.md
Rt Hon Joan Ruddock MP pays a visit to Alumasc at Ecobuild One of the many visitors to the Alumasc stand at this year’s Ecobuild, was Rt Honourable Joan Ruddock MP, Minister of State, Department of Energy and Climate Change. Speaking with our Technical Development Manager Chris Lister, Ms Ruddock experienced the wide range of sustainable building products being showcased on Alumasc’s Stand, including natural cork insulation and ZinCo green roofs and she chatted with Chris about the use of Alumasc’s External Wall Insulation systems within the new government fundingscheme for low carbon refurbishment in the housing sector. Known as ‘Pay As You Save’ (PAYS), the concept is based on spreading the cost of refurbishment for an existing property over a substantial period of time, across a number of different owners. Ms Ruddock also took the opportunity to take advice from Chris about the advantages of installing a green roof, and revealed that it’s something she is considering for her own home.
[package] name = "rustpython-bytecode" description = "RustPython specific bytecode." version = "0.1.2" authors = ["RustPython Team"] edition = "2018" repository = "https://github.com/RustPython/RustPython" license = "MIT" [dependencies] bincode = "1.1" bitflags = "1.1" lz4-compression = "0.7" num-bigint = { version = "0.3", features = ["serde"] } num-complex = { version = "0.3", features = ["serde"] } serde = { version = "1.0", features = ["derive"] } itertools = "0.9"
A new 'Sesame Street' movie: Whom do you want to see? We may not be able to tell you how to get to Sesame Street, but we can tell you that the iconic children’s show will be making its way to the big screen again. Sources close to the project confirm that director Shawn Levy (Night at the Museum) and 20th Century Fox are taking on the third feature film outing for Children’s Television Workshop’s landmark program – as The Hollywood Reporterfirst reported. But it is still very early in the process – too early to say exactly what direction it’s going in or who should be the focus. But we’ve got some ideas for that. The first movie, Follow that Bird (1985), shined the spotlight on the big yellow bird who’s a friend to everyone. And by the time Elmo in Grouchland (1999) came along, the little red puppet with that earworm of a laugh was the hottest thing going. (The countless hours my young son spent watching that movie was only made tolerable by my enjoyment of Mandy Patinkin’s broad performance as the bad guy who learns a lesson.) So whose turn do you think it is to take the lead? My vote goes to Bert and Ernie . You want to talk about pop-culture staying power? Just last year, Sesame Street had to issue a release saying that contrary to popular opinion the two roommates were not gay. Not that there’s anything wrong with that. Vote in our poll below!
Medford Knife and Tool Medford Knife and Tool is an American custom and production knifemaking and tactical tool making facility founded by Greg Medford in 2010 in Arizona United States. The company The company was founded in Arizona, United States, by Greg Medford. Unlike most knife makers who start out as a home-based business, Medford opened a modern factory, complete with CAD and CNC milling machines. The knives are made in the US and most of the work is done by hand as opposed to automated machining. The company mainly produces folding knives, but at the same time it produces fixed blades knives and tactical tools such as Tomahawks,. machetes and Steel knuckles. A knife model called the "Praetorian" is considered the company's most recognized knife. Products The company's knives and tools feature minimal design elements and clean lines, a massive structure, and a combination of grinds and some describe them as overbuilt. Some knives models are combined with tool elements, such as screwdriver heads or glass breaker. Knife blades are usually made from D-2 Steel, CPM-S35VN Stainless steel and CPM3V Steel, for handles the company uses titanium, G-10, carbon fiber, or a Paracord. Cooperation with military units The USMC EOD-1 model was designed in collaboration with the US Marines according to their requirements. The TM-1 machete was designed according to the requirements of international security services companies. References Category:Knife manufacturing companies
Ex-Minister Urges Cameron To 'Move On' From Immigration After Speech: 'I Hope That'll Be The End Of It' Policing Minister Damian Green MP meets Police officers in Coventry city centre today, during his first walkabout as Policing Minister. The Conservative Party needs to be "very careful" about the language it uses about immigration and should move back to talking about the economy as quickly as possible, a former Tory immigration minister has said. David Cameron is expected to deliver a highly anticipated speech today, outlining a further crackdown on inward migration from the European Union. The prime minister, who had promised to reduce immigration to the tens of thousands, was dealt a blow ahead of his intervention, when official statistics revealed a surge in net inward migration of 260,000 over the last year. Labour said the figures showed Cameron's target had been "ripped to shreds". And Nigel Farage said it showed the Conservative Party's policy had been a "total failure". And a leading pollster has warned that the political advantage the Conservatives had on immigration has now "disappeared". Damian Green, who served as immigration minister from May 2010 until September 2012, told a meeting of the modernising Bright Blue Tory think-tank on Wednesday evening it made sense for the prime minister to make a speech on immigration. ADVERTISEMENT "What any prime minister has to do is address the issues people care about, people care about immigration so clearly it's a sensible thing for him to make a speech," he said. However he added that the party needed to focus on other issues. "I hope that will be the end of it," he said. "Next week we have the Autumn Statement, so we can move back on to the economic agenda where we all want to see us talking." Asked by The Huffington Post whether he was concerned about the growing anti-migrant rhetoric in the country, he said: "I spent five years in opposition shadowing immigration and two years in government as immigration minister and one of the things I was absolutely insistent about throughout was that language the Conservative Party used needed to be moderate, needed to be sensible, needed to be factually based. "We needed to get control of the immigration system so the policies we were implementing did involve taking tough decisions. But absolutely you have to be very, very careful about the language you use." Green was speaking after The Daily Express was sharply attacked by Labour for running a front page story that suggested the British born children of immigrants were "hidden" migrants. Writing on The Huffington Post, Lord Stewart Wood, one of Ed Miliband's closest advisers, said the spin on the story was "inaccurate" and "highly offensive". Green, was was sacked as police minister by Cameron in the 2014 reshuffle, said the Tories were not responsible for what appeared in the newspapers, but criticised the Daily Express' headline. "Children of migrants are not 'hidden migrants', they are British citizens," he said. The MP for Ashford had been giving a speech defending the merits of the Tory modernisation project, as the party leadership is under pressure to move to the right to combat the threat from Ukip. He warned colleagues that the party must not be seen to "subcontract compassion to the Lib Dems so everything that is nice and cuddly is seen as a Lib Dem thing to do". Ahead of Cameron's speech, Bobby Duffy, the managing director of pollster Ipsos MORI, said today that "the political advantage the Conservatives had on immigration has disappeared". "They had a significant lead over Labour, but now Ukip, Labour and the Conservatives are all on a very similar footing as best party on this key issue," he told The Huffington Post. "It should be no surprise that trust in David Cameron on immigration is low – making promises that aren’t kept is a really effective way to lose trust." He added: "But to be fair this is nothing new – there has been very little trust among the public that any government or politician in power is in control of immigration since we started tracking views in the 2000s. In our most recent polling it’s worrying for the PM that 72% of people think immigration would be the same or higher if there is a Conservative government next May. The PM’s got some convincing to do."
Q: WPF - Command in a MenuItem in a DataTemplate I have a DataTemplate containing an Image. To the Image I added a ContextMenu with a MenuItem. To the MenuItem I associated a command. I then handle the command in the view using the DataTemplate. In the CanExecute handler I have e.CanExecute = true. But the Executed handler is never executed. If I remove the Command assignment the MenuItem, the Menu is shown correctly when I right-click on the Image. What am I doing wrong? Thanks! A: I figured this out - After e.CanExecute = true; I had a MessageBox.Show, and this was preventing the Executed from being called. I am not sure why though.
Hawk of the Wilderness Hawk of the Wilderness (1938) is a Republic Movie serial based on the Kioga novel of the same name by pulp writer William L. Chester. Kioga is very similar to the character of Tarzan, whom Herman Brix had also played on film in the 1935 Edgar Rice Burroughs-produced serial The New Adventures of Tarzan. Plot Dr Lincoln Rand Sr, leading an expedition to an uncharted island in the Arctic circle that may be the ancestral home of all Native Americans, is shipwrecked. The only survivors are Lincoln Rand Jr, Dr Rand's son and his servant Mokuyi. Years later, a message from the sinking ship is found and an expedition sets out to find the island again. Part of the crew, led by smuggler Solerno, mutinies when they reach the island, abandoning Dr Munro and his expedition. Dr Munro and company are rescued by Lincoln Rand Jr, alias Kioga, the adult son of Dr Rand, who has been raised on the island by Mokuyi. Cast Herman Brix as Lincoln Rand Jr/Kioga ("Hawk of the Wilderness"), son of Dr Lincoln Rand Sr, a survivor of the initial shipwreck and raised by Mokuyi on the island Ray Mala as Kias, Kioga's servant Monte Blue as Yellow Weasel, villainous shaman opposed to Kioga, the Munros and the Smugglers Noble Johnson as Mokuyi, the former servant of Kioga's late father. Rescued Kioga and, as the only other survivor of the shipwreck, raised him on the island William Royle as Manuel Solerno, smuggler searching for wealth on the uncharted island Tom Chatterton as Dr Edward Munro, a scientist who leads an expedition to discover the fate of his old friend Dr Rand George Eldredge as Allen Kendall, a member of Dr Munro's expedition Patrick J. Kelly as William 'Bill-Bill' Williams, another member of Dr Munro's expedition Dick Wessel as Dirk Fred Toones as George, Dr Munro's servant Tuffie the dog as Tawnee James Dime as Dark Cloud Production Hawk of the Wilderness was filmed between 18 September and 13 October 1938, with location filming in Mammoth Lakes, California. The serial was budgeted for $117,987 but the final negative cost rose slightly to $121,168. Tuffie was cast when his trainer, during the interview, said "Tuffie, it's dark in here. Turn on the light." Tuffie did so by finding the switch, pulling a chair across to reach it and flipping the switch with his paw. Silent parts of the serial were filmed with a one-inch lens. Cameraman Edgar Lyons had initially been filming more of the clouds in the sky than the actors, with the effect of partially cutting them out of the shot. The studio complained. Director William Witney compromised with the use of the wider lens, which would take in both cloudscape and actors. Only silent scenes were shot in this manner because the camera would be both closer to the actors and take in more of the surroundings, preventing the microphone from getting close enough to work properly. Special Effects The special effects in this serial were created by the Lydecker brothers. Stunts Ted Mapes as Kioga (doubling Herman Brix) James Dime George Montgomery Henry Wills Release Theatrical Hawk of the Wilderness''' official release date is 3 December 1938, although this is actually the date the sixth chapter was made available to film exchanges. Television In the early 1950s, Hawk of the Wilderness was one of fourteen Republic serials edited into a television series. It was broadcast in six 26½-minute episodes. It was also one of twenty-six Republic serials re-released as a film on television in 1966. The title of the film was changed to Lost Island of Kioga. This version was cut down to 100 minutes in length. Critical reception The burial of Kias in the final chapter is regarded by Cline as one of the "very few successful attempts at drama in serials." Chapter titles Mysterious Island (28min 59s) Flaming Death (16min 40s) Tiger Trap (16min 46s) Queen's Ransom (16min 50s) Pendulum of Doom (16min 35s) The Dead Fall (16min 40s) White Man's Magic (16min 41s) Ambushed (16min 41s) Marooned (16min 41s) - a re-cap chapter Camp of Horror/Caves of Horror (16min 39s) Valley of Skulls (16min 41s) Trail's End (16min 40s) Source: This was one of the two 12-chapter serials released by Republic in 1938, the other was The Fighting Devil Dogs''. This year began the studio's standard release pattern of two 12-chapter and two 15-chapter serials in every year. This pattern remained until 1944 with the exception of 1942, which had only one 15-chapter serial released instead of two. References External links Category:1938 films Category:American films Category:English-language films Category:1930s adventure films Category:1930s fantasy films Category:American black-and-white films Category:Republic Pictures film serials Category:Films directed by William Witney Category:Films directed by John English Category:Films based on American novels Category:Films based on Western (genre) novels Category:Films scored by William Lava Category:American adventure films Category:American fantasy films
Testing a User-Initiated Remote Transfer Test FASP transfers initiated from a client computer. Important: The instructions require you to take steps on both Point-to-Point and a client computer. Ensure that you are performing the task on the indicated machine. As a prerequisite, you will need to have at least one transfer user added to Point-to-Point. For instructions, see Setting up Users. On your client machine, verify your connection to Point-to-Point. On the client machine, use the ping command in a Terminal window to verify connectivity to the host. In this example, the address of Point-to-Point is 10.0.0.2.
Age influences the relation between subjective valence ratings and emotional word use during autobiographical memory retrieval. Recent research reveals an age-related increase in positive autobiographical memory retrieval using a number of positivity measures, including valence ratings and positive word use. It is currently unclear whether the positivity shift in each of these measures co-occurs, or if age uniquely influences multiple components of autobiographical memory retrieval. The current study examined the correspondence between valence ratings and emotional word use in young and older adults' autobiographical memories. Positive word use in narratives was associated with valence ratings only in young adults' narratives. Older adults' narratives contained a consistent level of positive word use regardless of valence rating, suggesting that positive words and concepts may be chronically accessible to older adults during memory retrieval, regardless of subjective valence. Although a relation between negative word use in narratives and negative valence ratings was apparent in both young and older adults, it was stronger in older adults' narratives. These findings confirm that older adults do vary their word use in accordance with subjective valence, but they do so in a way that is different from young adults. The results also point to a potential dissociation between age-related changes in subjective valence and in positive word use.
BEIJING - Food exporters including the United States and European Union are stepping up pressure on China to scale back plans for intensive inspections of imports that they say would hamper access to its fast-growing market. The group, which also includes Japan and Australia, sent a joint letter to Chinese regulators asking them to suspend a proposed requirement, due to take effect Oct. 1, for each food shipment to have an inspection certificate from a foreign government. They say that would disrupt trade and ask Beijing to follow global practice by applying the requirement only to higher-risk foods. The dispute, about which governments have said little in public, adds to complaints Beijing is reducing market access for goods ranging from medical technology to farm-related biotech in violation of its free-trade commitments. The letter, dated June 12 and seen by The Associated Press, was sent by an unusually broad group including the 28-nation European Union, the United States, Japan, Australia, Argentina and Israel and four other countries. It is addressed to the director of the General Administration of Quality Supervision, Inspection and Quarantine, known as AQSIQ, and the Chinese commerce minister. A foreign official who asked not to be identified further due to the sensitivity of the issue confirmed the letter was sent to Chinese regulators. The letter says the rules would affect billions of dollars' worth of meat, fruit, dairy and other products and thousands of suppliers who look to China as a growing export market. Foreign suppliers complain Beijing already uses safety rules in ways that hamper access for beef and other goods in violation of its market-opening commitments. AQSIQ did not reply to a request for comment or questions sent by fax about how regulations might be changed in response to foreign appeals. The depth of U.S. concern about the impact on American farmers and food processors is reflected in Washington's decision to take part in the group at a time when President Donald Trump has downplayed trade disputes with Beijing to gain Chinese support in dealing with North Korea. The EU role highlights the broad scope of foreign anxiety. Action by the EU requires unanimous agreement by its members, which means nations including Greece and Hungary that want to attract Chinese investment consider the threat serious enough to risk a possible backlash. Eastern European countries with little manufacturing pay for Chinese goods by selling ham, apples and other food to China. Chinese food imports in the first four months of this year rose 17 percent over a year earlier to $39.4 billion. Foreign governments have been lobbying Beijing since last year to scale back the proposed regulations. European officials complained they appeared to be intended to shield Chinese suppliers from competition and allow Beijing to block imports from individual countries if it chose. China submitted its proposed regulations to the World Trade Organization as an official notice to other governments, which have 60 days to comment on them. They were posted this week on a WTO website. In a possible concession to foreign appeals, the regulations on the WTO website say inspection certificates would be required to say food items were made by a supplier supervised by government regulators and were fit for human consumption. That appeared to be a significant change from an earlier proposal to require inspectors to confirm that food complies with China's quality standards, a provision to which foreign governments objected. The latest version still says each "batch of food" would require a certificate, a step foreign officials previously complained would waste resources that should be focused on high-risk products such as dairy. The June 12 letter appeals to Chinese regulators to alter the proposed rules to allow imports from foreign suppliers that are approved by government inspectors without requiring a separate certificate for each shipment. The rules would apply to items from meat and dried fruit to cocoa and spices, according to the document. Foreign officials earlier expressed concern they might extend to such products as coffee, wine, pasta and chocolate, but it was unclear whether the list submitted to the WTO included such processed foods. China contends the inspection requirement is supported by the Codex Alimentarius, the "Food Code" of the U.N. Food and Agriculture Organization and World Health Organization. The Codex sets quality standards but other nations say it recommends certificates only for risky products. The EU and other governments arranged for the president of the Codex council, Awilo Ochieng Pernet, a Swiss lawyer, to attend an April 6 seminar with Chinese officials in Beijing to explain its standards. The proposed rules follow an avalanche of scandals over Chinese suppliers caught selling tainted milk and other shoddy or counterfeit food products. Western officials say the proposed food rules appear meant to shift responsibility away from AQSIQ, which Chinese consumers often blame for safety failures. Beijing already is at odds with the U.S. and Europe over low-priced exports of steel and aluminum they say are hurting foreign competitors. In the Trump administration's first trade complaint, a group for American aluminum producers asked March 9 for higher import duties on Chinese-made aluminum foil to counter what it said were improper subsidies.
package com.talentica.androidkotlin.sqlitedatabase; import android.content.Context; import android.support.test.InstrumentationRegistry; import android.support.test.runner.AndroidJUnit4; import org.junit.Test; import org.junit.runner.RunWith; import static org.junit.Assert.; /* * Instrumentation test, which will execute on an Android device. * * @see <a href="http://d.android.com/tools/testing">Testing documentation</a> */ @RunWith(AndroidJUnit4.class) public class ExampleInstrumentedTest { @Test public void useAppContext() throws Exception { // Context of the app under test. Context appContext = InstrumentationRegistry.getTargetContext(); assertEquals("com.talentica.androidkotlin.sqlitedatabase", appContext.getPackageName()); } }
Q: Flushing Fabric/Crashlytics non fatals and events I have an Android app that's deployed on a bunch of tablets my company owns and manages. These tablets are single purpose devices - they run this app and nothing else. The app doesn't ever stop unless it crashes. In fact, we use AirWatch to lock the device into single task mode, so it's more or less impossible for the app to get killed. From what I've read, this does not sit well with Fabric, which likes to send its non fatal errors and events only once the app is killed. What can I do about this? Can I turn this behaviour off or somehow programmatically flush the list of events and non fatals to be sent to the server? A: Mike from Fabric here. There isn't a way to manually flush or push the events to our servers currently. It's not on our immediate roadmap to add in, but will update my answer if there is a change.
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Q: Run RapSearch-Program with Torque PBS and qsub My problem is that I have a cluster-server with Torque PBS and want to use it to run a sequence-comparison with the program rapsearch. The normal RapSearch command is: ./rapsearch -q protein.fasta -d database -o output -e 0.001 -v 10 -x t -z 32 Now I want to run it with 2 nodes on the cluster-server. I've tried with: echo "./rapsearch -q protein.fasta -d database -o output -e 0.001 -v 10 -x t -z 32" \| qsub -l nodes=2 but nothing happened. Do you have any suggestions? Where I'm wrong? Help please. A: Standard output (and error output) files are placed in your home directory by default; take a look. You are looking for a file named STDIN.e[numbers], it will contain the error message. However, I see that you're using ./rapsearch but are not really being explicit about what directory you're in. Your problem is therefore probably a matter of changing directory into the directory that you submitted from. When your terminal is in the directory of the rapsearch executable, try echo "cd \$PBS_O_WORKDIR && ./rapsearch [arguments]" \| qsub [arguments] to submit your job to the cluster. Other tips: You could add rapsearch to your path if you use it often. Then you can use it like a regular command anywhere. It's a matter of adding the line export PATH=/full/path/to/rapsearch/bin:$PATH to your .bashrc file. Create a submission script for use with qsub. Here is a good example.
Venture into an exciting new world; forego all preconceived ideas of traditional museum visits, dispel all notions of tiptoeing through silent art galleries to view masterpieces from afar, change how you engage with art. In an instant, Van Gogh Alive – The Experience transports visitors to another time and place, immersing them in the artists’ world. Adults and children alive will forge their own paths and find their own meaning as they wander through the galleries, exploring hidden nooks, viewing artworks from new angles and discovering unique perspectives. Transcend time and space as you accompany Vincent van Gogh on a journey through Arles, Saint Rémy and Auvers-sur-Oise, where he created most of his timeless masterpieces. See these works in hyper-fine detail, with special attention paid to key features, allowing you time to study color and technique. Synchronized to a powerful classical score, more than 3,000 Van Gogh images at enormous scale create a thrilling display that fills giant screens, walls, columns, ceilings and even the floor – immersing you entirely in the vibrant colors and vivid details that constitute Van Gogh’s unique style. THE VIBRANT COLOURS AND VIVID DETAILS OF VAN GOGH'S WORK ARE TRULY BREATHTAKING AN EXPERIENCE THAT IS SIMULTANEOUSLY ENCHANTING, ENTERTAINING AND EDUCATIONAL
Interaction between virion-bound host intercellular adhesion molecule-1 and the high-affinity state of lymphocyte function-associated antigen-1 on target cells renders R5 and X4 isolates of human immunodeficiency virus type 1 more refractory to neutralization. The oligomeric nature of the viral envelope proteins has been partly held responsible for the observed differences in neutralization sensitivity between primary and laboratory-adapted strains of human immunodeficiency virus type 1 (HIV-1). However, recent evidence suggests that host factors can also modify the sensitivity of HIV-1 particles to neutralization. Having previously demonstrated that the acquisition of host-encoded intercellular adhesion molecule (ICAM)-1 proteins by newly formed viruses has a functional significance for the life cycle of HIV-1, we investigated whether the acquisition of host-derived ICAM-1 by HIV-1 could affect the virus sensitivity to neutralization. In this study, we have first shown that the physical presence of host cell membrane ICAM-1 on HIV-1 was not modifying virus sensitivity to neutralization by either two different anti-gp120 monoclonal antibodies (0.5beta and 4.8D) or soluble CD4. However, the ability of the F105 anti-gp120 monoclonal antibody (specific for the CD4-binding site) to neutralize ICAM-1-bearing virions was diminished when target cells were pretreated with an lymphocyte function-associated antigen-1 (LFA-1)-activating antibody. Interestingly, ICAM-1/POS progeny viruses were found to be slightly more resistant to neutralization by individual human sera in target cells expressing a low-affinity form of LFA-1 than viruses devoid of host-encoded ICAM-1 proteins. This resistance was markedly enhanced when target cells expressed an activated LFA-1 form on their surface. These results suggest that the interaction between virally embedded host ICAM-1 and target cell surface LFA-1 should be considered a factor modulating neutralization sensitivity of HIV-1 by human sera from HIV-1-infected individuals.
ISLANDER SOFTBALL ENDS FALL BALL WITH TWO WINS OVER DUST DEVILS Oct 25, 2009 The Texas A&M-Corpus Christi softball ended their fall season with two impressive wins over Texas A&M-International winning 13-0 and 12-0 on Saturday afternoon. The Islander pitching and defense did the job with two shutouts and committing one error. Sandy Schumann helped the team at the plate and in the field turning in a few defensive gems on the day. "Today we were solid hitting the ball and playing good defense," said softball head coach Jake Schumann "Sandy Schumann would get a game ball today if we gave one out with her effort hitting line drives all over and playing great at third base," Schumann added. In game one TAMUCC belted out 16 hits and scored 13 runs against Texas A&M-International. The Islanders widened the margin with a seven fun fifth inning, which the offense strung together six straight hits and nine base runners overall. Alex Hutchinson was perfect in the circle through the first four innings before yielding the lone hit to the Dust Devils in the fifth. Five Islanders had two-hits in the game combining for 10 of the 16 total. Caley Jeter and Lauren Dodson both scored three runs each. Margo Hurdt and Cassie Redman tied for the team lead in the first game with three RBIs in the route. Texas A&M-Corpus Christi jumped right on the opposition immediately in the second game scoring five runs on three errors in the opening inning. Landry Moore capped the scoring in the first with a two out triple that scored two runs. Hannah Schwarz dazzled in the field making a couple great catches on hard hit balls. The Islanders offense continued in the 12-0 route to complete play for the fall. "We accomplished what we wanted to today defensively and pitching, in addition a lot of kids got some playing time today," said Shumann.
import { Rule } from '@angular-devkit/schematics'; import { NxJson, updateJsonInTree } from '@nrwl/workspace'; import { NormalizedSchema } from '../schema'; export function updateNxJson(options: NormalizedSchema): Rule { return updateJsonInTree<NxJson>('nx.json', (json) => { json.projects[options.projectName] = { tags: options.parsedTags }; return json; }); }
<manifest xmlns:android="http://schemas.android.com/apk/res/android" package="me.shouheng.commons" > <uses-permission android:name="android.permission.ACCESS_NETWORK_STATE" /> <uses-permission android:name="android.permission.ACCESS_WIFI_STATE" /> <uses-permission android:name="android.permission.INTERNET" /> <uses-permission android:name="android.permission.READ_PHONE_STATE" /> <uses-permission android:name="android.permission.WRITE_EXTERNAL_STORAGE" /> <application> <activity android:name=".activity.ContainerActivity" android:screenOrientation="portrait"/> <activity android:name="me.shouheng.commons.minipay.DonateActivity" android:configChanges="keyboardHidden\|orientation\|screenSize" android:exported="false" android:screenOrientation="portrait" android:theme="@style/PayTheme"/> </application> </manifest>
Hidayet Mosque The Hidayet Mosque (:tr:Hidayet Camii), located on Yalı Köşkü Street in Istanbul’s Eminönü district, was built in 1813 (Islamic Calendar 1229) under Mahmud II. Originally of wood construction, it was reconstructed by the French architect Alexander Vallaury in 1887 under the direction of Abdul Hamid II, as described by the inscription on the entrance to the courtyard. The design of the two-story mosque can be described as Orientalist. There are two large pointed-arch windows on the Eastern and Western sides of the mosque and 21 windows in the dome. Stairs lead to the second floor, where there is a prayer room and a domed sanctuary. History Before Hidayet Mosque was built, the small district called tr:Bahçekapı, located between Eminönü and Sirkeci, was a rough district known for murders, prostitution, and general poor conditions. It was given the informal name of :tr:Melek Girmez Sokağı ("The street that angels abandoned") by the locals. After the plague of 1812, Mahmud II ordered many Istanbul districts including Bahçekapı demolished, and in order to obscure the history of the area, he had the mosque built with the name Hidayet, a word coming from Arabic meaning "seeking the right path". References Category:Religious buildings and structures completed in 1813
What Buhari needs to succeed – Jonathan By Isiaka Wakili \| Publish Date: Apr 6 2015 4:01AM (0 Likes) President Goodluck Jonathan has asked Nigerians to be ready to make sacrifices in order to help the President-elect retired General Muhammadu Buhari succeed.Jonathan spoke at the Presidential Villa, Abuja yesterday when he received a delegation of the Federal Capital Territory residents led by his vice, Mohammed Namadi Sambo, who paid him Easter homage.The president described Easter, as a period of sacrifice. He said: “Whenever we talk about this period, the key lesson there is sacrifice. Somebody sacrificed for our own salvation. “Now, Buhari is coming on board; it is not about supporting Buhari or government, but what sacrifice, as individuals, are you willing to make for government and for the nation?”He asked whether Nigerians would be ready to make the sacrifice of backing Buhari if he should increase Value Added Tax (VAT) from five to 10 percent.There is already a proposal in the medium term expenditure framework now before the National Assembly to increase VAT from five percent. The President said: “In the ECOWAS sub-region for example, Nigeria has the lowest VAT, other countries pay up to 12 percent. “If for instance, Buhari decides to increase VAT from 5 to 10 percent, will Nigerians support him? That is sacrifice, and we must make sacrifice.”The president maintained that no government would survive if the citizens, especially businessmen, refuse to pay tax.“If you are a businessman and you say you are supporting government, but you don’t pay tax; how do you expect that government to survive? That government will not survive,” he said.He recalled that as a deputy governor in Bayelsa State his people used to come to him to pledge their loyalty. He said he often responded, “Don’t tell me you are loyal; tell me you are patriotic to the country and that you believe in Bayelsa State.“To me, whenever I travel to different countries and see things work, those things didn’t fall down as many people made sacrifice.“Therefore, in Nigeria, people must also be ready to make the required sacrifice. Whoever becomes president is immaterial so long as the citizens are happy; our children go to school, when they are sick, they go to good hospital and of course, the economy blossoms.“Nation building depends on the sacrifices of individuals and the patriotism of the citizens. These are two key elements. “We are talking about Boko Haram or terror; soldiers are dying for us to live, police are dying for us to live. That is sacrifice. As individuals, you don’t need to die, but there are various roles you need to play. You must make sacrifice.“The economy of China was threatened, but they locked up themselves for a period of time. And by the time they opened their doors, they become even a threat to the biggest economy.“Are we ready for that kind of sacrifice for the government? Whenever we talk of Easter, these are the key lessons of sacrifice”, Jonathan said.The president reminisced about his years of service from being the deputy governor of Bayelsa State to being the nation’s number one citizen and said: “I think it is enough”.The president said since 1999, he had been in a cage “being taken care of by the government”.“For me as an individual, this Easter coincides with the time I’m leaving. But I always say that I’m one of the luckiest Nigerians. I’m yet to see somebody luckier than me. From 1999, I was in the hands of government for 16 years.“I was in a cage, being taken care of by the government. From May 29, 1999 to date; 16 good years! I think it is enough and I am happy. Help me to thank God for that ...Today is a glorious day for me.”Those in the delegation were Secretary to the Government of the Federation Anyim Pius Anyim; Chief of Staff Jones Arogbofa; Head of Service Danladi Kifasi; Archbishop of the Anglican Church of Nigeria Most Rev. Nicholas Okoh; Catholic Archbishop of Abuja Cardinal John Onaiyekan; Executive Secretary of the Nigerian Christian Pilgrims Commission John Kennedy-Opara; Chief Imam of the National Mosque Alhaji Muhammed Musa, among others. (0 Likes) What do you think about this story Please include a contact number if you are willing to speak to a Daily Trust journalist. You can also contact us in the following way: Name Your E-mail address (required) Town & Country Your telephone number Comments If you are happy to be contacted by a Daily Trust journalist please leave a telephone number that we can contact you on. In some cases a selection of your comments will be published, displaying your name as you provide it and location, unless you state otherwise. Your contact details will never be published. When sending us pictures, video or eyewitness accounts at no time should you endanger yourself or others, take any unnecessary risks or infringe any laws. Please ensure you have read the terms and conditions.
Extensioneshttps://addons.mozilla.org/EN-US/firefox/Download Management Add-onsen-USTue, 03 Mar 2015 09:40:48 -0800Click to Play per-element 0.3.0https://addons.mozilla.org/EN-US/firefox/addon/click-to-play-per-element/<b>Version 0.0.8 is now working with e10s mode.</b> <a rel="nofollow" href="https://addons.mozilla.org/de/firefox/addon/click-to-play-per-element/versions/0.3.0" title="">Version 0.3.0</a> In about:config "<b>plugins.click_to_play</b>" must be "<b>true</b>". On about:addons (plugins page) required <b>plugin</b> must be "<b>Ask to activate</b>". By this <a rel="nofollow" href="https://addons.mozilla.org/en-us/firefox/addon/click-to-play-per-element/reviews/504258/">review</a> of <a rel="nofollow" href="https://addons.mozilla.org/en-us/firefox/user/tedych/">tedych</a>: if you want to enable the plugin on the page and not the whole website by clicking the "Allow Now" button from urlbar plugin icon (like in Firefox 23 "Activate" button) in about:config "plugin.sessionPermissionNow.intervalInMinutes" set it to 0 (zero) Tip: If you want to disable the html5 player on youtube and use flash again use this <a rel="nofollow" href="https://addons.mozilla.org/en-US/firefox/addon/youtube-flash-player/">add-on</a> latest beta on Development Channel about:config?filter=extensions.uaSad@ClickToPlayPerElement upd: + css from <a rel="nofollow" href="https://addons.mozilla.org/firefox/addon/hide-plugin-notifications/">Hide Plugin Notifications</a> by <a rel="nofollow" href="https://addons.mozilla.org/user/bsmedberg/">bsmedberg</a> <a rel="nofollow" href="https://addons.mozilla.org/firefox/addon/hide-plugin-notifications/reviews/548902/">How to hide plugin notifications bar</a> example <a rel="nofollow" href="http://outgoing.mozilla.org/v1/6d05e350e3cfd7a19e4902a4a8741deeaf1537adab567431dc48838365374ac5/http%3A//kb.mozillazine.org/UserChrome.css">userChrome.css</a>: <code>notification[value="plugin-hidden"] { display: none !important; }</code> <strong>Warning: This example is not recommended anymore because this will also hide the notification bar for insecure (vulnerable) plugins.</strong> Note: Version 0.3.0 has a new setting called "Hide plugin notifications". This allows you to block the plugin notifications bar.def00111Tue, 03 Mar 2015 09:40:48 -0800https://addons.mozilla.org/EN-US/firefox/addon/click-to-play-per-element/versions/0.3.0NoPremium.pl 0.12.1https://addons.mozilla.org/EN-US/firefox/addon/nopremiumpl/Natywna wtyczka dla serwisu <a href="http://outgoing.mozilla.org/v1/31ea01397834d55d6c558b7b646ac308177d418530d6e3d9f08fc081622e5e12/http%3A//NoPremium.pl" rel="nofollow">NoPremium.pl</a>, udostępniająca szereg ułatwień dla klientów serwisu: * sprawdzaj typ i stan konta * błyskawiczny dostęp do doładowania konta, wyszukiwania i pobierania plików * automatyczna detekcja obsługiwanych linków na wszystkich stronach * zaznaczaj linki i kliknij prawym przyciskiem myszy na zaznaczeniu, a następnie wybierz "Pobierz z <a href="http://outgoing.mozilla.org/v1/31ea01397834d55d6c558b7b646ac308177d418530d6e3d9f08fc081622e5e12/http%3A//NoPremium.pl" rel="nofollow">NoPremium.pl</a>" - zostaniesz automatycznie przekierowany do podstrony pobierania plików * bezpośrednia integracja z podstronami hostingów - po przejściu na podstronę hostingu pojawia się przycisk "Pobierz z <a href="http://outgoing.mozilla.org/v1/31ea01397834d55d6c558b7b646ac308177d418530d6e3d9f08fc081622e5e12/http%3A//NoPremium.pl" rel="nofollow">NoPremium.pl</a>", umożliwiający pobranie pliku z aktualnie wyświetlanej podstrony jednym kliknięciem * NATYCHMIASTOWE POWIADOMIENIA O PROMOCJACH I BONUSACH * wersja rozwojowa - prosimy o sugestie nowych funkcjonalności oraz zgłaszanie problemów. Wszelkie problemy z wtyczką prosimy zgłaszać na adres: nopremium@nopremium.pl.File Sharing LTDTue, 03 Mar 2015 09:39:15 -0800https://addons.mozilla.org/EN-US/firefox/addon/nopremiumpl/versions/0.12.1Rapideo.pl extension 0.13.2https://addons.mozilla.org/EN-US/firefox/addon/rapideo-pl/Rapideo becomes bilingual! Polish / english version. Native <a href="http://outgoing.mozilla.org/v1/70f8f10c58cce5875daad6ef7c96a4436ae15ddbb3235fdbe0606f1993e4c838/http%3A//Rapideo.pl" rel="nofollow">Rapideo.pl</a> extension, making use of our services much easier: * instant access to account refill, search and files download * RapiParse - automatic detection of supported links on all pages * mark the links and click the right mouse button and select "Download with <a href="http://outgoing.mozilla.org/v1/70f8f10c58cce5875daad6ef7c96a4436ae15ddbb3235fdbe0606f1993e4c838/http%3A//Rapideo.pl" rel="nofollow">Rapideo.pl</a>" - you will be automatically redirected to the download page * direct integration with supported web hostings pages - after opening to file hosting page, the "Download with <a href="http://outgoing.mozilla.org/v1/70f8f10c58cce5875daad6ef7c96a4436ae15ddbb3235fdbe0606f1993e4c838/http%3A//Rapideo.pl" rel="nofollow">Rapideo.pl</a>" button will appears to download the file with one click * IMMEDIATE NOTIFICATIONS ABOUT PROMOTIONS Plugin is still in development stage. Please send suggestions for new features and report problems to dev@rapideo.pl.File Sharing LTDTue, 03 Mar 2015 09:38:16 -0800https://addons.mozilla.org/EN-US/firefox/addon/rapideo-pl/versions/0.13.2ScrapBook 1.5.12https://addons.mozilla.org/EN-US/firefox/addon/scrapbook/ScrapBook is a Firefox extension, which helps you to save Web pages and easily manage collections. Key features are lightness, speed, accuracy and multi-language support. Major features are: * Save Web page * Save snippet of Web page * Save Web site * Organize the collection in the same way as Bookmarks * Full text search and quick filtering search of the collection * Editing of the collected Web page * Text/HTML edit feature resembling Opera's NotesGomitaTue, 03 Mar 2015 08:25:48 -0800https://addons.mozilla.org/EN-US/firefox/addon/scrapbook/versions/1.5.12Double-click Image Downloader 4.2.3https://addons.mozilla.org/EN-US/firefox/addon/double-click-image-download/Double-click any image to download it! <b>Glitch</b> When the link/image hybrid workaround is enabled, alt-tabbing out of Firefox and returning via any method other than alt-tab will cause the current tab's links to stop working. Refreshing the page or hitting the alt-key fixes this. There is no workaround for this type of glitch besides changing the key combo, which would just move the problem to a different key. <b>Features</b> <ul><li>ability to rename images and store them in subfolders. Both names can be specified with variables: a counter (creating a sequence), the source website (per-website folders), the tab's title and the original filename</li><li>toolbar button that contains the file/folder name settings in addition to the standard settings screen, for quicker access</li><li>preview toaster popup that shows you the image once it's downloaded, or an error message. Click this popup to open the image's folder in a new tab in Firefox</li><li>domain exclusion list with realtime validation</li></ul> Check the settings and experiment before reporting avoidable complaints, please. <b>Please rate/review! :)</b> Feel like donating? You can use the button for Paypal, or help me out with Bitcoin! 1DpTx1SCABnEpADefcAmeCYdBfBXxPQTrX <b>Issues/notes</b> <ul><li>some websites are known to protect their images from tools like this. Nothing can be done about that</li><li>no longer detects CSS backgrounds (conscious choice)</li></ul>MarnesMon, 02 Mar 2015 20:45:31 -0800https://addons.mozilla.org/EN-US/firefox/addon/double-click-image-download/versions/4.2.3Copy Selected Links 1.0.5https://addons.mozilla.org/EN-US/firefox/addon/copy-selected-links/When you select text in a page and your selection contains links, you can right-click anywhere to copy the URLs of each link at once. <b>Please rate/review! :)</b> Feel like donating? You can use the button for Paypal, or help me out with Bitcoin! 1DpTx1SCABnEpADefcAmeCYdBfBXxPQTrXMarnesMon, 02 Mar 2015 09:42:56 -0800https://addons.mozilla.org/EN-US/firefox/addon/copy-selected-links/versions/1.0.5NetVideoHunter - YouTube Video Downloader 1.17https://addons.mozilla.org/EN-US/firefox/addon/netvideohunter-video-downloade/This addon is a download helper tool that lets you easily download videos (FLV, MP4, WEBM) and music (MP3, OGG) from almost any video-sharing site. For example from: <b>Youtube</b>, Facebook, Metacafe, Dailymotion, Break, VKontakte, DivShare, etc... On YouTube it's possible to download in different qualities (360p, 480p, 720p) if it's available (you have to right click in the list to select the quality). By default it downloads in the best available quality. Before the download you can preview videos and music in a built-in media player to make sure you will download the right video. <b>If you have some problem with the addon then please send a message from <a rel="nofollow" href="http://outgoing.mozilla.org/v1/645015ae54de15daef816dd0c98d399fed392c9ee7514f8012369f78ac54a48e/http%3A//netvideohunter.com/contact">here</a></b> For more help check out the homepage: <br> <h2> <a rel="nofollow" href="http://outgoing.mozilla.org/v1/684322b3c5060d6c2810cc60cef39aaacf9867e1758d20d046d85236bfff2299/http%3A//netvideohunter.com">http://netvideohunter.com/pages/how-to-use</a></h2><h2></h2>netvideohunterMon, 02 Mar 2015 08:27:40 -0800https://addons.mozilla.org/EN-US/firefox/addon/netvideohunter-video-downloade/versions/1.17网盘离线下载 1.0https://addons.mozilla.org/EN-US/firefox/addon/%E7%BD%91%E7%9B%98%E7%A6%BB%E7%BA%BF%E4%B8%8B%E8%BD%BD/leeSun, 01 Mar 2015 11:02:53 -0800https://addons.mozilla.org/EN-US/firefox/addon/%E7%BD%91%E7%9B%98%E7%A6%BB%E7%BA%BF%E4%B8%8B%E8%BD%BD/versions/1.0Easy Youtube Video Downloader Express 8.0https://addons.mozilla.org/EN-US/firefox/addon/easy-youtube-video-download/The original version of this addon was filled with advertisements and is also no longer available, this one is the simplest and fastest Youtube video downloader you will find. <strong><em>Major Features :</em></strong> 1). Only addon to offer 1080p Full-HD downloads after recent Youtube changes breaking other downloaders. 2). Instant single-click, direct 192kbps HQ MP3 downloads. 3). Simple, elegant and minimal download button. <b>--------------------------------------------------------------------------------------------------------------------------------------------</b> Pls, use the <a rel="nofollow" href="http://outgoing.mozilla.org/v1/cb9a8ae9038e8b11c5fed4b4990e4e17d518efbd4239e54ccde4908eab29ced5/http%3A//yourvideofile.com/support.html">support system</a> to ask for assistance if having any issues. The review section below is not for that. <b>--------------------------------------------------------------------------------------------------------------------------------------------</b>DishitaFri, 27 Feb 2015 14:39:29 -0800https://addons.mozilla.org/EN-US/firefox/addon/easy-youtube-video-download/versions/8.0Easy media download 0.1https://addons.mozilla.org/EN-US/firefox/addon/easy-media-download/This add-on opens "View Page info" -> "Media" tab with a single click. You can download any media file (flash games, videos, images, swf, embedded) on the web. Super easy and fast! Have fun:)JaanThu, 26 Feb 2015 22:32:09 -0800https://addons.mozilla.org/EN-US/firefox/addon/easy-media-download/versions/0.1courserax 1.3.2https://addons.mozilla.org/EN-US/firefox/addon/courserax/Coursera courses Bulk Downloader. * Install addon (no restart required). * Make your firefox add-on bar visible (<b>View > Toolbars > Add-on Bar</b>) * In a new tab, go to your coursera class and navigate to the 'Video Lectures' page. * Click on the courserax icon in the add-on bar (at the bottom of the browser window). * Select the items you want to download and the destination folder Enjoy ! Brought to you by Helio Labs. Many thanks to <i>H.M.</i> for her support ;-)Guillaume Yawo KPOTUFEThu, 26 Feb 2015 21:18:15 -0800https://addons.mozilla.org/EN-US/firefox/addon/courserax/versions/1.3.2Download Flash and Video 1.68https://addons.mozilla.org/EN-US/firefox/addon/download-flash-and-video/FLASH AND VIDEO DOWNLOAD: Download Flash and videos with a single click - the only download tool that is a video downloader and a flash downloader mix together. You can download any flash file on the web plus Flash games on Facebook or any other web site of Flash games. Compatible with DownThemAll and NoScript. The downloader is great for users who like to visit YouTube and download videos, or like to play Flash games on the internet and download them later. DOWNLOAD VIDEOS FROM: Download web videos from YouTube, Dailymotion, Google Videos, Facebook, Metacafe, MySpace Video, <a href="http://outgoing.mozilla.org/v1/277315e85be62023438ad4944b0dad1a8fb936bb299eaf9a9432275f0769af24/http%3A//Break.com" rel="nofollow">Break.com</a>, <a href="http://outgoing.mozilla.org/v1/5f6a1f39a82388b3104182591a2728f23425a67f315d7c131c2d650134d7da20/http%3A//Blip.tv" rel="nofollow">Blip.tv</a>, <a href="http://outgoing.mozilla.org/v1/017f5610bbf33c0edc91587c97591a155694a7ecc4a4139993794355b3959258/http%3A//MyVideo.de" rel="nofollow">MyVideo.de</a>, Spike, <a href="http://outgoing.mozilla.org/v1/70c76b6b557d6cd282639efefc046f4d1287efaa8a09ad09c66f34f4954a04f9/http%3A//vimeo.com" rel="nofollow">vimeo.com</a>, YourFileHost, <a href="http://outgoing.mozilla.org/v1/271ab7a1bb74ac8680017a82f17e19cc9b12fc3bd7fb78cd1d5e368187e74d14/http%3A//zippyvideos.com" rel="nofollow">zippyvideos.com</a>, <a href="http://outgoing.mozilla.org/v1/485cc833332212dd4b6fe4e8ef18f58eac0649e2bc720135c0f40ee8744fb60e/http%3A//yikers.com" rel="nofollow">yikers.com</a>, <a href="http://outgoing.mozilla.org/v1/24ba3120388c611c760ff0cd1801996f5927cdd352b0cf5f82d456e29531d9c4/http%3A//revver.com" rel="nofollow">revver.com</a>, <a href="http://outgoing.mozilla.org/v1/fc016d2a0108371576959213804659c61eb46a8fb94cac1593d77bd3eed24edd/http%3A//kontraband.com" rel="nofollow">kontraband.com</a>, <a href="http://outgoing.mozilla.org/v1/b56d0c790486c10403abfb3441cc570409f32bbbd2c4f880d659fcea4c2f1c26/http%3A//collegehumor.com" rel="nofollow">collegehumor.com</a>, <a href="http://outgoing.mozilla.org/v1/a17f3072eb761d47540100c8af5d7708210348a443ae79ff136b813347aee22e/http%3A//blastro.com" rel="nofollow">blastro.com</a> and all the other popular of flash videos sites. You can download videos in popular formats. DOWNLOAD FLASH FROM: Download Flash Games from <a href="http://outgoing.mozilla.org/v1/fc7829ebf65a7f03c3f03463eaf3bb50cd8dff1e1381fad3eff9a805ce3a23aa/http%3A//community.games.com" rel="nofollow">community.games.com</a>, <a href="http://outgoing.mozilla.org/v1/991e6eb90a6868442404390ec7ad1d4e05491b571b0296d049bc7255bb64ab1c/http%3A//gamespot.com" rel="nofollow">gamespot.com</a>, <a href="http://outgoing.mozilla.org/v1/5be496d300c80a125de9b3e51c0f5324f108658708eb2be54b14bb626e93e0cd/http%3A//zoopgames.com" rel="nofollow">zoopgames.com</a>, <a href="http://outgoing.mozilla.org/v1/ddf9fb172470d548b9f3378c09a75de2ce5da31a8d67ba30c37dc1bca8b8bf9c/http%3A//armorgames.com" rel="nofollow">armorgames.com</a>, <a href="http://outgoing.mozilla.org/v1/18c89fc0a5603e1a9f3da4208cd4f35c917d3449fd82c64e1c09021ad7be77df/http%3A//net-games.biz" rel="nofollow">net-games.biz</a>, <a href="http://outgoing.mozilla.org/v1/b503c7f8d0770a96394ccc3ded26dec6f6a2779b356daa65aa1e416dce0050ab/http%3A//gamesvine.com" rel="nofollow">gamesvine.com</a>, <a href="http://outgoing.mozilla.org/v1/14b1f26de65a9af3c28d71be49fd203b66cb23880e6cc9527f1be17fb384883e/http%3A//flashgames247.com" rel="nofollow">flashgames247.com</a> and other popular flash download web sites. DOWNLOAD PROCEES: The download process is very easy, whenever you want to download a flash or a video from a site, just click on the status bar icon (see screenshots), and choose the desired file to download and the downloader will start immediately (to download Flash files you need to choose the files with the swf extension, downloading videos option will be enabled once you're visit one of the popular videos websites) As a super user myself who likes to download videos from the internet (as a super user, FlashGot Downthemall NoScript and AdBlock are my must addons of course :)), if you are like me, this download helper is for you.Download Flash and VideoThu, 26 Feb 2015 21:12:39 -0800https://addons.mozilla.org/EN-US/firefox/addon/download-flash-and-video/versions/1.68All Downloader Professional 1.00.15https://addons.mozilla.org/EN-US/firefox/addon/all-downloader-professional/- Find and download all elements of a website - find hidden pictures on websites - Download many files at once - Filter by file type or sizestartpage24Thu, 26 Feb 2015 03:53:07 -0800https://addons.mozilla.org/EN-US/firefox/addon/all-downloader-professional/versions/1.00.15ReDisposition 0.2.5https://addons.mozilla.org/EN-US/firefox/addon/redisposition/When downloading file, this extension help you: <ul> <li>fix the filename wrong encoding</li> <li>inline mode, view file directly in Firefox</li></ul>It provide a toolbar button to quick switch. For technology detail, please read the project <a href="http://outgoing.mozilla.org/v1/3ab04f9a6ce31c2e8b1c81b8d0e08d39988a2dee6b54f6d71d07ae6710dd9014/https%3A//github.com/muzuiget/redisposition/wiki" rel="nofollow">wiki</a>.muzuigetThu, 26 Feb 2015 00:54:27 -0800https://addons.mozilla.org/EN-US/firefox/addon/redisposition/versions/0.2.5Magnetz 1.4https://addons.mozilla.org/EN-US/firefox/addon/magnetz/Converts Torrentz links to magnet URIs automatically, so you don't need to visit the respective listed sites for the torrents or magnet links. This add-on works on the recent listing page as well as search pages. When a torrent is converted to a magnet link, you'll see a "magnetz" link at the end of the link. Clicking this link will open the magnet link in your default BitTorrent client. Sometimes, the links aren't converted. In this case, Magnetz can also be forced to run on any site by clicking the toolbar button. You can add/remove trackers via preferences, so they are automatically included in the magnet link. Magnetz currently works with <a rel="nofollow" href="http://outgoing.mozilla.org/v1/a82ce518cdde4971ce8cfe29b559bfcc5e6f868fb1a2735677f5dfb871d10182/http%3A//torrentz.com">torrentz.com</a>, <a rel="nofollow" href="http://outgoing.mozilla.org/v1/7badcd154d9b51d6a9efc6c0ec8b8ab0e7a198fafd6af173edfa8a0c1b3b82b1/http%3A//torrentz.eu">torrentz.eu</a> and <a rel="nofollow" href="http://outgoing.mozilla.org/v1/2da0907ce2dd12b42182ca1aa27659ffda550ddcd3c30d2b7351ff54d2d31850/http%3A//torrentz.in">torrentz.in</a>. If you know any other mirrors, let me know and I'll add them in.Aalaap GhagTue, 24 Feb 2015 06:53:25 -0800https://addons.mozilla.org/EN-US/firefox/addon/magnetz/versions/1.4Pushbullet 179https://addons.mozilla.org/EN-US/firefox/addon/pushbullet/Never miss another phone call or text message again while using your computer! Pushbullet automatically shows you all of your phone's notifications right on your computer. This means you can see who's calling or read and reply to text messages even if your phone is on silent or in another room. Pushbullet also makes it easy to send pictures, files, links, and more to your devices and even to friends. Sending things with Pushbullet is the easiest way to share things between your devices: • Push a link to your phone by just right-clicking on it on your computer. You can then go right to the link by tapping on the notification. • Send pictures and other files to your phone wirelessly from your computer and open them right from the notification. No more digging things out of your email inbox or Dropbox. • Send any address over to your phone so you can get right into Google Maps instead of having to look it up again on your phone. • Put a todo list right in your notification tray and check of items as you go.pushbulletTue, 24 Feb 2015 01:20:02 -0800https://addons.mozilla.org/EN-US/firefox/addon/pushbullet/versions/179copyLinks 0.3.1https://addons.mozilla.org/EN-US/firefox/addon/copylinks/copyLinks copy selected or all URL links to clipboard, show notifications with number of links copied and remove duplicate links. It's inspired by Copy Link URL addon, plus no restart and Firefox Multiprocess (e10s) compatible.BL33DFri, 20 Feb 2015 08:32:31 -0800https://addons.mozilla.org/EN-US/firefox/addon/copylinks/versions/0.3.1Download Panel Tweaker 0.2.3https://addons.mozilla.org/EN-US/firefox/addon/download-panel-tweaker/Some tweaks for built-in download panel, see screenshots for more details. Support in English: <a href="http://outgoing.mozilla.org/v1/a5b2977f48060d4793b90cc5e60192dae21006eff7dc67439d402f1aca5cfec4/http%3A//forums.mozillazine.org/viewtopic.php%3Ff=48&t=2805791" rel="nofollow">http://forums.mozillazine.org/viewtopic.php?f=48&t=2805791</a> Support in Russian: <a href="http://outgoing.mozilla.org/v1/77c40615525a408367942aeafe2e1bc1a07d5e90940e47d6ce38ac66ec7a067c/http%3A//forum.mozilla-russia.org/viewtopic.php%3Fid=61868" rel="nofollow">http://forum.mozilla-russia.org/viewtopic.php?id=61868</a> Source code and issues tracker: <a href="http://outgoing.mozilla.org/v1/0a7aa1fa9708192779b9f99ade749a0128470e82980f21a20c11e2928ba3ef99/https%3A//github.com/Infocatcher/Download_Panel_Tweaker" rel="nofollow">https://github.com/Infocatcher/Download_Panel_Tweaker</a>InfocatcherMon, 16 Feb 2015 10:58:33 -0800https://addons.mozilla.org/EN-US/firefox/addon/download-panel-tweaker/versions/0.2.3Premium downloader for Alldebrid 1.1.30https://addons.mozilla.org/EN-US/firefox/addon/premium-downloader-for-alldebr/Alldebrid as other multi-host premium services provides a web interface to convert hosters url's into Alldebrid url's. You need to login into Alldebrid, copy & paste the hoster file url and convert before download. Alldebrid provides a FF addon but uses a different and more intrusive approach, as try to modify your page with a frame or with a floating window to download. This extension does all this work in a transparent way; you can download directly from the hoster page, using toolbar button, or from the hoster file link, using context menu option.Manolo EstevezMon, 16 Feb 2015 10:10:43 -0800https://addons.mozilla.org/EN-US/firefox/addon/premium-downloader-for-alldebr/versions/1.1.30Mozilla Archive Format, with MHT and Faithful Save 3.0.4https://addons.mozilla.org/EN-US/firefox/addon/mozilla-archive-format/This extension enhances the way web pages are saved on your computer. It provides the following advantages over the built-in save system: — A complete page can be saved as a <b>single file</b> (web archive) — You can name files using the <b>title of the page</b> (title save) — The saved pages are <b>faithful to the original</b> (exact save) You can view and save MHT (MHTML) files, with <b>excellent compatibility with Internet Explorer</b>; but more importantly, you can use the <a href="http://outgoing.mozilla.org/v1/bf9f22d03936dac3c837bca8c440e22620747726/http%3A//maf.mozdev.org/maff-file-format.html" rel="nofollow">MAFF file format</a>, with the following advantages: — <b>Save disk space</b>, since MAFF files are compressed — <b>Include video and audio</b> embedded in the pages — <b>Be universal</b>, since MAFF is based on ZIP and compatible with Linux and other platforms — <b>Use an open format</b>, with no risk of vendor lock-in The MAFF format is exceptional when combined with the built-in browser support for the <b>Ogg Vorbis</b> and <b>Ogg Theora</b> media formats in web pages: you can save everything in a single file. You can even save <b>more than one tab</b> in a single MAFF file. The MAF extension allows you to <a href="http://outgoing.mozilla.org/v1/ce4ebfc07900a9f7fab5a755362017a1e7801da1/http%3A//maf.mozdev.org/documentation.html%23converting" rel="nofollow">convert your already saved pages</a> to the format of your choice. You can use this feature to save disk space, or even to convert MAFF to the other formats, should you ever decide to go back. MAF also <a href="http://outgoing.mozilla.org/v1/caf38c4b396a9f3d3b1dd78e89ec32fcb8f40219/http%3A//maf.mozdev.org/documentation.html%23extensions" rel="nofollow">interoperates with other extensions</a>, for example: — Multiple Tab Handler (easily select the tabs to save) — UnMHT (additional expert features to read and write MHTML) The MAF extension is <a href="http://outgoing.mozilla.org/v1/f999b43321d4fa777596e73742c52ba6ece73792/http%3A//maf.mozdev.org/screenshots.html" rel="nofollow">intuitive and easy to use</a>, but empowers you with advanced features: see the <a href="http://outgoing.mozilla.org/v1/76eff210ff76940728e1efa96dc1fdcabad8730e/http%3A//maf.mozdev.org/documentation.html" rel="nofollow">user manual</a> if you want to find out more! <b>Do you think something could be improved?</b> <a href="http://outgoing.mozilla.org/v1/24587026157d64c77b5192aa981d52695fb18158/http%3A//maf.mozdev.org/feedback.html" rel="nofollow">Let us know!</a> But don't forget to check out the <a href="http://outgoing.mozilla.org/v1/d684e3157c9f85891e06ebce6f99c7b06df37790/http%3A//maf.mozdev.org/" rel="nofollow">latest development version</a> first: maybe the feature you need is <a href="http://outgoing.mozilla.org/v1/92186321ef4b61238147922900d1cc31070c5ba8/http%3A//maf.mozdev.org/installation.html%23whatsnew" rel="nofollow">already there</a>!Christopher OttleyMon, 16 Feb 2015 06:28:58 -0800https://addons.mozilla.org/EN-US/firefox/addon/mozilla-archive-format/versions/3.0.4
Twice-Baked Sweet Potatoes With Bacon and Sour Cream Just like traditional baked potatoes, these loaded sweet potatoes get the royal treatment when topped with bacon and sour cream. They're savory, delicious, and work well as weeknight meal idea. Ingredients 2 medium sweet potatoes (8 to 10 ounces each) 3 ounces Canadian bacon, diced 2 tablespoons reduced-fat sour cream 3 teaspoons chopped fresh chives 2 tablespoons shredded reduced-fat sharp cheddar cheese Nutritional Information Calories 341 Fat 6g Satfat 3g Monofat 2g Polyfat 1g Protein 15g Carbohydrate 57g Fiber 7g Cholesterol 30mg Iron 2mg Sodium 681mg Calcium 109mg Calories 341 Fat 6g Satfat 3g Monofat 2g Polyfat 1g Protein 15g Carbohydrate 57g Fiber 7g Cholesterol 30mg Iron 2mg Sodium 681mg Calcium 109mg How to Make It Pierce potatoes with a fork, and arrange on paper towels. Microwave on high 8 minutes; turn potatoes over after 4 minutes. Cut each potato in half lengthwise, and scoop out the pulp, leaving 1/4-inch-thick shells. Mash pulp with 3 ounces Canadian bacon, 2 tablespoons sour cream, and 2 teaspoons chives in a bowl. Spoon mixture into shells. Sprinkle 2 tablespoons cheese over tops of potatoes. Microwave on high 2 minutes, and sprinkle with 1 teaspoon chives.
Maximizing discovery efficiency with a computationally driven fragment approach. A reliable and accurate method for the computational design of novel drug candidates has been a passionate pursuit of the pharmaceutical industry. Such technology would dramatically improve the efficiency of drug discovery by quickly and inexpensively providing potent molecules that can be further prioritized for synthesis based on characteristics such as patentability, specific protein-ligand interactions, ease of chemical synthesis, protein selectivity and pharmacological considerations. Described herein is the progress made at Locus Pharmaceuticals Inc toward achieving this ideal with a fragment-driven, computationally directed approach to small-molecule discovery. Specific lead identification examples from Locus Pharmaceuticals discovery programs demonstrate the efficiency and cost-effectiveness realized by such an approach.
This work was partially supported in part by the NSF grants CCR-0132780, CNS-0720884, CCR-0225610, by the Swiss National Science Foundation, ERC Start Grant Graph Games (Project No. 279307), FWF NFN Grant S11407-N23 (RiSE), and a Microsoft faculty fellowship. This paper is an improved version of Chatterjee et al. (2006, 2009) [@br0040; @br0030]. There is a serious and irreparable error in Theorem 4.3 of Chatterjee et al. (2009) [@br0030] regarding the convergence property of the improvement algorithm for concurrent safety games. This is illustrated in an example of Chatterjee et al. (2012) [@br0020]. In the present version the result is presented for turn-based stochastic safety games. We thank anonymous reviewers for many insightful comments that helped us immensely, and warmly acknowledge their help.
Over 11,000 women will soon be recruited in central security forces for combat duties such as border guarding and law and order assignments. The government has already set in motion its plan to hire 8,533 women constables in paramilitary forces such as CRPF, BSF, CISF and ITBP. Also, sanctions have been granted by the Union Home Ministry for raising 2,772 women personnel in the Sashastra Seema Bal by 2017. “The recruitments are being done to take the representation of women in central forces to at least 5 per cent of the total strength in the coming days. At present, women constitute about 2.15 per cent of the total strength of these forces,” a senior officer said. A special sanction has also been accorded to the CRPF to raise two exclusive women battalions within its establishment to bolster the strength of the existing three such units. “The CRPF has tasked its women units with rendering extensive law and order duties apart from their recent and small-scale induction in anti-Naxal operations theatre in Chhattisgarh and Jharkhand. They are also being increasingly deployed for static guard duties and escorting pilgrims of Mansarovar and Amarnath yatras,” the officer said. Three-tier exam The Staff Selection Commission (SSC) will hold a three-tier examination for these posts with the stages being physical tests, written efficiency and medical tests. Candidates, who have passed Class X and are between 18-23 years of age, are eligible to apply for these posts. The expected salary for those hired would be around Rs 20,200 apart from other benefits that the government extends to the Central Armed Police Forces.
In this blog I present, in an informal way, core ideas in philosophy and their application to current events and everyday life. For critical thinking lessons and resources, please check out my free online course reasoningforthedigitalage.com
The expression of tomato prosystemin in Escherichia coli: A structural challenge. Prosystemin is the 200-amino-acid prohormone of the 18-amino-acid polypeptide called systemin, a systemic mobile signal that activates the synthesis of defense genes in solanaceous plants in response to herbivore attacks. The unusual primary structural features of the tomato prosystemin cDNA and protein provided an extraordinary challenge in devising an expression system to obtain the full-length protein. Prosystemin expression inhibited the growth of a eukaryotic and several prokaryotic hosts used. Prosystemin was initially synthesized as a truncated protein of 185 amino acids in length using a T7 RNA polymerase expression system in E. coli strain BL21[DE3]. The truncation was found to be due to two factors: (1) the intramolecular associations of the 5' coding region of the prosystemin sequence with the expression vector's ribosome binding site and (2) the presence of a translation start site just prior to the amino acid methionine at position 15. Mutations that permitted the synthesis of the full-length prosystemin protein were introduced into the amino-terminal 5' coding region of the prosystemin cDNA. A 199-amino-acid recombinant prosystemin lacking the N-terminal methionine was purified from lysates and confirmed by N-terminal amino acid sequence and immunoblot analysis.
Choose a station: Transportation In Cleveland: How Public vs. Private Transportation Affects Daily Life The future of Northeast Ohio rests with how well we can move goods and people in the 21st century. A transportation summit was recently held called "Moving Toward 2025." Among the topics covered at the conference was public transportation. The experts say the area is in relatively good shape. But the ability to move around is actually a problem in itself. How we travel is also having a big impact on the way we behave outside of our cars. Mike West has this report. Friday, June 22, 2001 at 8:22 am Mike West- Here at the Cleveland State University Convocation Center, about 200 business, government and political leaders gathered to go over all aspects of transportation. One of the top priorities of some of the planners and agency leaders is getting more people off the road and onto trains and busses. There are more reasons than ever to do this. Frank Polivka is the general manager of Laketran, Lake county's transit agency. He says there's now proof, the more time people spend in traffic, the less time they have for becoming involved with civic groups, schools and other neighborhood activities. Frank Polivka- The new data that has come out of Harvard has found a correlation between the amount of time that people spend in their cars on the way to work and the percentage of decrease in community involvement. MW- According to the latest census numbers, Northeast Ohio is not growing. But more people are moving out of the city and using up land, causing sprawl. Polivka feels many suburbanites are now discovering they are making a big trade off, and it's not a good one. FP- People (who) typically move to the suburbs to seek a better quality of life find out that they're spending more time in their cars and they don't really have the opportunity to enjoy that quality of life because they spend their hours commuting. MW- But if workers do have to travel, Polivka says they will find their quality of life improves on public transit. Not only do they save money and driving expenses, he says people start talking to each other every day at bus stops and train stations. Friendships can develop or at least conversations and ties to the neighborhood. FP- It's communal, I mean, you share seats. Public transportation used to be called mass transportation because you become involved with people, you make new friends. Our situation on a couple of our busses the people all know each other by their first name. I think it's phenomenal to see that kind of closeness. MW- But how do you get more people to take the public transportation? Joe Calabrese is the head of Cleveland's RTA. He says for a city of our size we actually have it pretty good. You can get from most areas into downtown in about 20 minutes. The only time your likely to run into problems is during rush hour. But ease of mobility also hampers his efforts to increase rider ship. Joe Calabrese- We are blessed here, for a city our size certainly in terms of growth and development we have some of the best transportation and the least expensive parking of any city in the country. That's a real advantage to the people who live here. It's a real difficult time when you are trying to promote public transportation. MW- Business leaders feel another good reason to invest in Cleveland's public transportation is the Boeing example. The Seattle-based company recently moved to Chicago. Boeing leaders say they wanted to spend less time at the airport and flying to meetings in other cities. Laketran's Frank Polivka says they were also driven out by traffic problems. He insists if we want to attract more companies and retain others, our transportation systems must to continue to improve or we will have our own Boeing stories. FP- They were tired of the gridlock and what that did to their employees, you know, getting to work every morning. So they moved, they're in Chicago by a transit station. They're looking at how they can improve the quality of life for their employees. Another perfect example is Bell South in the Atlanta area. It took three suburban offices and consolidated them into one at a major transit stop in Atlanta. MW- Every day RTA serves over 200,000 passengers, eliminating 30,000 cars from the road. Joe Calabrese of the RTA says they could do better. But he cites several roadblocks - they include discrimination in the workplace against people who choose to ride the bus or train. JC- We need to work with employers. Right now there is an unspoken and really unrealized process where many transit riders are discriminated against because their employers provide free parking for them. Yet if I decide to use public transit and not free parking I have to pay for that. If you provide free parking for your employees, provide a free bus pass. You very often go to a store or restaurant downtown and say, "did you drive, I'll validate your parking," but how many are saying, "I'll validate your bus pass"? MW- Another problem facing planners is the aging baby boomers. In only a few decades more drivers than every will be too old to get behind the wheel. But they will still have to find a way to get to the store, doctor's office and other destinations. Transit leaders say if we don't expand service now we will be in big trouble in the years to come. Again, Laketran General Manager Frank Polivka. FP- It's a big issue. In Ohio, it's typically been, let's build roads, let's build roads - the philosophy is changing because we know we can't build our way out of congestion, it's far too costly. Plus once we make the investment, (that) investment only lasts about 8 years because you induce demand and in 8 years you're back to where you started from. Meaning you have to make another investment. With transit now if you put that kind of investment in a rail line your investment is going to pay you back for year. MW- Plans are already in the works to extend locals rail lines and increase bus service. But a lack of money plagues all efforts. However, public transportation is becoming more popular. In fact, the use of public transportation is now growing faster than auto use. That means growth can help fund itself. In Cleveland, I'm Mike West, 90.3 WCPN 90.3 FM. Comments Statehouse News Bureau The Statehouse News Bureau provides educational, comprehensive coverage of legislation, elections, issues and other activities surrounding the Statehouse to Ohio's public radio and television stations. ideastream® is a not-for-profit multiple-media public service organization serving the communities of Northeast Ohio and based in Cleveland, Ohio. ideastream's mission is to strengthen our communities.
Saidapet Saidapet is a neighbourhood in Chennai (Madras), India. The Saidapet Court, the only other court of judicature in Chennai city apart from the Madras High Court, and the Saidapet bus depot are located here. Prior to its incorporation in Madras city, Saidapet functioned as the administrative headquarters of Chingleput district. Saidapet is also known as Saidai. The neighbourhood is served by Saidapet railway station of the Chennai Suburban Railway Network. Saidapet was occupied by the British East India Company and was made the administrative headquarters of Chingleput district. The health district in Chengalpet district is split into Saidapet hud and Kanchipuram hud. Panagal building which is a part of Saidapet is a famous landmark. History The Maraimalai Adigal Bridge (previously the Marmalong Bridge) connects the northern banks of the Adyar river with the south. This bridge was originally built in 1726 by Coja Petrus Uscan. The dilapidated old bridge was replaced by a new one in the 1960s built as part of the reconstruction and modernization efforts. Saidapet was obtained by the British East India Company in the 1700s along with the jaghir of Chingleput. From 1859 to 1947, Saidapet served as the district headquarters of Chingleput District. In 1947, the headquarters was shifted to Chengalpattu. Saidapet was included in Madras city during 1945-46 and since then forms a part of the corporation. Saidapet had a large weaver population and handlooms were in operation as late as 1990. It was quite notorious for filariasis in the olden day. Transportation Railway station The suburban railway station in Saidapet is located between the stations of Guindy and Mambalam. It is easily accessible from the main road. Recently, automatic ticket vending machines have been introduced here. Buses Saidapet has a MTC bus terminus located on Anna Salai. There are frequent bus services originating from this place to other important parts of the city and outskirts. Many buses also pass through this area and offers excellent connectivity to various places and West Saidapet has a MTC bus terminus located on West Jones Road. Metro Rail Saidpet has a Metro station and the first phase of Chennai metro was inaugurated 2019 . The station has bus terminus nearby and connects to all the southern destination in the city . The only complaint it has been built so far away from the actual saidapet . Still it will supply adjacent areas . Bridges The bridge located near the market on Jeenis road serves as a vital link to Mount Road from West Saidapet. Jones Road underpass serve an important link for West Saidapet and Jaffarkhanpet. Aranganathan subway serves to connect Ashok Nagar and Mambalam. Alandhur bridge to connect Guindy Industrial Estate and West Saidapet, it helps to by-pass Guindy Katipara bridge to reach Mount road from 100 Feet road. Important places Saidapet has a very busy shopping market place called the Bazaar Road. It is famous for its fish and meat market attracting buyers from faraway places. Educational institutions Schools Alpha Matriculation Higher Secondary School St. Mary's Higher Secondary School Fathima Matriculation Higher Secondary School Corporation Boys Higher Secondary School (primitively named as Manthoppu School, since the place was a mango groove which belonged to the temple) Girls Higher Secondary School respectively (primitively named as Manthoppu School, since the place was a mango groove which belonged to the temple) Annai Veilankanni's Matriculation Higher Secondary School Government Model Higher Secondary School Geetha Matriculation Higher Secondary School Cambridge Matriculation Higher Secondary School Colleges The most familiar college in Saidapet is the Teachers Training College. Tamilnadu Open University which is the latest university for distance education has established. Annai Veilankanni's College for Woman is there in Saidapet Familiar Anna University in Guindy and Government Arts College in Nandanam are closely located to Saidapet. Places of worship Temples Karaneeswarar temple This temple is located next to the Saidapet Railway station. This temple has a 7-storied Gopuram with two prakarams (closed precincts of a temple). The main deity is Lord Karaneeswara and Goddess Swarnaambikai. This temple has a beautiful tank. The temple is heavily crowded on Pradhosham days. Annual ten-day Brahmotsavam takes place in the Tamil month of Chithirai. During Chitirai thirvizha, people visit the temple in huge numbers and there will be a daily spiritual talk on Thiruvasagam about Lord Shiva. Sri Devi Ankgalamman Koil This temple is located near Saidapet Railway station. During the Tamil month of Masi, Mayana Kollai is organized in this temple. Prasanna Venkatesa Perumal kovil According to an old inscription, This temple was constructed in the middle of the 15th century. It is popularly known as Perumal Kovil of Saidapet. The main deity is Prasanna Venkatesa Perumal. Annual Brahmotsavam takes place during the Tamil month of Chithirai. Vaikunta Ekadasi festival is very famous here. Other two famous festivals are Rathasapthami held in the month of February and Thotta Urchavam held in the month of march. One more important function in this temple is that Sri Parthasarathy Swamy of Triplicane visits this temple yearly once on the first Sunday of February. Kadumbaadi Chinnamman kovil This is a famous Shakthi temple in West Saidapet. Annual brahmotsavam takes place during the Tamil month of Aadi. Ilangaali Amman Kovil This is a very famous and popular temple in saidapet. People of all caste come here and pray to illangaali amman. During the Adi season the temple is flooded with the followers. Great thiruvizha functions will be held during adi seasons. Anjaneyar temple This Hanuman temple is situated on the banks of the Adyar river which is said to be a 1000 year old temple. There is one more Anjaneyar temple facing the Prasanna Venkatesa Perumal kovil. It is said the Hanuman in this temple is incarnated in such a way that he is worshipping Lord Rama situated at the Narasimha temple. Subramanya Swamy temple This temple is situated in the center of Saidapet. Its main deity is Lord Subramanya Swamy (Muruga) and has a 5 storied gopuram. Annual brahmotsavam takes place in the month of Masi and the deity is taken in procession for 10 days. Soundareswarar temple This temple is situated in the centre of Saidapet, near to the newly constructed Market Subway which links to the Anna Salai and Alandur. Its main deity is Lord Soundareswarar and Lord Thirupurasundari. Lord Varasithi Vinayar facing West is a famous one. The Stala Virutcham is Vanni Maram and is being worshipped on Saturdays by the devotees of Saidapet, Mambalam, K K Nagar, Velacherry etc. The temple is also known as Vada Thirunaraiyur. Vanni, Vilvam and Konrai, the three trees are known for Shiva's worship, are available in this temple. Leaves of Vanni maram is used for the archana for Saneesvaran. Annual brahmotsavam take place in the month of Ani and the deity is taken in processing for 10 days. This Temples comes under HR&CE control. Last Kumbabizhegam was performed in 1988 by the temple Sivachariar Late.C.K.Krishnamurthy Gurukkal. The temple is further renovated and a Kumbabhizegam was performed on 11 March 2012 with the support of generous donors of the temple devotees through the campaign of the Kumbabizega Committee of temple and the Kumbabhizegam went well with the presence the holiness Salem Swamigal, Thiruvanammali Sisters, Thirupananthal madam Kattalai and Sannitham and the Government Officials viz. Chennai Mayor - Mr. Duraiswami, Saidapet Legislative member - Mr.G.Senthimazhan participated the Kumbabhizegam. The temple is very nice to see and the breeze of three vrikchas providing the heeling touch to all the devotees and the spiritual vibration of temple lead each of us to have a Dharshan of Sri Soundareswarar and Thirupurasundari at least once in a life to cleanse our sins and make our soul happy and peaceful. Blessings from Lord Soundareswarar and Thirupurasundari with their son who faces west Varasithi Vinayagar who help the entire city with his blessings. Churches Saidapet has about seven churches, Our Lady of Good Health church has a congregation of 1000 families and is situated on LDG street, the NLAG Church is situated across the bridge. It is the biggest Assembly of God church in Tamil Nadu. C.S.I Church of Jesus the Savior located in prime location in Saidapet was congregated in 1902 and one among the oldest congregation in Chennai. C.S.I St. Thomas Church located in Saidapet is 85 years old with 400 families as its members. It was re-constructed in 2012. Little Mount Church A few meters south of the MaraiMalai Adigalar Bridge is the hill formation called Little Mount. On top of this mountain is a church dedicated to Our Lady of Good Health. The original church was built by the Portuguese in 1551 AD. The new church was built after demolishing a part of old church in the 1970s. According to history - 'St. Thomas the Apostle' lived in a cave under the Church, which is well preserved even today. The Church holds an annual festival in honor of Our Lady on the fifth Saturday of Easter. Recently, this Church was elevated to the status of a Shrine. Mosques Dastagir Sahib Jamia Mosque, East Jones Road, East Saidapet, Saidapet Masjid-ul-Hafiz, Anna Nagar, West Saidapet, Saidapet Masjid Hudha, Godamedu, Dhideer Nagar, Anna Nagar, Saidapet Jafferkhanpet Mosque, Jawahar Nagar, West Saidapet, Saidapet Engineering College Mosque, Near Anna University Campus, 1st St, Srinagar Colony, West Saidapet, Saidapet Masjid-e-Mohammedia, Venkta Puram, West Saidapet, Saidapet Masjid E Hidayah, Venkta Puram, West Saidapet, Saidapet Masjid-e-Mohammedia, Karpaga Vinayaka Nagar, West Saidapet, Saidapet Hanafi Masjid, Venkta Puram, West Saidapet, Saidapet TNTJ Masjid, Appavu Nagar, West Saidapet, Saidapet Community halls St. Thomas Community Hall This hall is located opposite Our Lady of Good Health church and is run by the church officials. The hall in the first floor has a capacity of about 250 people and the dining hall on the ground floor can seat about 70 people. Car parking is inadequate inside the compound. Cars are usually parked outside the compound in the land belonging to church. Politics Saidapet assembly constituency is part of Chennai South (Lok Sabha constituency). It occupies an important place in Tamil Nadu politics being the starting place for election rallies. Karunanidhi was once elected from this constituency. Location in context External links http://www.fallingrain.com/world/IN/25/Saidapet.html http://www.hinduonnet.com/thehindu/mp/2008/06/16/stories/2008061650530500.htm http://www.saidaimart.com References Category:Neighbourhoods in Chennai Category:Suburbs of Chennai Category:Cities and towns in Chennai district
Q: Adding a Image Upload Button in CKEditor I have installed CKEditor in Wysiwyg profiles. While publishing any node if i click on the image upload button it shows options to add images by a image link, but what is the way to add a dynamic image upload button so that users will be able to Browse and choose any image from their computer in content? A: Check out IMCE with IMCE WYSIWYG bridge. Once you install and configure those two modules, select "IMCE" as a button in CKEditor and then you can upload and insert images in WYSIWYG. A: I know I'm somewhat late to this question, but I just found out about One Click Upload which does exactly what you want and may help others that have this same problem and arrive to this question (the only caveat is that it needs flash to be enabled to work).
2013–14 UNLV Runnin' Rebels basketball team The 2013–14 UNLV Runnin' Rebels basketball team represented the University of Nevada, Las Vegas during the 2013–14 NCAA Division I men's basketball season. The team was coached by Dave Rice, in his third year with the Runnin' Rebels. They played their home games at the Thomas & Mack Center on UNLV's main campus in Paradise, Nevada and were a member of the Mountain West Conference. They finished the season 20–13, 10–8 in Mountain West play to finish in a tie for third place. They advanced to the semifinals of the Mountain West Conference Tournament to San Diego State. They did not play in a postseason tournament for the first time since 2009. Departures Recruiting Roster Schedule and results \|- !colspan=9 style="background:#666666; color:#C10202;"\| Exhibition \|- !colspan=9 style="background:#666666; color:#C10202;"\| Regular Season \|- !colspan=9 style="background:#666666; color:#C10202;"\| Mountain West Tournament See also 2013–14 UNLV Lady Rebels basketball team References UNLV Category:UNLV Runnin' Rebels basketball seasons Run Run
--- abstract: 'In these proceedings, we summarize recent results from our “SINS" [VLT]{}/SINFONI integral-field survey, focusing on the 52 detected UV/optically-selected star-forming galaxies at $z \sim 2$. Our H$\alpha$ emission-line imaging and kinematic data of these systems illustrates that a substantial fraction ($\geq 1/3$) of these galaxies are large, rotating disks and that these disks are clumpy, thick, and forming stars rapidly. We compare these systems to local disk scaling relations and find that the backbones of these relations are already in place at $z \sim 2$. Detailed analysis of the large disks in our sample provides strong evidence that this population cannot result from a merger-dominated formation history and instead must be assembled by the smooth but rapid inflow of gas along filaments. These systems will then secularly evolve from clump-dominated disks to bulge-dominated disks on short timescales, a phenomenon that is observed in our SINS observations and is consistent with predictions from numerical simulations. These results provide new and exciting insights into the formation of bulge-dominated galaxies in the local Universe.' author: - 'Kristen L. Shapiro, Reinhard Genzel, Nicolas Bouché, Peter Buschkamp, Giovanni Cresci, Ric Davies, Frank Eisenhauer, Natascha Förster Schreiber, Shy Genel, Erin Hicks, Dieter Lutz, Linda Tacconi' title: \| Star-Forming Galaxies at $z \sim 2$:\ An Emerging Picture of Galaxy Dynamics and Assembly --- Introduction: The SINS Survey {#sec:intro} ============================= The $z \sim 2$ Universe is now known to represent a critical epoch in matter assembly; during this era, both the cosmic star formation rate and the luminous quasar space density are at their peaks [e.g. @Fan+01_KLS; @Cha+05_KLS]. The assembly of galaxies is correspondingly rapid, with the total stellar mass density in galaxies increasing from $\sim 15$% to $50-75$% it current value between $z \sim 3$ and $z \sim 1$ [e.g. @Dic+03_KLS; @Rud+03_KLS; @Rud+06_KLS]. Observations of the dynamical and baryonic processes driving this evolution are therefore central to our understanding of galaxy formation. To this end, we have conducted the SINS survey (Spectroscopic Imaging in the Near-infrared with SINFONI). The near-infrared integral-field capabilities of SINFONI allow us to probe the two dimensional distribution and kinematics of redshifted H$\alpha$ and other key diagnostic emission lines. Our selection techniques and large sample size (52 detected UV/optically-selected galaxies, of 62 observed) enable us to probe a representative subset of the population of star-forming galaxies at $z \sim 2$, with an observationally-imposed slight bias towards more massive and more rapidly star-forming galaxies ($\langle M_* \rangle \sim 3 \times 10^{10}\ M_\odot$, $\langle {\rm SFR} \rangle \sim 50\ M_\odot\ {\rm yr}^{-1}$; Förster Schreiber et al. in preparation). With SINFONI, we study this population with typical spatial resolution of $0.5-0.6$ ($\sim 4-5$ kpc) and spectral resolution of $70$ km s$^{-1}$. A subset of this sample has additionally been observed with adaptive optics and resolved at $0.15-0.3$ ($\sim 1-2$ kpc). The SINS data reveal a diversity in kinematics and morphologies of these systems, as seen in H$\alpha$ emission (@For+06_KLS [@Gen+06_KLS; @Bou+07_KLS]; see also related work by @Law+07_KLS [@Wri+08_KLS]). The population at this redshift includes large rotating disks, compact dispersion-dominated systems, and several interacting or merging galaxies, each accounting for roughly $1/3$ of the total population (Förster Schreiber et al. in preparation). Of these, the large rotating disks, discovered and probed for the first time with our SINS observations, have revealed much about the nature and evolution of high-redshift galaxies. In these proceedings, we summarize the properties of the large rotating disk population at $z \sim 2$ and review the implications of this population for galaxy assembly. These proceedings are organized as follows: In §\[sec:prop\], we present the main properties of the large rotating disk population revealed in our SINFONI integral-field spectroscopic data (originally presented in @For+06_KLS [@Gen+06_KLS; @Bou+07_KLS; @Sha+08_KLS]). In §\[sec:cold\], we examine the fueling mechanisms for the high star formation rates in these systems and find that the smooth but rapid accretion of cold gas is the only mechanism consistent with the observations (see also @Gen+06_KLS [@Sha+08_KLS]). In §\[sec:bulge\], we show that detailed dynamical modeling of these galaxies reveals an evolutionary sequence through which young classical bulges are secularly formed (originally presented in @Gen+08_KLS). Finally, in §\[sec:conclu\], we conclude. Properties of $z \sim 2$ Star-Forming Disks {#sec:prop} =========================================== Characteristics of the Population {#sec:prop_char} --------------------------------- Perhaps the most surprising result of the SINS survey was the discovery of a significant population of large ($r_{1/2} \sim 5-10$ kpc) rotation-dominated objects. The shape and amplitudes of the rotation curves in these galaxies are consistent with those measured in ionized gas in local spiral galaxies [@Bou+07_KLS]. Fourier decomposition (kinemetry) of the velocity and velocity dispersion maps of these galaxies and comparison with local systems establishes quantitatively that these galaxies have “spider diagrams" consistent with those observed in local disk galaxies [@Sha+08_KLS]. However, though dynamically similar to local spiral galaxies, high-redshift disks have many characteristics unparalleled in the $z=0$ Universe. The spatial distribution of H$\alpha$ emission reveals a marked “clumpiness" of the star formation activity into regions of FWHM size $= 1-3$ kpc [e.g. @Gen+08_KLS]. Broad-band [Hubble Space Telescope]{} imaging of these systems illustrates that these features are also prominent in the stellar distribution (@ElmElm06_KLS; Förster Schreiber et al. in preparation). Dynamical and spectral energy distribution fitting converge on masses of these super-star-forming clumps of $10^8-10^9\ M_\odot$ [@Gen+06_KLS; @Elm+09_KLS], a few percent of the total galaxy stellar mass (typically $5 \times 10^{10}\ M_\odot$). The typical $z \sim 2$ disk galaxy contains $8-10$ such clumps [@Gen+06_KLS; @Elm+09_KLS]. Observations of both face-on and edge-on systems suggests that these clumps are roughly spherical, implying a large scale-height in the disks ($h_z \sim 1$ kpc, versus $r_{1/2} \sim 5-10$ kpc; e.g. @For+06_KLS [@ElmElm06_KLS; @Gen+08_KLS]). This is confirmed in the large velocity dispersions observed with SINFONI; detailed dynamical modeling accounting for projection and observational effects indicates the typical random motions are large, $v/\sigma \sim 1-7$ (@Gen+08_KLS; Cresci et al. submitted). High-redshift disks are therefore much thicker than their low redshift counterparts ($v/\sigma \sim 10-20$), and the implications of this difference are examined in §\[sec:bulge\] below. Finally, high-redshift disks also exhibit much larger star formation rates ($\sim 30-200\ M_\odot\ {\rm yr}^{-1}$) than local disk galaxies, indicative of the high gas fractions in these systems [@For+06_KLS; @Gen+06_KLS; @Gen+08_KLS]. In the local Universe, such high SFR are nearly always associated with a recent major merger; however, at high redshift, kinemetry analysis has shown these galaxies to have kinematic properties inconsistent with recent major interactions [@Sha+08_KLS]. Moreover, modeling of the spectral energy distributions of these galaxies indicates that the current SFR has been roughly constant over at least $0.5$ Gyr in these systems (@Gen+06_KLS [@Dad+07_KLS]; Förster Schreiber et al. in preparation). Such long-lasting high SFR and gas fraction suggests that the fueling of high SFR at high redshift occurs very differently than that at low redshift (see discussion in §\[sec:cold\]). The Appearance of Local Scaling Relations ----------------------------------------- The above evidence suggests that high-redshift disks, given their clumpiness and thickness, cannot passively evolve into their low-redshift late-type disk counterparts (see §\[sec:bulge\]). Nevertheless, their rotation curves obey the same radius-velocity relation as observed at $z=0$ [@Bou+07_KLS]. It is therefore of interest to examine scaling relations at $z \sim 2$, in order to probe the fundamental physics governing these relations. Despite $z \sim 2$ systems having similar rotation velocities to local disk galaxies, detailed dynamical modeling of these systems coupled with spectral energy distribution analysis reveals that high-redshift disks are significantly offset from the local Tully-Fisher ($M_-v$) relation (Cresci et al. submitted). This may reflect the high gas fractions in these $z \sim 2$ disks relative to local disks, or it may reflect a fundamental evolution of this relation with time. In contrast, the high gas fractions and gas surface densities present at $z \sim 2$ drive star formation with an efficiency consistent with a universal Schmidt-Kennicutt scaling relation at high and low redshifts [@Bou+07_KLS]. The presence of super-star-forming clumps in $z \sim 2$ disks thus does not seem to fundamentally alter the physics of star formation within these galaxies. In cosmological models, this rapid star formation is often associated with rapid accretion onto a growing supermassive black hole (SMBH), a process that should be apparent via broad emission lines in our SINS galaxies. Indeed, stacking of our SINFONI spectra for all objects reveals a broad component underneath the H$\alpha$-\[N[II]{}\] complex (Shapiro et al. in preparation). If this feature is interpreted as evidence of active galactic nuclei in the SINS galaxies, SMBH masses can be inferred from the luminosity and FWHM of the broad line. These SMBH masses are offset from local relations by an order of magnitude, in that the SMBH are under-massive for their host galaxies, implying a delayed assembly of black holes in $z \sim 2$ disk galaxies (Shapiro et al. in preparation). It seems, then, that some processes (star formation and the physics governing the radius-velocity relation of galaxy disks) are independent of redshift, while those involving the gradual growth of stellar and SMBH mass are not preserved out to $z \sim 2$. Creating Clumpy Disks: Cold Flows vs. Major Mergers {#sec:cold} =================================================== Differences from Major Merger Remnants -------------------------------------- Given the lack of low-redshift analog for the clumpy, thick, rapidly star-forming disks seen at $z \sim 2$, the formation of these high-redshift objects begs explanation. The traditional paradigm through which systems with high SFR were explained was via gas-rich major mergers. Indeed, it has been known for some time that a merger with a sufficiently large gas fraction can result in very high SFR and in a gas-rich remnant disk [e.g. @BarHer96_KLS]. However, this almost certainly is not the explanation for the high-redshift disks seen in our SINS sample. As described above, the SINS high-redshift disks show no kinematic evidence of recent disturbances and have likely experienced constant SFR over at least $0.5$ Gyr, unlike the bursty star formation histories associated with galaxy interactions. Several other key features in the data argue against a major merger origin for these systems. Most critically is the lack of central mass concentrations in some systems. While a major merger always creates a central concentration of mass, a significant fraction of high-redshift disks exhibit mass concentrations that peak in rings located $2-8$ kpc away from the galaxy center [@Gen+08_KLS], a configuration that cannot readily be created in a major merger. Another relevant characteristic of the high-redshift disks is the observed clumpiness; the $\sim 10$ clumps in a galaxy, each with a few percent of the galaxy’s mass, together make up a dynamically important component in these systems. With this significant fragmentation, high-redshift disks do not resemble the smooth and idealized remnants of simulated gas-rich major mergers; it is not obvious that such a merger could simultaneously produce gas-rich and fragmented disks, as are observed. In contrast, these mergers probably correspond to the sub-mm population detected at $z \sim 2$, whose compact and bursty star formation history almost certainly results from a major merger of two gas-rich systems [@Tac+08_KLS]. Evidence for a Smooth Accretion Mechanism ----------------------------------------- Consequently, an alternative mechanism must fuel the constant high SFR seen in high-redshift disks. A natural explanation can be found in the “cold" (with respect to the virial temperature) gas flows entering these (high-$\sigma$ peak) haloes along filaments. Such accretion has been shown to penetrate through to the center of the halo, replenishing the gas reservoir within the galaxy in a smooth (average merger ratio $>$ $10$:$1$) manner [e.g. @DekBir06_KLS]. This picture is in keeping with the SINS observations of kinematically undisturbed disks forming stars at constant and very high rates [@Gen+06_KLS; @Sha+08_KLS]. Statistical studies of high-redshift populations are also converging on this picture with independent arguments. The detection of a tight SFR-$M_$ relation from $z \sim 0-2$ implies that the primary driver for star formation cannot be a bursty mechanism such as a series of major mergers and instead must be a smooth mass-dependent process [@Noe+07_KLS; @Dad+07_KLS]. Additionally, analysis of the accretion histories of dark matter haloes in the Millennium simulation indicates that only a small fraction of galaxies with the masses and star formation rates of the SINS high-redshift disks would be expected to have undergone a recent major ($<$ $3$:$1$) merger [@Genel+08_KLS]. Evolution of Clumpy Disks and the Formation of Bulges {#sec:bulge} ===================================================== In addition to revealing the importance of the cold flow accretion mechanism in galaxy formation at high redshift, the SINS galaxies have also provided detailed insight into the modes of galaxy and bulge growth in the high gas fraction, high turbulence regime. In particular, the observed clumpiness can be understood simply as the characteristic Jeans length in these systems [@Gen+08_KLS]. The expectation for a gas-rich disk to fragment in this manner has also been borne out in hydrodynamical simulations of this process, which generate systems remarkably similar to the observations [e.g. @Imm+04_KLS; @BouElmElm07_KLS]. Once present, the dynamical timescale of these clumps in such highly turbulent, gas-rich disks implies that they should migrate to the center of the disk within $\sim 1$ Gyr [@Gen+08_KLS]. The coalescence of several such clumps would then be expected to produce a young classical bulge, despite its secular origins [@ElmBouElm08_KLS]. Indeed, such features are observed in some of the SINS galaxies (@Gen+08_KLS; Förster Schreiber et al. in preparation). Moreover, the mass of the central concentration correlates well with the metallicity and therefore chemical age of the galaxy; older galaxies in which clumps would have had more time to migrate and merge are observed to contain the expected massive bulges [@Gen+08_KLS]. These bulges can then stabilize the remaining disk against the formation of future super-star-forming clumps [@DekSarCev09_KLS], such that the remaining disk, supplemented by subsequent gas accretion, exhibits a smooth exponential surface brightness profile [@BouElmElm07_KLS]. In this manner, the high-redshift disks can evolve into local bulge-dominated systems (e.g. elliptical, lenticular, and Sa galaxies). This scenario is in keeping with the similar number densities of the high-redshift disks and their probable descendants and with predictions based on cosmological simulations [e.g. @Con+08_KLS; @Genel+08_KLS]. Conclusions {#sec:conclu} =========== From the SINS survey, and from complementary observational and theoretical campaigns, a new understanding of the formation and evolution of massive galaxies has emerged. In particular, a substantial fraction of these systems are now known to undergo a disk-like stage, in which the galaxy consists of a large, rotating, thick, clumpy disk. Moreover, these disks are observed to form stars rapidly and to do so at a continuous rate for up to and exceeding one Gyr. In contrast to local objects with high SFR, these galaxies are inconsistent with a major merger origin; evidence against a recent major merger is apparent in both their star formation histories and their internal dynamics. Instead, the high SFR in $z \sim 2$ star-forming disks is likely driven by the smooth but rapid inflow of gas along filaments in the cosmic web. The gas-rich disks that result from this process are globally unstable and are observed to collapse into kpc-scale clumps, in keeping with theoretical expectations. With time, these clumps migrate to the center of the potential and combine to form a nascent bulge, a process that is directly observed in the SINS data. At $z=0$, the eventual product of this system will be a bulge-dominated galaxy, whose central mass concentration was generated without a major merger. 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Cleaner, and possibly more appealing as well. As visually amusing as the waco is, it seems like it would be a decent-enough tasting product, although each one is essentially like eating a breakfast cheeseburger in terms of nutrition. The crunchwrap in particular looks like something I'd actually WANT to eat. Cheese, eggs and sausage wrapped up in a tortilla? It's simple and it's been done a million times before, but it's a combo that works. They even took my advice from nine months ago to “consult the pork council” and started offering bacon versions of the waco in addition to the breakfast sausage version. Taco Bell declined to give USA Today their sales figures, but said sales of the breakfast items have, to date, “exceeded expectations.” One would think so, if the menu is receiving a nationwide release. It will be interesting to see if they can achieve solid market presence while going up against the likes of McDonald's, Burger King, Dunkin' Donuts and Starbucks, which have all had their breakfast items established for a long while. Finally, I'd just like to call attention to a couple amazing quotes from that piece. First, Taco Bell President Brian Niccol saying that you get people to change breakfast patterns by “better meeting their needs.” He immediately follows this up by saying “We're exploring how to get pancakes portable. We're close.”
The histamine H4 -receptor (H4 R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice. Via the histamine H4 -receptor (H4 R), histamine promotes the pathogenesis of experimental allergic asthma in mice. Application of H4 R antagonists during sensitization as well as during provocation reduces the severity of the disease. However, the specific cell types functionally expressing H4 R in experimental allergic asthma have not been well characterized in vivo. In this study, we identified the cell type(s) responsible for H4 R activity in experimental asthma and related physiological mechanisms. Using H4 R-deficient mice, we studied the role of H4 R in the sensitization and effector phase. DCs lacking H4 R expression during the in vitro sensitization reaction resulted in effector T cells unable to induce an entire eosinophilic inflammation in the lung upon adoptive transfer in vivo. Recipient mice lacking H4 R expression, which were adoptively transferred with H4 R(+/+) T cells polarized in the presence of H4 R(+/+) DCs, showed reduced signs of inflammation and ameliorated lung function. Here, we provide in vivo evidence that in experimental asthma in mice the H4 R specifically regulates activation of DCs during sensitization, while in the effector phase the H4 R is active in cells involved in the activation of eosinophils, and possibly other cells. A putative therapy targeting the H4 R may be an option for asthma patients developing IL-5-dependent eosinophilia.
Sensing of oligopeptides using localized surface plasmon resonances combined with Surface-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Gold nanorods were fixed on an ITO plate and used for the spectroscopic sensing and Surface-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SALDI-MS) of oligopeptides (angiotensin I). The longitudinal surface plasmon bands of the gold nanorods responded to the 10(-10) M angiotensin solution that was cast on the ITO plate. The SALDI-MS measurements had an ultra-high sensitivity to the angiotensin on the ITO plate. A very small surface density (5 × 10(-19) mol cm(-2)) of angiotensin could be detected at m/z = 1297 with a good signal/noise ratio (S/N = 11). The ITO plate, which was modified with gold nanorods, was found to be effective in collecting angiotensin molecules adjacent to the gold nanorods, and the SALDI processes that were induced by the photoabsorption of the gold nanorods efficiently contributed to the desorption and ionization of the angiotensin.
Q: Load url from CSV to scrape data I would load a list of urls from csv to scrape data with selenium. I used this code: with open('urls.csv', 'r') as file: reader = csv.reader(file) for row in reader: print(row) driver.get(row) urls.csv: https://www.betexplorer.com/soccer/france/ligue-1-2010-2011/results/ https://www.betexplorer.com/soccer/france/ligue-1-2011-2012/results/ https://www.betexplorer.com/soccer/france/ligue-1-2012-2013/results/ print(row) ['https://www.betexplorer.com/soccer/france/ligue-1-2010-2011/results/'] But I got this error on driver.get(row) selenium.common.exceptions.InvalidArgumentException: Message: invalid argument: 'url' must be a string A: A CSV file has rows and columns like a two-dimensional array. In your code, you iterated over the rows with for row in reader:, but you forgot to specify the column of the row with the [n] operator, with n being a natural number. This means that you pass an array instead of a string to the driver (shown by the square brackets in your print output) and selenium throws an exception. Your URLs are in the first column of the CSV file. To get the strings, you specify the row with row[0] like this: with open('urls.csv', 'r') as file: reader = csv.reader(file) for row in reader: print(row[0]) driver.get(row[0]) You could also use a .txt file for the urls and iterate over the rows, because you are only using the first column of the CSV file.
Introduction {#s1} ============ Recent reports of the success of Phase I clinical trials of gene therapy for Leber congenital amaurosis (LCA) and X-linked adrenoleukodystrophy (ALD) indicate that we are entering an era of genetic therapies, at least for some forms of genetic disease [@pone.0043251-Maguire1]--[@pone.0043251-Cartier1]. Since these initial successes are based on gene augmentation therapy, it has become increasingly important to determine the mechanisms by which mutations identified to cause inherited disorders such as LCA and retinitis pigmentosa (RP) exert their pathologic effects. Mutations can cause disease via a protein's loss-of-function, gain-of-function or dominant-negative activity [@pone.0043251-Herskowitz1], [@pone.0043251-Wilson1]. Disease caused by loss-of-function or dominant-negative mutations, in which the mutant protein competes with the wild-type protein and blocks its full function, are potentially amenable to treatment with gene augmentation therapy. In contrast, treatment of dominant disorders in which the mutant protein acquires a novel toxic function (gain-of-function mutations) will require removal or suppression of the mutant allele [@pone.0043251-Herskowitz1], [@pone.0043251-Wilson1]. Despite the importance of distinguishing between different function of mutations, mechanisms have been determined for only a limited number of dominantly inherited disorders [@pone.0043251-Veitia1]. This is especially true for inherited retinal degenerations (IRDs), one of the most genetically diverse group of inherited disorders [@pone.0043251-Hsiau1]. IRDs result in blindness by causing dysfunction and ultimately death of the rod and cone photoreceptor cells of the retina [@pone.0043251-Pierce1], [@pone.0043251-denHollander1]. Since the first IRD genes, rhodopsin (RHO) and CHM, were discovered two decades ago [@pone.0043251-Dryja1], [@pone.0043251-Cremers1], over 180 disease genes have been identified, which account for approximately 50--60% of the genetic causes of disease in IRD patients [@pone.0043251-RetNet1]--[@pone.0043251-Daiger1]. Retinitis pigmentosa (RP) is the most common form of IRD, affecting 1∶1000 to 1∶4000 people worldwide [@pone.0043251-Hartong1], [@pone.0043251-Xu1]. It is characterized by nyctalopia and visual field loss, followed by loss of central vision, eventually leading to blindness. Mutations in the RP1 gene are the second most common cause of autosomal dominant RP (adRP; 5.5%), and have also been found to cause autosomal recessive RP (arRP) [@pone.0043251-Pierce2]--[@pone.0043251-Singh1]. Studies to date have shown that the RP1 protein (2156 aa, 240 kDa) is part of the axoneme of photoreceptor sensory cilia (PSC; also called outer segments) [@pone.0043251-Liu1]. It is a photoreceptor-specific microtubule-associated protein (MAP) that is required for normal organization of membrane discs in the light-sensitive PSC of rod and cone cells. Microtubule binding domains in the N-terminal portion of RP1 mediate its interaction with the axoneme, and the C-terminal portion of the protein is hypothesized to interact with other proteins to help mediate the organization of outer segment discs [@pone.0043251-Gao1]--[@pone.0043251-Liu3]. To date, 33 mutations in RP1 have been identified to cause adRP ([Figure 1A](#pone-0043251-g001){ref-type="fig"}). These are all nonsense or frameshift mutations clustered at the beginning of the 4^th^ and final exon of RP1 ([Figure 1A](#pone-0043251-g001){ref-type="fig"}) [@pone.0043251-Pierce2]--[@pone.0043251-Roberts1]. Compared to the autosomal dominant form, only a small number of families with arRP due to mutations in RP1 have been reported, including 4 homozygous mutations (c.1606insTGAA, c.2847delT, c.4703delA, and c.5400delA) and one pair of compound heterozygous mutations (c.5_6delGT and c.4941_4942insT) ([Figure 1A](#pone-0043251-g001){ref-type="fig"})[@pone.0043251-Singh1], [@pone.0043251-Khaliq1]--[@pone.0043251-Chen1]. These are also frameshift mutations, with 5 out of 6 located in the final exon as well. Since nonsense-mediated decay (NMD) is thought not to occur if the nonsense mutation is in the last exon, all those dominant and recessive mutations in the last exon of RP1 are expected to produce stable transcripts, resulting in the production of truncated RP1 proteins that lack the C-terminal 1/3 rd to 2/3 rds of the full length RP1 protein in the photoreceptor cells of RP patients. Our previous studies on lymphoblasts of patients with RP1 disease and gene targeted Rp1-tm1EAP mice suggest that the mutant RP1 mRNAs with nonsense mutations in exon 4 are expected to escape NMD, but the hypothesis that premature termination codons in exon 4 lead to the production of truncated Rp1 proteins in vivo has not been tested empirically with a representative mutant allele [@pone.0043251-Liu2]. ![RP1 Gene, Clinical and Sequence Data for Family W04-348.\ A. RP1 gene and identified mutations. The gene structure of RP1 is depicted, with the locations of mutations that cause adRP and arRP indicated; the mutations above the RP1 gene structure cause dominant RP, labeled as adRP in red; whereas mutations below the RP1 gene structure cause recessive RP, labeled as arRP in blue; frameshift mutation p.P229QfsX35 reported to cause arRP in this study is in bold. The portion of the gene that encodes that DCX domains is also indicated. The arrow on the top indicates the location of the R677X (human) and Q662X (mouse) mutations. B. Pedigree for family W04-348. The c.686delC, p.P229QfsX35 mutation is designated by M. C. ERG traces from a normal control, the patient's parents (I-1, I-2 (age 57), and the affected patient (II-1). The five standard ISCEV recordings are shown, from the top including: scotopic rod responses, scotopic combined rod-cone responses, oscillatory potentials, photopic single flash and photopic 30Hz responses. The amplitude and time scales are indicated. The ERG responses of the patient's parents show normal amplitudes and implicit times; the patient had no recordable rod or cone responses. The deflections shown in the 30 Hz recordings for the patient are due to motion artifact. The thicker traces are from the right eye, the thinner from the left eye. D. Fundus photos (left) and fundus autofluorescence images (right) of the affected patient II-1(age 30) and his father I-1 (age 60). The patient has typical findings of RP, with optic disc pallor, attenuation of the retinal blood vessels, RPE atrophy and bone spicule pigmentation outside the macula. As shown in the autofluorescence image, the RPE in the macular region is relatively preserved. In contrast, the father's fundi are normal. E. Sequence traces showing the homozygous c.686delC mutation in patient II-1, carrier status of this mutation in the patient's father I-1, and the wild-type sequence in an unaffected Dutch control. Note that the sequence trace of the mutant allele in individual I-1 is shifted slightly.](pone.0043251.g001){#pone-0043251-g001} To elucidate the molecular mechanisms of RP1 mutations so that therapeutic strategies can be developed for RP1 disease, we performed human genetic studies and experiments using several lines of Rp1 gene targeted and transgenic mice. First, we evaluated the family of an adult patient with recessive RP due to a homozygous mutation in exon 3 of RP1, which is predicted to be null. The sibling and parents of this patient, who all carry a single mutant RP1 allele, do not exhibit evidence of RP, confirming that functional hemizygosity of RP1 does not cause disease [@pone.0043251-Chen1]. Next, we generated and characterized Rp1 knock-in mice with a Q662X nonsense point mutation in exon 4 of human RP1. As predicted, the mutant Rp1-Q662X allele produces a truncated Rp1 protein, and homozygous Rp1-Q662X experience photoreceptor degeneration. Third, we generated and characterized transgenic mice that produce a tagged version of the full-length Rp1 protein. Expression of normal levels of Rp1 protein from the transgene is well tolerated, but lines of transgenic mice that over-express the Rp1 protein experience retinal degeneration. Fourth, expression of wild-type Rp1 protein in homozygous Rp1-Q662X mice prevented photoreceptor degeneration. These results indicate that the truncated Rp1-Q662X protein does not exert a toxic gain-of-function effect in the retina, suggesting that dominant mutations in RP1 do not cause disease via a gain-of-function mechanism. Results {#s2} ======= Haploinsufficiency of RP1 does not Cause Retinal Degeneration in Humans {#s2a} ----------------------------------------------------------------------- As part of a large study to identify the genetic causes of RP in The Netherlands via homozygosity mapping [@pone.0043251-Collin1], we found the disease-causing mutation for a Dutch patient with RP ([Figure 1B--E](#pone-0043251-g001){ref-type="fig"}). In this patient, whole-genome homozygosity mapping revealed a significant homozygous region of 8.3 Mb on chromosome 8, between rs1394468 and rs936616, in which the RP1 gene resides. Mutation analysis of RP1 in this patient revealed the homozygous 1-bp deletion in exon 3 (c.686delC) that is predicted to result in a frame-shift and premature termination of the protein (p.P229QfsX35; [Figure 1A, E](#pone-0043251-g001){ref-type="fig"}). Mutation analysis in the unaffected parents and sister of the patient revealed that these three individuals carried the mutation heterozygously ([Figure 1B](#pone-0043251-g001){ref-type="fig"}). This is the first mutation reported to date that causes arRP in the homozygous state, but is not located in the final exon. The proband in this family (individual II-1, [Figure 1](#pone-0043251-g001){ref-type="fig"}) experienced nyctalopia from early childhood, and was diagnosed with RP at age 13. At that time, visual acuity was 0.6 in the right eye and 0.5 in the left eye, and electroretinogram (ERG) recordings were severely reduced with a rod-cone pattern. On recent examination at age 30, visual acuity was light perception in both eyes. The ERG was non-recordable ([Figure 1C](#pone-0043251-g001){ref-type="fig"}). Ophthalmoscopy revealed moderate pallor of the optic discs and attenuation of the retinal blood vessels ([Figure 1D](#pone-0043251-g001){ref-type="fig"}). The retinal pigment epithelium (RPE) in the posterior pole was relatively preserved, with subfoveal atrophy. Bone spicule pigmentation and RPE atrophy were observed in the retinal peripheries. In contrast, examination of the heterozygous parents (ages 60 and 57 respectively) and sister (age 28) did not reveal any abnormalities. None of these family members had nyctalopia, and ERG recordings showed normal retinal function for both parents ([Figure 1C](#pone-0043251-g001){ref-type="fig"}). The observation that carriers of the c.686delC mutation do not have RP is consistent with a recent report describing a patient with arRP due to compound heterozygous frameshift mutations in RP1, c.5_6delGT (p.S2RfsX16, exon 2) and c.4941_4942insT (p.P1648SfsX13, exon 4). In that family, the carrier of the p.S2RfsX16 allele, which creates a premature termination codon in exon 2, did not show evidence of RP either [@pone.0043251-Chen1]. Since the nonsense mutations, c.5_6delGT (p.S2RfsX16, exon 2) and c.686delC (p.P229QfsX35, exon 3), occur in the 2^nd^ or 3^rd^ rather than the final exon in these two families, they are expected to lead to NMD of the mutant mRNAs, and thus create null alleles [@pone.0043251-Chang1]. These findings from two recessive RP1 families suggest that haploinsufficiency of RP1 does not cause retinal degeneration in humans. Generation and Characterization of Rp1-Q662X Knock-in Mice {#s2b} ---------------------------------------------------------- We next focused on determining the possible disease mechanism for mutations identified in the final exon of human RP1. We hypothesized that RP1 transcripts with stop mutations in the 4^th^ exon can escape NMD and produce truncated proteins, as predicted from previous studies [@pone.0043251-Liu2]. To empirically address this question, we generated knock-in mice with a Q662X nonsense point mutation in the Rp1 gene to represent those mutations that create premature termination codons in exon 4 of human RP1 [@pone.0043251-Pierce2]--[@pone.0043251-Roberts1]. The Rp1-Q662X targeting vector was generated from a mouse bacterial artificial chromosome (BAC) clone by introducing the Q662X mutation along with a Frt-flanked neomycin selection cassette into the mouse Rp1 gene using recombination-based gene-targeting techniques ([Figure 2A](#pone-0043251-g002){ref-type="fig"}) [@pone.0043251-Copeland1], [@pone.0043251-Zhang1]. The neomycin selection cassette was then removed by crossing F1 Rp1-Q662X-Neo mice with universal FLPe deleter mice to generate the final excised targeted Rp1-Q662X knock-in allele (ki) ([Figure 2A](#pone-0043251-g002){ref-type="fig"}) [@pone.0043251-Rodriguez1]. Intercrosses of heterozygous Rp1 ^+/Q662X^ mice generated the expected number of wild-type, Rp1 ^+/Q662X^ and Rp1 ^Q662X/Q662X^ mice. The mutant mice are fertile, have normal weights and a normal lifespan. ![Generation and Characterization of Rp1 ^Q662X/Q662X^ Knock-in Mice. A.\ Gene targeting strategy to introduce Q662X mutation into the endogenous Rp1 locus. The gene targeting vector was produced by introducing the Neo-Zeo selection cassette and Q662X mutation into the Rp1 gene in a BAC which contains 140 kb of mouse genomic DNA including the Rp1 locus, using homologous recombination techniques. The gene targeting vector was then retrieved from the modified BAC, and used to transfect mouse ES cells. Correctly targeted ES cells were injected into blastocysts to generate Rp1-Neo-Q662X mice. Crosses to Flpe deleter mice were used to remove the Frt-flanked Neo-Zeo selection cassette and generate the final Rp1-Q662X allele. B, BamHI restriction sites; P, PmeI restriction sites. B. Southern blots using the 5′ and 3′ probes indicated in A demonstrating correct targeting of the Rp1 locus in mouse ES cells. The 12.6 and 18 kb bands in the 5′ and 3′ blots, respectively, indicate correct recombination to generate the Rp1-Neo-Q662X allele. The large size of the wild-type Pme1 restriction fragment (60 kb) in the 3′ blot makes it difficult to resolve this band with standard electrophoresis techniques. C. Sequence traces from PCR products amplified from wild-type, heterozygous (wt/ki) and homozygous (ki/ki) mice. D. Example PCR-based genotyping of Rp1-Q662X (ki) knock-in mice. Using PCR primers that amplify across the residual Frt-LoxP sites, the wild-type and ki alleles can be readily distinguished. E. RT-PCR of retinal RNA from mice of indicated genotypes showing the correct splicing of mutant Rp1-Q662X allele as that of wild type Rp1 allele, using primer sets bridging exon 2 to 3 and exon 3 to 4. F. Predicted proteins produced by the wild-type (wt) and knock-in (ki) Rp1 alleles, showing locations of the anti-N-Rp1 and anti-C-Rp1 antibodies used in panels G and H. G. Western blot of retinal extracts from mice of the indicated genotypes showing production of the 74 kD truncated protein by the knock-in (ki) allele. Note that there is no full-length Rp1 protein detected in the retinas of the homozygous ki/ki mice by either the anti-N-Rp1 or anti-C-Rp1 antibodies. H. Immunofluorescence analysis of Rp1 proteins (red) produced in the retinas of wild-type (wt/wt) vs. homozygous knock-in (ki/ki) mice using the anti-N-Rp1 and anti-C-Rp1 antibodies indicated in panel E. Note that the truncated Rp1 protein produced in the retinas of the ki/ki mice locates correctly to the axonemes of PSC, just like the full-length protein in the wt/wt retinas. Note also the lack of full-length Rp1 protein production in the retinas of the ki/ki mice (AX, axoneme; IS, inner segment; ONL, outer nuclear layer; OS, outer segment).](pone.0043251.g002){#pone-0043251-g002} To determine if the mutant Rp1-Q662X mRNA is spliced correctly and produces a truncated protein in photoreceptor cells, retinas from 4-week-old Rp1 ^+/+^, Rp1 ^+/Q662X^, and Rp1 ^Q662X/Q662X^ mice were evaluated using RT-PCR, Western blot and immunofluorescence analyses. The RT-PCR results showed that mutant Rp1-Q662X allele was correctly spliced ([Figure 2E](#pone-0043251-g002){ref-type="fig"}). To distinguish between the wild-type Rp1 and mutant Rp1-Q662X protein, we used two anti-Rp1 antibodies: anti-N-Rp1 and anti-C-Rp1, which recognize the N-terminal portion and C-terminal portion of Rp1 respectively ([Figure 2F](#pone-0043251-g002){ref-type="fig"}) [@pone.0043251-Liu1], [@pone.0043251-Liu3]. As expected, a 240 kDa wild-type Rp1 protein was detected in the retinas from wild-type and heterozygous mice by anti-C-Rp1 and anti-N-Rp1 antibodies ([Figure 2G](#pone-0043251-g002){ref-type="fig"}). No full length Rp1 protein could be detected in the homozygous Rp1 ^Q662X/Q662X^ mice by anti-C-Rp1 or anti-N-Rp1 antibodies. The levels of the normal Rp1 protein in heterozygous mice were approximately half of that detected in the wild-type mice. Probing with anti-N-Rp1 antibody revealed that a ∼74 kDa truncated protein was expressed in the heterozygous and homozygous mutant mice ([Figure 2G](#pone-0043251-g002){ref-type="fig"}). Interestingly, the truncated Rp1-Q662X protein was localized to the axoneme of PSCs using the anti-N-Rp1 antibody, which is identical to the location of the wild-type Rp1 protein detected by both anti-N-Rp1 and anti-C-Rp1 antibodies ([Figure 2H](#pone-0043251-g002){ref-type="fig"}). The retinal morphology and function of the mutant Rp1 knock-in mice and their littermate controls were evaluated at indicated time points ([Figure 3](#pone-0043251-g003){ref-type="fig"}). Mice homozygous for the Rp1-Q662X allele experienced progressive retinal degeneration. At 1 month of age, the outer nuclear layer (ONL) of retinas from the Rp1 ^Q662X/Q662X^ mice was two to three rows of nuclei thinner than that in wild-type controls. By 6 month of age, only 3--4 rows of photoreceptor nuclei remained in the Rp1 ^Q662X/Q662X^ mice ([Figure 3A](#pone-0043251-g003){ref-type="fig"}). Photoreceptor cell loss was completed by 12 month of age (data not shown). Ultrastructural analyses revealed grossly abnormal outer segments in homozygous Rp1 ^Q662X/Q662X^ mice. At 10 days of age, small packets of enlarged discs replaced the normal organized stacks of discs observed in control animals ([Figure 3B](#pone-0043251-g003){ref-type="fig"}). These changes were even more evident at 1 month of age, and recapitulate the phenotype observed in mice with other mutant Rp1 alleles ([Figure 3C](#pone-0043251-g003){ref-type="fig"}) [@pone.0043251-Gao1], [@pone.0043251-Liu2]. Consistent with the structural abnormalities, the Rp1 ^Q662X/Q662X^ mice demonstrated progressive degeneration of photoreceptor function. ERG analysis at 1 month of age showed the rod a-wave reduced by ∼50% in Rp1 ^Q662X/Q662X^ mice compared to littermate controls ([Figure 3D](#pone-0043251-g003){ref-type="fig"}). By 6 months of age, all measures of rod and cone function were decreased in the Rp1 ^Q662X/Q662X^ mice ([Figure 3E](#pone-0043251-g003){ref-type="fig"}). At 30 months of age, no recordable ERG responses were detected ([Figure 3F](#pone-0043251-g003){ref-type="fig"}). Mice heterozygous for the Rp1-Q662X allele did not show significant retinal structural or functional abnormality up to 30 months of age, consistent with results of our prior studies of the Rp1-tm1EAP mice which showed that truncated Rp1 proteins produce dominant disease on an albino background, but not a pigmented background [@pone.0043251-Liu4] ([Figure 3D, E, F](#pone-0043251-g003){ref-type="fig"}). ![Retinal degeneration phenotype in the Rp1-Q662X mice. A.\ Light microscopic images of semi-thin sections of retinas from wild-type (wt/wt) and homozygous Rp1-Q662X knock-in mice (ki/ki) of the ages indicated. Note that thinning of the outer nuclear layer in the ki/ki mice is evident at 1 month, and progresses so that by 6 months of age only 2--3 rows of photoreceptor nuclei remain. Note also the disorganization and shortening of the photoreceptor outer segments in the ki/ki mice. (GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; IS, inner segment; ONL, outer nuclear layer; OPL, outer plexiform layer; OS, outer segment; RPE, retinal pigment epithelium; 400× magnification for all images). B, C. Electron micrographs of retinas from wt/wt and ki/ki mice at 10 days (B) and 1 month of age (C). At 10 days of age small packets of enlarged disc membranes parallel to the axis of the axonemes replaced the normal perpendicularly orientated stacks of discs observed in control animals. These defects of outer segments were even more evident at 1 month of age, with disorganized membranous whirls in place of outer segments, compared to the well aligned, uniform discs in the control retina (IS, inner segments; OS, outer segments; RPE, retinal pigment epithelium; bars = 2 µm). D--F. Average rod and cone ERG amplitudes for wild-type (wt/wt), heterozygous (wt/ki) and homozygous (ki/ki) Rp1-Q662X knock-in mice. The amplitudes + SD are shown for mice of the three genotypes at 1 month (D), 6 months (E) and 30 months of age (F). Significant differences (P\<0.05) indicated by \. Note that the rod-a waves of the ki/ki mice were significantly decreased at 1 month of age. By 6 months of age, all measures of rod and cone function were decreased in the ki/ki mice. By 30 months of age, no recordable ERG responses were detected.](pone.0043251.g003){#pone-0043251-g003} Generation and Characterization of Rp1 Transgenic Mice {#s2c} ------------------------------------------------------ Expression of correctly localized truncated Rp1 protein in the retinas of the Rp1-Q662X mice raised the possibility that the truncated protein could have acquired an altered function, which disrupts the normal function of wild-type Rp1, and causes disease via a gain-of-function mechanism. However, the lack of retinal phenotype in the Rp1* ^+/Q662X^ heterozygous mice on the mixed 129Sv/C57BL6 genetic background used in the present studies did not allow us to formally distinguish between different disease mechanisms in heterozygous mice. As an alternative approach to address this question, we generated transgenic mice that express epitope-tagged versions of the full-length Rp1 protein, and then transferred the wild-type Rp1 transgene onto the Rp1^Q662X/Q662X^ background to study the interaction of mutant and wild-type Rp1 protein, and determine if the addition of wild-type Rp1 protein can modulate the phenotype in Rp1^Q662X/Q662X^ mutant mice. For these studies, we placed the SF-TAP (Strep-tag II - FLAG) and LAP (EGFP - S-tag) tags at the N-terminus of the Rp1 coding sequence in a BAC that contains 140 kb of genomic DNA surrounding Rp1 ([Figure 4A](#pone-0043251-g004){ref-type="fig"}) [@pone.0043251-Cheeseman1], [@pone.0043251-Gloeckner1]. Three lines of N-SF-TAP-Rp1 transgenic mice (designated T1--T3) and three lines of N-LAP-Rp1 transgenic mice (designated L1--L3) were produced following microinjection of each BAC into oocytes [@pone.0043251-Nagy1]. When backcrossed with C57BL/6J mice, all six founders passed the N-SF-TAP-Rp1 or N-LAP-Rp1 transgenes to approximately half of their offspring. ![Expression of N-SF-TAP-Rp1 and N-LAP-Rp1 Transgenes.\ A. Diagram of Rp1 gene, N-SF-TAP-Rp1 and N-LAP-Rp1 transgenes. The TAP and LAP tags were introduced into the beginning of the Rp1 coding sequence in exon 2 in BAC 314, which contains 140 kb of mouse genomic DNA surrounding the Rp1 locus. B-C. Western blot analyses of Rp1 proteins in N-SF-TAP-Rp1 and N-LAP-Rp1 mice. Equal amounts of protein from retinal extracts of wild-type, N-SF-TAP-Rp1 and N-LAP-Rp1 mice were analyzed by Western blotting using anti-Rp1 antibodies. The blots were also probed with antibodies to ATPase as a loading control. The Rp1 levels for the different transgenic lines were quantified and normalized to the ATPase signals. B. N-SF-TAP-Rp1 mice. The total level of Rp1 protein in line T1 was 144% of that observed in non-transgenic littermate controls, indicating that the transgene increased expression approximately 44%, or nearly the amount expected from a third Rp1 allele. The N-SF-TAP-Rp1 transgene in line T2 is over-expressed relative to the wild-type protein, as it increased the total Rp1 protein level to ∼300% of normal. The total level of Rp1 protein in line T3 was only slightly elevated, but the retinas in these mice were also significantly degenerated, with 40% of the photoreceptor nuclei remaining in the outer nuclear layer, suggesting that the N-SF-TAP-Rp1 protein in this transgenic line is also 2--3 fold greater than wild-type. C. N-LAP-Rp1 mice. The levels of N-LAP-Rp1 fusion protein in lines L1 and L2 mice were approximately half of that observed for the wild-type Rp1 protein, again indicating that the transgene increased expression approximately the amount expected from a third Rp1 allele. In contrast, N-LAP-Rp1 transgene in line L3 is over-expressed, and increased the total Rp1 protein level to ∼250% of normal. D. Immunofluorescence analyses of wild-type Rp1 protein (anti-Rp1 antibodies; red) and N-SF-TAP-Rp1 protein (anti-FLAG antibodies; green) in three N-SF-TAP-Rp1 transgenic lines and wild-type littermate control. Note that the wild-type Rp1 protein is located in the axoneme of photoreceptor outer segments. The N-SF-TAP-Rp1 protein in transgene line T1 shares the same location, as indicated by the overlap of the two signals in the merged image panel (bottom left). There is also some N-SF-TAP-Rp1 signal in the synaptic region of photoreceptor cells that is not present in wild-type retinas. The N-SF-TAP-Rp1 transgenes in T2 and T3 are over-expressed relative to the wild-type protein. The over-expressed N-SF-TAP-Rp1 protein localizes correctly to PSC axonemes, but also mis-localizes to photoreceptor inner segments. The N-SF-TAP-Rp1 signal in the synaptic region is also increased, especially in the line T3 retinas. Note that the outer nuclear layer is thinner in the line T3 sample, consistent with the photoreceptor degeneration observed in this transgene line. The ONL is also slightly thinner in the line T2 samples as well. E. Immunofluorescence analyses of wild-type Rp1 protein (anti-Rp1 antibodies; red) and N-LAP-Rp1 protein (EGFP; green) in three N-LAP-Rp1 transgenic lines and wild-type littermate control. The N-LAP-Rp1 protein in transgene line L1 is located in the axoneme of PSCs, like the wild-type protein. In addition, there is EGFP signal from N-LAP-Rp1 protein in the inner segments and cell bodies of the photoreceptors. Since this was not detected by the anti-Rp1 antibodies, it must be due to truncated versions of the N-LAP-Rp1 protein that retain the N-terminal EGFP tag, but have lost the C-terminal antibody binding domain. The N-LAP-Rp1 transgenes in line L3 is over-expressed relative to the wild-type protein. The over-expressed N-SF-TAP-Rp1 protein localizes correctly to PSC axonemes, but also mis-localizes to photoreceptor inner segments and cell bodies. As for the N-SF-TAP-Rp1 line T3, there is photoreceptor degeneration in the L3 line. The N-LAP-Rp1 transgene expression in line L2 is not completely uniform, with some cells that do not express the transgene evident. In addition, there are red signals in OPL in line L1 and L2, which could represent the non-specific signaling from the anti-c-Rp1 antibody. It is also possible that this immunoreactivity of Rp1 could correspond to the C-terminal fragments of Rp1. (IS, inner segment; ONL, outer nuclear layer; OPL, outer plexiform layer; OS, outer segment; 400X magnification for all images).](pone.0043251.g004){#pone-0043251-g004} To determine the expression level and location of the tagged Rp1 proteins produced by the N-SF-TAP-Rp1 and N-LAP-Rp1 transgenes, retinas from 2-month-old T1--T3 and L1--L3 transgenic lines were evaluated using Western blot and immunofluorescence analyses ([Figure 4B--4E](#pone-0043251-g004){ref-type="fig"}). In the N-SF-TAP-Rp1 transgenic lines, the N-SF-TAP-Rp1 protein was expressed at a normal level in line T1, but over-expressed in lines T2 and T3 ([Figure 4B](#pone-0043251-g004){ref-type="fig"}). The total level of Rp1 protein in line T1 was 144% of that observed in non-transgenic littermate controls, indicating that the transgene increased expression approximately 44%, or nearly the amount expected from a third Rp1 allele ([Figure 4B](#pone-0043251-g004){ref-type="fig"}). The N-SF-TAP-Rp1 transgene in line T2 increased the total Rp1 protein level to ∼300% of normal. The total level of Rp1 protein in line T3 was only slightly elevated, but the retinas in these mice were also significantly degenerated, with 40% of the photoreceptor nuclei remaining in the outer nuclear layer. Providing that the expression level of tagged Rp1 proteins are proportionate to the thickness of the outer nuclear layer of photoreceptor nuclei, the N-SF-TAP-Rp1 protein level in line T3 is about 2--3 fold greater than wild-type ([Figure 4B, D](#pone-0043251-g004){ref-type="fig"}). The higher expression level of tagged RP1 in line T3 was also evidenced by the signal intensity of Rp1 immunostaining in the retinal sections ([Figure 4D](#pone-0043251-g004){ref-type="fig"}). Immunofluorescence analyses using anti-Rp1 antibody to detect the total Rp1 protein and anti-flag antibody to detect the SF-TAP tagged Rp1 protein showed that the N-SF-TAP-Rp1 protein in line T1 co-localizes with the wild-type protein in the PSC axoneme ([Figure 4D](#pone-0043251-g004){ref-type="fig"}). There is also some N-SF-TAP-Rp1 signal in the synaptic region of photoreceptor cells that is not present in wild-type retinas. The over-expressed N-SF-TAP-Rp1 proteins in line T2 and T3 localized correctly to PSC axonemes, but also mis-localized to photoreceptor inner segments and synaptic region, especially in the line T3 retinas ([Figure 4D](#pone-0043251-g004){ref-type="fig"}). In the N-LAP-Rp1 transgenic lines L1--L3, the N-LAP-Rp1 protein was expressed at normal levels in lines L1 and L2, but over-expressed in line L3 ([Figure 4C](#pone-0043251-g004){ref-type="fig"}). For all lines, the N-LAP-Rp1 protein co-localized in the PSC axoneme with the wild-type Rp1 protein. As for the N-SF-TAP-Rp1 protein, there is also some N-LAP-Rp1 signal in the synaptic region of photoreceptor cells that is not present in wild-type retinas. In addition, there were EGFP signals in the inner segments and cell bodies of the photoreceptors ([Figure 4E](#pone-0043251-g004){ref-type="fig"}). Since this was not detected by the anti-Rp1 antibodies, it may be due to truncated versions of the N-LAP-Rp1 protein that retain the N-terminal EGFP tag, but have lost the C-terminal antibody binding domain. The N-LAP-Rp1 transgene expression in line L2 is not completely uniform, with a mixture of cells that do and do not express the transgene. As for the T3 line, there is also photoreceptor degeneration in the L3 line, with fewer photoreceptor nuclei remaining in the outer nuclear layer. To further evaluate the long-term effects of different levels of additional wild-type Rp1 protein on retinal function, detailed retinal histologic and functional analyses were performed in these transgenic lines at 1 year of age ([Figure 5](#pone-0043251-g005){ref-type="fig"}). Results showed that the histology of photoreceptors in lines T1, L1 and L2 are well preserved in mice up to 1 year of age ([Figure 5A](#pone-0043251-g005){ref-type="fig"}). In contrast, lines T2, T3 and L3 that over-express the tagged transgenes showed photoreceptor degeneration at 1 year of age, with shortened PSCs and loss of photoreceptor nuclei. Ultrastructural analyses of Line T1 and L2 confirmed normal PSC structure in these two lines of transgenic mice ([Figure 5B](#pone-0043251-g005){ref-type="fig"}). Consistent with the normal histology, ERG analysis showed that line T1 and L2 mice have normal retinal function at 1 year of age ([Figure 5C](#pone-0043251-g005){ref-type="fig"}). All together, these data suggest the N-SF-TAP-Rp1 and N-LAP-Rp1 proteins localize correctly to the PSC axonemes and function normally, but also indicate that over-expression of the transgene is associated with mislocalization of the tagged proteins and can lead to photoreceptor degeneration. ![Retinal phenotypes of N-SF-TAP-Rp1 and N-LAP-Rp1 transgenic mice.\ A. Retinal histology from 1-year-old mice of the genotypes indicated. Note that the retinal structure of the N-SF-TAP-Rp1 line T1 and N-LAP-Rp1 lines L1 and L2 is normal. In contrast, there is photoreceptor degeneration evident in N-SF-TAP-Rp1 lines T2 and T3, and N-LAP-Rp1 line L3, with loss of photoreceptor nuclei and shortening of photoreceptor outer segments. (INL, inner nuclear layer; IS, inner segment; ONL, outer nuclear layer; OS, outer segment; 400× magnification for all images). B. Ultrastructure of photoreceptor sensory cilia in one-year old N-SF-TAP-Rp1 line T1 and N-LAP-Rp1 line L2 mice, compared to that of wild-type littermate control. Note that the structure of the PSC and organization of the outer segment discs are normal in both transgenic lines, consistent with the histology shown in A. C. Amplitudes of ERG responses from 1-year-old N-SF-TAP-Rp1 line T1 and N-LAP-Rp1 line L2 mice, compared to that of wild-type littermate controls. Note that the rod and cone ERG amplitudes are normal in both lines of transgenic mice.](pone.0043251.g005){#pone-0043251-g005} Expression of Additional Full-length Rp1 Protein can Delay Photoreceptor Degeneration in Rp1^Q662X/Q662X^Mice {#s2d} ------------------------------------------------------------------------------------------------------------- The classic method to distinguish between dominant-negative and gain-of-function mechanisms of a dominant mutation is to evaluate the effect of different ratios of wild-type to mutant protein on modulating the phenotype [@pone.0043251-Herskowitz1], [@pone.0043251-Wilson1]. This can be achieved by creating transgenic mice expressing either a mutant allele on a wild-type background, or a wild-type allele on a mutant background. In this study, we transferred the wild-type N-SF-TAP-Rp1 or N-LAP-Rp1 transgenes onto the homozygous Rp1-Q662X background to generate new transgenic lines. Animals carrying two mutant Q662X alleles at the endogenous Rp1 locus and a tagged Rp1 transgene were designated as Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 or Rp1 ^Q662X/Q662X^ : N-LAP-Rp1 mice. We used lines T1 and L2 for these experiments, since these lines express the tagged-Rp1 proteins at relatively normal levels, and do not exhibit photoreceptor degeneration. As described above, the Rp1 ^Q662X/Q662X^ mice do not express full-length Rp1 protein and experience photoreceptor degeneration, with decreased retinal function evident as early as 1 month of age. Addition of the N-SF-TAP-Rp1 and N-LAP-Rp1 wild-type transgenes to the Rp1 ^Q662X/Q662X^ mutant mice resulted in restoration of expression of full-length Rp1 protein in the retina. As shown in [Figure 6A](#pone-0043251-g006){ref-type="fig"}, the transgenic full-length Rp1 protein was localized normally to the axonemes of PSCs. There is a mosaic pattern of full-length Rp1 protein expression in the Rp1 ^Q662X/Q662X^ : N-LAP-Rp1 mice, which is consistent with the expression pattern of tagged Rp1 in line L2. ![Expression of the full-length N-SF-TAP-Rp1 and N-LAP-Rp1 proteins prevents photoreceptor degeneration in Rp1^Q662X/Q662X^ knock-in mice.\ A. Frozen sections of retina from 2-month-old mice of the genotypes indicated were stained with anti-C-Rp1 antibodies (red). The wild-type Rp1 protein is located in the axonemes of PSC; full-length Rp1 protein is not detected in the Rp1-Q662X knock-in mice. Full-length Rp1 protein is also detected in the PSC axonemes of the Rp1-Q662X : N-SF-TAP-Rp1 and Rp1-Q662X : N-LAP-Rp1 mice. There is a mosaic pattern of full-length Rp1 protein expression in the Rp1-Q662X : N-LAP-Rp1 mice. (INL, inner nuclear layer; IS, inner segment; ONL, outer nuclear layer; OS, outer segment; 400X magnification for all images). B. Retinal histology from 2-month-old mice of the genotypes indicated. The retinal structure of the Rp1-Q662X : N-SF-TAP-Rp1 mice is normal, in contrast to the early photoreceptor degeneration in the Rp1-Q662X mice. There is partial preservation of retina structure in the Rp1-Q662X : N-LAP-Rp1 mice (INL, inner nuclear layer; IS, inner segment; ONL, outer nuclear layer; OS, outer segment; 400× magnification for all images). C. Ultrastructure of PSCs in two-month old mice of the genotypes indicated. Note that the structure of the PSC and organization of the outer segment discs are normal in the Rp1-Q662X : N-SF-TAP-Rp1 mice, in contrast to the disorganized PSC observed in the Rp1 ^Q662X/Q662X^ mice. There is a mixture of cells with normal PSC and cells with disorganized PSC in the Rp1-Q662X : N-LAP-Rp1 mice (OS, outer segment; RPE, retinal pigment epithelium. Bars = 2 µm). D. Amplitudes of ERG responses from 2 month-old and 12-month-old mice of the genotypes indicated. At 2 months not that the rod and cone ERG amplitudes are close to normal in the Rp1-Q662X : N-SF-TAP-Rp1 mice, in contrast to the reduction of photoreceptor function observed in the Rp1 ^Q662X/Q662X^ mice. There is partial restoration of photoreceptor function in the Rp1-Q662X : N-LAP-Rp1 mice. At 12 months photoreceptor function is relatively well preserved in the Rp1-Q662X : N-SF-TAP-Rp1 mice. There is also some residual photoreceptor function in the Rp1-Q662X : N-LAP-Rp1 mice. Significant differences compared to controls are indicated by \* (P\<0.01) and \\ (P\<0.05).](pone.0043251.g006){#pone-0043251-g006} The retinal structure was almost completely preserved in the Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice at 2 months of age. In the Rp1 ^Q662X/Q662X^ : N-LAP-Rp1 mice, electron microscopy showed a mixture of PSCs with normal and aberrant structures ([Figures 4E](#pone-0043251-g004){ref-type="fig"}, [6C](#pone-0043251-g006){ref-type="fig"}). At the age of 12 months, there was notable photoreceptor degeneration observed in the Rp1 ^Q662X/Q662X^ mice, with only a single layer of photoreceptor cells with no visible outer segments remaining ([Figure S1](#pone.0043251.s001){ref-type="supplementary-material"}). In contrast, the photoreceptor cells and organization of outer segments was greatly preserved in the Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice. In the Rp1 ^Q662X/Q662X^ : N-LAP-Rp1 mice, more significant retinal degeneration was observed, including shorter outer segments with a mixture of normal discs and disorganized discs ([Figure S1](#pone.0043251.s001){ref-type="supplementary-material"}). The phenotype seen in the Rp1 ^Q662X/Q662X^ : N-LAP-Rp1 mice is consistent with the mosaic pattern of expression of the N-LAP-Rp1 transgene in the line L2 mice ([Figures 4E](#pone-0043251-g004){ref-type="fig"}, [6C](#pone-0043251-g006){ref-type="fig"}). These data also indicate that Rp1 acts in individual cells in a cell-autonomous fashion, consistent with its function as a photoreceptor MAP [@pone.0043251-Liu3]. Consistent with the improved retinal structure, Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice had significantly improved scotopic and photopic ERG responses compared to Rp1 ^Q662X/Q662X^ mice ([Figure 6D](#pone-0043251-g006){ref-type="fig"}). At 2 months of age, the rod a-wave, rod b-wave and cone b-wave in the Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice showed no significant difference compared to the wild type controls. At the age of 12 months, when there were no detectable ERG responses in the Rp1 ^Q662X/Q662X^ mice, the maximum amplitude of the rod a-wave, rod b-wave and cone b-wave were preserved to 57%, 71% and 90% of normal levels, respectively, in the Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice; these values were not statistically different from those observed in the control mice. The restoration of retinal function in the Rp1 ^Q662X/Q662X^ : N-LAP-Rp1 mice was not as complete as that in Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice, presumably because only a portion of the photoreceptor cells in these mice expressed the N-LAP-Rp1 protein. At 2 month of age, the maximum amplitude of rod a-wave improved to 50% of normal, compared to 19% of normal in Rp1 ^Q662X/Q662X^ mice. At 12 months of age, the maximum amplitude of rod a-wave was 17% of normal in the transgenic mice, which is similar to the level in 2-month-old knock-in mice. Discussion {#s3} ========== The success of the Phase I clinical trials of gene therapy for LCA has led to rapid progress in developing genetic therapeutic strategies. However, efforts to develop gene therapy for dominant diseases have lagged behind those directed at recessive disease caused by loss-of-function mutations, in part because of the assumption that successful treatment of dominant diseases will require suppression or removal of the protein produced by the mutant allele [@pone.0043251-Gorbatyuk1]--[@pone.0043251-Chadderton1]. Some successes at this suppression or removal in conjunction with replacement approach have been reported, yet this approach is clearly more complicated than gene augmentation therapy and it is only necessary for gain-of-function mutations [@pone.0043251-Herskowitz1], [@pone.0043251-Wilson1]. Hence, it is critical to distinguish between the gain-of-function, dominant-negative and haploinsufficiency mutations when gene therapy is applied to dominant diseases. In this study, we present several important insights into the mechanisms by which mutations in RP1 cause retinal degeneration. Data from the family with a frameshift mutation in exon 3 of RP1 confirm that null alleles of RP1 cause arRP, but haploinsufficiency of RP1 does not cause RP. Data from the Rp1-Q662X knock-in mice show that mutant alleles with truncating mutations in the final exon can produce truncated proteins that retain their microtubule binding domains and localize correctly to the axonemes of PSCs. Photoreceptor degeneration in the Rp1-Q662X mice can be delayed or prevented by increasing the ratio of wild-type to mutant protein without removal of the mutant protein, demonstrating that the truncated Rp1-Q662X protein expressed in these mutant mice does not exert a toxic gain-of-function in the retina [@pone.0043251-Herskowitz1], [@pone.0043251-Wilson1]. These findings are important because they indicate that gene augmentation therapy, such as that used for recently reported LCA clinical trials, has the potential to be beneficial for both dominant and recessive RP1 patients. It is also evident that the levels of protein delivered for therapy will have to be carefully controlled because over-expression of Rp1 causes retinal degeneration. These results also raise the question of how many other forms of dominant retinal disorders have a comparable etiology, and thus could also be amenable to gene augmentation therapy. The human genetic study of the family with the p.P229GfsX35 mutation in exon 3 of RP1 provides confirming evidence that haploinsufficiency of RP1 cannot cause dominant RP. Because the premature termination codon produced by the resulting frameshift occurs in exon 3, the transcripts with the identified 1-bp deletion are expected to be subject to NMD, resulting in no expression of the mutant RP1 protein [@pone.0043251-Chang1]. Direct evidence of NMD of this mutant RP1 allele in the retina cannot be obtained from the patient; further study using lymphoblasts derived from the patient and/or an animal models is warranted. The parents and sister of the affected patient are heterozygous for this frameshift mutation, but show no evidence of retinal degeneration. This result is consistent with the recent report by Chen et al, who described a patient with recessive RP due to two novel frameshift mutations in RP1, and family member carrying a S2RfsX16 mutation in exon 2 that is unaffected [@pone.0043251-Chen1]. Together, these findings support the idea that functional hemizygosity of RP1 does not cause disease. The Rp1-Q662X mice provide the first clear demonstration that mutant Rp1 mRNA with a premature stop codon in the final exon can escape NMD, and produce truncated protein in photoreceptor cells in vivo. We have previously generated a gene targeted Rp1-tm1EAP mouse model that carries an artificial stop codon in last exon of Rp1 gene [@pone.0043251-Liu2], [@pone.0043251-Liu4]. In the Rp1-tm1EAP mice, the mutant Rp1 allele was produced by removing the majority of exon 4, and thus did not allow for testing the hypothesis that the premature termination codons in last exon lead to the production of truncated Rp1 proteins. The Rp1-Q662X allele produces the same 74 kDa truncated Rp1 protein localized correctly to the axonemes of PSCs as that produced in the retinas of Rp1-tm1EAP mice, consistent with retention of the DCX microtubule binding domains (amino acids 35--236) in the truncated N-terminal Rp1 protein. These results are also consistent with those from PCR of illegitimate transcripts from lymphoblasts of patients with the R677X mutation in RP1 [@pone.0043251-Liu2]. It is hypothesized that in patients with truncating RP1 mutations in the last exon, the mutant truncated protein is expressed and retains its ability to binding axonemal microtubules in the photoreceptor cells. The Rp1-Q662X mutant allele causes disorganized outer segment discs, but only when present in the homozygous state in the study reported here. The lack of phenotype in Rp1 ^+/Q662X^ heterozygous mice recapitulates the observation in Rp1-tm1EAP mice that a single Rp1 mutant allele in Rp1-tm1Eap mice causes dominant disease only on an congenic albino (A/J) background, but not on pigmented (mixed 129Sv/C57BL/6J) background [@pone.0043251-Liu4]. Since the truncated Rp1 proteins produced by the Rp1-tm1EAP and Rp1-Q662X mouse models are the same, we expect that the truncated Rp1-Q662X is functional in the retina and a single copy of Rp1-Q662X would cause dominant disease when it is expressed on an albino background. Genetic factors are also thought to play a role in modulating RP1 disease expression in human patients [@pone.0043251-Jacobson1], [@pone.0043251-Berson1], [@pone.0043251-Liu4]. While most truncating mutations in exon 4 of RP1 cause adRP, it has been reported that truncating mutations in RP1 may cause recessive disease in several Indian and Pakistani families ([Figure 1A](#pone-0043251-g001){ref-type="fig"}) [@pone.0043251-Singh1], [@pone.0043251-Riazuddin1]. We hypothesize that the mode of inheritance and/or the severity of disease caused by truncating mutation in RP1 or Rp1 may be controlled is part by genetic background or modifier genes. Evidence in support of this hypothesis includes the observation that the truncated protein produced by the Rp1-tm1EAP mice causes dominant disease on an albino background, but not pigmented backgrounds. The variation in RP1 disease severity may also be explained by sequence variants in genes that encode proteins that interact with RP1, or the level of expression of the normal allele, and warrants additional investigation [@pone.0043251-Nadeau1], [@pone.0043251-Haider1]. Additionally, the stability and localization of different mutant RP1 proteins produced in photoreceptor cells may contribute to determining the severity of RP1 disease. It has been experimentally demonstrated that the relative degree of protein retention/degradation and the subcellular localization of mutant proteins produced by different truncating mutations at a single site in the ROR2 gene can determine the phenotypic outcome [@pone.0043251-Bateman1]. The data from several lines of Rp1 transgenic mice showed that the phenotype of the transgenic mice and the location of the protein expressed by additional transgene are closely correlated to the protein expression levels in retina. In the N-SF-TAP-Rp1 line T1 and N-LAP-Rp1 line L2 mice that produce Rp1 proteins in amounts similar to those produced from a single endogenous Rp1 allele, the tagged Rp1 proteins were located normally in the axonemes of PSCs, and the retinal structure and function was normal up to at least one year of age in these transgenic line. This suggests that the epitope tags do not interfere with Rp1 function and the expression of 50% more Rp1 protein than usual is well-tolerated by photoreceptor cells. The tagged Rp1 proteins were partially mis-localized to other subcellular locations when expression of these proteins exceeded normal levels. Over-expression of Rp1 also resulted in photoreceptor degeneration, as has been reported for several other photoreceptor proteins, such as rhodopsin [@pone.0043251-Olsson1], [@pone.0043251-Tan1]. These findings imply that the levels of Rp1 protein are tightly regulated and thus, the levels of protein delivered for therapy, such as by gene therapy, will have to be carefully controlled. In this study, we found that a ratio of 1∶2 of wild-type vs. mutant protein is enough to significantly reduce the retinal degeneration caused by the truncated Rp1 protein, as evidenced by the relative preservation of retinal function and structure in the 12-month-old Rp1 ^Q662X/Q662X^ : N-SF-TAP-Rp1 mice compared to the Rp1 ^Q662X/Q662X^ mice. The level of full-length RP1 protein required to rescue the structure and function of photoreceptor cells in heterozygous mice or patients will need to be determined. It is worth noting that in the N-LAP-Rp1 transgenic mice, EGFP signal was found separately from Rp1 signal detected by anti-C-terminal Rp1 antibody ([Figure 4](#pone-0043251-g004){ref-type="fig"}). This suggests that the EGFP-Rp1 fusion protein underwent proteolysis, resulting in separation of the LAP-tag-containing N-terminal portion of the protein from the C-terminal portion of the protein to which the antibodies used are directed [@pone.0043251-Liu1]. This finding indicates that care is needed interpreting data obtained using EGFP and other fluorescent fusion proteins to localize proteins of interest in cultured cells and in vivo. While it has been suggested by other authors that validation of fluorescent fusion protein location by detecting the endogenous protein is important, we have not found other reports of separation of the EGFP tag from fusion proteins in vivo [@pone.0043251-Michaelson1]. In this study, although the Rp1-Q662X mice on a mixed 129Sv/C57BL/6J genetic background are not a model of dominant disease to test gene therapeutic approaches, the homozygous Rp1^Q662X/Q662X^ mice provide a valuable model system to determine if the truncated Q662X protein has a gain-of-function or a dominant negative effect in photoreceptor cells in vivo by expressing a wild-type Rp1 allele on this mutant background. The results from the crossing of Rp1^Q662X/Q662X^ knock-in mice and Rp1 BAC transgenic mice showed that the phenotype of the Rp1^Q662X/Q662X^ mice can be rescued without first removing the mutant protein, indicating that the truncated Rp1 protein does not exert a toxic gain-of-function effect in the photoreceptor cells in mutant Rp1 animal models. Based on the findings from human and animal studies, which rule out haploinsufficiency and gain-of-function as the cause of RP1 disease, the most logical conclusion would be that truncated RP1 proteins cause disease via a dominant-negative mechanism [@pone.0043251-Herskowitz1], [@pone.0043251-Wilson1]. This concept is consistent with the fact that all adRP mutations are spread over a large protein region in the last exon and that there are no missense mutations that lead to a very specific gain-of-function. It is also consistent with the findings that, in both Rp1-Q662X and Rp1-tm1EAP mouse models, truncated Rp1 proteins retain their ability to bind to axonemal microtubules in the photoreceptor cells, but may have lost the ability to interact with other proteins that are hypothesized to bind to the C-terminal portion of Rp1 and mediate organization of outer segment discs along the axoneme [@pone.0043251-Liu2], [@pone.0043251-Liu3]. It is hypothesized that, in dominant RP1 disease, the truncated RP1 proteins does not cause disease by generating a novel toxic function, but rather compete for binding to axonemal microtubules with full length RP1 protein, and thus interfering with RP1-mediated organization of outer segment discs along the axoneme. Additional studies of the genetic mechanism of and the gene therapeutic approaches for dominant RP1 disease using Rp1-Q662X or Rp1-tm1EAP mice on an albino background are warranted to further test this hypothesis. The finding that truncating mutations in RP1 does not cause dominant disease via a gain-of-function mechanism raises the question of how many other dominant forms of IRD are caused by a similar mechanism. Despite the great progress made in recent years discovering novel IRD disease genes, the mechanisms by which the identified mutations cause disease have only been evaluated thoroughly in vivo for a limited number of genes [@pone.0043251-Nour1]--[@pone.0043251-Tam1]. An important example of dominant IRD is RP caused by mutations in the rhodopsin (RHO) gene, which are the most common cause of adRP [@pone.0043251-Hartong1], [@pone.0043251-Sullivan2]. It is evident that haploinsufficiency of RHO does not cause dominant RP, since people heterozygous for null RHO mutations and heterozygous Rho knockout mice do not develop retinal degeneration [@pone.0043251-Rosenfeld1]. The most common mutation adRP mutation in RHO is the P23H mutation, which accounts for 10 to 15% of adRP in Western populations [@pone.0043251-Hartong1]. There are conflicting data, however, about whether P23H mutation in RHO causes adRP via a gain-of-function or dominant-negative mechanism [@pone.0043251-Chapple1]--[@pone.0043251-Saliba1]. A recent report that RHO gene augmentation therapy preserves retinal function in P23H RHO transgenic mice is consistent with a dominant-negative effect of the P23H mutation [@pone.0043251-Mao1]. It is possible, therefore, that the P23H mutation in RHO, and other dominant mutations in RHO and other IRD disease genes cause disease via dominant-negative mechanisms, and thus like dominant RP1 disease may also be amendable to gene augmentation therapy. Materials and Methods {#s4} ===================== Clinical Evaluations {#s4a} -------------------- The clinical study was approved by the ethical review board of The Rotterdam Eye Hospital and conformed to the tenets of the Declaration of Helsinki. Written consent was given by the participants for their information to be stored in the hospital database and used for research. Retrospective data of the index patient were evaluated. Ophthalmic examination of all family members included best-corrected visual acuity (Snellen), slitlamp examination, and fundoscopy. Fundus autofluorescense images (30^o^, alignment of 15 frames) were obtained with a confocal scanning laser ophthalmoscope with 488 nm excitation (Spectralis®, Heidelberg Engineering, Heidelberg, Germany). Electroretinograms (according to ISCEV standards) were performed in the index patient and his parents [@pone.0043251-Marmor1]. Fundus photographs were obtained in the index patient and his father. Genome-wide Homozygosity Mapping {#s4b} -------------------------------- In a large study aiming at the identification of the genetic causes of RP in The Netherlands via homozygosity mapping [@pone.0043251-Collin1], 231 Dutch arRP patients were genotyped on a high-resolution Genome-wide Human SNP array 5.0 that contains 500,000 SNPs and 420,000 non-polymorphic probes for copy number detection (Affymetrix, Santa Clara, CA, USA). Homozygous regions in the patients' genome were calculated using Partek Genomics Suite software (Partek, St. Louis, MO, USA). Stretches of DNA that contained 250 or more homozygous SNPs (1.5 Mb on average) were considered to be significant homozygous regions. RP1 Sequence Analysis {#s4c} --------------------- Patients that were homozygous for the genomic region containing the RP1 gene were selected for sequence analysis. Primers to amplify all exons and intron-exon boundaries of RP1 are available on request. PCR products were sequenced with the ABI PRISM Big Dye Terminator Cycle Sequencing V2.0 Ready Reaction kit and the ABI PRISM 3730 DNA analyzer (Applied Biosystems, Foster City, CA, USA). Generation of Rp1^Q662X/Q662X^ Knock-in Mice {#s4d} -------------------------------------------- This research followed the tenets of the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research, and the guidelines of the Massachusetts Eye and Ear Infirmary for Animal Care and Use, and was specifically approved by Institutional Animal Care and Use Committees at the Massachusetts Eye and Ear Infirmary. The Rp1-Q662X targeting vector was generated from a mouse bacterial artificial chromosome (BAC) clone that contains the entire mouse Rp1 gene using modified recombineering techniques ([Fig. 2A](#pone-0043251-g002){ref-type="fig"}). This BAC clone (314) was identified by screening high-density filters from the RPCI-22 (129S6/SvEvTac) Mouse BAC Library (BACPAC web site: <http://www.chori.org/bacpac/libraryres.htm/provided> in the public domain by the National Center of Excellence in Genomics at Children's Hospital Oakland Research Center, Oakland, CA). Briefly, the neomycin-zeocin resistance cassette from plasmid pKOEZ59 was inserted between exons 3 and 4 of the Rp1 gene in BAC 314 using recombination-based techniques [@pone.0043251-Zhang1], [@pone.0043251-Lee1]. A 23.8 kb portion DNA containing the modified Rp1 gene was then retrieved into pBluescript II via homologous recombination, to create wild type construct [@pone.0043251-Liu5]. This vector was mutagenized to introduce the Q662X mutation and then linearized to transfect into AB2.2 mouse ES cells (obtained from Dr. Allan Bradley at the Wellcome Trust Sanger Institute, UK website: <http://www.sanger.ac.uk/resources/mouse/micer/>) [@pone.0043251-RamirezSolis1]. Approximately 250 G418 resistant colonies were selected and expanded according to established techniques [@pone.0043251-Nagy1]. DNA prepared from the isolated clones was digested with BamHI and analyzed by Southern blot using a 5′ probe to identify correctly targeted ES cells. DNA from the single positive recombinant was also digested with PmeI, and analyzed by Southern blot using a 3′ probe. Probes for Southern blot analysis were amplified from BAC 314A DNA, and cloned into the pCRII-TOPO vector (Invitrogen, Carlsbad, CA). The 5′ probe was amplified with primers 5′-CAAGAATCTGGCGGCCGCTGGACTGAATGTCAC-3′, and 5′- GAGAATAGGAACTTCGATCCATAACTTCGTATAATG-3′, and the 3′ probe with primers 5′-GAATCCAGGTGGGGAAGAGCACGGGTAA-3′ and 5′-TATTTTATCTAAAAGACCTATCTCGAATCC-3′ ([Figure 2B](#pone-0043251-g002){ref-type="fig"}). One ES cell clone with the Rp1-Q662X-Neo allele was injected into blastocysts to generate chimeric mice [@pone.0043251-Nagy1]. Chimeric mice were generated using standard techniques, and the Frt-flanked neomycin selection cassette was removed by crossing the Rp1-Neo-Q662X mice with universal FLPe deleter mice [@pone.0043251-Rodriguez1]. The final excised targeted Rp1-Q662X knock-in allele was verified by PCR and sequencing ([Figure 2C](#pone-0043251-g002){ref-type="fig"}). Heterozygous and homozygous animal were generated by intercrossing the F1 progeny. Genotyping was performed by PCR analysis of tail DNA using primers: 5′-TACTGTTTTTCCTTGGCTTACTC-3′ and 5′-ACTTTGGCTGTTGTGTTTCTTA-3′. The sizes of the PCR products amplified from wild-type and mutant Rp1 alleles are 231 bp and 497 bp, respectively ([Figure 2D](#pone-0043251-g002){ref-type="fig"}). Generation of Rp1 BAC Transgenic Mice {#s4e} ------------------------------------- To attempt to fully recapitulate Rp1 expression with a transgene, we used a BAC genomic clone containing a 140 kb fragment of mouse genomic DNA to produce the transgenic mice. This 140 kb fragment encompassed the complete Rp1 gene and, in addition, contained 53 kb of 5-flanking DNA and 62 kb of 3-flanking DNA ([Fig. 4](#pone-0043251-g004){ref-type="fig"}). The transgenic construct was produced by incorporating two different tags, SF-TAP (Strep-tag II-FLAG) and LAP (EGFP-S-tag) into the N-terminus of the Rp1 coding sequence in exon 2 of the Rp1 gene in the BAC ([Fig. 4A](#pone-0043251-g004){ref-type="fig"}) [@pone.0043251-Cheeseman1], [@pone.0043251-Gloeckner1]. Three lines of N-SF-TAP-Rp1 transgenic mice (designated T1--T3) and three lines of N-LAP-Rp1 transgenic mice (designated L1--L3) were produced following microinjection of each BAC into oocytes [@pone.0043251-Nagy1]. The Rp1 transgenes present in the Rp1 transgenic lines were distinguished from the endogenous Rp1 locus by PCR amplification with TAP-specific primers 5′-CATTGTTTGAGTGTAAATATCCGCATTGG-3′, 5′-CGCTTCCTCCTCCCTTCTCGAACTGAG-3′ and LAP-specific primers 5′-TCGCCGGACACGCTGAACTTGTG-3′, and 5′-CATTGTTTGAGTGTAAATATCCGCATTGG-3′. Transgenic progeny were backcrossed to C57BL/6J mice to establish lines from each founder. In the present study, transgenic line T1 and L2 were used for crosses with Rp1-Q662X knock-in mice. All progeny were then genotyped for the presence of the Rp1 transgene and for the presence of the mutant Q662X allele. Electroretinography {#s4f} ------------------- Electroretinography (ERG) testing in the mice was performed as previously described [@pone.0043251-Liu2]. In brief, the pupils of dark-adapted, anesthetized mice were dilated with 1% tropicamide and the mice were placed on a stage maintained at 37°C. Retinal responses were detected with platinum electrodes placed in contact with the corneas. A platinum wire loop placed in the mouth served as the reference and a ground electrode. ERG were recorded with Espion Electrophysiology System (Diagnosys LLC, Lowell, MA) calibrated by the vendor. A stage with the mouse was positioned in such a way that the mouse head was located inside the ColorDome stimulator thus ensuring full-field uniform illumination. All manipulations were performed under dim red light, and after being placed into the ColorDome the animal was left in darkness for 10 min for complete dark re-adaptation. The ERG recordings followed in general guidelines recommended by the "Standard for Clinical Electroretinography" [@pone.0043251-MichaelFMarmor1]. The rod b-wave ("weak flash rod response" by the Standard) was recorded at a response to green (λ = 513 nm) flash intensity of 1.08×10^−2^ scot cd s m^−2^. The saturating rod a-wave was elicited by a white flash of 500 scot cd s · m^−2^ intensity produced by a xenon lamp ("High-intensity ERG" by the Standard). The single cone ERG was elicited by a 500 scot cd s · m^−2^ intensity white flash delivered on a 30 scot cd · m^−2^ background suppressing the rod activity. The ERGs were recorded in a 0.1 to 300 Hz bandwidth, digitized at 1 kHz, and the amplitudes of the respective responses were measured from the baseline to peak for the a-wave, and from the trough to peak for the rod and cone b-waves. Each trace is the average of 3 to 10 individual records (the traces of the two eyes were also averaged during analysis). Statistical analysis was performed using Prism v3.02 software (GraphPad, San Diego, CA). RT-PCR {#s4g} ------ Retinas from animals of different genotypes at the desired ages were collected and homogenized in Trizol (Invitrogen, Carlsbad, CA). Total RNA was extracted from one retina and reverse transcribed using Superscript II (Invitrogen). The PCR reactions were then performed using 2 µL of first-strand cDNA to amplify the region of RP1 transcript containing exon 2 to 3 and exon 3 to 4. The primer sets used were: forward, 5′-TCGGCCCTGGCTGAGTAGTCG-3′ (on exon 2), reverse, 5′-TTCCTGGTTTAAATGGCTCCCTTCC-3′ (on exon 3); and forward, 5′-TGCCAAGTTACCAGGAATCTC-3′ (on exon 3), reverse, 5′-CGACCGTCATCGTACCATCTTG-3′ (on exon 4). Western Blotting {#s4h} ---------------- Retinas from animals of different genotypes at the desired ages were collected and homogenized in sample buffer (NuPAGE; Invitrogen). Solubilized retinal protein samples were then processed for Western blot analysis as described [@pone.0043251-Liu1]. Briefly, equivalent amounts of protein from each genotype were separated on 4% to 12% Tris-acetate gel (NuPage; Invitrogen) and transferred to polyvinylidene difluoride (PVDF) membrane (Millipore, Bedford, MA). The membranes were blocked with 10% nonfat dry milk in TBS-T and incubated with primary antibodies. Chicken polyclonal anti-C-Rp1 antibody and anti-N-Rp1 antibodies were used to detect the normal full length Rp1 and the mutant truncated Rp1 protein. Monoclonal anti-alpha 1 Sodium Potassium ATPase antibody from Abcam (Cat. ab7671) antibody was used as internal control to quantify the expression level of transgenic Rp1 protein. Antibody binding was detected with alkaline phosphatase conjugated or Odyssey IRDye secondary antibodies. Positive signals were visualized and quantified by Odyssey Infrared Imaging System (Li-Cor Biosciences, Lincoln, NE). Immunofluorescence, Light and Electron Microscopy {#s4i} ------------------------------------------------- Eyes from Rp1-Q662X knock-in mice and transgenic mice were processed for immunostaining experiments as described previously [@pone.0043251-Liu2]. Ten micron cryosections were cut and evaluated using anti-N-Rp1 and anti-C-Rp1 and anti-flag (Sigma, St. Louis, MO) antibodies. Sections were incubated overnight at 4°C with primary antibodies followed by Alexa 488- and Alexa 555-conjugated secondary antibodies (Invitrogen). Stained sections were viewed with a Zeiss LSM 510 Meta confocal microscope, and the images were processed with Zeiss Meta 510 software. Preparation of retinas for light and electron microscopy was performed as previously described [@pone.0043251-Liu2], [@pone.0043251-Liu3]. Semithin (0.75 µm) sections were cut and stained with alkaline toluidine blue for light microscopy, and 60- to 80-nM ultrathin sections were stained with 2% uranyl acetate and lead citrate, and photographed using a transmission electron microscope. Supporting Information {#s5} ====================== ###### Expression of the full-length N-SF-TAP-Rp1 and N-LAP-Rp1 proteins prevents photoreceptor degeneration in Rp1^Q662X/Q662X^ knockin mice. A. Retinal histology from 12-month-old mice of the genotypes indicated. The retinal structure of the combined Rp1-Q662X : N-SF-TAP-Rp1 mice is essentially normal, in contrast to the early photoreceptor degeneration in the Rp1-Q662X mice. There is partial preservation of retina structure in the combined Rp1-Q662X : N-LAP-Rp1 mice (INL, inner nuclear layer; IS, inner segment; ONL, outer nuclear layer; OS, outer segment; 400× magnification for all images). B. Ultrastructure of PSCs in 12-month old mice of the genotypes indicated. Note that the structure of the PSC and organization of the outer segment discs are normal in the combined Rp1-Q662X : N-SF-TAP-Rp1 mice, in contrast to the grossly disorganized PSC observed in the Rp1 ^Q662X/Q662X^ mice. More significant disorganization of PSCs was observed in the combined Rp1-Q662X : N-LAP-Rp1 mice, including shorter outer segments with a mixture of normal discs and disorganized discs (OS, outer segment; RPE, retinal pigment epithelium. Bars = 2 µm). (TIF) ###### Click here for additional data file. We would like to thank Alexei Saveliev, Jonathan Weiner, Yun Liu, Jian Li, Arkady Lyubarsky, Saskia van der Velde-Visser, Christel Beumer, Marta de Castro-Miró, and Frans Riemslag for their excellent technical assistance, and we are grateful to the patients and their relatives for their participation in this study. [^1]: Competing Interests:The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: QL RWC EAP. Performed the experiments: QL RWJC AIdH LIvdB FPMC EAP. Analyzed the data: QL RWJC FPMC EAP. Contributed reagents/materials/analysis tools: QL RWJC AIdH LIvdB FPMC EAP. Wrote the paper: QL RWJC FPMC EAP.
Trace element determination using static high-sensitivity inductively coupled plasma optical emission spectrometry (SHIP-OES). A low-flow air-cooled inductively coupled plasma (ICP) design for optical emission spectrometry (OES) with axial plasma viewing is described and an evaluation of its analytical capabilities in trace element determinations is presented. Main advantage is a total argon consumption of 0.6 L min(-1) in contrast to 15 L min(-1) using conventional ICP sources. The torch was evaluated in trace element determinations and studied in direct comparison with a conventional torch under the same conditions with the same OES system, ultrasonic nebulization (USN) and single-element optimization. A variety of parameters (x-y-position of the torch, rf power, external air cooling, gas flow rates and USN operation parameters) was optimized to achieve limits of detection (LOD) which are competitive to those of a conventional plasma source. Ionic to atomic line intensity ratios for magnesium were studied at different radio frequency (rf) power conditions and different sample carrier gas flows to characterize the robustness of the excitation source. A linear dynamic range of three to five orders of magnitude was determined under compromise conditions in multi-element mode. The accuracy of the system was investigated by the determination of Co, Cr, Mn, Zn in two certified reference materials (CRM): CRM 075c (Copper with added impurities), and CRM 281 (Trace elements in rye grass). With standard addition values of 2.44+/-0.04 and 3.19+/-0.21 microg g(-1) for Co and Mn in the CRM 075c and 2.32+/-0.09, 81.8+/-0.4, 32.2+/-3.9 for Cr, Mn and Zn, respectively, were determined in the samples and found to be in good agreement with the reported values; recovery rates in the 98-108% range were obtained. No influence on the analysis by the matrix load in the sample was observed.
VANCOUVER — The new owners of the Westin Bayshore Hotel will be in for a public fight if they expect to redevelop the site for more than the modest increases already allowed, according to the city's top planner. Brian Jackson, the director of planning, said Friday he couldn't confirm that Concord Pacific Developments had bought the 2.4 hectare (six acre) site, which includes the elegant 510-room hotel and accompanying marina at 1601 Bayshore Drive. But he said any redevelopment is limited to two modest tower sites, and that he had warned all prospective buyers not to think they could fully redevelop the site and remove the hotel and convention centre. Any idea that the entire site could be converted to much higher density or heights, he said, would be met with "a very long and very contentious zoning process." Jackson's comments come as Concord Pacific awaits the legal completion of a real estate deal it signed with the hotel's owners in early July. Concord Pacific won't confirm that it bought the complex, saying it was under a legal obligation not to comment on the proceedings. However, Bob Levine, a founding partner of Avison Young, which represented another interested buyer, confirmed the sale Friday. === VIEW MORE PHOTOS HERE, or if you're using a mobile app, tap the story image and swipe. === Levine said he didn't know the final price but estimated it to be around $290 million. That is far more than what every other potential buyer thought the property was worth, he said, and indicates that Concord Pacific has hopes of developing it in the future. Levine said based on the price Concord reportedly paid, the small amount of remaining development potential "is not what is driving that deal." "No way. None of that makes any sense," he said. "I think what is driving the deal is a wish and a prayer that some time down the road the city will look at a new plan." Levine said there were only a small handful of interested buyers but the price paid surprised them all. "I wouldn't call it close," he said. "The bidders that were in it at the end — and I don't know how many there were, maybe three or four — were all way higher than what any of us thought the property was worth." Jackson said the hotel had been on the market for up to a year, and drew interest from a handful of large development companies, many of whom appeared interested in whether the site could be redeveloped in its entirety. He said the city warned all comers. "We were very clear that the redevelopment potential of that site is one rental tower and one additional hotel tower," Jackson said. "If they purchased it with the expectation that they could do more with it, that was not based on the advice they received from us." Jackson said those inquiring also wanted to know whether heights and densities on the site could be increased and he warned them the city would oppose such ideas. "Other developers came and spoke to us about whether it would be possible for complete redevelopment of the hotel . . . whether it was possible to redevelop the entire site and eliminate the hotel. We were very clear that it would not be our advice to recommend that," he said. "They also talked to us about increasing height and density and we were very clear that we did not see any major redevelopment opportunity beyond what I've already mentioned. If anybody has any plan for redeveloping the site in a significant way going above and beyond what the existing zoning contemplates, it will be a very long and very contentious zoning process." When the city rezoned the adjacent land for Bayshore Gardens development, a forest of 10 towers, it also allowed room for two modest buildings on the hotel site, an 18-storey hotel tower on the existing hotel's front courtyard and a 16-storey residential tower on the southwest corner behind the convention facilities. Those sites have yet to be developed and have some restrictions on them. Ultimately, the city wants to make sure the hotel and convention services remain in the same size they now are, Jackson said. Peter Webb, the senior vice-president of development for Concord Pacific, said in an email July 24 that he couldn't confirm the purchase. "We were one of the original bidders for the site. We are under a legal obligation not to comment on these proceedings," he said. The hotel sits at the entrance to Stanley Park and has long been a premier destination for the demi-royalty, from the International Olympic Committee during the Vancouver 2010 Winter Olympics to FIFA executives during the recent World Women's Cup. The original nine-storey main wing of the hotel also has some heritage potential. "The hotel was reviewed as part of the recent landmarks study. The original section, completed in 1960, was identified as a candidate to be listed on the heritage register in the 'B' category. So we would ask any applicant to prepare a statement of significance about its heritage value," Jackson said. The hotel became a centre of attention in March 1972, when reclusive U.S. billionaire Howard Hughes, who was on the run from U.S. tax authorities, phoned up the management and demanded the top four floors of the 20-storey tower on the property's northwest corner. When the hotel resisted, saying many of the rooms were rented, he threatened to buy the hotel outright. Management complied, and for the next four months Hughes made the penthouse his home. His staff occupied the other three floors. The hotel was refurbished in 2000 for $51 million. It last traded hands in 2013 when Starwood Capital and investors from the Middle East bought it as part of a $765 million deal involving five Westin hotels, including hotels in Ottawa, Toronto, Calgary and Edmonton. The Westin Bayshore was valued in the deal at $150 million, or $295,000 per room, according to a 2014 report by Colliers International Hotels. When it was last sold in 2005, it was valued at $120 million. jefflee@vancouversun.com Twitter.com/sunciviclee With a file from Matthew Robinson === Click here to report a typo or visit vancouversun.com/typo. Is there more to this story? We'd like to hear from you about this or any other stories you think we should know about. CLICK HERE or go to vancouversun.com/moretothestory === VIEW MORE PHOTOS HERE, or if you're using a mobile app, tap the story image and swipe. ===
Q: Создание обязательной с обеих сторон связи в mySQL Создаю внешний ключ, строю диаграмму при помощи Reverse Engineer в mySQL workbench, на диаграмме связь обозначается как необязательная. Как создать обязательную связь? Таблица-предок: CREATE TABLE `discipline` ( `short_disc_name` varchar(50) CHARACTER SET utf8 NOT NULL, `full_name` varchar(150) CHARACTER SET utf8 DEFAULT NULL, PRIMARY KEY (`short_disc_name`) ) ENGINE=InnoDB DEFAULT CHARSET=utf8 COLLATE=utf8_unicode_ci; Таблица с внешним ключом: CREATE TABLE `teacher` ( `full_name` varchar(100) CHARACTER SET utf8 NOT NULL, `post` varchar(100) CHARACTER SET utf8 DEFAULT NULL, `qualification` varchar(100) CHARACTER SET utf8 DEFAULT NULL, `autohrity` tinyint(1) DEFAULT NULL, `discipline` varchar(50) CHARACTER SET utf8 NOT NULL, PRIMARY KEY (`full_name`), KEY `discipline` (`discipline`), CONSTRAINT `teacher_ibfk_1` FOREIGN KEY (`discipline`) REFERENCES `discipline` (`short_disc_name`) ON DELETE CASCADE ON UPDATE CASCADE) ENGINE=InnoDB DEFAULT CHARSET=utf8 COLLATE=utf8_unicode_ci; Вот какая получается связь: A: Можно долго бегать за следствиями неверного предположения, хе-хе. У вас всё правильно: есть внешний ключ и ограничение на не-NULL. Отсутствие связи исключено. Ах да, пунктир. Пунктир не про необязательность. Он указывает на то, что связь не идентифицирующая. И здесь это именно так: внешний ключ этой связи не является частью первичного ключа таблицы. В данном случае связь была бы идентифицирующей, если бы первичный ключ teachers содержал discipline. Не уверен, что это хорошая идея для вашего случая, потому что для формально точной идентификации учителя в базе потребуется не только его имя, но и дисциплина. Немного странно. У вас учитель может преподавать несколько дисциплин? Хм... Решайте. Можете это проверить, нарисовав такую связь в редакторе и посмотрев на изменения.
Q: set curect address to <form action="> i create simple plugin wordpress , one validationform.php and rflinsertdb.php when user click on submit form , i want got rflinsertdb.php the page validation and insert information to db , but wordpress give me Object not found! The requested URL was not found on this server. The link on the referring page seems to be wrong or outdated. Please inform the author of that page about the error. this 2 php page in one folder that name in public ,i see to many codes in internet but not help, how can i do that ? thx alot i try this codes for action form <form method="post" action="<?php bloginfo('template_url'); ?>/rflInsertdb.php"> <p id="errorMessage"></p> <p>name: <input type="text" class="register" name="name" id="name"></p> <p>family: <input type="text" class="registerForm" id="family" name="family"></p> <p>numbers :<input type="number" class="registerForm" id="numbers" name="numbers" min="1" max="200" value="1"></p> <p>tell: <input type="text" class="registerForm" id="tell" name="tell"></p> <p><input type="submit" value="ثبت" class="registerForm" id="submit" name="submit"></p> </form> A: This happens to you, because you are using template directory for: /rflInsertdb.php Try to use <form method="post" action="<?php echo plugin_dir_url( __FILE__ ); ?>/rflInsertdb.php"> If your file is under the public (what is under the plugin dir), then maybe: <form method="post" action="<?php echo plugin_dir_url( __FILE__ ); ?>/public/rflInsertdb.php"> See here: https://codex.wordpress.org/Function_Reference/plugin_dir_url
By Pam Martens and Russ Martens: September 20, 2018 ~ Michael Bloomberg served three terms as New York City’s Mayor from January 2002 to January 2014. In 2009, the New York Times reported that Bloomberg had spent “$261 million of his own money” in order to get elected to those three terms as Mayor. When Bloomberg took office, there was a two-term limit in place which had been voted on in public referendums in 1993 and 1996. But two years before Bloomberg’s second four-year term ended, he asked the City Council to repeal the two-term limit to allow him to serve a third term. Because voters had already expressed their will in a public referendum twice, numerous members of the City Council felt it would be unethical for them to repeal that decision and that the matter should be determined by another voter referendum. But the City Council went forward … Continue reading →
Q: How to add span class caret inside anchor in cakephp I have a dropdown navigation bar , built in bootstrap 3. The anchor tag in plain HTML is : <a href="#" class="dropdown-toggle" data-toggle="dropdown" data-hover="dropdown" data-delay="1000"> Destinations <span class="caret"></span> </a> In cakephp, I have written as : <?php echo $this->Html->link( 'Destinations', '#', array( 'class' => 'dropdown-toggle', 'data-delay' => '1000', 'data-hover' => 'dropdown' ) ); ?> I want to know where should I add the <span class="caret"></span> to the above so that the caret appears near the link ? NB: I am using CakePHP 2.6.1 A: I have found a solution, as below: <?php echo $this->Html->link('Destinations<span class="caret"></span>','#',array('class' => 'dropdown-toggle', 'data-delay' => '1000', 'data-hover' => 'dropdown', 'escape' => false)); ?> NB : don't forget to use 'escape' => false to the array
// Check that the explain result count does proper deduping. t = db.jstests_explain5; t.drop(); t.ensureIndex( {a:1} ); t.ensureIndex( {b:1} ); t.save( {a:[1,2,3],b:[4,5,6]} ); for( i = 0; i < 10; ++i ) { t.save( {} ); } // Check with a single in order plan. explain = t.find( {a:{$gt:0}} ).explain( true ); assert.eq( 1, explain.n ); assert.eq( 1, explain.allPlans[ 0 ].n ); // Check with a single out of order plan. explain = t.find( {a:{$gt:0}} ).sort( {z:1} ).hint( {a:1} ).explain( true ); assert.eq( 1, explain.n ); assert.eq( 1, explain.allPlans[ 0 ].n ); // Check with multiple plans. explain = t.find( {a:{$gt:0},b:{$gt:0}} ).explain( true ); assert.eq( 1, explain.n ); assert.eq( 1, explain.allPlans[ 0 ].n ); assert.eq( 1, explain.allPlans[ 1 ].n ); explain = t.find( {$or:[{a:{$gt:0},b:{$gt:0}},{a:{$gt:-1},b:{$gt:-1}}]} ).explain( true ); assert.eq( 1, explain.n ); assert.eq( 1, explain.clauses[ 0 ].n ); assert.eq( 1, explain.clauses[ 0 ].allPlans[ 0 ].n ); assert.eq( 1, explain.clauses[ 0 ].allPlans[ 1 ].n ); assert.eq( 0, explain.clauses[ 1 ].n ); assert.eq( 0, explain.clauses[ 1 ].allPlans[ 0 ].n ); assert.eq( 0, explain.clauses[ 1 ].allPlans[ 1 ].n );
<?xml version="1.0" encoding="UTF-8"?> <!DOCTYPE plist PUBLIC "-//Apple//DTD PLIST 1.0//EN" "http://www.apple.com/DTDs/PropertyList-1.0.dtd"> <plist version="1.0"> <dict> <key>BuildMachineOSBuild</key> <string>18F132</string> <key>CFBundleDevelopmentRegion</key> <string>en</string> <key>CFBundleExecutable</key> <string>Sourcery</string> <key>CFBundleIdentifier</key> <string>Pixle.Sourcery</string> <key>CFBundleInfoDictionaryVersion</key> <string>6.0</string> <key>CFBundleName</key> <string>Sourcery</string> <key>CFBundlePackageType</key> <string>APPL</string> <key>CFBundleShortVersionString</key> <string>0.17.0</string> <key>CFBundleSignature</key> <string>????</string> <key>CFBundleSupportedPlatforms</key> <array> <string>MacOSX</string> </array> <key>CFBundleVersion</key> <string>1</string> <key>DTCompiler</key> <string>com.apple.compilers.llvm.clang.1_0</string> <key>DTPlatformBuild</key> <string>10G8</string> <key>DTPlatformVersion</key> <string>GM</string> <key>DTSDKBuild</key> <string>18G74</string> <key>DTSDKName</key> <string>macosx10.14</string> <key>DTXcode</key> <string>1030</string> <key>DTXcodeBuild</key> <string>10G8</string> <key>LSMinimumSystemVersion</key> <string>10.11</string> <key>NSHumanReadableCopyright</key> <string>Copyright © 2016 Pixle. All rights reserved.</string> <key>NSMainNibFile</key> <string>MainMenu</string> <key>NSPrincipalClass</key> <string>NSApplication</string> </dict> </plist>
Transjugular kidney biopsy. Most previous studies demonstrating the feasibility of transjugular kidney biopsy have used a modified Colapinto aspiration biopsy needle. We present 25 high-risk patients, with contraindications to percutaneous renal biopsy, who underwent transjugular kidney biopsy using a transvenous side-cut needle. This technique is easier to learn and can be performed by an interventional radiologist with transjugular liver biopsy experience and equipment. The needle is designed for optimal cortical sampling but has a high incidence of capsular perforation. Elective coil embolization was used in selected patients to reduce the risk of bleeding. We retrospectively reviewed the indications for obtaining renal histology, based on clinical presentation, and the specific indications for transjugular biopsy. Transjugular kidney biopsy was assessed for sampling effectiveness and adequacy, the impact of histology on patient management, and technique complication rates. Renal tissue was obtained in 23 cases, with diagnostic biopsies in 21 of 23 (91.3%). A mean of 3.5 cores were obtained with 9.9 glomeruli per procedure for light microscopy (range, 0 to 32), 2.2 (range, 1 to 7) for electron microscopy, and adequate tissue for immunoflorescence available in 11 of 23 biopsies. Histology influenced patient management in all 23 cases. Capsular perforation was recorded in 73.9% (17 of 23) of cases with 6 undergoing elective coil embolization. Two major complications occurred, both in patients with multiple risk factors for bleeding. One required coil embolization of an arterio-calyseal system fistula. A further patient developed renal vein thrombosis 6 days after a failed transjugular kidney biopsy. Transjugular kidney biopsy provides a histological diagnosis in high-risk patients, making an important contribution to patient management.
RS MEMBER DIARY Rule of Law a Dead Letter in U.S.? [Additional author's comments for Red State: It will be interesting to see what happens with the pending Chrysler bankruptcy and pending sale to Fiat. I was watching Glenn Beck tonight and Judge Napolitano seems to think that the Supreme Court will uphold the Constitution and Rule of Law and send the whole Chrysler bankruptcy back to square one. I hope he is correct. Undoubtedly, some have cheered the Obama administration's actions, but it would be wise to consider what unintended political, economic and Constitutional consequences will arise from government meddling in contracts.] The Rule of Law may not be a dead letter in the United States, but it is definitely on life support. The Obama administration’s Unconstitutional manipulation of the Chrysler bankruptcy to reward its political allies, not only poses a threat to the rule of law and Constitutional order, it also creates a dangerous precedent of government voiding legal contracts. A secondary effect of government’s Unconstitutional meddling in contracts is lack of certainty that some or any future contracts will be honored. This will have a chilling effect on any organization that seeks to raise money through the issuance of bonds – whether business, state or local. Todd J. Zywicki, in a Wall Street Journal article titled “Chrysler and the Rule of Law: The Founders put the contracts clause in the Constitution for a reason” writes: The rule of law, not of men — an ideal tracing back to the ancient Greeks and well-known to our Founding Fathers — is the animating principle of the American experiment. While the rest of the world in 1787 was governed by the whims of kings and dukes, the U.S. Constitution was established to circumscribe arbitrary government power. It would do so by establishing clear rules, equally applied to the powerful and the weak. Fleecing lenders to pay off politically powerful interests, or governmental threats to reputation and business from a failure to toe a political line? We might expect this behavior from a Hugo Chávez. But it would never happen here, right? Until Chrysler. Unfortunately, we are governed by so-called leaders, who do not respect the Constitutional principles put forward by our Founding Fathers. Instead our elected officials use a series of crises to dismantle the protections so carefully assembled by the Founders. While it may be easy for favored groups, such as the unions, to cheer on the current administration, they – and their supporters – ought to be careful. Today’s insider can become tomorrow’s outsider. It is not a far stretch to imagine a future where government interferes with contracts to reward a favored interest at your expense. Would Obama’s supporters favor government expropriation of land to drill for oil? Take this a step further. Imagine a landowner selling the land to a nature conservancy and then having the contract invalidated by presidential decree. It may sound absurd, but in reality that is that path we are heading down. The close relationship between the rule of law and the enforceability of contracts, especially credit contracts, was well understood by the Framers of the U.S. Constitution. A primary reason they wanted it was the desire to escape the economic chaos spawned by debtor-friendly state laws during the period of the Articles of Confederation. Hence the Contracts Clause of Article V of the Constitution, which prohibited states from interfering with the obligation to pay debts. Hence also the Bankruptcy Clause of Article I, Section 8, which delegated to the federal government the sole authority to enact “uniform laws on the subject of bankruptcies.” The Obama administration’s behavior in the Chrysler bankruptcy is a profound challenge to the rule of law. Secured creditors — entitled to first priority payment under the “absolute priority rule” — have been browbeaten by an American president into accepting only 30 cents on the dollar of their claims. Meanwhile, the United Auto Workers union, holding junior creditor claims, will get about 50 cents on the dollar. The absolute priority rule is a linchpin of bankruptcy law. By preserving the substantive property and contract rights of creditors, it ensures that bankruptcy is used primarily as a procedural mechanism for the efficient resolution of financial distress. Chapter 11 promotes economic efficiency by reorganizing viable but financially distressed firms, i.e., firms that are worth more alive than dead. It is easy to dislike creditors. Many of us have owed money to a creditor we felt was predatory or unfair. However, imagine the shoe on the other foot. Suppose you had invested or loaned a business or individual a significant sum of money. The business goes bankrupt and you hope to collect on the debt. It is your money and it is your right to collect on the debt ahead of junior creditors. However, at the last moment the government intervenes and gives you only 25 cents on the dollar of what you are owed. Meanwhile, you learn, a junior creditor, with less priority than you has received 40 cents on the dollar. They are well connected politically and it appears they are being rewarded for supporting the right politicians. Violating absolute priority undermines this commitment by introducing questions of redistribution into the process. It enables the rights of senior creditors to be plundered in order to benefit the rights of junior creditors. The U.S. government also wants to rush through what amounts to a sham sale of all of Chrysler’s assets to Fiat. While speedy bankruptcy sales are not unheard of, they are usually reserved for situations involving a wasting or perishable asset (think of a truck of oranges) where delay might be fatal to the asset’s, or in this case the company’s, value. That’s hardly the case with Chrysler. But in a Chapter 11 reorganization, creditors have the right to vote to approve or reject the plan. The Obama administration’s asset-sale plan implements a de facto reorganization but denies to creditors the opportunity to vote on it. By stepping over the bright line between the rule of law and the arbitrary behavior of men, President Obama may have created a thousand new failing businesses. That is, businesses that might have received financing before but that now will not, since lenders face the potential of future government confiscation. In other words, Mr. Obama may have helped save the jobs of thousands of union workers whose dues, in part, engineered his election. But what about the untold number of job losses in the future caused by trampling the sanctity of contracts today? The actions of the Obama administration with regards to Chrysler are extremely short-sighted, or worse. They undermine the rule of law and the Constitution. They rewrite the law and Constitution as if by decree. Furthermore, they undermine the economic order by creating uncertainty and unnecessary political risk. The Obama administration’s Unconstitutional actions will almost certainly lead to capital flight from corporate bonds, state bonds, municipal bonds or other financial instruments where the acceptance of government funds may lead to government meddling. The value of the rule of law is not merely a matter of economic efficiency. It also provides a bulwark against arbitrary governmental action taken at the behest of politically influential interests at the expense of the politically unpopular. The government’s threats and bare-knuckle tactics set an ominous precedent for the treatment of those considered insufficiently responsive to its desires. Certainly, holdout Chrysler creditors report that they felt little confidence that the White House would stop at informal strong-arming. Chrysler — or more accurately, its unionized workers — may be helped in the short run. But we need to ask how eager lenders will be to offer new credit to General Motors knowing that the value of their investment could be diminished or destroyed by government to enrich a politically favored union. We also need to ask how eager hedge funds will be to participate in the government’s Public-Private Investment Program to purchase banks’ troubled assets. And what if the next time it is a politically unpopular business — such as a pharmaceutical company — that’s on the brink? Might the government force it to surrender a patent to get the White House’s agreement to get financing for the bankruptcy plan? When we allow the government to break the law and undermine the Constitution we undermine our own freedom and liberty. While some might be cheering the administration’s current actions to reward the unions the precedent is a terrible one. What is to keep a future president from invalidating a union contract to help a favored industry or interest? The rule of law and Constitution is there for a reason – to provide equal justice under law. If you depend on this president, or the next, or the next, you likely won’t like the result – and you shouldn’t have to. We don’t live in a kingdom. We live in a Constitutional Republic guided by the law and the Constitution, rather than whims or decrees…at least for now.
[A case of giant gastric villous tumor with carcinomatous change]. Villous tumors of the stomach are somewhat rare with approximately 100 cases only reported in the literatures and have tendency to undergo malignant transformation as high as 72%. They are frequently multiple and associated with other gastrointestinal neoplasm. Thirty percent of them are associated with an independent gastric carcinoma. Gastric villous tumor has certain radiologic characteristics that may permit a preoperative diagnosis and also some distinctive clinicopathologic features which make early diagnosis and proper treatment possible. We experienced a 64-year-old man who complained of prolonged general weakness, weight loss for several months and left upper quadrant pain for four days. Esophagogastroduodenoscopy and barium study of upper gastrointestinal tract demonstrated typical, irregular, frond-like surfaced villous tumor occupying nearly whole gastric lumen and located eccentrically along the lesser curvature side. Endoscopic biopsy of the tumor revealed a gastric villous tumor with carcinomatous change.
Download speed up to 280 MB per second. Upload speed up to 317 MB per second. Each one of the setup can provide speed up to one GB per second. The range of each setup is around 150 feet from the kiosk. These are staggering numbers, aren’t they! Remember the public Wi-Fi system in New York? Well, on January 21, 2016, LinkNYC, a one-of-its-kind communication network, launched a comprehensive public Wi-Fi system to facilitate internet users. Currently, there are 150 Wi-Fi kiosks in the New York City. It has been nearly two months since the project launched. The residents of New York City have experienced breathtakingly fast speed during this time period. The unprecedented hike in speeds of Wi-Fi networks has become a cause of concern for the New York Civil Liberties Union (NYCLU), about the so called privacy and security of the users’ data. In a letter, addressed to New York Mayor, Mayor Bill de Blasio, the NYCLU has raised concern against the CityBridge- the company that manages Link NYC’s Wi-Fi kiosks – that people, who tend to use the kiosks, are entitled to provide their personal data at the time of registration. This allows, CityBridge to collect massive amount of data. The data includes information about frequently visited websites, time duration of the session, and the number of links available to click to an individual user. The company calls the collection a ‘massive database”. Meanwhile, Donna Lieberman, executive director of the NYCLU holds the point of view that private online activities of people, living in New York City, should not be collected to create a database that is under the grasp of New York Police Department (NYPD). “New Yorkers’ private online activities shouldn’t be used to create a massive database that’s within the ready grasp of the NYPD,” said Donna Lieberman, executive director of the NYCLU. “Free public Wi-Fi can be an invaluable resource for this city, but New Yorkers need to know there are too many strings attached.” This practice will only give an open chance of breach of online privacy and security, paving the way for an unnecessary NYPD surveillance. Although free Wi-Fi network facility should taken in a positive perspective, but New Yorkers must realize and understand that there are other things. attached to the system as well. The NYCLU has also shown concerns about the privacy policy of CityBridge. The Union wants the organization to clarify its instance on an individual internet users privacy and security. According to NYCLU, the privacy policy of CityBridge promises to make ‘reasonable efforts’ to clear out any identifiable personal information for a user, who has been inactive for the past 12 month”. A senior staff attorney at NYCLU, Mariko Hirose is also concerned about the security and privacy of New York City residents. It is a fact that internet is not a choice anymore. It has become a modern-day necessity of life. “The city’s public Wi-Fi network should set the bar for privacy and security to help ensure that New Yorkers do not have to sacrifice their rights and freedoms to sign online,” he says. Meanwhile, LinkNYC has dismissed all the concerns shown by NYCLU in connection with any illegal use of user information. “The company has a customer-first privacy policy. LinkNYC does not collect or store any data on users’ personal web browsing on their own devices”, says Jen Hensley, general manager of LinkNYC. As far as access to kiosk information by NYPD or any other law enforcement agencies is concerned, they are required to present CityBridge with subpoena and other similar legal requests. Well, nothing is good enough. How the stakeholders of the public Wi-Fi system are going to address the privacy and security issue of the internet users. Only time will tell. Let’s wait and watch.
1. Preliminary Recalls about the Predominant Clonal Evolution (PCE) Model {#sec1-pathogens-09-00356} ========================================================================= The predominant clonal evolution (PCE) pattern does not mean that genetic recombination is either absent, or of little evolutionary significance \[[@B1-pathogens-09-00356]\], but rather, that it is not effective enough to erase a persistent and highly detectable phylogenetic signal at all evolutionary scales. The definition of clonality in PCE is therefore based on severe restriction to genetic recombination, a definition that is shared by many authors working on pathogen population genetics (see many references in \[[@B2-pathogens-09-00356]\]). The criteria selected for stating that the phylogenetic signal is reliable are the classic, widely accepted, means used in the articles analyzed by us in the present study---(i) mutual corroboration by different markers (see Table 1 in \[[@B3-pathogens-09-00356]\]); (ii) posterior probabilities when Bayesian analysis is concerned; (iii) bootstrap, with the limit value of 0.70 considered as significant \[[@B4-pathogens-09-00356]\]. PCE is therefore not rejected by the sole detection of genetic exchange, hybridization and meiosis \[[@B5-pathogens-09-00356],[@B6-pathogens-09-00356]\]. As recalled many times \[[@B7-pathogens-09-00356]\], the PCE model is compatible with such traits. Which makes it possible to definitely and specifically challenge the PCE hypothesis is the absence of a stable phylogenetic signal at any evolutionary scale and a population structure that meets panmictic expectations, particularly lack of a statistically significant linkage disequilibrium (nonrandom association of genotypes occurring at different loci) \[[@B7-pathogens-09-00356]\]. We have coined the term "near-clades" \[[@B8-pathogens-09-00356]\] to designate, within pathogen species, genetic subdivisions that are discrete and stable, but that could be somewhat clouded by occasional genetic exchange. As a matter of fact, "true" clades are supposed to be strictly separated from each other. Now in virtually all pathogen species, even if PCE obtains, as noted above, occasional bouts of genetic exchange are recorded. The term "clade" therefore is not adequate. 2. Trypanosoma cruzi and the PCE Model {#sec2-pathogens-09-00356} ======================================== Trypanosoma cruzi is the parasite responsible for Chagas disease in the New World. It has been the object of early, pioneering studies dealing with its isoenzyme variability, making it possible to characterize its strains \[[@B9-pathogens-09-00356]\]. The interpretation of this isoenzyme diversity in population genetic terms has made it possible to propose that this parasite has a predominantly clonal population structure \[[@B10-pathogens-09-00356]\]. The evidence for it is as follows---at the level of the whole species, several multilocus genotypes occur at frequencies that are at variance with panmictic expectations, and are widely distributed in various ecosystems and hosts. A highly significant linkage disequilibrium is recorded \[[@B10-pathogens-09-00356]\]. The species is subdivided into at least six main "discrete typing units" or DTUs \[[@B11-pathogens-09-00356],[@B12-pathogens-09-00356]\], namely Tc I to VI. Evolutionary speaking, these DTUs amount to near-clades \[[@B8-pathogens-09-00356]\]. More recently, an additional discrete typing unit/near clade has been described under the name of TcBat. It has been isolated exclusively from bats and is widespread over vast geographical areas and time spans \[[@B12-pathogens-09-00356]\]. The available data do not make it possible to test our PCE model within TcBat. 3. T. cruzi PCE Challengers {#sec3-pathogens-09-00356} ============================= Obstacles to genetic recombination and the presence of a ubiquitous, stable, phylogenetic signal at the level of the whole T. cruzi species is no longer under debate. However, the PCE model in T. cruzi has been challenged with two lines of arguments, namely---(i) it is based on outdated markers that lack resolution \[[@B13-pathogens-09-00356]\]. This is not a valid argument---markers that lack resolution should favor the null hypothesis of panmixia (random genetic exchange) through a mechanism of statistical type II error (impossibility to reject the null hypothesis, not because this null hypothesis is true, but because of a lack of resolution of the used means to test it) rather than the working hypothesis of clonality ([Figure 1](#pathogens-09-00356-f001){ref-type="fig"}). (ii) The presence of genetic subdivisions (="near-clades") within T. cruzi would be "self-evident", which amounts to saying that the outcome of any population genetics and phylogenetic analysis is self-evident. Evidencing obstacles to recombination at the level of the whole species is therefore trivial and vain \[[@B14-pathogens-09-00356]\]. However, high-resolution genomic typing will show that similar patterns of obstacles to genetic exchange are not recorded at lower evolutionary scales, under the level of the near-clades \[[@B14-pathogens-09-00356]\]. This last argument aims at specifically challenging the "Russian doll model" \[[@B15-pathogens-09-00356]\], which states that PCE is verified at all evolutionary scales, and within-near-clade population structure is a miniature form of the population structure of the whole species ([Figure 2](#pathogens-09-00356-f002){ref-type="fig"}). At this microevolutionary level, within each of the main genetic clusters (near-clades) that subdivide the species, two evolutionary models would imply that the Russian doll pattern is not verified. They both deal with lack of restriction to genetic recombination:(a)Biological speciation---each of the near-clades correspond to cryptic species that are genetically isolated from each other, but within which genetic exchange is random, except for physical obstacles (time and/or space) to this random gene flow (see [Figure 3](#pathogens-09-00356-f003){ref-type="fig"}). This hypothesis of speciation has been invoked to claim that the main subdivisions (Savannah, Killifi, Forest) within Trypanosoma congolense are not evidence for PCE, because they could correspond to cryptic "species". However, the authors did not clearly refer to a model of biological speciation \[[@B17-pathogens-09-00356]\]; and 1. Progressive clonality---this situation refers to the case where the amount of genetic exchange is inversely proportional to the evolutionary distance between any two given genotypes \[[@B16-pathogens-09-00356]\]. If the genotypes are either identical or very similar, genetic exchange is abundant (homogamy, selfing). If they are distantly related, genetic exchange is either severely limited or lacking ([Figure 4](#pathogens-09-00356-f004){ref-type="fig"}). Such an evolutionary model is believed to be frequent in bacteria \[[@B19-pathogens-09-00356]\]. It is clear that, first, (a) and (b) mean that genetic recombination is not limited or is poorly limited at microevolutionary scales (under the level of the near-clade); second, the means to distinguish the Russian doll model from either (a) or (b) is to give evidence for the presence of PCE traits (linkage disequilibrium and, most of all, constant phylogenetic signal---see [Figure 2](#pathogens-09-00356-f002){ref-type="fig"}) within each of the near-clades that subdivide the species under study. However, this demands the use of genetic markers with a sufficient resolution. If this is not the case, lack of resolution of the markers could lead to a wrong hypothesis of panmixia due to a statistical type II error (see [Figure 1](#pathogens-09-00356-f001){ref-type="fig"}). 4. New Analyses with High-Resolution Typing Challenge the Challengers {#sec4-pathogens-09-00356} ===================================================================== Our previous articles did already include the analysis of studies based on high-resolution markers and genomics data. However, to address the criticisms that (i) our model is based on outdated markers that lack resolution \[[@B13-pathogens-09-00356]\]; (ii) our model will not be verified at lower evolutionary scales \[[@B14-pathogens-09-00356]\], we have reconsidered the problem of PCE in T. cruzi in the light of numerous new published articles. This makes it possible to reliably test the Russian doll model within T. cruzi near-clades, and to illustrate some important aspects of the PCE model that are frequently misunderstood. A wealth of studies show that within the near-clade TcI, in various countries, Russian doll patterns with a highly detectable phylogenetic signal are present. This is against the hypotheses of biological speciation ([Figure 3](#pathogens-09-00356-f003){ref-type="fig"}) and progressive clonality ([Figure 4](#pathogens-09-00356-f004){ref-type="fig"}). In the Atlantic forest region of Brazil, the analysis of 107 wild strains, all identified as TcI and isolated from Didelphis sp., were analyzed with 27 microsatellite loci (hence coded by nuclear genes), while a subset of this sample was analyzed with 10 maxicircle loci (that are equivalent to mitochondrial genes) \[[@B20-pathogens-09-00356]\]. The double tree obtained ([Figure 5](#pathogens-09-00356-f005){ref-type="fig"}) shows that this TcI sample is strongly subdivided into various lesser near-clades, with several significant bootstrap values. Some discrepancies are recorded between the two trees, which can be explained by either occasional introgression \[[@B20-pathogens-09-00356]\] or different evolutionary patterns, or both. The main fact is that this TcI sample exhibits a highly detectable phylogenetic signal, with a clear Russian doll pattern. In Brazil, 78 TcI strains isolated from various hosts, including Didelphis sp., primates, rodents, bats, triatomine bugs, collected over five ecologically diverse biomes, were analyzed with the sequencing of six housekeeping nuclear genes (Multilocus Sequence Typing or MLST), 25 microsatellite loci and one maxicircle gene (COII), thus combining slow- and fast-evolving markers \[[@B21-pathogens-09-00356]\]. The phylogenies based on individual housekeeping genes exhibit moderate levels of incongruence. However, the concatenated tree shows a clear structuration into several lesser near-clades, many of them being supported by significant bootstrap values ([Figure 6](#pathogens-09-00356-f006){ref-type="fig"}). This clustering can be explained by neither geographical repartition nor host specificity. In Venezuela, 246 TcI human strains, some of them being isolated after an outbreak of oral transmission, were typed with 23 microsatellite loci \[[@B22-pathogens-09-00356]\]. The tree obtained ([Figure 7](#pathogens-09-00356-f007){ref-type="fig"}) again shows the presence of various lesser near-clades with several significant bootstrap values. In Bolivia, 199 clones isolated from 68 sylvatic TcI strains from both the lowlands and the highlands of the country were typed with 26 microsatellite loci and 10 maxicircle (=mitochondrial) loci \[[@B23-pathogens-09-00356]\]. The microsatellite and maxicircle phylogenies show some discrepancies, which the authors explain by introgression events. However, they broadly agree, which shows that these two very different parts of the genome do not evolve independently (linkage disequilibrium). When microsatellite diversity is considered, high levels of linkage disequilibrium are recorded, including within each subpopulation of the sample. The microsatellite phylogeny shows strong clustering patterns (lesser near-clades) that are not explained by either host specificity or geographical separation ([Figure 8](#pathogens-09-00356-f008){ref-type="fig"}). In Ecuador, a population genomics survey has revealed within the near clade TcI two distinct genetic clusters (=lesser near-clades) \[[@B6-pathogens-09-00356]\]. One shows clear indications of meiosis, whereas the other one does not. However, as already exposed, the isolated observation of meiosis is not in itself sufficient to conclude a panmictic pattern and to challenge the PCE model. As a matter of fact, in \[[@B6-pathogens-09-00356]\], (i) the evidence of two distinct clusters (=near-clades) within the near-clade TcI is in itself a Russian doll pattern; (ii) the occurrence of meiosis proves to be an exceptional event (3 meioses/1000 mitoses \[[@B6-pathogens-09-00356]\]); (iii) although the difference in population structure between the two clusters is undisputable, the number of different individuals remains weak---eight individuals, since several samples correspond to laboratory clones of the same isolate. This limited sample size leads to the risk of a statistical type II error with possible erroneous hypothesis of panmixia; (iv) in the first population (Bella Maria locality), even if one considers only the eight isolates that are supposed to exhibit meiosis, in spite of this limited sample size, the phylogenetic signal still is highly detectable---"support is unambiguous for main clusters and high within subclusters, except where last branch lengths are quite short in Cluster 2" (P. Schwabl, personal communication) (see [Figure 9](#pathogens-09-00356-f009){ref-type="fig"}). This is evidence that genetic exchange is not frequent and not effective enough to erase a clear phylogenetic signal. This is the very definition of PCE. This is even more evident when including the whole Bella Maria population, which comprises an isolate that pertains to the second cluster and is phylogenetically quite distinct---see [Figure 9](#pathogens-09-00356-f009){ref-type="fig"}. When other T. cruzi near-clades are considered, within TcII, a phylogenetic signal has been evidenced by genomic data \[[@B24-pathogens-09-00356]\]. The study dealt with a limited number (seven) of TCII strains isolated in Minas Gerais (Brazil) and surveyed for both nuclear and mitochondrial genomes. Phylogenies based on the nuclear and mitochondrial genomes show that the majority of branches are shared by both sequences. This gives evidence for the fact that nuclear and mitochondrial genomes do not evolve independently (linkage disequilibrium). The strength of the results is diminished by the limited number of strains. However, clustering (lesser near-clades) is apparent among these strains ([Figure 10](#pathogens-09-00356-f010){ref-type="fig"}B in \[[@B24-pathogens-09-00356]\]). Lastly, 19 stocks representative of the 6 T. cruzi near-clades (TcI-VI) were analyzed for 335 distinct satellite DNA sequences \[[@B25-pathogens-09-00356]\]. The Bayesian phylogeny shows that each of the six near-clades is strongly divided into many lesser near-clades ([Figure 10](#pathogens-09-00356-f010){ref-type="fig"}A) with highly significant bootstrap values ([Figure 10](#pathogens-09-00356-f010){ref-type="fig"}B). 5. Concluding Remarks {#sec5-pathogens-09-00356} ===================== Genomics and high-resolution typing data show that evolutionary patterns at a microevolutionary level (within near-clades) look like a miniature picture of the evolutionary pattern of the full T. cruzi species. This is especially well ascertained for the near-clade TcI, for which more data are available. However, data from other near-clades are consistent with this Russian doll pattern \[[@B15-pathogens-09-00356]\]. The fact that evolutionary patterns are similar at micro- and macroevolutionary scales suggests that the agent of Chagas disease undergoes progressive, gradual, rather than saltatory, evolution. The indications for meiosis within TcI in Ecuador \[[@B6-pathogens-09-00356]\] undoubtedly constitute a very relevant piece of information about T. cruzi evolution. However, this does not challenge the hypothesis of a Russian doll pattern within TcI and the PCE hypothesis in T. cruzi. As a matter of fact, the existence of occasional bouts of introgression and hybridization at the level of the whole species \[[@B23-pathogens-09-00356],[@B26-pathogens-09-00356],[@B27-pathogens-09-00356]\] does not challenge PCE in T. cruzi, since these occasional events do not break the prevalent PCE pattern (presence of a stable and detectable phylogenetic signal and of near-clades). This maintenance of a detectable phylogenetic signal corroborated by various genetic markers (congruence criterion) corresponds to the "clonality threshold", which is the main trait that specifically gives evidence for PCE \[[@B2-pathogens-09-00356]\]. As a matter of fact, beyond this clonality threshold, genetic exchange and recombination are efficiently countered by PCE, and near-clades diverge in an irreversible way. Quite similarly, occasional meiosis events within TcI \[[@B6-pathogens-09-00356]\] do not challenge PCE at the within near-clade level, since they do not hamper the persistence of a stable and detectable phylogenetic signal and of lesser near-clades within this near-clade, as clearly evidenced by the many cases exposed in this article ([Figure 5](#pathogens-09-00356-f005){ref-type="fig"}, [Figure 6](#pathogens-09-00356-f006){ref-type="fig"}, [Figure 7](#pathogens-09-00356-f007){ref-type="fig"}, [Figure 8](#pathogens-09-00356-f008){ref-type="fig"}, [Figure 9](#pathogens-09-00356-f009){ref-type="fig"} and [Figure 10](#pathogens-09-00356-f010){ref-type="fig"}). These results show that molecular epidemiology (typing of multilocus genotypes and of lesser near-clades) remains possible within each of the six T. cruzi near-clades, since the stability of genotypes is maintained by PCE at this evolutionary level. It remains to be seen whether genetic clustering and lesser near-clades within each of the six T. cruzi near-clades exhibit constant patterns over space and time, in different ecosystems and hosts, and so behave like simili-taxa, a pattern that is observed for example in the yeast Cryptococcus neoformans \[[@B2-pathogens-09-00356]\]. We thank Jenny Telleria (IRD, Montpellier, France) for designing [Figure 2](#pathogens-09-00356-f002){ref-type="fig"}. Conceptualization, M.T. and F.J.A.; methodology, M.T.; formal analysis, M.T.; investigation, M.T.; resources, M.T.; data curation, M.T.; writing---original draft preparation, M.T.; writing---review and editing, F.J.A. All authors have read and agreed to the published version of the manuscript. This research received no external funding. The authors declare no conflict of interest. ![The impact of marker resolution on population genetics and phylogenetic analysis. If a marker with low resolution is used (a), the lesser genetic subdivisions of the species (right part of the figure) will show limited or null genetic variability, which may make it impossible to reject the null hypothesis of panmixia, due to a statistical type II error (after \[[@B16-pathogens-09-00356]\]).](pathogens-09-00356-g001){#pathogens-09-00356-f001} !["Russian doll" model. When population genetic analysis is performed with adequate markers (of sufficient resolution) within each of the near-clades that subdivide the species under study (large tree, left), they reveal a miniature picture of the whole species, with the two main predominant clonal evolution features, namely, linkage disequilibrium and lesser near-clades (small tree, right). This is evidence that within the near-clades, predominant clonal evolution also operates (after \[[@B2-pathogens-09-00356]\]).](pathogens-09-00356-g002){#pathogens-09-00356-f002} ![Cryptic biological speciation: the evolutionary lines that subdivide the species are genetically isolated from each other. However, within each of them, genetic recombination occurs randomly, except when physical obstacles (space and/or time) occur (after \[[@B18-pathogens-09-00356]\]).](pathogens-09-00356-g003){#pathogens-09-00356-f003} !["Progressive clonality". The frequency of genetic exchange is inversely proportional to the evolutionary distance between any two different genotypes. It is virtually random among identical or very closely related genotypes (homogamy, selfing) and is progressively inhibited as genetic distances increase (after \[[@B16-pathogens-09-00356]\]).](pathogens-09-00356-g004){#pathogens-09-00356-f004} ![Double phylogenetic tree based on nuclear genes (left) and mitochondrial genes (right) in a sample of TcI Brazilian strains (after \[[@B20-pathogens-09-00356]\]). The TcI discrete typing unit/near clade, itself a discrete subdivision of the species T. cruzi, is clustered into various lesser near-clades. Several of these lesser near-clades are supported by significant bootstrap values (numbers along the branches); example---top lesser near-clade---bootstrap 96,6.](pathogens-09-00356-g005){#pathogens-09-00356-f005} ![Concatenated Multilocus Sequence Typing (MLST) tree in a sample of TcI Brazilian strains (after \[[@B21-pathogens-09-00356]\]). Similarly to [Figure 5](#pathogens-09-00356-f005){ref-type="fig"}, a different sampling of Brazilian strains of TcI shows various lesser near-clades within this near-clade. Many of them are supported by bootstrap values that are above the limit of 0.70 used in the present paper \[[@B4-pathogens-09-00356]\].](pathogens-09-00356-g006){#pathogens-09-00356-f006} ![Multilocus microsatellite phylogenetic tree of 246 TcI Venezuelan strains. In Venezuela, the TcI near-clade is also subdivided into many lesser near-clades. Black circles indicate nodes with \>60% bootstrap support \[[@B22-pathogens-09-00356]\].](pathogens-09-00356-g007){#pathogens-09-00356-f007} ![A microsatellite phylogenetic tree of sylvatic TcI strains in Bolivia (after \[[@B23-pathogens-09-00356]\]). In Bolivia also, TcI selvatic strains show clustering into many lesser near-clades. Closed grey triangles are adjacent to nodes that receive \>60% bootstrap support. Genetic separation accounts only partly for this clustering pattern.](pathogens-09-00356-g008){#pathogens-09-00356-f008} ![Two lesser near-clades within the TcI near-clade in Ecuador. In spite of clear indications of meiosis in the top cluster, a clear phylogenetic signal is evidenced at the level of the whole sample and within each of the two lesser near-clades (after \[[@B6-pathogens-09-00356]\]). "Support is unambiguous for main clusters and high within subclusters, except where last branch lengths are quite short in Cluster 2" (P. Schwabl, personal communication).](pathogens-09-00356-g009){#pathogens-09-00356-f009} ###### (A) The analysis by 335 independent satellite DNA sequences of 19 T. cruzi strains reveals various lesser near-clades within each of the six T. cruzi near-clades (after \[[@B25-pathogens-09-00356]\]). (B) (Original figure communicated by J.C. Ramírez). The lesser near-clades within each of the six T. cruzi near-clades are supported by highly significant bootstrap values (J.C. Ramírez, personal communication). ![](pathogens-09-00356-g010a) ![](pathogens-09-00356-g010b)
The United States Mint will begin accepting orders for the 2016 Standing Liberty Quarter Centennial Gold Coin (product code 16XC) on September 8 at noon Eastern Time (ET). The Standing Liberty Centennial Gold Coin is the second of three 24-karat gold coins the United States Mint is issuing this year to commemorate the 100th anniversary of three iconic coin designs that were first issued in 1916. Its obverse design depicts Liberty holding a shield and an olive branch as she steps through an opening in a wall bearing 13 stars. Its reverse design depicts an eagle in flight flanked by 13 stars. Additional inscriptions to the originals will include “AU,” “24K,” and “1/4 OZ.” Both the obverse and reverse are by sculptor Hermon A. MacNeil. Pricing for the Standing Liberty Centennial Gold Coin will be based on the United States Mint’s pricing schedule for products containing gold. These products are priced according to the range in which they appear on the United States Mint Gold Coin Pricing Grid. Orders will be accepted at https://www.usmint.gov/catalog/ and at 1-800-USA-MINT (872-6468). Hearing- and speech-impaired customers with TTY equipment may order at 1-888-321-MINT. There is a household order limit of one for this product, while mintage is limited to 100,000 units. Note: To ensure that all members of the public have fair and equal access to United States Mint products, orders placed prior to the official on-sale date and time September 8, 2016, at noon ET, will not be deemed accepted by the United States Mint and will not be honored. About the United States Mint The United States Mint was created by Congress in 1792 and became part of the Department of the Treasury in 1873. It is the Nation’s sole manufacturer of legal tender coinage and is responsible for producing circulating coinage for the Nation to conduct its trade and commerce. The United States Mint also produces numismatic products, including proof, uncirculated, and commemorative coins; Congressional Gold Medals; and silver and gold bullion coins. The United States Mint’s numismatic programs are self-sustaining and operate at no cost to taxpayers. 1) the edition size is 100k (gold dime had 120k edition size). So both are pretty similar. 2) gold dime has an order limit of 10, this only has 1. 3) this quarter will be much more expensive given the size. When you add up all those factors, this coin will not be soldout quickly like the dime. I am surprised how high they made the edition size, it should have been 50k or even 25k, given the limit on 1 per household and priced much higher than the dime.
Fall earnings season brought a barrage of new data on the performance of rooftop solar installers, since all the large national players are publicly traded. For one thing, the national residential solar company is very much alive, contrary to fears of years past that these companies couldn’t survive and arguments that solar is an inherently local business. Sunrun is looking at double-digit percentage growth in deployments compared to last year. Vivint is cranking along. Tesla met the lower bar of proving it can grow deployments quarter-over-quarter instead of declining. And Sunnova, which finances and partners with a network of local installers, launched an initial public offering. Meanwhile, a series of wildfires and wildfire-related grid outages in California, solar’s largest market, made the combination of home solar-plus-batteries look more important than ever. Here are three takeaways from the residential solar horse race at this pivotal moment. Rooftop solar deployments now rival massive utility-scale plants By definition, residential solar is small and utility-scale is very large. But recently, the annual output of the most prolific rooftop solar installers is starting to rival utility-scale plants. Sunrun leads the pack; it is on track to install more than 400 megawatts this year through its in-house crews and installer partners. That puts it on par with, for instance, the 400-megawatt Eland project 8minute Solar Energy is developing for the Los Angeles Department of Water & Power. That project’s scale helped it nab the lowest price for combined solar-storage in the country. But Eland got final approval this fall and will take three to four years to fully complete. Rooftop solar costs more than massive plants in the desert, but it can move much more quickly through the contracting and installation processes. The actions of the biggest installers are validating the argument that small-scale solar can add up to big capacity, a key test as California in January begins implementation of its mandate that all new homes install solar. And Sunrun’s annual installations keep growing, expected to rise about 10 percent this year; the company reported that labor constraints will prevent a higher rate of deployment, but sales track with 15 percent growth year-over-year. The problem, as far as rapid grid decarbonization is concerned, is that there’s only one Sunrun. Runner-up Vivint installed about two-thirds of what Sunrun did last quarter, 65 megawatts. No. 3 installer Tesla did even less, 43 megawatts, and that was a surprise improvement from the previous quarter’s paltry 29 megawatts. It’s clear that national rooftop installers can contribute serious scale. The next question is whether there’s a market for several companies pumping out a decentralized 400-megawatt power plant every year. Will residential leaders eventually dwarf even that level of achievement? Give me a P, give me an S... About 150,000 Californians braced for another round of preemptive power shutoffs Wednesday, as utility Pacific Gas & Electric warned of exceedingly dry and windy conditions in 18 counties. The threat of days without power has become business as usual in particular parts of the state this fall, with PG&E initiating rounds of blackouts to deter wildfires (it’s unclear whether it’s worked; the state is still investigating the cause of Sonoma’s Kincade fire, but the utility reported a malfunction in the area). The situation has created dangerous conditions for vulnerable residents, riled up policymakers and caused a headache for PG&E. But home solar-and-storage companies say they’re seeing the upside. Vivint Solar CEO David Bywater said in November that the shutoffs provided a “reset” in California, offering the company a renewed entrance into a market where lots of early adopters have already gone solar. Residential solar executives including Sunnova’s John Berger and SunPower’s Tom Werner have also noted increased interest coming from customers in the state, though they’ve so far demurred on offering specific figures on any increase in sales. SunPower cited residential storage attach rates averaging 20+ percent in Q3 — fortuitously, it unveiled its in-house residential storage product in September — but said that percentage is higher in California. Sunnova reported Q3 battery attachment rates at 15 percent, up from 11 percent in Q2, citing a “large growth opportunity surrounding storage.” “With the devastation in California caused by wildfires and the resulting blackouts and deliberate power shutdowns across the state, it is clear we are witnessing a critical moment across the energy landscape,” said Berger. “As a result, we are seeing stronger demand for our storage products as customers look for alternatives that provide energy resiliency and reliability in the face of the effects of climate change.” In a particularly stark snapshot of changing customer attitudes, Sunrun CEO Lynn Jurich told GTM that the percentage of Bay Area customers choosing storage alongside solar doubled in October, from 30 percent to 60 percent. That was the month PG&E initiated its biggest power shutoffs so far. Sunrun's rate of storage adoption was 30 percent for California overall in the third quarter. The demand for backup power is also compelling companies to shift their offerings. Vivint, a bit of a laggard in the residential storage space, expanded its financing options in California to include storage in solar power-purchase agreements (more on that below). And in September, Sunnova added a 10-year finance agreement to its existing stable of options, which includes leases and loans. Vivint is behind on storage, but doesn’t seem to care Vivint doesn't seem to be in a hurry when it comes to solar-plus-storage. The No. 2 rooftop solar installer initially staked its storage success on a partnership with Mercedes-Benz Energy back in 2017. What the latter lacked in market-ready products, it made up for with great brand recognition. A year later, the German carmaker gave up on residential storage, and Vivint never followed up with a similarly high-profile replacement (but it did start stocking LG Chem’s Resu battery). That quiet touch is surprising, given that competitors Sunrun and Tesla talk up their energy storage achievements on each quarterly earnings call, and companies like SunPower increasingly frame the solar value proposition as inseparable from storage. Vivint, instead, only sells solar-plus-storage in California and Hawaii, making it easily the most geographically limited of the major rooftop solar companies. And Vivint declined to launch a no-money-down offering in California, the largest market by far, until this month. It’s possible to convince customers to buy batteries outright, but no money down sweetens the deal by lowering upfront sticker price. Leadership launched the service after conducting a survey of several hundred California homeowners in August, in which the company noted increasing interest in the product. That result shouldn’t come as much of a surprise to Vivint — for the last few months, the news has been awash with coverage of California’s fires and Pacific Gas & Electric’s deliberate grid outages. Adding batteries gives solar installers a chance to upsell. In places where time-of-use rates hurt standalone solar returns, it may even be vital to the economics. Given the upside, it’s hard to see the strategic value of trailing the competition on this growing sector of the market. Then again, home storage sales are small enough that Vivint hasn’t missed out on much in terms of revenue. It’s more the opportunity to get the hang of a product that will play an increasingly central role in the industry.
Q: TeamCity how to set JVM Arguments my teamcity build server has following JVM Arguments: -Xmx512m -XX:MaxPermSize=270m sometimes it shows some memory problem message like "TeamCity server memory usage for PS Old Gen pool exceeded 91% of 341 MB maximum available. 437 MB used of 506 MB total heap available. See the TeamCity documentation for possible solutions." i read here https://confluence.jetbrains.com/display/TCD8/Installing+and+Configuring+the+TeamCity+Server#InstallingandConfiguringtheTeamCityServer-SettingUpMemorysettingsforTeamCityServer that the minimum recommended settings are: -Xmx750m -XX:MaxPermSize=270m. how/where do i change this setting? A: I would recommend adding the JVM memory options in the startup script (start.sh) for server based startup using the variable TEAMCITY_SERVER_MEM_OPTS . Please do not set it in the profile of the userid that runs teamcity. This link should be helpful to you. In case you want different memory settings for server and agent(usually that's the case), please be selective in naming the variables so that there is a difference in identifying the JVM options for server and agent startup. As a rule of thumb for teamcity setups, I normally let my teamcity server have 20% more memory than my avg usage to account for any increased load during peak usage periods. A: For the record, Igor's answer is wrong. Not sure why it was upvoted. I cannot comment or down vote because my rep numbers are low. However, internal properties are read after the JVM is started and so the heap settings will not take effect if put there. I was looking into how to do this for a TeamCity container. Best option seems to be to use environment variables (TEAMCITY_SERVER_MEM_OPTS). For a container, those can be set by passing -e TEAMCITY_SERVER_MEM_OPTS='...' when creating the container.
"When I became a man I put away childish things, including the fear of childishness and the desire to be very grown up.” – C.S. Lewis Bakunin Tactica (Infinity the Game)coming eventually I’ve been playing Infinity pretty regularly since January 2016. I am by no means an expert, but I do try to get in a game a week. I’ve also played in a handful of tournaments. These are my thoughts. There are plenty of people more knowledgeable than me. However, Nomad focused articles are few and far between from what I’ve seen. I figured I might as well share what I think. I will do articles on the main page in sections while the complete Bakunin tatica is a work in progress here.
Q: Write formula for matrix in terms of Fibonacci numbers How could I express this matrix in terms of Fibonacci numbers? It seems like I'd have to use induction once I have a candidate for a formula but I'm unsure of where to start with expressing the matrix in terms of Fibonacci numbers. Thanks in advance! Let $T:\mathbb{R^2}\rightarrow \mathbb{R^2}$ be a linear map such that $$T\left( \begin{array}{c} x\\ y\\ \end{array} \right)=\left( \begin{array}{c} y\\ x+ y\\ \end{array} \right)$$ using the basis $\beta=\{e_1,e_2\}$ $$e_1=\left( \begin{array}{c} 1\\ 0\\ \end{array} \right),\quad e_2=\left( \begin{array}{c} 0\\ 1\\ \end{array} \right)$$ Write a formula for the matrix$$ [T^n]_\beta, \forall n\in\mathbb{N}$$ in terms of Fibonacci numbers. A: Let us try to do it for $n = 1$. In that case, $T(e_1) = e_2$ and $T(e_2) = e_1 + e_2$, so this gives the matrix $\begin{pmatrix}0 \quad 1 \\ 1 \quad 1\end{pmatrix}$ for $T$. If we have to find $T^n$ now, the first thing that we do is to find some elementary powers of $T$. Let's try to find $T^2$: $$ T^2 = \begin{pmatrix}1 \quad 1\\ 1 \quad 2\end{pmatrix}, T^3 = \begin{pmatrix}1 \quad 2\\ 2 \quad 3\end{pmatrix},T^4 = \begin{pmatrix}2 \quad 3\\ 3 \quad 5\end{pmatrix} $$ So the pattern, as can be seen clearly, is that $T^n = \begin{pmatrix} F_{n-1} \quad F_n \\ F_{n} \quad F_{n+1}\end{pmatrix}$. The best we can do is to prove this by induction : Note that $T\begin{pmatrix}F_{n-1} & F_{n}\\ F_{n} & F_{n+1}\end{pmatrix} = \begin{pmatrix} F_{n} & F_{n+1} \\ F_{n-1} + F_n & F_{n} + F_{n+1}\end{pmatrix}$, from where you can conclude.
Efficient production of an avian adeno-associated virus vector using insect cell/baculovirus expression system. Recombinant avian adeno-associated virus (rAAAV) is a promising gene transfer vector for avian cells. Although rAAAV can be produced by co-transfection of HEK293 cells with three plasmids, both scalability and productivity of the transient transfection method can not meet the demand for large-scale in vivo experiments. In this study, a scalable rAAAV production method was established by using insect cell/baculovirus expression system. Three recombinant baculoviruses, namely BacARep, BacAVP and BacAGFP, were generated by transfection of Sf9 cells with the three plasmids expressing AAAV Rep genes, modified VP gene or the inverted terminal repeats-flanked green fluorescent protein (GFP) gene. After demonstration of the correct expression of AAAV genes, rAAAV-GFP was produced by triple infection of insect cells or triple transfection of HEK293 cells for comparison purpose. Electron microscopy revealed the formation of typical AAAV particles in the insect cells. Western blotting showed the correct assembly of rAAAV particles with a VP protein ratio similar to that of AAAV. Quantitative PCR showed that the insect cell-produced rAAAV yield was almost 25-fold higher than that produced by HEK293 cells. Fluorescent microscopy showed that the insect cell-produced rAAAV could transfer GFP reporter gene into two avian cell types with similar transfer efficiency to that of HEK293 cell-produced rAAAV. These data suggest that insect cell/baculovirus expression system could be used for scalable production of rAAAV, and the viral vector produced could be used as the gene transfer vehicle for avian cells.
New coaches usually have to rebuild both sides of the ball, but Marc Trestman was brought in with this mandate: Fix Jay Cutler and score more points. Revamping the Bears' offensive line is a good place to start.
NUMBERS 13-01-337-CR AND 13-01-338-CR COURT OF APPEALS THIRTEENTH DISTRICT OF TEXAS CORPUS CHRISTI ___________________________________________________________________ LAWRENCE KENT CHRISTIAN, Appellant, v. THE STATE OF TEXAS, Appellee. ___________________________________________________________________ On appeal from the County Court at Law No. 3 of Jefferson County, Texas. __________________________________________________________________ O P I N I O N Before Chief Justice Valdez and Justices Dorsey and Rodriguez Opinion by Justice Rodriguez On July 22, 1999, in accordance with a plea agreement, appellant, Lawrence Kent Christian, pleaded nolo contendere to the offense of driving while intoxicated. The trial court found appellant guilty, but deferred the imposition of sentence and placed him on community supervision for a period of two years, and imposed a fine in the amount of $600.00. On May 1, 2000, in accordance with a plea agreement, appellant pleaded nolo contendere to the offense of driving while license suspended. The trial court found appellant guilty, but deferred the imposition of sentence and placed him on community supervision for a period of one year, and imposed a fine in the amount of $100.00. On November 13, 2000, the State filed motions to revoke probation in both cases. Following a hearing, the trial court found appellant had violated several conditions of each of his community supervision orders. The trial court revoked the community supervision imposed on July 22, 1999, and assessed punishment at one hundred-eighty days confinement. The trial court also revoked the community supervision imposed on May 1, 2000, and assessed punishment at thirty days confinement. Appellant appeals from these two judgments.[1] Appellant=s counsel has filed briefs in which he concludes the appeals are wholly frivolous and without merit. The briefs meet the requirements of Anders v. California, 386 U.S. 738 (1967), as they present a professional evaluation of why there are no arguable grounds for advancing an appeal. See Stafford v. State, 813 S.W.2d 503, 510 n.3 (Tex. Crim. App. 1991); High v. State, 573 S.W.2d 807, 812 (Tex. Crim. App. 1978). Counsel certifies in his briefs that he served appellant with a copy of each brief and informed appellant of his right to examine the appellate record and to file a pro se brief. Counsel also filed, on appellant=s behalf, a motion for an extension of time to file a pro se brief, which we granted. No pro se brief has been filed. Upon receiving an Anders brief, an appellate court must conduct Aa full examination of all proceedings to decide whether the case is wholly frivolous.@ Penson v. Ohio, 488 U.S. 75, 80 (1988). We have carefully reviewed the record in each appeal and, finding nothing that would arguably support an appeal in either cause, agree that each appeal is wholly frivolous and without merit. See Stafford, 813 S.W.2d at 511. The judgments of the trial court are AFFIRMED. Furthermore, we order counsel to notify appellant of the disposition of each appeal and of the availability of discretionary review. See Ex parte Wilson, 956 S.W.2d 25, 27 (Tex. Crim. App. 1997). NELDA V. RODRIGUEZ Justice Do not publish. Tex. R. App. P. 47.3. Opinion delivered and filed this 25th day of April, 2002. [1]Since both cases address the same issues for our review, we address both appeals with a single opinion.
Cows that Burp Less Cows are responsible for about three-quarters of total methane emissions, a gas that is 20 times more portent than carbon dioxide as a greenhouse gas. Therefore, Canadian scientists are trying to breed cows that would burp less. To read the full article please search online for Canadian Scientists Breeding Cows that Burp Less It’s saddening that instead of showing compassion and mercy to cows, humanity is trying to manipulate them even more, as if mere commodities. The most efficient way to reduce greenhouse gases from cattle is to stop raising them for food.
Leptin and peroxisome proliferator-activated receptors: impact on normal and disturbed first trimester human pregnancy. Recent in vitro and in vivo studies emphasize the impact of leptin, peroxisome proliferator-activated receptors (PPAR) and PPAR coactivators (retinoic X receptor a (RXR), amplified in breast cancer-3 gene (AIB3)) on placental and fetal development. Therefore, the frequency and distribution pattern of PPAR, RXR, AIB3 and leptin expression in normal human first trimester pregnancy, miscarriage and hydatidiform mole was investigated by immunohistochemistry and double immunofluorescence staining. Enhanced expression of PPAbeta/delta, RXR and AIB3 was identified in miscarried placentas. With regard to hydatidiform mole, increased expression of PPARgamma and PPARbeta/delta was observed, whereas RXR was significantly down-regulated. Leptin expression was lowest in miscarriage and highest in mole pregnancies. In contrast to trophoblast tissue, expression of leptin in glandular epithelial cells of the decidua was increased in miscarriage. PPAR and leptin expressing cells at the feto-maternal interface were identified as extravillous trophoblast (EVT) by double immunofluorescence and CK7 staining. In summary, significantly reduced leptin expression was accompanied by enhanced PPARbeta/delta, RXR and AIB3 expression in miscarried placentas. However, in mole pregnancy, up-regulation of leptin and increased expression of PPAR was detected. RXR, on the other hand, was down-regulated in mole decidua. So far, the study results implicate strong regulatory interaction of PPARs, their coactivators and leptin in human placentas. PPAR and leptin are potential targets for new treatment strategies concerning pregnancy disorders, such as miscarriage. The increasing knowledge about the role of PPARs and leptin in normal and disturbed pregnancy may help to improve pregnancy outcome.
package quickml.supervised.inspection; import quickml.supervised.tree.decisionTree.nodes.DTCatBranch; import quickml.supervised.tree.decisionTree.nodes.DTNumBranch; import quickml.supervised.tree.decisionTree.valueCounters.ClassificationCounter; import quickml.supervised.tree.nodes.Node; import quickml.utlities.SerializationUtility; import quickml.supervised.tree.decisionTree.DecisionTree; import quickml.supervised.tree.nodes.NumBranch; import quickml.supervised.ensembles.randomForest.randomDecisionForest.RandomDecisionForest; import java.io.; import java.util.; public class RandomForestDumper { public void summarizeForest(PrintStream out, RandomDecisionForest randomDecisionForest) { summarizeModel(out, randomDecisionForest); } public void summarizeForest(PrintStream out, String file) { SerializationUtility<RandomDecisionForest> serializationUtility = new SerializationUtility<>(); RandomDecisionForest randomDecisionForest = serializationUtility.loadObjectFromGZIPFile(file); summarizeModel(out, randomDecisionForest); } public void summarizeModel(PrintStream out, RandomDecisionForest forest) { List<TreeSummary> summaries = new ArrayList<>(); for (DecisionTree t : forest.decisionTrees) { TreeSummary summary = new TreeSummary(); summary.summarizeNode(t.root, 0); summaries.add(summary); } TreeSummary summary = new TreeSummary(); for (TreeSummary t : summaries) { summary.splits += t.splits; for (AttributeSummary as : t.attributes.values()) { AttributeSummary fas = summary.attributes.get(as.name); if (fas == null) { fas = new AttributeSummary(); fas.name = as.name; summary.attributes.put(as.name, fas); } fas.splitCount+= as.splitCount; fas.weightedSplitCount +=as.weightedSplitCount; fas.treeCount++; for (int i = 0; i < as.depths.length; i++) { fas.depths[i]+= as.depths[i]; } } } // Output trees, total splits, distinct attributes out.format("%d trees, %d total splits, %d distinct attributes\n", forest.decisionTrees.size(), summary.splits, summary.attributes.size()); // Get attributes, sort, emit: // - name, # trees, # splits, depths List<AttributeSummary> attributes = new ArrayList<>(summary.attributes.values()); Collections.sort(attributes); for (AttributeSummary s : attributes) { out.format("%s : %f weightedSplits, %d trees, %d splits\n", s.name, s.weightedSplitCount, s.treeCount, s.splitCount); out.format(" depths = %s\n", Arrays.toString(s.depths)); } } public static class TreeSummary { private int splits; private Map<String, AttributeSummary> attributes = new HashMap<>(); private void summarizeNode(Node<ClassificationCounter> node, int currentDepth) { if (node instanceof DTCatBranch) { summarizeCategoricalNode((DTCatBranch)node, currentDepth); } else if (node instanceof NumBranch) { summarizeNumericNode((DTNumBranch) node, currentDepth); } } private void addAttribute(String name, int depth) { AttributeSummary attrSummary = attributes.get(name); if (attrSummary == null) { attrSummary = new AttributeSummary(); attrSummary.name = name; attributes.put(name, attrSummary); } attrSummary.splitCount++; attrSummary.weightedSplitCount = attrSummary.weightedSplitCount + Math.max(0.00000001, 1.0/Math.pow(2, depth)); attrSummary.depths[depth]++; } private void summarizeCategoricalNode(DTCatBranch node, int currentDepth) { splits++; addAttribute(node.attribute, currentDepth); summarizeNode(node.getTrueChild(), currentDepth+1); summarizeNode(node.getFalseChild(), currentDepth+1); } private void summarizeNumericNode(DTNumBranch node, int currentDepth) { splits++; addAttribute(node.attribute, currentDepth); summarizeNode(node.getTrueChild(), currentDepth+1); summarizeNode(node.getFalseChild(), currentDepth + 1); } } private static class AttributeSummary implements Comparable<AttributeSummary> { private String name; private int treeCount; private int splitCount; private double weightedSplitCount; private int[] depths= new int[20]; public int compareTo(AttributeSummary other) { int result = -Double.compare(weightedSplitCount, other.weightedSplitCount); if (result == 0) { result = -Integer.compare(treeCount, other.treeCount); } if (result == 0) { result = -Integer.compare(splitCount, other.splitCount); } if (result == 0) { result = name.compareTo(other.name); } return result; } } }
Esmeralda, Queensland Esmeralda is a rural locality in the Shire of Croydon, Queensland, Australia. In the , Esmeralda had a population of 21 people. History The locality takes its name from a local hill named on 30 September 1873 by explorer George Elphinstone Dalrymple. References Category:Shire of Croydon Category:Localities in Queensland
1. Field of the Invention This invention relates to a process for enhancing the solution diffusibility of a developing liquid in a semiconductor wafer developing unit. 2. Description of the Prior Art The current practice is to develop a photoresist on the surface of a substrate while the substrate is rotating on a wafer chuck. This mechanical rotation is essentially static, as far as the developer is concerned, and developing speed is limited by solution diffusibility. This is because the developer becomes stagnant with photoresist and fresh developing liquid cannot diffuse toward the photoresist. As a result, development ceases. While integration density is steadily increasing, the art of improving methods of developing photoresist has lagged behind with respect to increased solution diffusibility, developing speed, or feature uniformity. A variety of methods have been described in the patent literature dealing with irradiation of photoresist, depositing of photoresist, or applying of spin-on-glass. But there appear to be no prior art teachings regarding methods of enhancing developers, be they organic solvents for negative resists or alkaline solutions for positive resists. U.S. Pat. No. 4,612,267 (Heitmann et al.) discusses the ultrasonic irradiation of a resist layer. U.S. Pat. No. 5,395,803 (Adams) discloses a method of depositing a material, such as a photoresist, upon a substrate. U.S. Pat. No. 5,454,871 (Liaw et al.) describes an apparatus for applying spin-on-glass material to a wafer under controlled humidity conditions.
Access to fracture risk assessment by FRAX and linked National Osteoporosis Guideline Group (NOGG) guidance in the UK-an analysis of anonymous website activity. In the UK, fracture risk guidance is provided by the National Osteoporosis Guideline Group (NOGG). NOGG usage showed widespread access through direct web-based linkage to FRAX. The facilitated interaction between fracture risk assessment and clinical guidelines could usefully be adopted in other countries. In the UK, guidance on assessment of osteoporosis and fracture risk is provided by the National Osteoporosis Guideline Group ( www.shef.ac.uk/NOGG ). We wished to determine access to this guidance by exploring website activity. We undertook an analysis of FRAX and NOGG website usage for the year between 1st July 2013 and 30th June 2014 using Google Analytics software. During this period, there was a total of 1,774,812 sessions (a user interaction with the website) on the FRAX website with 348,964 of these from UK-based users; 253,530 sessions were recorded on the NOGG website. Of the latter, two-thirds were returning visitors, with the vast majority (208,766; 82 %) arising from sites within the UK. The remainder of sessions were from other countries demonstrating that some users of FRAX in other countries make use of the NOGG guidance. Of the UK-sourced sessions, the majority was from England, but the session rate (adjusted for population) was the highest for Scotland. Almost all (95.7 %) of the UK sessions arose from calculations being passed through from the FRAX tool ( www.shef.ac.uk/FRAX ) to the NOGG website, comprising FRAX calculations in patients without a bone mineral density (BMD) measurement (74.5 %) or FRAX calculations with a BMD result (21.2 %). National Health Service (NHS) sites were identified as the major source of visits to the NOGG website, comprising 79.9 % of the identifiable visiting locations, but this is an underestimate as many sites from within the NHS are not classified as such. The study shows that the facilitated interaction between web-based fracture risk assessment and clinical guidelines is widely used in the UK. The approach could usefully be adopted in other countries for which a FRAX model is available.
Cytochrome oxidase promotes the transfer of electrons from reduced cytochrome c to molecular oxygen, the terminal step of the respiratory chains of mitochondria and aerobic microorganisms. In S. cerevisiae, this membrane complex is composed of 10 different subunit polypeptides of which three are encoded in mitochondrial DNA. The two genetically distinct groups of polypeptides are assembled into the holoenzyme by an elaborate process that requires the expression of some 40 nuclear genes. The products of two such genes, COX10 and COX11, have recently been implicated to function in the synthesis of heme A, a prosthetic group unique to cytochrome oxidase. One of the goals of this proposal is to characterize the roles of the COX10 and COX11 proteins in farnesylation of the 8-vinyl and oxidation of the 2-methyl substituents of the porphyrin ring and to screen for other heme A mutants. These strains will be used to used to identify the intermediates and enzymes of heme A biosynthesis, a pathway about which virtually nothing is known at present. A substantial number of non-maternally inherited human myopathies have been ascribed to decreased levels of cytochrome oxidase in muscle mitochondria. Despite extensive studies, none of these fatal diseases have been correlated with mutations in the structural or catalytic subunits of this respiratory complex. It is not unreasonable to think that in some cases the enzyme deficiency may stem from mutations affecting heme A biosynthesis. To assess this possibility, muscle biopsies from patients with cytochrome oxidase defects will be analyzed for the accumulation of heme A intermediates. This approach has been helpful in identifying a novel heme compound in a cox11 mutant of yeast. Secondly, the human cDNA homologs of COX10 and COX11 will be cloned in order to facilitate a molecular analysis of the comparable cDNAs from myopathic tissues. The cytochrome oxidase deficient phenotype of yeast strains assigned to approximated 11 complementation groups is elicited by mutations affecting late events in the enzyme assembly pathway. The third goal of this proposal is to complete the analysis of this set of genes and to clarify the functions supplied by the encoded proteins. These studies are anticipated to provide a blueprint of the genetic information and the molecular mechanisms governing assembly of the functional complex.
Q: Raster format to read with python I currently have a DEM raster stored in an ESRI geodatabase. I've been asked to create a purely python (e.g., no arcpy functions) program that works with the values. Therefore, I need to convert the raster into something that can be read by python as an array. What file format would that be? (Alternatively, is this a terrible idea and should I argue for sticking with arcpy functions?) A: I'd recommend using the GDAL Pytho API as a substitute for ArcPy, which will give you an extensive range of functions. If you are using GDAL then you have quite an extensive list of possible formats but GeoTiff is always a popular choice but there are plenty of other options (check the GDAL documentation). Alternatively, if you don't want to use GDAL, then you will still need some serious array-crunching modules, so NumPy and SciPy spring to mind (in fact you will probably want these tools even with GDAL). If you are going down this route you will find it easiest to save your DEM as an image (so again GeoTiff is still a good choice).
Barratt forward sales up 8.4% 15 November 2017, 07:09 Source - SMW Barratt Developments has made a strong start to its financial year with customer demand for new homes supported by wide availability of attractive mortgage finance. In a trading update ahead of today's annual general meeting, the group said the strength of demand across its regions was demonstrated by net private reservations per average week of 268 (2016: 265) for the period, resulting in a sales rate of 0.74 (2016: 0.74) net private reservations per active outlet per average week. Total forward sales (including joint ventures) were up by 8.4% to £2,876.0m (2016: £2,654.3m) The group said that as previously announced, the board has proposed a record dividend payment of £348m (comprising £173m final dividend and £175m special dividend) payable on 20 Nov, subject to approval at the AGM. Chief executive David Thomas 'We have started the financial year strongly with a good sales rate, driven by customer demand for new homes, and supported by an attractive lending environment. 'We remain committed to quality, build excellence and market leading customer service and are working hard to increase the supply of houses across the UK. 'We remain focused on driving operational improvements through the business and we continue to be confident in delivering a good performance in FY18.' Market Overview UK 350 Risers and Fallers We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we'll assume that you are happy to receive all cookies from this website. If you would like to change your preferences you may do so by following the instructions here.
Star Trek is often thought of as being a science fiction franchise about brainy people who generally get along and find themselves involved in complex morality plays, and yeah, it is. However, Star Trek is also full of dark, mysterious, physically commanding and sexy bad guys (and girls). View Photo Gallery Between the evil “mirror universe” versions of the ship’s heroes, and bombastic bad guys like Ricardo Montalban‘s Khan and Benedict Cumberbatch‘s John Harrison, Star Trek has a long list of compelling villains to find yourself sympathizing (a little too much) with. Not to mention the fact that patently sexy people such as Kim Cattrall, Tom Hardy and Iman have also shown up to threaten the Enterprise on the big screen. I mean, sure, it’s a little weird to find yourself sexually attracted to a Klingon or an Android off his rocker, but Star Trek has always been about exploration. And who hasn’t been a wee bit intrigued by Gorn? And while we’re on the subject of villains…who are Benedict Cumberbatch’s and Zachary Quinto‘s favorite Star Trek foes????

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