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The camp at Dachau is one of the first and largest concentration camps in Germany. The area, comprising about one square mile, is enclosed by a concrete wall seven feet high and covered with barbed wire. In the southwestern corner there are thirteen crude barracks, originally built for military purposes. They are in a dilapidated condition because of sixteen years of weathering, and were only superficially restored to serve as a shelter for 1,800 Bavarian workmen, political adversaries of the new regime.
British servicemen Denis Norden and Eric Sykes, who later became popular comedians, stumbled upon the camp in 1945 shortly after liberation; "Appalled, aghast, repelled - it is difficult to find words to express how we felt as we looked upon the degradation of some of the inmates not yet repatriated," Sykes later wrote. "They squatted in their thin, striped uniforms, unmoving bony structures who could have been anywhere between 30 and 60 years old, staring ahead with dead, hopeless eyes and incapable of feeling any relief at their deliverance."
In France Jews under Fascist Italian occupation in the southeast fared better than the Jews of Vichy France, where collaborationist French authorities and police provided essential support to the understaffed German forces. The Jews in those parts of France under direct German occupation fared the worst. Although allied with Germany, the Italians did not participate in the Holocaust until Germany occupied northern Italy after the overthrow of Fascist leader Benito Mussolini in 1943.
The Nuremberg Laws, issued on Sept. 15, 1935, was designed to exclude Jews from public life. The Nuremberg Laws stripped German Jews of their citizenship and prohibited marriages and extramarital sex between Jews and Gentiles. These measures set the legal precedent for anti-Jewish legislation that followed. Nazis issued numerous anti-Jewish laws over the next several years. Jews were banned from public parks, fired from civil service jobs, and forced to register their property. Other laws barred Jewish doctors from treating anyone other than Jewish patients, expelled Jewish children from public schools, and placed severe travel restrictions on Jews.
Several thousand Catholic clergy members were also incarcerated at Dachau. One was Titus Brandsma (1881-1942), a Carmelite cleric, philosopher, writer, teacher and historian as well as an avowed anti-Nazi. Brandsma arrived at Dachau in June 1942, and died the following month after being given a lethal injection. In 1985, he was beatified by Pope John Paul II (1920 -2005). MichaÅ‚ Kozal (1893-1943), a Polish priest, arrived at Dachau in 1941, and for two years, he attended to the spiritual needs of his fellow prisoners. In January 1943, Kozal perished from a lethal injection. Pope John Paul II beatified him in 1987.
For the role, Spielberg cast then relatively unknown Irish actor Liam Neeson, whom the director had seen in a Broadway play called Anna Christie. “Liam was the closest in my experience of what Schindler was like,” Spielberg told The New York Times. “His charm, the way women love him, his strength. He actually looks a little bit like Schindler, the same height, although Schindler was a rotund man,” he said. “If I had made the movie in 1964, I would have cast Gert Frobe, the late German actor. That’s what he looked like.”
In many instances, their imprisonment was a result of the emergency decree that Adolf Hitler proposed and President Paul Von Hindenberg approved on February 28, 1933. The Decree for the Protection of the People and the State (commonly called the Reichstag Fire Decree) suspended the civil rights of German civilians and prohibited the press from publishing anti-government materials.
Responding with alarm to Hitler’s rise, the Jewish community sought to defend their rights as Germans. For those Jews who felt themselves fully German and who had patriotically fought in World War I, the Nazification of German society was especially painful. Zionist activity intensified. “Wear it with pride,” journalist Robert Weltsch wrote in 1933 of the Jewish identity the Nazis had so stigmatized. Religious philosopher Martin Buber led an effort at Jewish adult education, preparing the community for the long journey ahead. Rabbi Leo Baeck circulated a prayer for Yom Kippur (the Day of Atonement) in 1935 that instructed Jews on how to behave: “We bow down before God; we stand erect before man.” Yet while few, if any, could foresee its eventual outcome, the Jewish condition was increasingly perilous and was expected to worsen.
The fire signaled the demise of German democracy. On the next day, the government, under the pretense of controlling the Communists, abolished individual rights and protections: freedom of the press, assembly, and expression were nullified, as well as the right to privacy. When the elections were held on March 5, the Nazis received nearly 44 percent of the vote, and with 8 percent offered by the Conservatives, won a majority in the government.
By the end of the war, Schindler had spent his entire fortune on bribes and black market purchases of supplies for his workers. Virtually destitute, he moved briefly to Regensburg and later Munich, but did not prosper in postwar Germany. In fact, he was reduced to receiving assistance from Jewish organisations. In 1948 he presented a claim for reimbursement of his wartime expenses to the American Jewish Joint Distribution Committee, and received $15,000. He estimated his expenditures at over $1,056,000, including the costs of camp construction, bribes, and expenditures for black market goods, including food. Schindler emigrated to Argentina in 1949, where he tried raising chickens and then nutria, a small animal raised for its fur. When the business went bankrupt in 1958, he left his wife and returned to Germany, where he had a series of unsuccessful business ventures, including a cement factory. He declared bankruptcy in 1963 and suffered a heart attack the next year, which led to a month-long stay in hospital. Remaining in contact with many of the Jews he had met during the war, including Stern and Pfefferberg, Schindler survived on donations sent by Schindlerjuden from all over the world. He died on 9 October 1974 and is buried in Jerusalem on Mount Zion, the only member of the Nazi Party to be honoured in this way. For his work during the war, on 8 May 1962, Yad Vashem invited Schindler to a ceremony during which a carob tree planted in his honor on the Avenue of the Righteous. He and his wife, Emilie, were named Righteous Among the Nations, an award bestowed by the State of Israel on non-Jews who took an active role to rescue Jews during the Holocaust, on 24 June 1993. Other awards include the German Order of Merit (1966).
Schindler was founded in 1874 by Robert Schindler and Eduard Villiger. Soon, they established a mechanical engineering workshop on an island in the Reuss River in Lucerne, Switzerland. At that time, the company was called "Schindler & Villiger". In 1892, Eduard Villiger leaves the partnership and the company continues under the name of Robert Schindler, Machinery Manufacturer.
Historians are divided about the motivations of the members of these mobile killing units. American historian Christopher Browning described one such unit, Police Battalion 101, as ordinary men in extraordinary circumstances in which conformity, peer pressure, careerism, obedience to orders, and group solidarity gradually overcame moral inhibitions. American writer Daniel Goldhagen viewed the very same unit as “willing executioners,” sharing Hitler’s vision of genocidal anti-Semitism and finding their tasks unpleasant but necessary. The diversity of the killers has challenged Goldhagen’s view that the motivation was a distinct form of German anti-Semitism. Yet both Browning and Goldhagen concurred that none of these killers faced punishment if he asked to be excused. Individuals had a choice whether to participate or not. Almost all chose to become killers.
Although she struggled with resentment towards her late husband for his womanizing and marital neglect, Emilie still had profound love for Schindler. Revealing her internal dialogue when she visited his tomb almost 40 years after his passing, she had said to him: "At last we meet again . . .I have received no answer, my dear, I do not know why you abandoned me . . . But what not even your death or my old age can change is that we are still married, this is how we are before God. I have forgiven you everything, everything. . ."
Fermented blackberry and raspberry leaves from the Dachau farm were used to create German tea, reducing dependency on imports. Work was done on growing German pepper and gladioli flowers were grown in great quantities for their vitamin C. The gladioli leaves were dried and pulverized, then combined with a mixture of spices, beef fat and cooking salt to make a food supplement for SS soldiers.
With the invasion of the Soviet Union on June 22 1941, the Nazis launched a crusade against 'Judaeo-Bolshevism', the supposed Jewish-Communist conspiracy. Behind the front lines, four police battalions called Einsatzgruppen (operations groups) moved from town to town in the newly occupied Soviet territories, rounding up Jewish men and suspected Soviet collaborators and shooting them. In subsequent sweeps, making heavy use of local volunteers, the Einsatzgruppen targeted Jewish women and children as well. In total, the Einsaztgruppen murdered some two million people, almost all Jews.
While there will always be those who question the motives of others, those who have examined Schindler’s efforts find him heroic. “The defining measure of Schindler’s commitment to doing everything possible to save his Jewish workers came in the fall of 1944, when Oskar chose to risk everything to move his armaments factory to Brunnlitz,” writes David Crowe, citing Dr. Moshe Bejski, who was saved by Oskar Schindler during the Holocaust. “Oskar could easily have closed his Krakow operations and retreated westward with the profits he had already made. Instead, he chose to risk his life and his money to save as many Jews as he could.”
Sanitation was incredibly inadequate, with few latrines and water faucets for the tens of thousands of prisoners interned in Bergen-Belsen at this time. Overcrowding, poor sanitary conditions, and the lack of adequate food, water, and shelter led to an outbreak of diseases such as typhus, tuberculosis, typhoid fever, and dysentery, causing an ever increasing number of deaths. In the first few months of 1945, tens of thousands of prisoners died.
After Schindler got a good grip on the art of hydraulic and traction elevators in the US, they came out with the 300A (in-ground hydraulic), then later the 321A (a holeless telescoping hydraulic model). Both models were then superseded by the 330A (released March 15, 2001), which comes in the standard in-ground system as well as the Holeless Telescoping Hydraulic system. The 330A Holeless Telescoping Hydraulic elevator is based off the design that DEVE used in Sweden (also used in Australia and the United Kingdom ), whereby the hydraulic pistons are inverted (turned up-side down) and the casing is mounted to the side of the elevator car. This model comes in both single-post and twin-post models. After the 330A came the 400A Traction elevator system which comes in MRL, standard MRA (Machine room Above) and MRS (Machine room on Side), and has since been improved and now known as 400AE (AE which is stand for Advanced Editon.). This model has a capacity of up to 4000lbs or 1818KG travelling at up to 500fpm or 2.5m/s and can be integrated with Schindler Miconic 10 or PORT Destination Dispatch systems. 500A mid to high rise model in the United States launched in 2001.
You find the stories of Irena Sendler, who defied the Nazis and saved 2,500 Jewish children by smuggling them out of the Warsaw Ghetto .. Maria von Maltzan, who risked everything to defy Hitler and the Nazi Régime .. Miep Gies, who risked her life daily to hide Anne Frank and her family .. the Rescue of the Danish Jews, Varian Fry, the American Schindler, Kurt Gerstein SS Officer, the site Courage and Survival ..
Jehovah's Witnesses, homosexuals, and emigrants were sent to Dachau after the 1935 passage of the Nuremberg Laws which institutionalized racial discrimination. In early 1937, the SS, using prisoner labor, initiated construction of a large complex capable of holding 6,000 prisoners. The construction was officially completed in mid-August 1938. More political opponents, and over 11,000 German and Austrian Jews were sent to the camp after the annexation of Austria and the Sudetenland in 1938. Sinti and Roma in the hundreds were sent to the camp in 1939, and over 13,000 prisoners were sent to the camp from Poland in 1940.
A few days later a transport arrived with 200 prisoners from northern Bavaria, some of whom were at once inhumanly beaten. Among these prisoners were twelve Jews who were picked out immediately and brought to the guard room. They were stripped of their clothing, their heads were wrapped in blankets to smother their cries and they were beaten barbarously. Later, after kicks on the testicles and further beating, they were driven to the barracks. The body of each, from the waist to the knee, was one complete wound. The entire scene took place in the presence of a high police official, Dr. Frank, and fifteen Special Police headed by Steinbrenner, Hofmann and Kantschuster.
The total number of German guards killed at Dachau during that day most certainly does not exceed fifty, with thirty probably being a more accurate figure. The regimental records of the 157th Field Artillery Regiment for that date indicate that over a thousand German prisoners were brought to the regimental collecting point. Since my task force was leading the regimental attack, almost all the prisoners were taken by the task force, including several hundred from Dachau.
The Germans invaded the Netherlands, Luxembourg, Belgium, and France in May 1940. In the Netherlands, the Germans installed Arthur Seyss-Inquart as Reichskommissar, who quickly began to persecute the approximately 140,000 Dutch Jews. Jews were forced out of their jobs and had to register with the government. Non-Jewish Dutch citizens protested these measures, and in February 1941 they staged a strike that was quickly crushed. After Belgium's surrender at the end of May 1940, it was ruled by a German military governor, Alexander von Falkenhausen, who enacted anti-Jewish measures against the country's 90,000 Jews, many of whom were refugees from Germany or Eastern Europe.
But if the 10,000 bodies found in the camp by the British liberators weren't victims of mass gassing, how did so many die in such a short time? It was easy for viewers of the British documentary film, made immediately after the liberation, to believe that the emaciated corpses were those of prisoners who had been deliberately starved to death by the evil Nazis, especially because the film made no mention of epidemics in the overcrowded camp, or that the camp was right in the middle of a war zone and had even been hit in an Allied bombing attack.
Menachem Rosensaft's parents, Josef Rosensaft (1911-1971) and Hadassah Bimko (1910-1997), were important leaders of the DP community. Josef Rosensaft was born in Bedzin, Poland. He was deported to Auschwitz-Birkenau in April 1944, after a number of escapes from the Nazis. He ended up at Bergen Belsen two weeks before its liberation. After liberation, Josef remained at Bergen Belsen and served as Chairman of the Central Committee of the British Zone. In this position, he led all attempts to improve the lives of the Jewish survivors in the DP camps in British-occupied Germany. He possessed natural wisdom, a keen sense of justice and a fine sense of humor.
Oskar Schindler was born into a German Catholic family on April 28, 1908. After attending trade schools, he worked for his father’s farm machinery company. He worked for German intelligence and later joined the Nazi Party. An opportunist businessman with a taste for the finer things in life, he seemed an unlikely candidate to become a wartime hero. During the war, however, he operated a factory that employed more than 1,000 Polish Jews, saving them from concentration camps and extermination. In 1993 his story was made into the Steven Spielberg feature film Schindler's List.
A final and complete deterioration of the prisoners living conditions set in when tens of thousands of prisoners poured in – survivors of the death marches who had been evacuated from the camps in the east. These included 20,000 women prisoners from the Auschwitz- Birkenau concentration camps who had passed through the Gross- Rosen concentration camp on the death march to Bergen-Belsen.
In nearly every country overrun by the Nazis, the Jews were forced to wear badges marking them as Jews, they were rounded up into ghettos or concentration camps and then gradually transported to the killing centers. The death camps were essentially factories for murdering Jews. The Germans shipped thousands of Jews to them each day. Within a few hours of their arrival, the Jews had been stripped of their possessions and valuables, gassed to death, and their bodies burned in specially designed crematoriums. Approximately 3.5 million Jews were murdered in these death camps.
Gun wrote that the International Committee of Dachau, headed by Patrick O'Leary, had set up its headquarters at 9 a.m. on April 29th in Block 1, the barracks building that was the closest to the gate house of the prison compound. This was the building that housed the camp library. Gun also wrote that Lt. Heinrich Skodzensky had arrived at Dachau on April 27th and on the day of liberation, he had remained in the gate house all that day.
I can only repeat what my late father told me. The wooden building appeared to be disguised as a shower room with a water tank on the roof. He did mention that there was a crematorium oven nearby but I cannot remember exactly what he said. My father died in 1972 so my memories are over 30 years old. He did explore the complex which had been built recently and noted the blast proof hermetically sealed doors. There was a hatch in the ceiling leading to the hut above. Each hatch was also hermetically sealed and identified by a letter and a number such as A3.
A British documentary film shows healthy Jewish liberated prisoners lined up, screaming at the top of their lungs at the SS men and women as they go about their macabre task. On the day that the German civilians were brought to the camp, the Jewish women in the camp screamed at them as the Germans were forced to watch the loading of the corpses. Later the Bergen residents were forced to evacuate their homes and former Jewish prisoners moved in; the Germans were ordered to leave all their silverware, china and linens for the use of the former prisoners.
One of the witnesses to the liberation of Bergen-Belsen by British soldiers on April 15, 1945 was Iolo Lewis, a 20-year-old soldier from Wales. He recalled that, as he arrived at Belsen, Commandant Kramer and his assistant, Irma Grese, were standing at the gates to greet them. Most of the SS men, who were the guards in the camp, had escaped before the British arrived. Commandant Josef Kramer and 80 of the SS men and women had volunteered to remain in the camp to carry out their duties. He said that he counted 13,000 unburied corpses at the time of the liberation, and that the haunting memory never left him, particularly the pearly colour of the piled-up bodies, small, like the bodies of children.
During much of the 12th century, Dachau was the primary residence of a smaller branch from the House of Wittelsbach led by Otto I, Count of Scheyern-Dauchau. When Conrad III died in 1182, Duke Otto I of Bavaria purchased the land and granted it market rights, that were then affirmed between 1270 and 1280 by Duke Ludwig II der Strenge (the Strict).
The site is open to the public and includes monuments to the dead, including a successor to the wooden cross of 1945, some individual memorial stones and a "House of Silence" for reflection. In addition to the Jewish, Polish and Dutch national memorials, a memorial to eight Turkish citizens who were killed at Belsen was dedicated in December 2012.


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FEB172214 - Seventeen years before the Pirates of the Caribbean attraction first opened at Disneyland, the Walt Disney C..
DEC162216 - Untie the string and unwrap the brown paper to reveal... the Journal 3 Limited Edition! This 288-page book c..
AUG172340 - Fun, funny, and feisty patterns and character designs permeate the near-ninety-year history of Disney's belo..
MAR172349 - Relax, and let the creativity flow through you. Whether you are a skilled artist or a casual doodler, you wi..
MAY172163 - Relax, and let the creativity flow through you. Whether a skilled artist or an everyday dabbler of drawings ..
AUG172307 - In 1945, Walt Disney and Salvador Dali began working on a project together, intended to be a short animated ..
SEP172196 - Featuring five spreads with over 30 pop-ups from New York Times-bestselling author, artist, and pop-up maste..
JUL172429 - Although Disneyland opened in 1955, its culinary history dates back to 1923 when Walt Disney first arrived i..
JUL172430 - Walt Disney s pioneering efforts in animation transformed novelty cartoons into visual masterpieces, establi..
JUN172276 - A Kiss Goodnight is a valentine to Walt Disney from the legendary songwriter Richard Sherman. Opening with a..
JUL172431 - Relive the magic of Snow White and the Seven Dwarfs, Cinderella, Sleeping Beauty, The Little Mermaid, Beauty..
JUN172277 - Oswald the Lucky Rabbit: The Search for the Lost Disney Cartoons is an in-depth look at the origins of the D..
MAR172336 - Timed to the release of the new feature film Cars 3 from Pixar Animation Studios, this collector's art book ..
AUG181823 - Experience Tim Burton's iconic film like never before with this nightmarish pop-up of monstrous proportions!..
AUG172310 - There are nine flip books inside this box that pays tribute to Disney's early animators. Legendary animators..
SEP172197 - Yesterday's Tomorrow is a valentine to an era of optimism, relaxed lifestyle, and innovative design; a large..

domain: entertainment


I would like to play with developing Android ROMs for learning purposes and for maybe I can fork my current ROM and change interesting stuff in it.
I would rather be not happy at all with a bricked device, but how likely is that to happen?
As far as I know, if the bootloader is untouched, flashing even garbage should leave the device repairable since one can still go in flash mode and flash a new rom because the bootloader is fine. Right?
Also I presume hardware can't really be damaged by bad software, can it? (I need a compelling reason if you say yes)
So theoretically, my device can't really break by flashing and trying a custom ROM even if its faulty or even there happens an error during flash, no? (given I don't touch the bootloader)


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676 total views, 2 views today
Five bills including the Ogun State Judicial Officers Administration of Pensions Law, 2020, Ogun State Legislative Administration of Pensions Law, 2020 and Ogun State Public Procurement (Amendment) Law, 2020 today scaled first reading in the Hallowed Chambers of the State House of Assembly.
Others are Ogun State Statistics (Amendment) Law, 2020 and Ogun State Waste Management Authority Law, 2020, which were read for the first time before the lawmakers by the Clerk and Head of Legislative Service, Mr. ‘Deji Adeyemo at a plenary presided over by the Speaker, Rt. Hon. Olakunle Oluomo, at the Assembly Complex, Oke-Mosan, Abeokuta.
The bills are with the long titles: “H.B. No 042/OG/2020- A Bill for a Law to transfer the responsibility, administration and payment of pensions of Ogun State Judicial Officers from the Department of Establishments and Pensions in the Office of the Head of Service of Ogun State to the Ogun State Judicial Service Commission for the payment of pension and other retirement benefits and other related matters; H.B. No 043/OG/2020- A Bill for a Law to transfer the responsibility, administration and payment of pensions of Ogun State Legislative Officers from the Department of Establishment and Pensions in the Office of the Head of Service of Ogun State to the Ogun State House of Assembly Service Commission for the payment of pensions and other retirement benefits and other related matters”.
Others are “H.B. 046/OG/2020- A bill for a law to amend the Ogun State Public Procurement Law, 2014; H.B. 047/OG/2020- A Bill for a law to amend the Ogun State Statistics Law, 2012 and H.B. 048/OG/2020- A Bill for a law to provide for the establishment of the Ogun State Waste Management Authority and other matters connected therewith”.
In another development, Speaker Oluomo has called on the State Command of the Nigerian Police Force to step up measures towards carrying out a thorough investigation into the crisis within the transport union at Ijebu-Igbo which led to the vandalization of properties, with a view to arresting and prosecuting perpetrators as well as ensuring arrest of cultists involved in various criminal acts in the area.
The Speaker stated this while responding to the submissions of his Deputy, Oludare Kadiri, representing Ijebu North 2, and his Ijebu North I counterpart, Sylvester Abiodun under Personal Explanations, on the crisis and leadership tussle within the transport union in the area.

domain: news


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One of the most difficult parts of a hospital stay during the pandemic has been the restrictions on visitors. Thanks to your donations, we’ve invested in tech for the hospitals so that patients and their loved ones can still stay in touch.
Feeling isolated at the most critical time
The Adult Critical Care Unit (ACCU) treats some of the most seriously ill patients at The Royal London Hospital.
Thanks to generous fundraising, the staff at the ACCU have purchased new equipment to support communication for patients too ill to speak.
“Many of our patients in the intensive care unit have communication difficulties as a result of their injuries, or the treatment they are receiving such as tracheostomy and ventilation,” says Dr Parjam Zolfaghari, consultant in Anaesthesia and Intensive Care Medicine.
This means they can feel isolated from friends and family in this stressful time, and it makes it difficult for them to communicate their needs to the doctors and nurses treating them. To help with this, two pieces of equipment have been purchased that let patients communicate using their eyes.
Using eye movements to communicate
The first is a simple solution involving a sheet of transparent plastic called an ‘E-Tran communication frame’, onto which symbols or words can be attached. The second is a more advanced version of this idea, using digital eye-tracking software that can be run on an iPad. The iPad is attached to the patient’s bed so that it can monitor eye movements, giving the patient greater freedom and independence of communication.
“Once patients learn to use their gaze, they can start to communicate with family, friends and staff, where this was not possible before. They can enjoy interacting with their environment once again. Staff will also be able to provide better care knowing what the needs of the patients are,” says Dr Zolfaghari.
Allowing simulation training anywhere
The funds raised also went towards an ALSi medical simulation kit. This is a device used to train staff for a variety of clinical scenarios, often emergencies.
Dr Zolfaghari says, “Simulation teaching usually takes place in dedicated simulation rooms and centres, which are often overbooked and difficult to access. With this portable device, we are able to train all our staff (more than 200 nursing staff!) in the ACCU. It allows for the scenarios to be made realistic and in the staff’s own familiar clinical environment.”
The clinical scenarios simulated by the device are often life-threatening in the real world. With this education and training, staff learn to manage them even more rapidly and effectively, improving safety for patients.
Tom Hume was treated in the ACCU. To honour his memory, his dad Gary walked the Minster Way – 52 miles in two days, from York Minster to Beverley Minster – raising over £17,000.
Tom’s uncle Craig ran a 10k in Leeds where Tom’s family lives and was supported all the way with donations.
Also, funds were raised by New Chapter Consulting, where Tom worked. The New Chapter team fundraised in both London and Leeds including running the Hackney Half marathon and holding a 24 hour Bike-a-thon in Leeds.
Thank you to Tom’s father Gary, all of Tom’s family and friends, and everyone at New Chapter, who contributed to this fundraising. The equipment that you’ve provided will hugely help staff on the unit to provide even better, and safer, care.

domain: medical


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Resources and support materials for the Australian Curriculum: Technologies are available as PDF documents.
Design and Technologies: Sequence of content
Digital Technologies: Sequence of content
This site was developed in collaboration with ACARA by Education Services AustraliaEducation Services Australia
© Australian Curriculum, Assessment and Reporting Authority

domain: library


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We noticed that you're using an unsupported browser. The TripAdvisor website may not display properly.We support the following browsers: Windows: Internet Explorer, Mozilla Firefox, Google Chrome. Mac: Safari.
An awesome experience if you are wanting to get away from the hustle and bustle of life.Friendly staff and superb meals.Un-crowded beaches and surf with amazing fishing and spearfishing.Private bungalows with bathrooms or camping.Loved the peace and tranquility.Situated 25m from the beach.
My wife and I stayed with Cameron and his crew for 7-nights. 4 in the open-air bamboo hut and 3 in the brand new enclosed A-frame. Both were very comfortable. More importantly, we had an incredible time in Sumba. We surfed easy going shoulder to...More
Response from IndoIrisCharters, Owner at Sumba Adventure ResortResponded 20 May 2017
Hi Eric and Tara. Thank you so much for staying with us. It was really fun having you guys around. Hope to see you again and until then, happy travels.
The Sumba Adventure Resort really lives up to its name. Boat trips out on the reef for surfing and fishing, quad bikes to ride on the endless beach and daytrips to remote and beautiful locations!
It is also the perfect place to just relax and...More
1 Thank Petter H
Response from IndoIrisCharters, Owner at Sumba Adventure ResortResponded 18 April 2017
Hi Petter, thanks for the Review. Great to meet you and Kristin. You guys are always welcome like family. Till next time. 🏄🏼🌊
Excuse the title I wasn't really dancing, just lazing and grazing.
Short trip to enjoy some relaxing time in the sunshine in tranquility.
Excellent location, wonderful people and the local Indonesian food is fantastic!
Thoroughly recommend it here, and its a great alternative to the...More

domain: travel


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While our nation faces a number of external threats, not the least of which rhymes with “dim kong bun”, there is one issue that is tearing away at our heartland.
The over-use of opioid painkillers is one of the most egregious threats that the people of America face today. The Big Pharmaceutical industry has been pushing these dangerous and addictive drugs on the population for decades, with rebates and kickbacks for doctors willing to prescribe their patients drugs such as Oxycontin and Vicodin. These drugs carry with them a ridiculous likeness to narcotics such as heroin, leading many Americans down a path of addiction that ends either in failure, rehabilitation, illness, and often death.
Opioid dependency is an extremely difficult problem to treat. Not only are the drugs unbelievably addicting, but the pressure that doctors and hospitals are under to prescribe their use is borderline criminal.
Now, the state of Ohio is taking a long, hard look at what the government can do to curb the abuse of such drugs.
“Officials are putting strict new limits on how many painkillers doctors in Ohio are allowed to prescribe after a report released Wednesday shows overdose deaths spiked again in 2016.
“Data released by the Ohio Department of Health Wednesday shows opioid overdose deaths increased last year over the record breaking numbers seen in 2015. Roughly 11 people die each day in the state from accidental overdoses, with the majority of deaths connected to heroin and fentanyl combinations, reports FOX 45 Now.
“Deaths from drug overdoses increased by exactly 1,000 over 2015, totaling 4,050. In response, Republican Gov. John Kasich announced he is placing new restrictions on opioids, limiting prescriptions to a seven-day supply for adults and a five-day supply for minors.
“’When you’re dispensing this stuff, in some aspects its like walking around with a loaded gun,’ Kasich said at a press conference Wednesday, according to FOX 45 Now. ‘You have a responsibility to do this the right way.’”
Another aspect to consider when working to eradicate needless overdoses is the coming of age of marijuana, and the widespread decriminalization of the plant.
In areas where pot is legal, either medicinally or recreationally, opioid abuse becomes a far smaller concern. Those seeking the escape of recreational drugs are far more likely to turn to the relative safety of cannabis for their kicks or their pain management, over the hassle and difficulty of procuring these highly sought after opiate-based narcotics.

domain: health


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domain: pet


Mariners 2, Red Sox 1: Extra effort no solace for Sox
For such a beautiful city, Seattle has left nothing but scars on the Red Sox for quite some time now.
In a game in which the Sox virtually did nothing wrong, they still lost, 2-1, in 11 innings, to finish their long road trip on a sour note.
The Sox' eighth consecutive loss at Safeco Field gave them a record of 4-5 on the three-city trip, and they now have a day off to adjust their internal clocks to Eastern time before a visit from the last-place Texas Rangers.
Perhaps the fact the Sox still hold a big lead in the American League East will make memories of Seattle fade away.
Or maybe not.
"It's not the park, it's the way they play," Sox manager Terry Francona said. "We've played more than our share of games like this where we've walked off not feeling very good."
Daisuke Matsuzaka was the ultimate tough-luck victim. He did not get saddled with the loss, but he also wasn't rewarded for his eight sharp innings, in which he allowed one run on three hits and struck out eight.
Two of those hits came back-to-back with two outs in the third inning - a two-out double by No. 9 hitter Jamie Burke and a bloop single by Ichiro Suzuki that gave the Mariners a 1-0 lead. Matsuzaka allowed just two more baserunners after that, and the M's never posed another threat against the Japanese right-hander, who pitched with a rhythm as crisp as his fastball and saw his ERA fall to 3.80.
Matsuzaka's performance nearly was as stellar as his best start of the season, a 1-0 win against the Giants at Fenway Park in which he allowed three hits and three walks with eight strikeouts in seven shutout innings.
Unfortunately for the 26-year-old rookie, he also seems to have taken on Tim Wakefield's tendency to sap the power out of his teammates' bats. The Sox have scored just five total runs in Matsuzaka's past five starts, and he is 2-2 in that stretch.
"He was great," Francona said of Matsuzaka. "That (lack of run support) can go in cycles. You pitch according to the scoreboard. He did that. He's a smart enough kid. He did everything he could. He won't hang his head. He probably would still like to be pitching."
The Sox couldn't catch a break at the plate, but the Mariners pitching staff had a lot to do with that. Lefty starter Ryan Feierabend tossed five shutout innings despite allowing five hits and two walks, and the impressive Seattle bullpen took over from there. Five relievers combined to allow one run on just two hits in six innings.
Coco Crisp tied the game at 1 in the seventh with a sacrifice fly that scored pinch-hitter J.D. Drew (single), but the Sox couldn't get a run across after that.
They had a chance to take the lead in the eighth, but shortstop Julio Lugo extended his agonizing slump to 0-for-31 by striking out with the bases loaded. Francona said he did not want to pinch hit lefty Eric Hinske because the Mariners had plenty of left-handers in the bullpen.
The Mariners won the game in the 11th against Joel Pineiro. With one out, Ichiro drew a walk and then Jose Lopez laced a RBI double off the wall in left-center field.
"At the wrong time, we hit balls at the wrong people," captain Jason Varitek said. "We pitched real well early. We just couldn't get things going offensively.
"We hit balls well today. There were some bang-bang plays, and we didn't get any bang-bang plays (go our way). That's not an excuse. We just didn't get any."


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I'm running a gaming community and all my members are worth gold!
I also want to reflect how the community is in a banner on my website (frontpage).
I recently bounced upon an art image that totally represents the style I would like to have!
So what am I asking?
Converting an amount of people into art for a website banner.
Based on real life pictures. Around plusminus 8 people as well.
I'm into all drawing styles, as long it's clear!
Hoping for some good offers!

domain: hobby


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The value of Fed-talk
Ben Bernanke made news yesterday by committing to provide more accommodative monetary policy in an effort to spur a faster recovery—and specifically linking his moves to the Federal Reserve’s disappointment in the labor market recovery so far.
This is a welcome, if still insufficient, development.
Bernanke’s move comes after a widely-circulated paper by Michael Woodford was presented at the Fed’s Jackson Hole conference. The paper argued that the main beneficial impact of Fed easing was through its impact on expectations—that is, if the Fed could convince the public that it will not pull the plug on its support to the economy even if inflation begins to pick up, then they can convince businesses and households to start spending (the mechanisms is that the higher expected inflation rates can drive real interest rates lower even as the Fed’s nominal policy interest rates are stuck at zero). Woodford argues that the most powerful way these expectations are changed are simply through the Fed’s “forward guidance,” or, well, talking.
This raises two quick issues.
First, another key value in the Fed “talking” like it did yesterday isn’t just in trying to convince market participants about what future inflation will look like, it should also help to convince Congress that there remains a jobs crisis that they themselves can help solve. He specifically noted that too-tight fiscal policy was a clear “headwind” to growth in the coming year. In fact, the most valuable outcome of yesterday’s monetary policy moves may well be the nudge they give to changing the direction of fiscal policy.
Second, it’s hard to ignore that the finding on how powerful Fed-talk can be in spurring a depressed economy doesn’t hang very well with claims made during both the stock and housing market bubbles that there was nothing really the Fed could have done to keep them from inflating. After all, if Fed-talk can convince people, purely on the Fed’s say-so, that inflation will be higher three years from now than what they currently expect, then surely the Fed can also point out that when asset prices (stock prices and housing prices) are far out of line from economic fundamentals, that markets better do something about this imbalance or the Fed itself will.
Hopefully this new assessment of the value of Fed-talk will carry over to help prevent tomorrow’s bubbles.
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Ancient egypt women
Discover Pinterest’s 10 best ideas and inspiration for Ancient egypt women. Get inspired and try out new things.
When you ask AI what the queens of ancient Egypt looked like, this is the result
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A scene from the tomb of Menna ( TT69 ) showing Menna and his wife, seated, receiving offerings from a man with shaven head. This is possibly their son.
History saved to Ancient Egypt
An Egyptian woman at her devotions, 1925Illustration by Amédée Forestier (French, 1854-1930)
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Explore Valeria. V.'s 3150 photos on Flickr!
A woman in Ancient Egypt spent a lot of time with a broom in her hand because it’s a country with a lot of sand. Constant sweeping wasn’t the worst of it, though, because the ubiquity of sand meant she probably had rotten teeth, too, finds JOHN HARDING
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We know a lot about Ancient Egypt and its fashionable clothing, jewelry, and makeup from the movies, pictures, and books. But how do you think, have you seen and heard everything there is to know? Of course, not. There are still curious facts about the traditional attire and style of Ancient Egypt that we are glad to share with you. For instance, ever wondered why wigs were so popular in Ancient Egypt? Or are you aware that on some Egyptian statues, the beards are removable and why?
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Do you know your ba from your ka? What’s a vizier? How about a cartouche? Our handy glossary of Ancient Egyptian terms will have you speaking like a pharaoh in no time.
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domain: history


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Films of the day; What's on the small screen this week.
HOWTO TRAIN YOUR DRAGON BBC1, 3.10PM
A young Viking becomes friends with one of the dragons that have been terrorising his village and learns that his people may have misjudged the species. Animated adventure, with the voice of Jay Baruchel.
ET - THE EXTRA TERRESTRIAL STV, 3.20PM
Steven Spielberg's sci-fi classic is a warming tale of friendship. A young alien finds himself left behind when a group of his kind pay a visit to Earth. Stranded and alone, the creature seeks refuge in the home of a suburban family. He finds a friend in 10-year-old Elliott (Henry Thomas) who protects him from the agents who are tasked with hunting him and tries to help the visitor get back home.
AT A ONEMENT STV, 10.15PM
Keira Knightley and James McAvoy star as a pair of star-crossed lovers in this highly-acclaimed war drama by director Joe Wright. In a pre-Second World War England, Cecilia and Robbie's budding relationship is ruined when Cecilia's jealous younger sister Briony (Saoirse Ronan) accuses Robbie of a terrible crime he didn't commit. The fallout from the lie affects their future forever.
PIRATES O F THE CARIBBEAN: AT WORLD'S END BBC1, 11.25PM
In the final instalment of the trilogy, Jack Sparrow (Johnny Depp) is trapped in Davy Jones's Locker, and in his absence the East India Trading Company is taking over the seas. Jack's former crew and friends must join forces with Captain Barbossa (Geoffrey Rush) to save Captain Jack and bring the entire pirate community together.
CAPE FEAR STV, 12.05M
So the bells have struck, glasses downed and kisses given. What now? Well for those of you staying in, bringing in 2015 with this thrilling 1991 film starring Robert De Niro and directed by Martin Scorsese is a very good suggestion. A remake of the 1962 it stars De Niro as rapist Max Cady who is released from prison and exacts revenge on the lawyer who could have kept him out of jail.
SNOWWHITE AND THE HUNTSMAN CHANNEL 4, 8P
A dark take on the classic fairytale. Chris Hemsworth is cast as the Hunstman who is sent to track down Snow (Kristen Stewart) so that Queen Ravenna can stay forever young and beautiful.
UP BBC1, 4.30PM
Among Pixar's very best works, this animated adventure tells the story of pensioner Carl Fredrickson (voiced by Ed Asner) who, after the death of his beloved wife, decides to fulfil their dream of travelling to Paradise Falls. He turns his house into a makeshift airship with hundreds of balloons but only when airborne does he realise he has a stowaway - an eight-year-old boy scout.
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|Publication:||Daily Record (Glasgow, Scotland)|
|Date:||Dec 27, 2014|
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John Boehner was so thrilled to meet Pope Francis when he appeared before Congress, that he may have made a life-altering decision based on his holiness’ inspirational words of peace. What was John’s REAL reason for early resignation?
John Boehner, 65, made a shocking admission during the press conference dressing his resignation from his chair as House Speaker: he was inspired to leave his position early after meeting personally with Pope Francis! Well, it certainly sounded like that! John was visibly shaken during the press event as he explained to reporters why he was evacuating the position he’s held for so long.
Call it holy intervention, call it the word of the Lord, call it whatever you want! “This morning I woke up, said my prayers, and paid my dues,” John told reporters on the afternoon of Friday, September 25.
John said his meeting with Pope Francis after his historic address to a joint session of Congress made him reflect on his words regarding the “Golden Rule” — and his own life. It certainly sounded like he was crediting his Holiness for the early departure, doesn’t it?
Everyone gets inspired by meeting their heroes, and encouraged to do what they feel is right. John is the politician who invited Pope Francis to speak in front of Congress in the first place; he must be a devout follower of his message!
A reporter in the audience asked John point blank if he was saying that meeting with the pope was what made him step down, but John replied in the negative; he said he had been planning this move for some time. Strange that he would reference Pope Francis at all then, right?
John will be leaving his role as House Speaker in Congress at the end of October 2015. HollywoodLifers, are you shocked that John is stepping down?
— Samantha Wilson


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The immediate past National Chairman of the All Progressives Congress (APC), Chief John Odigie-Oyegun, has called on President Muhammadu Buhari to wade into the crises rocking the party. The party’s Deputy National Publicity Secretary, Mr Yekini Nabena, similarly argued that Buhari’s intervention was required to save the party from imminent collapse.
The duo spoke separately in Abuja.
Odigie-Oyegun, in a statement, said APC is fast becoming the single most dangerous threat to the legacy of President Muhammadu Buhari-led administration.
Recalling the circumstances that led to the party’s victory in 2015, he lamented that there has been a steady erosion of democratic tenets in the party in recent times.
Odigie-Oyegun, in a vitriolic critic of the leadership style of his successor, Comrade Adams Oshiomhole, said the immediate constitution of a caretaker committee remains the panacea to crises rocking the party.
He said: “As a major stakeholder and a founding member of APC, I have made various efforts to add my voice to those of several other well-meaning party leaders, in ensuring that the ideals we fought for are not completely thrown overboard.
“However, I have come to realise that those who feel more entitled to the party are no longer capable of hearing alternative viewpoints, other than those counselled by their ego and self-serving interests, which they have promoted over all other considerations, including that of common decency. Yet, no political party will survive for long, which is unwilling to accommodate competing ideas and provide the space for healthy debates.
“This statement is, therefore, a clarion call to party leaders, particularly the Governors and Mr President to urgently bring a stop to the disgraceful and humiliating charade occurring within our great party’s National Secretariat.
“There is a most urgent need for the party NEC to meet and institute for the party Caretaker Committee (even if we have to invoke the doctrine of necessity), whose main responsibility will be to arrange for a special National Convention…”
Nabena, who spoke to reporters in Abuja, alleged that Mr Victor Giadom, who is at the centre of the leadership crises rocking the party, must have been sponsored by fifth columnists bent on undermining the party.
The Bayelsa-born party chieftain stressed the need for the convocation of party NEC meeting to deliberate on consolidating APC’s control of Edo and Ondo states, ahead of the forthcoming governorship elections.
“The APC is clearly at a tipping point,” he said. “At least, four people are laying claim to APC chairmanship, following the court-ordered suspension of Comrade Adams Oshiomhole. All manner of court cases and orders are flying around, contesting party decisions and National Working Committee positions. Factions are festering at the national level and many states…”
He said this does not speak well of a ruling party.


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We no longer offer this title for sale, this listing is here for reference. Screen Archives still carries a wide selection of Twilight Time titles.
The lavish Technicolor extravaganza, Cover Girl (1944), is a landmark in Hollywood musical history: the first to integrate songs (by the superb team of Jerome Kern and Ira Gershwin) with narrative; the incandescent Rita Hayworth’s first musical in color; and the first in which the iconic Gene Kelly was allowed full choreographic charge of his own dance numbers, devised with once and future collaborator, Stanley Donen. Directed by Charles Vidor and shot by Rudolph Maté and Allen M. Davey, the film is a backstage romance between a nightclub owner (Kelly) and his favorite dancer (Hayworth), who catches lightning in a bottle when she wins a magazine cover girl contest and overnight becomes the toast of New York.
Starring: Rita Hayworth, Gene Kelly, Lee Bowman, Phil Silvers, Otto Kruger, Eve Arden and Jinx Falkenburg
Directed By: Charles Vidor
Written By: Virginia Van Upp
Score By: Jerome Kern
Video: 1080p High Definition / 1.33:1 / Color
Audio: English 1.0 DTS-HD MA
Subtitles: English SDH
Theatrical Release: 1944
Runtime: 107 Minutes
Rating: NR (Not Rated)
Region Code: Region Free (A/B/C)
Special Features: N/A
Limited Edition of 3,000 Units


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VIDEO: Mofe Kin Dabi Jesu | @AfiAdeshewa
Zion Music Recordz newly signed artiste Adeshewa who debuted her first single “MOFE KIN DABI JESU” has released visuals to this awesome song which received a massive welcome upon its release.
Adeshewa was officially unveiled at the just concluded 10years music anniversary concert ‘The Praise Feast Concert’ of the label’s CEO Dabo Williams which took place on the 17th of April 2015.
She wowed the audience as she performed her debut single ‘Mofe Kin Dabi Jesu’ and also did a solo song with Boss on the stage.
MOFE KIN DABI JESU has not failed to crawl into people’s hearts and melting it and bringing them to the message of the Cross.
The video was shot by an outfit which is said to be one of the CEO’s Company “Big God Productions.”
VIDEO : Dorcas – GREATER
Tweet Award winning gospel recording artiste, Dorcas More O’Ferrall best known as Dorcas unwraps theRead More
VIDEO : Jahdiel – JUST LIKE YOU
Tweet Jahdiel comes to you this time with the outstanding and amazing video of her popularRead More

domain: artistic


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This easy Cheese Fondue recipe lives up to its name! It’s one of the quickest and easiest ways to make Swiss fondue for any party or get-together. A creamy, flavorful crowd pleaser!
Do you love fondue as much as I do?
Growing up in the 70’s, my mom made her fair share of it which inspired my love for these easy recipes. My most favorite was this French Toast Fondue with the sweet maple butter for dipping.
You might just want to take a look in some thrift stores for your own fondue set and keep your eyes peeled for more fondue recipes here in the future!
SAVE THIS EASY CLASSIC CHEESE FONDUE RECIPE TO YOUR FAVORITE PINTEREST BOARD!
When our kids were growing up, we discovered the Melting Pot restaurant. We all fell in love with their cheddar cheese fondue, and dipping our cubes of bread into the combination of creamy cheeses.
We also had so much fun when it came time for dessert when we dunked our strawberries, slices of cheesecake, and Angel Food cake into the chocolate fondue. YUM!
Fondue is really so much more than just a meal or an appetizer. It’s an experience. Everyone gathers around the classic fondue pot to get a taste, sharing, laughing and connecting over one of life’s greatest joys–cheese!
Here’s another thing to love abut cheese fondue: it’s super quick and simple to make with the right recipe.
My Quick and Simple Cheese Fondue recipe is exactly that. It takes a few basic ingredients and melts them together to create a hot cheese fondue that tastes like it came from a fancy restaurant.
There are plenty of other sites out there that claim to have the best cheese fondue made with a variety of cheese, a little wine, little bit of white pepper, some dijon mustard, etc. Don’t get me wrong, those are definitely good options, but whether it’s your first time, you don’t want to go to all that trouble of using grated cheese or are nervous your end result won’t be a smooth fondue, then this easy appetizer recipe is just the one you need!
Once you learn how to make fondue at home, you’ll always be able to make a delicious party dip or family-style meal at a moment’s notice!
What essential ingredients do I need?
Put down the different types of cheese and rest assured that you won’t be spending a lot of money for some good quality cheese. You only need a few simple ingredients for this easy fondue recipe.
- Cheese Whiz –
Yes, the kind that comes in a spray can. Trust me; it tastes amazing here! But of course, you’ll want the jar.
- Cream of mushroom soup
- Worcestershire sauce
- Hot sauce –
Use your favorite brand!
- Garlic powder – or swap it out for garlic salt or even a minced garlic clove or two if that’s what you have on hand.
You can even get creative and give it a Mexican spin by adding some diced jalapeños to it.
Do I need a fondue pot?
You don’t need electric fondue pots or a fondue burner to make this fondue recipe. A crockpot or slow cooker works just as well, and you can also make it stove top using a double boiler.
To make cheese fondue in the crockpot, stir everything together and heat on low, stirring continuously until the fondue thickens and bubbles.
It takes a few minutes of stirring for the mixture to come together. As the cheese melts, it distributes heat through the other ingredients, making them easier to combine.
What to serve with cheese fondue?
I love serving fondue with large bowl of bread cubes for dipping. All those nooks and crannies in good bread are perfect for soaking up the creamy fondue. We especially like French bread and enjoy rye bread as well.
It’s also amazing with crackers, steamed or raw cauliflower florets, pearl onions, broccoli or even apples! Just about everything is better when it’s dipped in hot melted cheese, so you almost can’t go wrong.
How should I store this cheese sauce?
Let the cheese completely cool down, then store it in the refrigerator in an airtight container for 2-3 days. To reheat leftover cheese fondue, place it in a microwave safe container and heat in the microwave for 30 seconds. Stir, then continue heating in 30 second increments until warmed through.
Should I eat this hot or cold?
Fondue is best enjoyed warm! I like to serve it right after I make it for that irresistibly rich, creamy, cheesy taste.
The good news is that leftovers are easy to reheat, so don’t worry if you end up with some extra.
My quick and easy fondue recipe makes an ideal meal for two, served with plenty of dippers (and maybe a bottle of wine!). Consider adding it to your next at-home date night menu.
Most of the time I make cheese fondue, I serve it as an appetizer or party snack. Add it to your spread along with these Sausage Balls or a tray of Cream Cheese Stuffed Mushrooms and your guests will have plenty to munch on while they wait for dinner.
For a more elegant hors d’oeuvres option, impress your guests with a Poached Pear and Goat Cheese Appetizer. It looks as good as it tastes!
You might have gathered by now that I’m slightly obsessed with cheese. And I know I’m not alone!
Today’s quick and simple cheese fondue recipe is just the latest in a long line up of favorite cheese recipes. From homemade cheese crackers to classic Chicken Mozzarella Pasta, my site is packed with fun and family-friendly ways to cook with cheese!
A family and reader favorite is this Beer Cheese Dip made with shredded cheese. The homemade soft pretzels used for dipping are sooo good, too! It’s been on a lot of our game day menus and will continue to be.
When you don’t feel like cooking, or want to keep the goodness of cheese front and center without all those pesky distractions, you can always make a cheeseboard! I have a guide for how to make cheese boards that are both beautiful and delicious, to help you get started.
From game day to holidays like New Years Eve to an impromptu dinner party with friends, this easy cheese fondue recipe is a delicious appetizer that everyone will enjoy dipping into!
Quick and Simple Cheese Fondue
- 15 ounces Cheese Whiz
- 10.5 ounces cream of mushroom soup
- ½ teaspoon Worcestershire sauce
- ¼ teaspoon hot sauce
- ¼ teaspoon garlic powder or garlic salt
- In a crockpot or fondue pot, all all of the ingredients. On low heat, stir constantly while cooking until the sauce is bubbling and well combined.
- Serve with cubed bread, chips, steamed cauliflower & broccoli, apples, crackers, or any food to dip that you like.

domain: food


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Charlie Puth, “See You Again” OMI, “Cheerleader” Rachel Platten, “Fight Song” The Weeknd, “The Hills” Top Radio Song: Adele “Hello” Wiz Khalifa ft.
Charlie Puth, “See You Again” Mark Ronson Featuring Bruno Mars, “Uptown Funk!
Nicki Minaj, Bebe Rexha & Afrojack, “Hey Mama” Major Lazer & DJ Snake Featuring MØ, “Lean On” -- WINNER Skrillex & Diplo, “Where Are Ü Now” with Justin Bieber Top Christian Song: Hillsong UNITED, “Oceans (Where Feet May Fail)” -- WINNER Hillsong UNITED, “Touch the Sky” Mercy Me, “Flawless” NEEDTOBREATHE Featuring Gavin De Graw, “Brother” Chris Tomlin, “Good Good Father” Top Gospel Song: Anthony Brown and group ther APy, “Worth” Erica Campbell feat.
Big Shizz, “I Luh God” Kirk Franklin, “Wanna Be Happy?
'There’s a book by Alfred Tomatis about why some people like certain people’s voices and other people hate them, like Bob Dylan or me or whoever, some people say, "Oh, I hate that voice", so there’s a thing about people’s frequency responses – what they are pleased by.
Adele and The Weeknd were the big winners at Sunday night's Billboard music Awards.
The British superstar, who received eight nominations but wasn't present at the ceremony as she continues her world tour, scooped the award for Top Artist, beating Justin Bieber, Drake, Taylor Swift and The Weeknd. Have a drink for me." Justin Bieber took home the Top Male Artist Award, while The Weeknd took home a huge 8 awards - more than any male artist in history - including the Top Hot 100 Artist award. He'll always be an inspiration." Rihanna picked up the Billboard Chart Achievement award after winning the public vote ahead of Drake, Adele, Little Big Town and The Weeknd.
She also took home the Top Billboard 200 Album award for 25 - beating Justin's Purpose, Ed Sheeran's x, Taylor Swift's 1989 and The Weeknd's Beauty Behind The Madness. During his acceptance speech, he hailed Prince as an "inspiration". On stage, she said: "I have to thank, obviously, my fans and also my supporters - people who probably haven't been fans over the years but are inspired by the music and the art that I do and make." While Celine Dion broke down in tears as her son presented her with the Icon Award, Billboard's lifetime achievement honour, after a traumatic start to 2016 for the singer.
In a pre-recorded video message, the British star said: "I can't believe I won another one. "I want to dedicate this award to the late, great Prince. She sang Queen's The Show Must Go On in her first televised performance since her husband Rene Angelil and brother Daniel died from cancer just days apart in January. "Music has been my passion since before I remember. Most importantly, my beloved husband who I know will continue to watch over me from up above. The show must go on." Read more: Ariana Grande takes epic tumble live on air as she walks Billboard Music Awards red carpet Read more: Celine Dion breaks down on stage as son Rene Charles surprises her with Billboard Icon award Top Artist: Adele -- WINNER Justin Bieber Drake Taylor Swift The Weeknd Billboard Chart Achievement Award (Fan-Voted): Rihanna -- WINNER Adele Drake The Weeknd Little Big Town Top R&B Song: Alessia Cara “Here” Omarion Featuring Chris Brown & Jhene Aiko, “Post To Be” The Weeknd, “Can’t Feel My Face” The Weeknd, “Earned It (Fifty Shades of Grey)” The Weeknd, “The Hills” -- WINNER Top Billboard 200 Album: Adele, 25 -- WINNER Justin Bieber, Purpose Ed Sheeran, x Taylor Swift, 1989 The Weeknd, Beauty Behind The Madness Top Male Artist: Justin Bieber -- WINNER Drake Fetty Wap Ed Sheeran The Weeknd Top Country Song: Sam Hunt, “Break Up In A Small Town” Sam Hunt, “Take Your Time” Little Big Town, “Girl Crush” Thomas Rhett, “Die A Happy Man” -- WINNER Chris Young, “I’m Comin’ Over” Top Hot 100 Song: Adele, “Hello” Fetty Wap, “Trap Queen” Wiz Khalifa ft.
After receiving her award from 15-year-old Rene Charles, Dion said: "I want to be strong for my family and my kids. Charlie Puth, “See You Again” -- WINNER The Weeknd, “Can’t Feel My Face” The Weeknd, “The Hills” Top Hot 100 Artist: Justin Bieber Drake Fetty Wap Taylor Swift The Weeknd -- WINNER Top New Artist: Fetty Wap -- WINNER OMI Charlie Puth Silentó Bryson Tiller Top Female Artist: Adele -- WINNER Selena Gomez Ariana Grande Rihanna Taylor Swift Top Duo/Group: Maroon 5 One Direction -- WINNER twenty one pilots The Rolling Stones U2 Top Billboard 200 Artist: Adele -- WINNER Justin Bieber Drake Taylor Swift The Weeknd Top Song Sales Artist: Adele Justin Bieber Drake Fetty Wap The Weeknd -- WINNER Top Radio Songs Artist: Justin Bieber Ellie Goulding Ed Sheeran Taylor Swift The Weeknd -- WINNER Top Streaming Songs Artist: Justin Bieber Drake Fetty Wap Silentó The Weeknd -- WINNER Top Social Media Artist: Justin Bieber -- WINNER Selena Gomez Ariana Grande Demi Lovato Taylor Swift Top Touring Artist: Madonna One Direction The Rolling Stones Taylor Swift -- WINNER U2 Top R&B Artist: Chris Brown Jeremih Rihanna Bryson Tiller The Weeknd -- WINNER Top Rap Artist: Drake -- WINNER Fetty Wap Future Wiz Khalifa Silentó Top Country Artist: Zac Brown Band Luke Bryan -- WINNER Sam Hunt Chris Stapleton Carrie Underwood Top Rock Artist: Fall Out Boy Elle King twenty one pilots -- WINNER Walk the Moon X Ambassadors Top Latin Artist: Banda Sinaloense MS De Sergio Lizárraga Juan Gabriel Nicky Jam Ariel Camacho y Los Plebes del Rancho Romeo Santos -- WINNER Top Dance/Electronic Artist: The Chainsmokers DJ Snake David Guetta -- WINNER Major Lazer Zedd Top Christian Artist: Casting Crowns Lauren Daigle Hillsong United -- WINNER Mercy Me Chris Tomlin Top Gospel Artist: Anthony Brown and group ther APy Tasha Cobbs Kirk Franklin -- WINNER Travis Greene Marvin Sapp Top Soundtrack: Empire: Original Soundtrack from Season 1 Fifty Shades of Grey Furious 7 Guardians of the Galaxy: Awesome Mix Vol.
1 Pitch Perfect 2 -- WINNER Top R&B Album: Chris Brown, Royalty Rihanna, Anti Bryson Tiller, T R A P S O U L Tyrese, Black Rose The Weeknd, Beauty Behind the Madness -- WINNER Top Rap Album: Drake, If You’re Reading This It’s Too Late Drake & Future, What A Time To Be Alive Dr.


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The concentra tion of tamoxifen and a few of its metabolites in tumor within this examine are in line with past scientific studies in man and rats exhibiting up to tenfolds higher concentrations in tissues. Working with LC MSMS technological innovation we were now capable also to measure tamNox. As opposed to another metabolites, both NDDtam and tamNox had been detected at decrease concentrations than the parent drug in serum samples and tumor tissue. Interestingly, tamNox was the sole me tabolite with larger concentrations noticed in serum com pared to tumor tissue. This could possibly be explained by the in vitro observation that tamNox can quickly be diminished back to tamoxifen in tissues. This reduction of tam Nox is catalyzed by numerous CYPs not having significant choose ivity. On this animal model, 4OHNDtam was noticed at increased concentration than the other hydroxylated metabo lites in each tumor and serum.
Also in humans 4OHND tam is the hydroxylated metabolite with the highest concentration in serum and tissues. A limitation on the existing study may be the high concentration of tamoxi fen and its metabolites observed in contrast to past scientific studies working with rats. selleck The variability in drug and metabolite concentrations involving research is often explained by components such as tamoxifen dose, duration of remedy and interstrain variability in uptake, deposition and metabolic process of tamoxifen as linked on the variability in expression and inducibility of CYPs all through tamoxifen remedy. However, it really should be noted that the me taboliteparent drug ratios of NDtam and NDDtam plus the accumulation of tamoxifen and metabolites in tumor tissue are in line with preceding findings from clinical tamoxifen trials. Conclusions We observed an induction within the SRCs, HER two and HER three expression while in tamoxifen treatment in DMBA induced, endocrine responsive breast cancer.
There have been signifi cantly beneficial correlations among SRC 1, SRC 2TIF 2 and HER 2, and among SRC 3AIB1, HER four and Ets 2 mRNA amounts in tumor tissue. More, HER two mRNA was correlated together with the gene expression of your other HERs, an observation which signifies the significance of learning the many HERs in breast cancer. DMBA induced breast cancer could be a suitable model for studies within the cross talk among HERs, ER and SRCs selleck chemicals in vivo. Background CRC is definitely the third most typical kind of cancer on the planet with an annual around the world incidence of over one million circumstances. Early detection, adequate surgical excision and optimal utilization of adjuvant remedy are of vital importance for that clinical outcome. Now, tumour stage at diagnosis is the most critical prognostic issue and adjuvant chemotherapy is recom mended for all sufferers with stage III condition to cut back the relative threat of recurrence with somewhere around 30%. The purpose of adjuvant chemotherapy in stage II disease is even more unclear, and there’s an ongoing debate on the right way to determine patients with high possibility illness who have a better risk of recurrence and may well benefit from adjuvant ther apy.
Silencing of HNF1a lasted till 7 days in HepG2, but was not maintained beyond three days in Hep3B. Expression of HNF1a homologue, HNF1b, was not diminished by HNF1a siRNA at 24 and 48 h immediately after transfection, assessing that HNF1a siRNA did not target HNF1b mRNA. Cells transfected with HNF1a siRNA had a diverse phenotype from cells transfected with management siRNA. On phase contrast microscopy, they looked elongated and had misplaced cell cell contacts. This pheno style was maintained till at the least 7 days following transfec tion in HepG2 cells. Phalloidin labelling revealed reorganized actin cytoskeleton with advancement of actin structures seeking like lamelipodia and filopodia in the two cell variety. Time lapse microscopy of HepG2 cells transfected with HNF1a siRNA showed the cytoplasmic protrusions observed in people cells have been dynamic structures protruding from the cell.
Expression of albumin, a liver certain gene, and of transcription aspects concerned selleck in hepatocyte differentia tion, assessed by quantitative RT PCR, was diminished three days after transfection in each cell type, and was maintained lower until eventually at the least seven days after trans fection in HepG2. Especially, HNF4a expression, which has been proven for being regu lated by HNF1a, was decreased early soon after trans fection and this lower was strongly correlated to HNF1a expression, which was modulated by utilizing sev eral concentrations of siRNA. These final results revealed dedifferentiation of cells transfected with HNF1a siRNA. Epithelial markers are below expressed and mesenchymal markers are overexpressed in HNF1a siRNA transfected cells Epithelial mesenchymal transition is defined by reduction of epithelial cell polarity, disappearance of differen tiated junctions, reorganization on the cytoskeleton and changes in migration skills.
For the duration of this professional cess, epithelial markers such as E cadherin are underneath selleck chemicals expressed and mesenchymal markers are more than expressed. In HepG2 cells transfected with HNF1a siRNA, E cad herin is strongly under expressed with the transcription degree too as at protein degree. Immunostaining of E cadherin showed presence at cell cell junctions in handle siRNA transfected cells whereas cells transfected with HNF1a siRNA showed no staining at cell borders, suggesting reduction of adherens junction in people cells. Interestingly, the lessen of E cadherin mRNA was drastically correlated to HNF1a mRNA lower, when it was modulated using a variety of siRNA. Moreover, zonula occlu dens 1, a tight junction protein, was also beneath expressed at transcriptional level. In HNF1a inhibited HepG2 cells, the mesenchymal mar kers vimentin and fibronectin had been more than expressed each at RNA and protein amounts. Sev eral proteins associated with bassement membrane degrada tion, metalloproteinases two, 3 and 9, have been also in excess of expressed in HepG2 cells transfected with HNF1a siRNA.
As proven in Figure 7B, Bmi one was strongly up regulated in breast cancer tis sues in contrast with paired non cancerous tissues, whereas E cadherin was markedly down regulated. Addi tionally, an inverse correlation was found amongst Bmi 1 and E cadherin at the transcriptional degree. To more decipher the purpose of Bmi one while in the invasion and metastasis of breast cancer, EMT markers have been analyzed in primary xenografts and spontaneous metastatic lung lesions by immunohistochemistry. As proven in Figure eight, Bmi 1 repression enhanced the expression of b Catenin and concomitantly decreased the expression of Fibronectin in key xenografts and metastatic lung lesions. As demonstrated above, Bmi 1 is negatively correlated together with the expression of E cadherin, that is necessary for EMT in breast cancer.
Bmi 1 activates the AktGSK 3bSnail pathway Steady with our former reviews that Bmi one could regulate Akt action in breast cancer cells as well as AktGSK 3bSnail pathway in NPC cells, the overex pression of Bmi one facilitated the expression of phosphory lated Akt. Furthermore, the knockdown of Bmi one inhibited the expression of phosphorylated Akt, but total read review Akt remained unaffected. As anticipated, the expression of Snail and phosphorylated GSK 3b was up regulated by Bmi 1 overexpression and down regulated by Bmi 1 knockdown, but the amounts of complete GSK 3b remained unaffected. Nevertheless, the tran scriptional level of Snail was not affected by Bmi one overex pression, suggesting the modulation of Snail might be as a result of a post transcriptional modifica tion. Bmi 1 could extend the half existence of Snail in NPEC cells by directing the subcellular localization, as demon strated by our earlier data. For this reason, we analyzed the localization of Snail in MCF 10A cells.
As proven in Figure 9B, Snail can be detected in the nucleus and cyto plasm of your controls, nevertheless it was principally localized inside the nucleus of your Bmi one transfected cells. Collectively, it seems that Bmi one induces the activation extra resources of Akt and the inactivation of GSK 3b by phosphorylation, facilitates the stabilization and nuclear translocation of Snail, and eventually outcomes during the deregulation of EMT markers, hence promot ing the migration and invasion of breast cancer cells. Discussion Breast cancer, a typical malignant disease in gals, is prone to invade into adjacent regions and also to metasta size to lymph nodes and distant organs. To create novel treatments and cures, it is critical to tackle the factors underlying tumorigenesis, invasion and metastasis. Within this examine, we recognized and functionally characterized Bmi one as a significant player in breast cancer progression. The present review initial illustrated the expression of Bmi 1 in key breast cancer tissues, followed by demonstrating the association concerning the Bmi 1 expression and clinicopathologic parameters and finally addressed the position of Bmi 1 in breast cancer prognosis within a substantial series of 252 samples.
As shown in Figure 7B, Bmi 1 was strongly up regulated in breast cancer tis sues in contrast with paired non cancerous tissues, whereas E cadherin was markedly down regulated. Addi tionally, an inverse correlation was noticed amongst Bmi one and E cadherin at the transcriptional level. To even further decipher the position of Bmi one while in the invasion and metastasis of breast cancer, EMT markers had been analyzed in major xenografts and spontaneous metastatic lung lesions by immunohistochemistry. As shown in Figure 8, Bmi 1 repression enhanced the expression of b Catenin and concomitantly diminished the expression of Fibronectin in major xenografts and metastatic lung lesions. As demonstrated above, Bmi 1 is negatively correlated with all the expression of E cadherin, which can be crucial for EMT in breast cancer.
Bmi one activates the AktGSK 3bSnail pathway Constant with our previous reviews that Bmi one could regulate Akt action in breast cancer cells plus the AktGSK 3bSnail pathway in NPC cells, the overex pression of Bmi one facilitated the expression of phosphory lated Akt. In addition, the knockdown of Bmi one inhibited the expression of phosphorylated Akt, but complete selleck chemical HER2 Inhibitors Akt remained unaffected. As anticipated, the expression of Snail and phosphorylated GSK 3b was up regulated by Bmi one overexpression and down regulated by Bmi one knockdown, but the levels of complete GSK 3b remained unaffected. Nevertheless, the tran scriptional level of Snail was not impacted by Bmi 1 overex pression, suggesting the modulation of Snail may be as a result of a submit transcriptional modifica tion. Bmi one could lengthen the half lifestyle of Snail in NPEC cells by directing the subcellular localization, as demon strated by our past information. Consequently, we analyzed the localization of Snail in MCF 10A cells.
As proven in Figure 9B, Snail could be detected within the nucleus and cyto plasm of the controls, however it was mostly localized while in the nucleus of the Bmi 1 transfected cells. Collectively, it appears that Bmi 1 induces the activation selleck inhibitor of Akt as well as the inactivation of GSK 3b by phosphorylation, facilitates the stabilization and nuclear translocation of Snail, and eventually outcomes while in the deregulation of EMT markers, so promot ing the migration and invasion of breast cancer cells. Discussion Breast cancer, a frequent malignant illness in women, is susceptible to invade into adjacent areas and also to metasta dimension to lymph nodes and distant organs. To produce novel therapies and cures, it truly is essential to address the aspects underlying tumorigenesis, invasion and metastasis. Within this review, we recognized and functionally characterized Bmi one as a vital player in breast cancer progression. The current research very first illustrated the expression of Bmi 1 in principal breast cancer tissues, followed by demonstrating the association involving the Bmi 1 expression and clinicopathologic parameters and last but not least addressed the position of Bmi 1 in breast cancer prognosis in a substantial series of 252 samples.
It’s turn into one of several top rated leads to of extreme hepatic dysfunction from the modern globe. Liver fibrosis, by which NASH develops into cir rhosis, can be a healing response to chronic injuries. Fibro genesis consists of multifactorial oxidative stress, cytokine imbalance, and hepatic stellate cells activation. Unfortunately, currently there’s no precise and successful antifibrotic therapy on the market, for that reason it can be rather vital that you realize liver fibrosis in its early phases and search for new remedy technique to prevent even further progression. Fuzheng Huayu recipe, a compound of Chinese herbal medicine, consists of 6 Chinese medicinal herbs, namely Semen Persicae, Radix Salvia Miltiorrhizae, Gynostemma Pentaphyllammak, Cordyceps, Pollen Pini, Fructus Schisandrae Chinensis. The prior clinical trials showed that FZHY could appreciably improve clin ical signs and symptoms, liver function, reverse hepatic fibrosis and decrease portal pressure in sufferers with chronic hepatitis B and liver cirrhosis.
Nevertheless, the impact of FZHY on fibrosing steatohepatitis remains unknown. On this review, we investigated the purpose and molecular basis of FZHY during the evolution of nutritional fibrosing steatohe patitis in mice. Material and procedures Animals and therapies Eight week old male C57BL6 J mice with physique bodyweight concerning twenty 25 g have been obtained through the Experimental Animal Center of the full details Chinese Academy of Healthcare Sciences, and had been bred inside a temperature controlled animal facility that has a twelve h light dark cycle. They had no cost entry to water and were allowed to adapt to their foods and environment for 1 week just before the start from the experiment.
The C57BL 6 J mice have been randomly divided into 5 groups, one MCD group, mice fed methionine read the article choline defi cient diet program, two manage group, mice fed MCD food plan supplemented with choline bitartate and DL methionine, three MCD hemin group, mice fed MCD eating habits administered with heme oxygenase 1 chemical inducer hemin by intraperitoneal injections 3 times per week, 4 MCD FZHY group, mice fed MCD diet supple mented with FZHY, 5 MCD FZHY hemin group, mice fed MCD diet program administered with FZHY and hemin. The duration from the experiment is up to eight weeks. During the experiments, their body excess weight and price of eating habits consumption have been recorded. All the animals had been sacrificed after overnight fasting at the finish of experi ments. Blood samples have been collected from femoral artery for biochemical evaluation. Livers were weighed and fixed in 10% formalin for histological examination or snap frozen in lipid nitrogen followed by storage at 80 C freezer until demanded. All the protocols and procedures have been per formed following the pointers of the Hebei Committee for Care and Use of Laboratory Animals and have been accredited by the Animal Experimentation Ethics Commit tee within the Hebei Medical University.
On top of that, it’s been reported that carba chol, by activation of muscarinic receptors, is able to improve inflammatory gene expression in ASM, includ ing IL 6, IL eight and cyclooxygenase two. Furthermore, acetylcholine can induce leuko triene B4 release from sputum COPD cells, also indicating a regulatory function for ACh in inflamma tory cells. Taken together, this signifies that acetylcho line is importantly involved inside the regulation of professional inflammatory responses. Our current results deliver new insights as we demonstrate the activation of muscarinic receptors interacts with various cytokines and development components, particularly with TNF a, PDGF AB and CSE to enhance their inflammatory response in hASMc. HASMc create a wide range inflammatory mediators. This suggests an essential function for ASM in inflammatory responses in COPD.
Certainly, hASMc really are a supply of chemokines and cytokines that play a purpose in chronic pulmonary diseases like COPD and asthma, together with IL 8 and IL six. The amounts of IL 8 are correlated with all the degree of order Cilengitide neutrophilic irritation and are improved in sputum in COPD individuals. Numerous pro inflammatory stimuli, which include IL 17, gram positive and gram negative bacteria, b tryptase, IL 1b and TNF a can induce IL 8 secre tion from human ASM. Additionally, CSE synergizes with TNF a to enhance IL 8 secretion by ASM. We pre viously demonstrated that CSE and muscarinic M3 recep tor stimulation prospects to a synergistic boost in IL eight secretion by hASMc, which as demonstrated within this review, is dependent on downstream signalling to PKC plus the I Ba/NF B and MEK/ERK1/2 pathways. Nicoti nic receptors and muscarinic M2 receptors aren’t concerned in this synergism, as gallamine had no result on IL eight release induced by either CSE or MCh.
This indicates that acetylcholine may additionally play a significant role while in the immunomodulatory processes driven by human ASM. Employing the PKC inhibitor GF109203X, we demonstrate selleck chemicals VX-661 that the synergism of MCh and CSE induced IL eight secre tion is mediated by PKC in hASMc. In fact, activation of PKC was sufficient to induce synergistic IL 8 secre tion in combination with CSE, which was confirmed through the utilization of the PKC activator, PMA. These observations correspond with an earlier review from our group demonstrating that MCh augments PDGF induced cell proliferation by means of the activation of PKC and seem to recommend that muscarinic M3 receptors exert their facil itatory results on remodeling and irritation to an essential extent through the activation of PKC. Down stream, we demonstrated that PKC is capable of induce the activation of I Ba/NF B and MEK/ERK1/2 pathways in hASMc and that these pathways are concerned during the secretion of IL eight induced through the co stimulation of mus carinic receptors and CSE.
5 ng/ml of IL 4 for 8 h, washed and re incubated in fresh medium devoid of IL four for an additional sixteen h. Inhibitor scientific studies were carried out by pre treating cultures separately with one,4 diamino two,3 dicyano one,four bis butadiene, 2 9 fluoro three,6 dihydro 7H benz imidazo isoquinolin 7 1 and 4 amino six, 7 dimethoxyquinazoline in DMSO at varying concentrations for thirty min just before publicity to IL 4. Immunohistochemistry The presence of IL selleck inhibitor 4 receptor chain about the cell surface was established by utilizing a rabbit polyclo nal anti human IL 4Rantibody. The harvested cells have been initially washed with phosphate buffered saline solution, fixed in 4% paraformaldehyde for five min and permeabi lized in 0. 1% Triton X one hundred. Blocking was performed with 4% BSA for 45 min prior to incubating with principal anti human IL 4R Ab at one.a hundred dilutions for 1 h. Secondary incubations were performed with Alexa Fluor labeled mouse anti rabbit Ab at 1.
250 for 10 min. The cells were counterstained with DAPI for 2 min prior to visualizing on the Zeiss Axioplan 2 microscope. Dilu ent selleckchem lacking primary Ab and non immune rabbit IgG had been utilized as controls. RNA extraction and reverse transcription Total RNA was extracted by RNeasy Mini kit following the manufactures protocol. The DNase digestion of the RNA samples was carried out on RNeasy columns using the RNAse no cost DNase set provided from the same producer. The integrity in the eluted RNA was confirmed by electrophoresing 5 of total RNA on one. 2% agarose/formaldehyde gels. The isolated RNA was reverse transcribed utilizing random hexamers and Super script II Initial Strand Synthesis kit following the manufacturers protocol. Real time PCR evaluation Authentic time PCR amplifications have been carried out during the pres ence of flurogenic Taqman 6 Fam Tamra probes on ABI Prism 7000 instrument.
Primers and Taqman probes for MUC4 have been sourced from published reports even though the endog enous human 18s rRNA standards were commercially obtained from Applied Biosystems. The optimal concentrations for MUC4 amplifi cation had been established for being 900 nM of forward, 300 nM of reverse and ultimate probe concentration of a hundred nM per response. Negative controls had been performed omitting the RT phase in advance of PCR amplifications. The relative abun dance of MUC4 was established by Ct strategy. Nuclear run on transcription assay The modified assay involving PCR was adopted from ear lier published literature by Rolfe, et al.. Nuclei were extracted from handle and IL four handled cells immediately after 4 and 8 h using the Nuclei Ez Prep isolation kit. An extra, lyse/wash was integrated while in the protocol to enhance the yields of nuclei. Isolated nuclei had been layered onto a sucrose cushion by cen trifugation for 40 min at 16000 g. Nuclei from treated and manage cells have been split into two aliquots.
The tissue array exposed a greater variety of dere gulated miRNAs and those that have been concurrently expressed in blood array had been picked for even further valid ation. The picked miRNAs consisted of two down regulated and five up regulated miRNAs. Validation of miRNA expressions by RT PCR The selected miRNAs from miRNA profiling have been vali dated with RT PCR utilizing an independent set of tissue and blood samples. RNU48 was selected since the endoge nous control in data normalization and its expression was discovered for being steady and reproducible. No significant difference was uncovered in the level of RNU48 among CRCs and controls. Utilizing a whole new subset of thirty paired cancer tissue and adjacent normal mucosa sam ples, vital deregulations were observed while in the panel of 7 miRNAs making use of paired t check.
For blood samples validation, major elevations have been detected during the levels of miR 193a 3p, miR 23a, miR 23b, miR 338 5p and miR 483 3p in CRC scenarios. Nonetheless, no major dif ference was observed while in the levels of miR 150 and miR 342 3p. The absolute Ct values of miRNAs in the two tissue and blood samples ranged from 21 to 28 for miR 150, 27 to 33 for miR selleck chemical PD184352 193a 3p, 23 to thirty for miR 23a, 23 to 31 for miR 23b, 28 to 33 for miR 338 5p, 25 to 29 for miR 342 3p and 26 to 33 for miR 483 3p. Partnership concerning tissue and blood miRNAs Provided that miR 193a 3p, miR 23a, miR 23b, miR 338 5p and miR 483 3p were significantly up regulated in the two tissue and blood samples from the validation examine, we’ve got proceeded to investigate the correlation between them.
The purpose is usually to provide a stronger confirmation that deregulated miRNA expressions in the systemic circulation are prospective indicators of what on earth is happening at tissue degree. Controlling for age, gender, race and TNM staging, correlation analyses between tissue and blood RT PCR information for miR 193a 3p, miR 23a, miR 23b, miR 338 5p and miR 483 3p were carried out. The results indi cated kinase inhibitor NSC-632839 significant good correlations inside the levels of miR 193a 3p, miR 23a and miR 338 5p amongst tissue and blood samples. MiR 23b was not appreciably correlated whilst miR 483 3p exposed weak correlation. Therefore, miR 193a 3p, miR 23a and miR 338 5p had been picked since the triple miRNA classifier in our research. In addition, an increas ing trend of expression was observed in these circulating blood miRNAs from the less superior phases for the more advanced stages when compared with controls.
Diagnostic value of your triple miRNA classifier, miR 193a 3p, miR 23a and miR 338 5p in CRC The predictive effectiveness of individual circulating blood miRNA as well as the triple miRNA classifier for defining CRC have been demonstrated by multivariate logistic regression examination. The triple miRNA classifier of miR 193a 3p, miR 23a and miR 338 5p gave the very best performance and could be a probable biomarker inside the detection of CRC.
In 61% of these ad enomatous polyps the transcript expression exceeded 100 fold relative to that of ordinary colon tissue. This observation gives you supportive proof of the position of CCAT1 while in the early neoplasia stage of colon carcinoma pathogenesis. The acquiring of imply CCAT1 expression in adenoma appreciably exceeding that of carcinoma more supports this hypothesis, since it factors to a down regulating result on CCAT1 expression the moment malignant transformation is attained. CCAT1 up regulation of 5 fold or increased compared to normal colon. Transcript up regulation was seen in 90. 1% of malignant key tumor samples obtained from patients with Stage I III colon adenocarcinoma. The fact that this non coding RNA is found on chromosome 8q24.
21, a hot spot for many cancer linked single nucleotide polymorphisms, sup ports a purpose for CCAT1 from the tumorigenesis of colon carcinoma. Existing histopathological nodal staging ways could overlook occult lymph node metastases amounting to pathological beneath staging and underneath remedy. Countless investigators have attempted to enhance WP1066 structure upon lymph node staging in sufferers with colon cancer. We analyzed lymph nodes from sufferers with colon cancer acquiring ob vious macro metastasis by regular histopathological staging for CCAT1 expression and compared this expres sion to that of damaging lymph nodes by histopathology obtained through the identical individuals and to that of benign lymph nodes for sufferers without the need of colon cancer. CCAT1 was highly up regulated in all 10 metastatic lymph nodes studied.
This kind of exceedingly large expression of CCAT1 could possibly propose an essential position of this unique non coding RNA in regional lymphatic and nodal dissem ination of colon adenocarcinoma. Moreover, this fin ding may very well be utilized clinically for your detection of occult metastatic disease in seemingly illness selleckchem totally free regional lymph nodes of patients undergoing surgical resection of colon cancer with curative intent. This would boost staging accuracy and individualized treatment setting up, specifically adjuvant systemic treatment in sufferers without dal disease. Two from the most common sites of metastatic spread of colon adenocarcinoma would be the liver and peritoneum. For this reason, we incorporated individuals operated on for treat ment of metastatic disease to these organ internet sites in our study.
Sadly, all individuals had been previously treated by systemic therapy, therefore, treatment method associated altera tions in CCAT1 expression can’t be excluded in these pre taken care of patients. Yet, the practical actuality is that accessibility to tissue of na ve patients with colon cancer metastatic towards the liver or peritoneum is limited, because it can be a distinctly unusual clinical scenario considering the fact that most individuals are handled, in accordance to our evidence primarily based tips, with systemic treatment ahead of surgery for metastatic disease. Taking this likely bias under consideration, we showed that CCAT1 was up regulated in liver also as in peritoneal metastasis of colon cancer sufferers.
The effect of EEGE about the survival time of Consume cells bearing mice was evaluated and it is presented in Figure 8. Eat cells had been injected intraperitoneally to mice and these cells grew as ascites tumor with accumulation of substantial volume of ascitic fluid while in the peritoneal cavity. Survival from the manage group was uncovered to be at 50% to the 32nd day right after tumor inoculation and no animal survived beyond the 34th day. Whereas survival of EEGE taken care of Eat cells bearing animals was 100% on the 38th day and 15% in the 45th day, with no animal alive be yond day 48. The many doses of your algae extract examined within this experiment drastically altered the charge of mice survival. No vital statistical recommended reading difference was observed between mice taken care of with one hundred and 200 mgkg of EEGE. The administration of a hundred, 200 and 300 mgkg of EEGE soon after tumor inocula tion resulted inside a vital inhibition of tumor development, as evident from a 75% reduction in intraperi toneal tumor cell burden within the day of death.
Mice taken care of with 100, 200 and 300 mgkg EEGE presented 3. 6 two. 3 107, three. eight 2. one 107 and three. 9 2. eight 107 viable ascites cells, respectively, while the management group presented selleckchem Avagacestat twelve. 1 three. 4 107. In vivo toxicity scientific studies Right after encouraging effect of EEGE in inhibiting cancer progression in vivo, we evaluated the undesired side ef fects of your i. p. administration of daily doses of one hundred, 200 and 300 mgkg of EEGE for 35 days in healthful adult swiss albino mice. Drug toxicity was assessed by clinical indicators of gross toxicity, behavioral improvements and mortality, such as hematological, biochemical and histopatho logical parameters. No animal death was observed in any with the groups in the course of the experimental time period of 35 days.
No abnormal clinical signs or behavioral improvements had been observed in any on the groups, and changes in physique weights with the EEGE taken care of groups weren’t signifi cantly various among any groups which includes the con trol group right after 35 days of therapy time period. There were no substantial alterations in hematological pa rameters in the EEGE taken care of groups. Similarly, no considerable variations had been discovered involving the EEGE treated groups as well as controls to the three blood chem ical parameters evaluated, AST, ALT, ALP and LDH, which were inside of the physiological selection of values expected to the strategy of blood collection. These data indicate that regular intraperitoneal injections of EEGE at doses as much as 300 mgkg for 35 days did not lead to hema totoxicity nor poses hazards of renal or hepatotoxicity. At necropsy, no visible pathological alterations had been mentioned within the livers and kidneys of mice administered EEGE at a hundred, 200 and 300 mgkg doses. Histological analysis of formaldehyde fixed, paraffin embedded liver and kidney sections stained with hematoxylin and eosin showed typical architecture in all experimental groups.