Tuesday, October 31, 2017

The Catalan Republic Collapses

The Catalan Republic was a short-lived unrecognized secessionist state that was declared on 27 October 2017. The Parliament of Catalonia unilaterally declared independence from Spain amid a constitutional crisis over the result of the 2017 Catalan independence referendum. By 30 October, Spanish authorities had reasserted control over Catalan territory with little resistance, with the independence declaration being suspended by the Constitutional Court of Spain on the next day.

Shortly after the Catalan parliament declared independence from Spain, the Spanish Senate triggered Article 155 of the Spanish Constitution of 1978, and Prime Minister Mariano Rajoy dismissed the Executive Council of Catalonia, dissolving the Parliament of Catalonia and calling a snap regional election for 21 December 2017. In response, Carles Puigdemont, President of the Generalitat of Catalonia, stated that only parliaments could elect or remove governments in a democratic society and asked Catalans to "democratically oppose" the enforcement of Article 155, without clarifying what his response would be to the Spanish government's orders.

By 30 October, work had resumed as normal throughout Catalonia as the Spanish government's takeover met with little resistance from Catalan authorities. Puigdemont and part of his cabinet fled to Belgium to escape action from the Spanish judiciary, having been formally accused of rebellion, sedition and embezzlement by the Spanish Attorney General.

                       https://en.wikipedia.org/wiki/Catalan_Republic_(2017)

Monday, October 30, 2017

America Loses "Fats" Domino

Antoine Dominique "Fats" Domino Jr. (February 26, 1928 – October 24, 2017) was an American pianist and singer-songwriter of Louisiana Creole descent. One of the pioneers of rock and roll music, Domino sold more than 65 million records. Between 1955 and 1960, he had eleven Top 10 hits. His humility and shyness may be one reason his contribution to the genre has been overlooked.

During his career, Domino had 35 records in the U.S. Billboard Top 40, and five of his pre-1955 records sold more than a million copies, being certified gold. His musical style was based on traditional rhythm and blues, accompanied by saxophones, bass, piano, electric guitar, and drums

By age 14, Domino was performing in New Orleans bars. In 1947, Billy Diamond, a New Orleans bandleader, accepted an invitation to hear the young pianist perform at a backyard barbecue. Domino played well enough that Diamond asked him to join his band, the Solid Senders, at the Hideaway Club in New Orleans, where he would earn $3 a week playing the piano. Diamond nicknamed him "Fats", because Domino reminded him of the renowned pianists Fats Waller and Fats Pichon, but also because of his large appetite.
                                                                Domino in 1962

Recordings for Imperial Records, 1949 to 1962

Domino was signed to the Imperial Records label in 1949 by owner Lew Chudd, to be paid royalties based on sales instead of a fee for each song. He and producer Dave Bartholomew wrote "The Fat Man", a toned down version of a song about drug addicts called "Junkers Blues"; the record had sold a million copies by 1951. Featuring a rolling piano and Domino vocalizing "wah-wah" over a strong backbeat, "The Fat Man" is widely considered the first rock-and-roll record to achieve this level of sales. In 2015, the song would enter the Grammy Hall of Fame.

Domino released a series of hit songs with Bartholomew (also the co-writer of many of the songs), the saxophonists Herbert Hardesty and Alvin "Red" Tyler, the bassist Frank Fields, and the drummers Earl Palmer and Smokey Johnson. Other notable and long-standing musicians in Domino's band were the saxophonists Reggie Houston, Lee Allen, and Fred Kemp, Domino's trusted bandleader.

Domino crossed into the pop mainstream with "Ain't That a Shame" (mislabeled as "Ain't It a Shame") which reached the Top Ten. This was the first of his records to appear on the Billboard pop singles chart (on July 16, 1955), with the debut at number 14. A milder cover version by Pat Boone reached number 1, having received wider radio airplay in an era of racial segregation. In 1955, Domino was said to be earning $10,000 a week while touring, according to a report in the memoir of artist Chuck Berry. Domino eventually had 37 Top 40 singles, but none made it to number 1 on the Pop chart.

Domino's debut album, Carry On Rockin, which contained several of his hits and tracks that had not yet been released as singles, was issued on the Imperial label (catalogue number 9009) in November 1955, and was reissued as Rock and Rollin' with Fats Domino in 1956. The reissue reached number 17 on the Billboard Pop Albums chart.

His 1956 recording of "Blueberry Hill", a 1940 song by Vincent Rose, Al Lewis and Larry Stock (which had previously been recorded by Gene Autry, Louis Armstrong and others), reached number 2 on the Billboard Juke Box chart for two weeks and was number 1 on the R&B chart for 11 weeks. It was his biggest hit, selling more than 5 million copies worldwide in 1956 and 1957. The song was subsequently recorded by Elvis Presley, Little Richard, and Led Zeppelin. Some 32 years later, the song would enter the Grammy Hall of Fame.

Domino had further hit singles between 1956 and 1959, including "When My Dreamboat Comes Home" (Pop number 14), "I'm Walkin'" (Pop number 4), "Valley of Tears" (Pop number 8), "It's You I Love" (Pop number 6), "Whole Lotta Loving" (Pop number 6), "I Want to Walk You Home" (Pop number 8), and "Be My Guest" (Pop number 8).

Domino appeared in two films released in 1956: Shake, Rattle & Rock! and The Girl Can't Help It. On December 18, 1957, his hit recording of "The Big Beat" was featured on Dick Clark's American Bandstand.

On November 2, 1956, a riot broke out at a Domino concert in Fayetteville, North Carolina. The police used tear gas to break up the unruly crowd. Domino jumped out a window to avoid the melee; he and two members of his band were slightly injured. During his career, four major riots occurred at his concerts, "partly because of integration", according to his biographer Rick Coleman. "But also the fact they had alcohol at these shows. So they were mixing alcohol, plus dancing, plus the races together for the first time in a lot of these places." In November 1957, Domino appeared on the Ed Sullivan TV program; no disturbance accompanied this performance.

In the same year, the article "King of Rock ’n’ Roll" in Ebony (magazine) featured Domino who said he was on the road 340 days a year, up to $2,500 per evening, and grossing over $500,000; Domino also told readers that he owned 50 suits, 100 pairs of shoes and a $1,500 diamond horseshoe stick pin.

Domino had a steady series of hits for Imperial through early 1962, including "Walking' to New Orleans" (1960, Pop number 6), co-written by Bobby Charles, and "My Girl Josephine" (Pop number 14) in the same year. He toured Europe in 1962 and met the Beatles who would later cite Domino as an inspiration. After returning, he played the first of his many stands in Las Vegas.

Imperial Records was sold in early 1963, and Domino left the label. "I stuck with them until they sold out," he said in 1979. In all, he recorded over 60 singles for Imperial, placing 40 songs in the top 10 on the R&B chart and 11 in the top 10 on the Pop chart. Twenty-seven of which were double-sided hits.

Death

Domino died on October 24, 2017, at his home in Harvey, Louisiana, at the age of 89, from natural causes, according to the coroner's office.

Influence and Legacy

Domino was one of the biggest stars of rock and roll in the 1950s and one of the first R&B artists to gain popularity with white audiences. His biographer Rick Coleman argues that Domino's records and tours with rock-and-roll shows in that decade, bringing together black and white youths in a shared appreciation of his music, was a factor in the breakdown of racial segregation in the United States. The artist himself did not define his work as rock and roll, saying, "It wasn't anything but the same rhythm and blues I'd been playin' down in New Orleans."

Domino was also an important influence on the music of the 1960s and 1970s and was acknowledged as such by some of the top artists of that era. Elvis Presley introduced Fats at one of his Las Vegas concerts, saying, "This gentleman was a huge influence on me when I started out." Presley also made this comment in a 1957 interview: "A lot of people seem to think I started this business. But rock ’n’ roll was here a long time before I came along. Nobody can sing that music like colored people. Let’s face it: I can’t sing it like Fats Domino can. I know that."

Both John Lennon and Paul McCartney recorded Domino songs. According to some reports, McCartney wrote the Beatles song "Lady Madonna" in emulation of Domino's style, combining it with a nod to Humphrey Lyttelton's 1956 hit "Bad Penny Blues". Domino also recorded the song in 1968. Domino returned to the "Hot 100" chart for the last time in 1968, with his recording of "Lady Madonna". That recording, as well as covers of two other songs by the Beatles, appeared on his Reprise album Fats Is Back, produced by Richard Perry and with several hits recorded by a band that included the New Orleans pianist James Booker.

Domino was present in the audience of 2,200 people at Elvis Presley's first concert at the Las Vegas Hilton on July 31, 1969. At a press conference after the show, when a journalist referred to Presley as "The King", Presley gestured toward Domino, who was taking in the scene. "No," Presley said, "that's the real king of rock and roll."

John Lennon covered Domino's composition "Ain't That a Shame" on his 1975 album "Rock 'n' Roll," his tribute to the musicians who had influenced him.

American band Cheap Trick recorded "Ain't That a Shame" on their 1978 live album Cheap Trick at Budokan and released it as the second single from the album. It reached 35 of the Billboard Hot 100. Reportedly, this was Domino's favorite cover.. It remains a staple of their live performances, including at their 25th Anniversary concert (which was recorded as the album and DVD Silver) and at their induction into the Rock and Roll Hall of Fame in 2016.

The Jamaican reggae artist Yellowman covered many songs by Domino, including "Be My Guest" and "Blueberry Hill."

Richard Hell, an early innovater of punk rock, covered Domino's "I Lived My Life" with his band, the Voidoids. Jah Wobble, a post-punk bassist best known for his work with Johnny Rotten, released a solo recording of "Blueberry Hill".

The Jamaican ska band Justin Hinds and the Dominoes, formed in the 1960s, was named after Domino, Hinds's favorite singer.

In 2007, various artists came together for a tribute to Domino, recording a live session containing only his songs. Musicians performing on the album, Goin' Home: A Tribute to Fats Domino, included Paul McCartney, Norah Jones, Willie Nelson, Neil Young, and Elton John.

According to Richie Unterberger, writing for AllMusic, Domino was one of the most consistent artists of early rock music, the best-selling African-American rock-and-roll star of the 1950s, and the most popular singer of the "classic" New Orleans rhythm and blues style. His million-selling debut single, "The Fat Man" (1949), is one of many that have been cited as the first rock and roll record. Robert Christgau wrote that Domino was "the most widely liked rock and roller of the '50s" and remarked on his influence:

Warm and unthreatening even by the intensely congenial standards of New Orleans, he's remembered with fond condescension as significantly less innovative than his uncommercial compatriots Professor Longhair and James Booker. But though his bouncy boogie-woogie piano and easy Creole gait were generically Ninth Ward, they defined a pop-friendly second-line beat that nobody knew was there before he and Dave Bartholomew created 'The Fat Man' in 1949. In short, this shy, deferential, uncharismatic man invented New Orleans rock and roll.

Domino's rhythm, accentuating the offbeat, as in the song "Be My Guest", was an influence on ska music.

                           https://en.wikipedia.org/wiki/Fats_Domino

Sunday, October 29, 2017

The Sakharov Prize

The Sakharov Prize for Freedom of Thought, commonly known as the Sakharov Prize, honours individuals and groups of people who have dedicated their lives to the defense of human rights and freedom of thought. Named after Russian scientist and dissident Andrei Sakharov, the prize was established in December 1988 by the European Parliament. A shortlist of nominees is drawn up annually by the Committee on Foreign Affairs and the Committee on Development, with the winner announced in October. The prize is accompanied by a monetary award of €50,000. The first prize was awarded jointly to South African Nelson Mandela and Russian Anatoly Marchenko. The 1990 award was given to Aung San Suu Kyi, but she could not receive it until 2013 as a result of her political imprisonment in Burma. The prize has also been awarded to organisations, the first being the Argentine Mothers of the Plaza de Mayo in 1992. Three Sakharov laureates were subsequently awarded the Nobel Peace Prize: Nelson Mandela, Aung San Suu Kyi, and Malala Yousafzai.

Razan Zaitouneh (2011) was kidnapped in 2013 and is still missing. Nasrin Sotoudeh (2012) was released from prison in September 2013, but is still barred from leaving Iran, along with fellow 2012 laureate Jafar Panahi.

The 2017 prize was awarded to the Democratic Opposition in Venezuela. European Parliament President Antonio Tajani stated that the award reaffirmed the EU's "unwavering support to the democratically-elected national assembly of Venezuela" going on to call for "the peaceful transition to democracy that the Venezuelan people are desperately calling for." The award was seen as rewarding the "courage of student activists and protesters in face of repression by Nicolas Maduro's government.”

                                   https://en.wikipedia.org/wiki/Sakharov_Prize

Saturday, October 28, 2017

The Catalan Republic

The Catalan Republic, also known as Catalonia, is a unilaterally declared state in the Iberian peninsula since 27 October 2017. The Parliament of Catalonia declared independence from Spain amid a constitutional crisis over the result of the 2017 Catalan independence referendum.

Shortly after the Catalan parliament declared independence from Spain, the Spanish Senate triggered Article 155 of the Spanish Constitution of 1978, and Prime Minister Mariano Rajoy dissolved the Parliament of Catalonia, dismissing the Executive Council of Catalonia and calling a snap regional election for 21 December 2017. In response, Carles Puigdemont, President of the Catalan, stated that only parliaments could elect or remove governments in a democratic society and asked Catalans to "democratically oppose" the enforcement of Article 155, but he did not clarify what his response would be to the Spanish government's orders.

As of 28 October 2017, the Catalan Republic is unrecognized by the international community, which regards the region as part of the Kingdom of Spain.

2017 Political Crisis

An independence referendum, which was suspended by the Constitutional Court of Spain after the Spanish government stated it was unconstitutional, was held in Catalonia on 1 October 2017. The referendum question, to which voters answered with a "Yes" or "No", was "Do you want Catalonia to become an independent state in the form of a republic?". The "Yes" side won, with 2,044,038 (92.01%) voting for independence and 177,547 (7.99%) voting against, albeit on a registered turnout of 43.03% and amid questions about compliance with basic voting regulations.

In an ambiguous speech during a parliamentary session in the Parliament of Catalonia on 10 October, Puigdemont declared that "Catalonia had earned the right to be an independent state" and that he defended "the mandate of the people of Catalonia to become an independent republic". However, he immediately announced that parliament should suspend a formal declaration of independence in order to pursue dialogue with the Spanish government. Puigdemont and other pro-independence deputies then signed a symbolic declaration of independence with no legal effect. On 11 October, after an extraordinary cabinet meeting intended to address the events on the previous day, Prime Minister Mariano Rajoy announced he was formally requiring the Catalan government to confirm whether it had declared independence before 16 October at 10 am, with a further three-day deadline until 19 October to revoke all deemed illegal acts if an affirmative answer—or no answer at all—was obtained. This requirement was a formal requisite needed to trigger article 155 of the Spanish Constitution, a so-called "nuclear option" that would allow the Spanish government to suspend Catalonia's political autonomy and impose direct rule from Madrid. Pressure mounted within the pro-independence coalition as the CUP demanded an unambiguous affirmation of Catalan independence, threatening to withdraw its parliamentary support from Puigdemont's government if he rescinded his independence claim. In his formal response to Rajoy's requirement hurrying the initial five-day deadline, Puigdemont failed to clarify whether independence had been declared and instead called for negotiations over the following two months. The Spanish government replied that this was not a valid response to its requirement and doubted that Puigdemont's offer for dialogue was sincere due to his lack of "clarity". The refusal from the Catalan government to either confirm or deny independence triggered a second deadline for them to backtrack before direct rule was imposed.

On 19 October, Prime Minister Mariano Rajoy confirmed that the Spanish government would trigger Article 155 and move to suspend Catalonia's autonomy after a cabinet meeting scheduled for 21 October, following a letter from Puigdemont in which he said that the independence declaration remained suspended but that the Catalan parliament could choose to vote on it if Spain continued its "repression". Subsequently, Rajoy announced the Spanish government would take direct control over the Generalitat of Catalonia, proceeding to remove Puigdemont and the entire Catalan government from their offices and call a regional election within six months, pending Senate approval.

On 26–27 October 2017, a debate over a possible declaration of independence was held in the Parliament of Catalonia, simultaneous to the Spanish Senate debating the enforcement of direct rule in Catalonia through the invoking of Article 155 of the Spanish Constitution of 1978. At the end of the debate, the Catalan parliament voted in a secret ballot a unilateral declaration of independence which was backed 70–10, two MPs casting a blank ballot, with all MPs from Citizens, the Socialists' Party of Catalonia and the People's Party boycotting a vote considered illegal by the lawyers of the Parliament of Catalonia.

The General Council of the Val d'Aran, an autonomous region of Catalonia since 2015 (in similar terms as the autonomous community of Catalonia inside Spain), announced it would hold an extraordinary meeting on 30 October to evaluate the consequences of the independence declaration and decide as well if declaring or not their independence from Catalonia.

Institutional Reactions in Spain

In response, Spanish Prime Minister Mariano Rajoy dissolved the Parliament of Catalonia, dismissed the Executive Council of Catalonia and called a snap regional election for 21 December 2017, after obtaining the Spanish Senate endorsement to the invoking of Article 155.

Soon after Rajoy's announcement, the director of the Mossos d'Esquadra, Catalonia's autonomous police force, sent a farewell letter that acknowledged his removal by the Spanish government. Major Josep LluĂ­s Trapero also acknowlegded his sacking and asked Catalan police officers to remain "loyal" to his successor.

While some media outlets hinted that the Puigdemont-led Catalan government was not going to resist the Spanish takeover of the government of Catalonia, Puigdemont did not consider himself sacked, asserting that it is parliaments "who elect or remove governments", and asked Catalans to "democratically oppose" the enforcement of Article 155. He, however, did not clarify whether he would acknowledge or refuse the Spanish government's orders.

European Union Membership

As a region of Spain, the autonomous community of Catalonia is also part of the European Union (EU), eurozone, and Schengen Area. Prior to the declaration, there was debate as to whether an independent Catalonia would retain membership in the EU and associated international arrangements, or would, upon independence, find itself outside of these arrangements. The secession of part of a member nation is not specifically addressed in the EU's treaties, though legal opinions have been offered both in the case of Catalonia and during the debate around the 2014 Scottish independence referendum. The "Prodi doctrine" followed by the European Commission states that a seceding state would exit the EU and would have to apply for membership as an external nation.

President of the European Council Donald Tusk stated that the independence declaration "changed nothing" and that the European Union would only deal with the Spanish government, while also urging Spain to use "force of argument, not argument of force.”

                            https://en.wikipedia.org/wiki/Catalan_Republic_(2017)

Friday, October 27, 2017

Late Onset Alzheimer's Research

Is Alzheimer’s Disease a Disorder of Energy Metabolism? New Study Shines New Light
By Laura Neves, McLean Hospital

October 26, 2017 -- Belmont, MA -- A team of investigators from McLean Hospital and Harvard Medical School, led by Kai C. Sonntag, MD, PhD, and Bruce M. Cohen, MD, PhD, has found a connection between disrupted energy production and the development of late-onset Alzheimer’s disease (LOAD). The findings appear in the current issue of Scientific Reports.

“These findings have several implications for understanding and developing potential therapeutic intervention in LOAD,” explained Sonntag, an associate stem cell researcher at McLean Hospital and an assistant professor of psychiatry at Harvard Medical School. “Our results support the hypothesis that impairment in multiple interacting components of bioenergetics metabolism may be a key mechanism underlying and contributing to the risk and pathophysiology of this devastating illness.”

For three decades, it has been thought that the accumulation of small toxic molecules in the brain, called amyloid beta, or in short, Aβ, is central to the development of Alzheimer’s disease (AD). Strong evidence came from studying familial or early-onset forms of AD (EOAD) that affect about five percent of AD patients and have associations with mutations leading to abnormally high levels or abnormal processing of Aβ in the brain. However, the “Aβ hypothesis” has been insufficient to explain the pathological changes in the more common LOAD, which affects more than 5 million seniors in the United States.

“Because late-onset Alzheimer’s is a disease of age, many physiologic changes with age may contribute to risk for the disease, including changes in bioenergetics and metabolism,” said Cohen, director of the Program for Neuropsychiatric Research at McLean Hospital and the Robertson-Steele Professor of Psychiatry at Harvard Medical School. “Bioenergetics is the production, usage, and exchange of energy within and between cells or organs, and the environment. It has long been known that bioenergetic changes occur with aging and affect the whole body, but more so the brain, with its high need for energy.”

According to Sonntag and Cohen, it has been less clear what changes in bioenergetics are underlying and which are a consequence of aging and illness. 

In their study, Sonntag and Cohen analyzed the bioenergetic profiles of skin fibroblasts from LOAD patients and healthy controls, as a function of age and disease. The scientists looked at the two main components that produce energy in cells: glycolysis, which is the mechanism to convert glucose into fuel molecules for consumption by mitochondria, and burning of these fuels in the mitochondria, which use oxygen in a process called oxidative phosphorylation or mitochondrial respiration. The investigators found that LOAD cells exhibited impaired mitochondrial metabolism, with a reduction in molecules that are important in energy production, including nicotinamide adenine dinucleotide (NAD). LOAD fibroblasts also demonstrated a shift in energy production to glycolysis, despite an inability to increase glucose uptake in response to the insulin analog IGF-1. Both the abnormal mitochondrial metabolism and the increase of glycolysis in LOAD cells were disease- and not age-specific, while diminished glucose uptake and the inability to respond to IGF-1 was a feature of both age and disease.

“The observation that LOAD fibroblasts had a deficiency in the mitochondrial metabolic potential and an increase in the glycolytic activity to maintain energy supply is indicative of failing mitochondria and fits with current knowledge that aging cells increasingly suffer from oxidative stress that impairs their mitochondrial energy production,” said Sonntag.

Cohen added that because the brain’s nerve cells rely almost entirely on mitochondria-derived energy, failure of mitochondrial function, while seen throughout the body, might be particularly detrimental in the brain.

The study’s results link to findings from other studies that decreasing energy-related molecules (and specifically NAD) are features of normal aging by suggesting that abnormalities in processes involving these molecules may also be a factor in neurodegenerative diseases like LOAD. Whether modulating these compounds could slow the aging process and prevent or delay the onset of LOAD is unknown. However, several clinical trials are currently under way to test this possibility. Other changes are unique to AD, and these, too, may be targets for intervention.

While these findings are significant, the paper’s authors emphasize that the pathogenesis of LOAD is multifactorial, with bioenergetics being one part of risk determination and note that the skin fibroblasts studied are not the primary cell type that is affected in LOAD.

“However, because bioenergetics changes are body-wide, observations made in fibroblasts may also be relevant to brain cells,” said Sonntag. “In fact, metabolic changes like diminished glucose uptake and insulin/IGF-1 resistance may underlie the association between various disorders of aging, such as type 2 diabetes and AD.”

Sonntag and Cohen are already in the midst of follow-up work aiming to study these bioenergetics features in brain nerve cells and astrocytes generated from LOAD patient-derived induced pluripotent stem cells, as an aging and disease model in the dish. It is the group’s hope that findings from these studies will reveal further insight into the role of bioenergetics in LOAD pathogenesis and novel targets for intervention—both prevention and treatment.

McLean Hospital is the largest psychiatric affiliate of Harvard Medical School and a member of Partners HealthCare. In 2017, it was named the #1 hospital for psychiatric care in the United States by U.S. News & World Report.

http://www.mcleanhospital.org/news/2017/10/26/alzheimers-disease-disorder-energy-metabolism-new-study-shines-new-light

Thursday, October 26, 2017

The Sunk Cost Fallacy

Escalation of commitment [the “sunk cost fallacy”] refers to a human behavior pattern in which an individual or group—when faced with increasingly negative outcomes from some decision, action, or investment—continues the same behavior rather than alter course. They maintain actions that are irrational, but align with previous decisions and actions.

Economists and behavioral scientists use a related term, sunk cost fallacy, to describe the justification of increased investment of money, time, lives, etc. in a decision, based on the cumulative prior investment ("sunk costs"); despite new evidence suggesting that the cost, beginning immediately, of continuing the decision outweighs the expected benefit. In the context of military conflicts, sunk costs in terms of money spent and lives lost are often used to justify continued involvement.

In sociology, irrational escalation of commitment or commitment bias describe similar behaviours; and the phenomenon and the sentiment underlying it are reflected in such proverbial images as "Throwing good money after bad" or "In for a penny, in for a pound".

Early Use

Escalation of commitment was first described by Barry M. Staw in his 1976 paper, "Knee deep in the big muddy: A study of escalating commitment to a chosen course of action".

Researchers, inspired by the work of Staw, conducted studies that tested factors, situations and causes of escalation of commitment. The research introduced other analyses of situations and how people approach problems and make decisions. Some of the earliest work stemmed from events in which this phenomenon had an effect and help explain the phenomenon.

Researchers define escalation of commitment


Over the past few decades, researchers have followed and analyzed many examples of the escalation of commitment to a situation. The heightened situations are explained in three elements. Firstly, a situation has a costly amount of resources such as time, money and people invested in the project. Next, past behavior leads up to an apex in time where the project has not met expectations or could in a cautious state of decline. Lastly, these problems all force a decision-maker to make choices that include the options of continuing to pursue a project until completion by adding additional costs, or canceling the project altogether.

Researchers have also developed an argument regarding how escalation of commitment is observed in two different categories. Many researchers believe that the need to escalate resources is linked to expectancy theory. "According to such a viewpoint, decision makers assess the probability that additional resource allocations will lead to goal attainment, as well as the value of goal attainment (i.e., rewards minus costs), and thereby generate a subjective expected utility associated with the decision to allocate additional resources." The next phase of the escalation process is self-justification and rationalizing if the decision the leader made used resources well, if the resources being used were used to make positive change, and assuring themselves that the decision they chose was right. Leaders must balance costs and benefits of any problem to produce a final decision. What matters most often in assuring the leader that they made the right choice regardless of the final outcome is if their decision is what others believed in.

Research conducted on the topic has been taken from many other forms and theories of psychology. Many believe that what researchers have done thus far to explain this behavior is best analyzed and tested through situational development and resource allocation.

Vietnam War


Escalation of commitment can many times cause behavior change by means of locking into resources. One of the first examples of escalation of commitment was described by George Ball, who wrote to President Lyndon Johnson to explain to him the predictions of the war outcome:

The decision you face now is crucial. Once large numbers of U.S. troops are committed to direct combat, they will begin to take heavy casualties in a war they are ill equipped to fight in a non-cooperative if not downright hostile countryside. Once we suffer large casualties, we will have started a well-nigh irreversible process. Our involvement will be so great that we cannot—without national humiliation—stop short of achieving our complete objectives. Of the two possibilities, I think humiliation would be more likely than the achievement of our objectives—even after we have paid terrible costs.

Theories

Self-justification theory


Self-justification thought process is a part of commitment decisions of leaders and managers of a group and can therefore cause a rise in commitment levels. This attitude provides "one explanation for why people escalate commitment to their past investments." Managers make decisions that reflect previous behavior. Managers tend to recall and follow information that is aligned to their behavior to create consistency for their current and future decisions. If a group member or outside party recognizes inconsistent decision making, this can alter the leadership role of the manager. Managers have external influence from society, peers, and authority, which can significantly alter a manager's perception on what factors realistically matter when making decisions.

Prospect theory


Prospect theory helps to describe the natural reactions and processes involved in making a decision in a risk-taking situation. Prospect theory makes the argument for how levels of wealth, whether that is people, money, or time, affect how a decision is made. Researchers were particularly interested in how one perceives a situation based on costs and benefits. The framing to how the problem is introduced is crucial for understanding and thinking of the probability that the situation will either work in favor or against you and how to prepare for those changes. "Whyte (1986) argued that prospect theory provides the psychological mechanism by which to explain escalating commitment to a failing course of action without the need to invoke self-justification processes. (Fiegenbaum & Thomas, 1988: 99)" Prospect theorists believe that one's use of this process is when there is a negative downfall in the stakes that will affect the outcome of the project. To ensure they will not fail, the individual may add more resources to assure them that they will succeed. Though this theory seems realistic, researchers "Davis and Bobko (1986) found no effect of personal responsibility on continued commitment to the previous course of action in the positive frame condition." Which means that escalation of commitment will be lower in the higher responsibility situation.

Attribution theory


The attribution theory, originating from Fritz Heider, "attempts to find causal explanations for events and human behaviors." This theory approaches two methods of inquiry including locus of causality and stability. Locus of causality reflects on internal haracteristics of an individual, such as intelligence levels and attention seeking, with the relationship of the external space such as weather forecasts and task difficulty. Aspects of control become a significant factor in how a manager justifies a decision made. Managers will use the relationship between internal and external factors to describe why they made a decision to a single point of view. Managers may justify their actions by explaining that this was out of their personal control of the event, or they could believe that the decision could not be controlled by anyone else. Research suggests that "the type of attribution made by an employee across these dimensions is likely to impact an employee's tendency to engage in the negative emotional activity referred to as escalation of commitment."

Social identity theory


Identity is a large part of how we move through the world. Private thoughts and opinions as well as the effect of others create the social identity theory. People make connections between their use of groups and their own view of themselves, which researchers have discovered motivates people to keep their social status and to defend it whenever it is endangered.

Theoretical models


Temporal model of escalation


Groups engage in temporal comparisons, which means that you compare actions and behaviors at "different points in time." This is a form of social identity scenario. This type of comparison can be made when a decision seems unproductive and forces team members to consider any threat to the group.

Aggregate model


"The aggregate model's emphasis is upon the accumulation and balance of forces rather than the ordering of effects over time." The model is general and can provide an ideal view as to how. The effects whether positive or negative are defined by micro and macro forces. This model goes by situation rather than what researchers have defined as the norm. There is no process to follow, which makes it very useful for researchers because they can understand a situation more clearly as well as see the bigger picture of the situation.

Examples

  • The dollar auction is a thought exercise demonstrating the concept.
  • After a heated and aggressive bidding war, Robert Campeau ended up buying Bloomingdale's for an estimated $600 million more than it was worth. The Wall Street Journal noted that "we're not dealing in price anymore but egos." Campeau was forced to declare bankruptcy soon afterwards.
  • Certain fraud schemes exploit this behaviour, such as the Nigerian 419 Scam, where victims continue to spend money for alleged business deals, although the fraudulent character of the deal appears obvious to uninvolved persons.
  • The Big Dig in Boston
  • Shoreham Nuclear Power Plant
  • Taurus IT Project
  • AIG Government Assistance
  • 30–40% of software projects experience escalation of commitment due to their complexity and uncertainty. Intangibility makes determining the current status of projects especially difficult.
  • Denver International Airport's baggage handling system that was 2 years and $2 billion over budget
  • 6 years and $1 billion spent by the U.S. Air Force on a dysfunctional combat support system
  • Sony's continued participation in electronics after $8.5 billion in losses over 10 years
  • Congress and advocacy group support and investment in the 21st Century Community Learning Center, which has been found to fail to meet its goals
  • Continued funding for the Drug Abuse Resistance Education Program, which doesn't lead to a meaningful decrease in drug use

                        https://en.wikipedia.org/wiki/Escalation_of_commitment

Wednesday, October 25, 2017

What Is a "White Elephant"?

A white elephant is a possession which its owner cannot dispose of and whose cost, particularly that of maintenance, is out of proportion to its usefulness. In modern usage, it is an object, building project, scheme, business venture, facility, etc., considered expensive but without use or value.

Background

The term derives from the sacred white elephants kept by Southeast Asian monarchs in Burma, Thailand, Laos and Cambodia. To possess a white elephant was regarded (and is still regarded in Thailand and Burma) as a sign that the monarch reigned with justice and power, and that the kingdom was blessed with peace and prosperity. The opulence expected of anyone that owned a beast of such stature was great. Monarchs often exemplified their possession of white elephants in their formal titles (e.g., Hsinbyushin, literally "Lord of the White Elephant" and the third monarch of the Konbaung dynasty). Because the animals were considered sacred and laws protected them from labor, receiving a gift of a white elephant from a monarch was simultaneously a blessing and a curse. It was a blessing because the animal was sacred and a sign of the monarch's favour, and a curse because the recipient now had an expensive-to-maintain animal he could not give away and could not put to much practical use.

In the West, the term "white elephant" relating to an expensive burden that fails to meet expectations, was first used in the 1600s and became widespread in the 1800s. According to one source it was popularized following P. T. Barnum's experience with an elephant named Toung Taloung that he billed as the "Sacred White Elephant of Burma". After much effort and great expense, Barnum finally acquired the animal from the King of Siam only to discover that his "white elephant" was actually dirty grey in color with a few pink spots.

The expressions "white elephant" and "gift of a white elephant" came into common use in the middle of the nineteenth century. The phrase was attached to "white elephant swaps" and "white elephant sales" in the early twentieth century. Many church bazaars held “white elephant sales” where donors could unload unwanted bric-a-brac, generating profit from the phenomenon that "one man’s trash is another man’s treasure" and the term has continued to be used in this context.

In modern British English, the term now often refers in addition to an extremely expensive building project that fails to deliver on its function and/or becomes very costly to maintain. Examples include prestigious but uneconomic infrastructure projects such as airports, dams, bridges, shopping malls and football stadia built for the FIFA World Cup. The term has also been applied to outdated or underperforming military projects like the U.S. Navy's Alaska-class cruiser and the F-35 Joint Strike Fighter.  The British East Africa Company came to regard Uganda as a white elephant when internal conflict made administration of the territory impossible.

See also

Bridge to nowhere

Pork barrel

Sunk Cost Fallacy [see tomorrow’s blog entry for the details]

                                          https://en.wikipedia.org/wiki/White_elephant

Tuesday, October 24, 2017

MIT Memory Breakthrough

MIT Neuroscientists Build Case for New Theory of Memory Formation
Existence of “silent engrams” suggests that existing models of memory formation should be revised.
ByAnne Trafton | MIT News Office

October 23, 2017 -- Learning and memory are generally thought to be composed of three major steps: encoding events into the brain network, storing the encoded information, and later retrieving it for recall.

Two years ago, MIT neuroscientists discovered that under certain types of retrograde amnesia, memories of a particular event could be stored in the brain even though they could not be retrieved through natural recall cues. This phenomenon suggests that existing models of memory formation need to be revised, as the researchers propose in a new paper in which they further detail how these “silent engrams” are formed and re-activated.

The researchers believe their findings offer evidence that memory storage does not rely on the strengthening of connections, or “synapses,” between memory cells, as has long been thought. Instead, a pattern of connections that form between these cells during the first few minutes after an event occurs are sufficient to store a memory.

“One of our main conclusions in this study is that a specific memory is stored in a specific pattern of connectivity between engram cell ensembles that lie along an anatomical pathway. This conclusion is provocative because the dogma has been that a memory is instead stored by synaptic strength,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, the director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, and the study’s senior author.

The researchers also showed that even though memories held by silent engrams cannot be naturally recalled, the memories persist for at least a week and can be “awakened” days later by treating cells with a protein that stimulates synapse formation.

Dheeraj Roy, a recent MIT PhD recipient, is the lead author of the paper, which appears in the Proceedings of the National Academy of Sciences the week of Oct. 23. Other authors are MIT postdoc Shruti Muralidhar and technical associate Lillian Smith.

Silent memories

Neuroscientists have long believed that memories of events are stored when synaptic connections, which allow neurons to communicate with each other, are strengthened. Previous studies have found that if synthesis of certain cellular proteins is blocked in mice immediately after an event occurs, the mice will have no long-term memory of the event.

However, in a 2015 paper, Tonegawa and his colleagues showed for the first time that memories could be stored even when synthesis of the cellular proteins is blocked. They found that while the mice could not recall those memories in response to natural cues, such as being placed in the cage where a fearful event took place, the memories were still there and could be artificially retrieved using a technique known as optogenetics.

The researchers have dubbed these memory cells “silent engrams,” and they have since found that these engrams can also be formed in other situations. In a study of mice with symptoms that mimic early Alzheimer’s disease, the researchers found that while the mice had trouble recalling memories, those memories still existed and could be optogenetically retrieved.

In a more recent study of a process called systems consolidation of memory, the researchers found engrams in the hippocampus and the prefrontal cortex that encoded the same memory. However, the prefrontal cortex engrams were silent for about two weeks after the memory was initially encoded, while the hippocampal engrams were active right away. Over time, the memory in the prefrontal cortex became active, while the hippocampal engram slowly became silent.

In their new PNAS study, the researchers investigated further how these silent engrams are formed, how long they last, and how they can be re-activated.

Similar to their original 2015 study, they trained mice to fear being placed in a certain cage, by delivering a mild foot shock. After this training, the mice freeze when placed back in that cage. As the mice were trained, their memory cells were labeled with a light-sensitive protein that allows the cells to be re-activated with light. The researchers also inhibited the synthesis of cellular proteins immediately after the training occurred.

They found that after the training, the mice did not react when placed back in the cage where the training took place. However, the mice did freeze when the memory cells were activated with laser light while the animals were in a cage that should not have had any fearful associations. These silent memories could be activated by laser light for up to eight days after the original training.

Making connections

The findings offer support for Tonegawa’s new hypothesis that the strengthening of synaptic connections, while necessary for a memory to be initially encoded, is not necessary for its subsequent long-term storage. Instead, he proposes that memories are stored in the specific pattern of connections formed between engram cell ensembles. These connections, which form very rapidly during encoding, are distinct from the synaptic strengthening that occurs later (within a few hours of the event) with the help of protein synthesis.

“What we are saying is that even without new cellular protein synthesis, once a new connection is made, or a pre-existing connection is strengthened during encoding, that new pattern of connections is maintained,” Tonegawa says. “Even if you cannot induce natural memory recall, the memory information is still there.”

This raised a question about the purpose of the post-encoding protein synthesis. Considering that silent engrams are not retrieved by natural cues, the researchers believe the primary purpose of the protein synthesis is to enable natural recall cues to do their job efficiently.

The researchers also tried to reactivate the silent engrams by treating the mice with a protein called PAK1, which promotes the formation of synapses. They found that this treatment, given two days after the original event took place, was enough to grow new synapses between engram cells. A few days after the treatment, mice whose ability to recall the memory had been blocked initially would freeze after being placed in the cage where the training took place. Furthermore, their reaction was just as strong as that of mice whose memories had been formed with no interference.

Sheena Josselyn, an associate professor of psychology and physiology at the University of Toronto, said the findings run counter to the longstanding idea that memory formation involves strengthening of synapses between neurons and that this process requires protein synthesis.

“They showed that a memory formed during protein-synthesis inhibition may be artificially (but not naturally) recalled. That is, the memory is still retained in the brain without protein synthesis, but this memory cannot be accessed under normal conditions, suggesting that spines may not be the key keepers of information,” says Josselyn, who was not involved in the research. “The findings are controversial, but many paradigm-shifting papers are.”

Along with the researchers’ previous findings on silent engrams in early Alzheimer’s disease, this study suggests that re-activating certain synapses could help restore some memory recall function in patients with early stage Alzheimer’s disease, Roy says.

Monday, October 23, 2017

Carbon Dioxide Emissions Are Flat

Global CO2 Emissions Stalled for the Third Year in a Row

The EU Science Hub – October 20, 2017 --The annual assessment of global greenhouse gas (GHG) emissions by the JRC and the Netherlands Environmental Assessment Agency (PBL) confirms that CO2 emissions have stalled for the third year in a row.

The report provides updated results on the continuous monitoring of the three main greenhouse gases: carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O).

Global GHG emissions continue to be dominated by fossil carbon dioxide (CO2) emissions, which however show a slowdown trend since 2012, and were stalled for the third year in a row in 2016.

Russia, China, the US and Japan further decreased their CO2 emissions from 2015 to 2016, while the EU's emissions remained stable with respect to the previous year, and India's emissions continued to increase.

Other greenhouse gases keep creeping up

Information on the other two greenhouse gases, methane (CH4) and nitrous oxide (N2O), is only available until 2012, as international statistics on agricultural activities – the main source of these emissions – are not updated as frequently as on energy and industry-related activities. 

Uncertainty is also higher for these emissions than for CO2 emissions.

However, the data until 2012 shows a steady increase in global GHG emissions, with an overall increase of 91% from 1970 to 2012.

CH4 is mainly generated by agricultural activities, the production of coal and gas, as well as waste treatment and disposal. N2O is mainly emitted by agricultural soil activities and chemical production.

In the EU, 60% of the CH4 and N2O emissions are emitted by the top six emitting countries – Germany, UK, France, Poland, Italy and Spain.

The upward trend in CH4 and N2O emissions is also visible in the US, China, Japan and India which all recorded increasing GHG emissions.

Europe's downward trend stalling

Over the past two decades, the EU28 has steadily decreased its CO2 emissions, which still represent two thirds of the EU's total greenhouse gas emissions.

In 2016, the EU's CO2 emissions were 20.8% below the levels in 1990 and 17.9% below the levels in 2005. Since 2015, the EU's CO2 emissions have stabilised, representing 9.6% of global emissions.

Country profile

The report is based on the JRC's Emissions Database for Global Atmospheric Research (EDGAR), which is not only unique in its space and time coverage, but also in its completeness and consistency of the emissions compilations for multiple pollutants: the greenhouse gases (GHG), air pollutants and aerosols.

The new report contains country-specific fact sheets for 216 countries. The factsheets show the evolution of country-level CO2 emissions from 1990 to 2016 and the evolution of country-level GHG emissions from 1970 to 2012.

Sunday, October 22, 2017

Ultra-thin Metal Foil for Electronics

Liquid Metal Breakthrough Ushers New Wave of Electronics
Liquid metal breakthrough ushers new wave of electronics

Melbourne, Australia – Oct. 20, 2017 --RMIT [Royal Melbourne Institute of Technology] researchers have used liquid metal to create two-dimensional materials no thicker than a few atoms that have never before been seen in nature.

The incredible breakthrough will not only revolutionise the way we do chemistry but could be applied to enhance data storage and make faster electronics. The “once-in-a-decade” discovery has been published in Science

The researchers dissolve metals in liquid metal to create very thin oxide layers, which previously did not exist as layered structures and which are easily peeled away.

Once extracted, these oxide layers can be used as transistor components in modern electronics. The thinner the oxide layer, the faster the electronics are. Thinner oxide layers also mean the electronics need less power.  Among other things, oxide layers are used to make the touch screens on smart phones.

The research is led by Professor Kourosh Kalantar-zadeh and Dr Torben Daeneke from RMIT’s School of Engineering, who with students have been experimenting with the method for the last 18 months.

“When you write with a pencil, the graphite leaves very thin flakes called graphene, that can be easily extracted because they are naturally occurring layered structures,” said Daeneke. “But what happens if these materials don’t exist naturally?

“Here we found an extraordinary, yet very simple method to create atomically thin flakes of materials that don't naturally exist as layered structures.

“We use non-toxic alloys of gallium (a metal similar to aluminium) as a reaction medium. This covers the surface of the liquid metal with atomically thin oxide layers of the added metal rather than the naturally occurring gallium oxide.

“This oxide layer can then be exfoliated by simply touching the liquid metal with a smooth surface. Larger quantities of these atomically thin layers can be produced by injecting air into the liquid metal, in a process that is similar to frothing milk when making a cappuccino.”

It’s a process so cheap and simple that it could be done on a kitchen stove by a non-scientist.

“I could give these instructions to my mum, and she would be able to do this at home,” Daeneke said.

Professor Kourosh Kalantar-zadeh said that the discovery now places previously unseen thin oxide materials into everyday reach, with profound implications for future technologies.

“We predict that the developed technology applies to approximately one-third of the periodic table. Many of these atomically thin oxides are semiconducting or dielectric materials.

“Semiconducting and dielectric components are the foundation of today’s electronic and optical devices. Working with atomically thin components is expected to lead to better, more energy efficient electronics. This technological capability has never been accessible before.”

The breakthrough could also be applied to catalysis, the basis of the modern chemical industry, reshaping how we make all chemical products including medicines, fertilisers and plastics.

The research is funded by the Australian Research Council Centre for Future Low-Energy Electronics Technologies (FLEET).


Saturday, October 21, 2017

More Efficient Nuclear Fusion

The blob that ate the tokamak: Physicists gain understanding of how bubbles at the edge of plasmas can drain heat and reduce fusion reaction efficiency
By Raphael Rosen, Princeton University

October 19, 2017 -- To fuse hydrogen atoms into helium, doughnut-shaped devices called tokamaks must maintain the heat of the ultra-hot plasma they control. But like boiling water, plasma has blobs, or bubbles, that percolate within the plasma edge, reducing the performance of the plasma by taking away heat that sustains the fusion reactions.

Now, scientists at the U.S. Department of Energy’s (DOE) Princeton Plasma Physics Laboratory (PPPL) have completed new simulations that could provide insight into how blobs at the plasma edge behave. The simulations, produced by a code called XGC1 developed by a national team based at PPPL, performed kinetic simulations of two different regions of the plasma edge simultaneously. This ability produces a more fundamental and fuller picture of how heat moves from plasma to the walls, potentially causing damage.

“In simulations, we often separate two areas at the plasma edge known as the pedestal and the scrape-off layer and focus on one or the other,” said PPPL physicist Michael Churchill, lead author of a paper describing the results in the journal Plasma Physics and Controlled Fusion. “XGC1 is unique because it is able to simulate both regions simultaneously, using kinetic ion and electron equations. In fact, it is important to include both regions in simulations because they affect each other.”

Simulations allow scientists to explore plasma, the fourth and hottest state of matter in which electrons are separated from atomic nuclei, without running physical experiments that could be costly. They also sometimes provide insights that physical experiments do not. Simulations of turbulence at the edge of the plasma, near where the plasma approaches a tokamak’s interior wall, are particularly important. The more that scientists understand such turbulence, the better able they will be to prevent moving blobs of plasma from forming in the plasma edge. If not controlled, these blobs could drain large amounts of heat from the confined plasma, and possibly either damage plasma-facing components or hinder the fusion reactions.

The XGC1 code simulated plasma in high-confinement mode, or H-mode, a set of conditions that helps plasma retain its heat. In H-mode, the results showed, a large number of blobs form between the pedestal and the scrape-off layer, two conditions near the edge, and move towards the outer edge, crossing the magnetic field lines as they go.

Blobs play an important role in the outward movement of particles in plasma. Blobs cause approximately 50 percent of the particle loss at the plasma edge, and researchers have observed blobs in a wide range of plasma devices, including tokamaks, figure-eight-shaped fusion devices known as stellarators, and linear machines. “The big picture is that blobs can pull energy and particles out of the plasma, and you don’t want that,” Churchill said. “You want to keep things confined.”

Scientists ran the simulation on America’s fastest supercomputer, called Titan, at the Oak Ridge Leadership Computing Facility, a DOE Office of Science User Facility in Oak Ridge, Tennessee. Much of the post-simulation analysis was performed at the National Energy Research Scientific Computing Center (NERSC), a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory in Berkeley, California. Coauthors of the Plasma Physics and Controlled Fusion paper included PPPL physicists C.S. Chang, Seung-Hoe Ku, and Julien Dominski.

Future research will focus on how the blobs form and how their behavior is affected by the shape of the tokamak. Scientists must also fully determine how density, temperature, and electromagnetic force affect the behavior of the blobs.

Friday, October 20, 2017

Suicide RNA Molecules Kill Cancer

Suicide Molecules Kill any Cancer Cell
Time traveling backward for hundreds of millions of years to unleash one of nature’s original kill switches
By Marla Paul, Northwestern University

CHICAGO – October 19, 2017 --  Small RNA molecules originally developed as a tool to study gene function trigger a mechanism hidden in every cell that forces the cell to commit suicide, reports a new Northwestern Medicine study, the first to identify molecules to trigger a fail-safe mechanism that may protect us from cancer.

The mechanism -- RNA suicide molecules -- can potentially be developed into a novel form of cancer therapy, the study authors said.

Cancer cells treated with the RNA molecules never become resistant to them because they simultaneously eliminate multiple genes that cancer cells need for survival.

“It’s like committing suicide by stabbing yourself, shooting yourself and jumping off a building all at the same time,” said Northwestern scientist and lead study author Marcus Peter. “You cannot survive.”

The inability of cancer cells to develop resistance to the molecules is a first, Peter said.

“This could be a major breakthrough,” noted Peter, the Tom D. Spies Professor of Cancer Metabolism at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.  

Peter and his team discovered sequences in the human genome that when converted into small double-stranded RNA molecules trigger what they believe to be an ancient kill switch in cells to prevent cancer. He has been searching for the phantom molecules with this activity for eight years.

“We think this is how multicellular organisms eliminated cancer before the development of the adaptive immune system, which is about 500 million years old,” he said. “It could be a fail safe that forces rogue cells to commit suicide. We believe it is active in every cell protecting us from cancer.”

This study, which will be published Oct. 24 in eLife, and two other new Northwestern studies in Oncotarget and Cell Cycle by the Peter group, describe the discovery of the assassin molecules present in multiple human genes and their powerful effect on cancer in mice.

Looking back hundreds of millions of years

Why are these molecules so powerful?

“Ever since life became multicellular, which could be more than 2 billion years ago, it had to deal with preventing or fighting cancer,” Peter said. “So nature must have developed a fail safe mechanism to prevent cancer or fight it the moment it forms. Otherwise, we wouldn’t still be here.”

Thus began his search for natural molecules coded in the genome that kill cancer.

“We knew they would be very hard to find,” Peter said. “The kill mechanism would only be active in a single cell the moment it becomes cancerous. It was a needle in a haystack."

But he found them by testing a class of small RNAs, called small interfering (si)RNAs, scientists use to suppress gene activity. siRNAs are designed by taking short sequences of the gene to be targeted and converting them into double- stranded RNA. These siRNAs when introduced into cells suppress the expression of the gene they are derived from.

RNA suicide molecules could be used for a novel form of cancel therapy.

Peter found that a large number of these small RNAs derived from certain genes did not, as expected, only suppress the gene they were designed against. They also killed all cancer cells. His team discovered these special sequences are distributed throughout the human genome, embedded in multiple genes as shown in the study in Cell Cycle. 

When converted to siRNAs, these sequences all act as highly trained super assassins. They kill the cells by simultaneously eliminating the genes required for cell survival. By taking out these survivor genes, the assassin molecule activates multiple death cell pathways in parallel.

The small RNA assassin molecules trigger a mechanism Peter calls DISE, for Death Induced by Survival gene Elimination.

Activating DISE in organisms with cancer might allow cancer cells to be eliminated. Peter’s group has evidence this form of cell death preferentially affects cancer cells with little effect on normal cells.

To test this in a treatment situation, Peter collaborated with Dr. Shad Thaxton, associate professor of urology at Feinberg, to deliver the assassin molecules via nanoparticles to mice bearing human ovarian cancer. In the treated mice, the treatment strongly reduced the tumor growth with no toxicity to the mice, reports the study in Oncotarget. Importantly, the tumors did not develop resistance to this form of cancer treatment. Peter and Thaxton are now refining the treatment to increase its efficacy.

Peter has long been frustrated with the lack of progress in solid cancer treatment.

“The problem is cancer cells are so diverse that even though the drugs, designed to target single cancer driving genes, often initially are effective, they eventually stop working and patients succumb to the disease,” Peter said. He thinks a number of cancer cell subsets are never really affected by most targeted anticancer drugs currently used.

Most of the advanced solid cancers such as brain, lung, pancreatic or ovarian cancer have not seen an improvement in survival, Peter said.

“If you had an aggressive, metastasizing form of the disease 50 years ago, you were busted back then and you are still busted today,” he said. “Improvements are often due to better detection methods and not to better treatments.”

Cancer scientists need to listen to nature more, Peter said. Immune therapy has been a success, he noted, because it is aimed at activating an anticancer mechanism that evolution developed. Unfortunately, few cancers respond to immune therapy and only a few patients with these cancers benefit, he said.

"Our research may be tapping into one of nature’s original kill switches, and we hope the impact will affect many cancers,” he said. “Our findings could be disruptive.”

Northwestern co-authors include first authors William Putzbach, Quan Q. Gao, and Monal Patel, and coauthors Ashley Haluck-Kangas, Elizabeth T. Bartom, Kwang-Youn A. Kim, Denise M. Scholtens, Jonathan C. Zhao and Andrea E. Murmann.

The research is funded by grants T32CA070085, T32CA009560, R50CA211271 and R35CA197450 from the National Cancer Institute of the National Institutes of Health.