New general concept for treatment of cancer

Featured Research

from universities, journals, and other organizations

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New general concept for treatment of cancer

Date:

April 2, 2014

Source:

Karolinska Institutet

Summary:

A team of researchers from five Swedish universities has identified a new way of treating cancer. The concept is based on inhibiting a specific enzyme called MTH1, which cancer cells, unlike normal cells, require for survival. Without this enzyme, oxidized nucleotides are incorporated into DNA, resulting in lethal DNA double-strand breaks in cancer cell.

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Dr. Thomas Helleday of Karolinska Institutet and his colleagues have identified a new way of treating cancer by inhibiting the enzyme MTH1, which cancer cells require for survival.

 

A team of researchers from five Swedish universities, led by Karolinska Institutet and the Science for Life Laboratory, have identified a new way of treating cancer. The concept is presented in the journal Nature and is based on inhibiting a specific enzyme called MTH1, which cancer cells, unlike normal cells, require for survival. Without this enzyme, oxidized nucleotides are incorporated into DNA, resulting in lethal DNA double-strand breaks in cancer cells.

"To accelerate the development of this treatment principle and to proceed with clinical trials in patients as quickly as possible, we are working with an open innovation model. Even before publication, we have sent out MTH1 inhibitors to a range of research groups worldwide," says Thomas Helleday, holder of the Söderberg Professorship at Karolinska Institutet, who heads the study.

In recent decades, the development of new anticancer agents has focused on targeting specific genetic defects in cancer cells. These are often effective initially, but are troubled with rapid resistance emerging. In the current study, the researchers present a general enzymatic activity that all cancers tested rely on and that seems to be independent of the genetic changes found in specific cancers. The research team shows that all the investigated cancer tumours need the MTH1 enzyme to survive. In this way, cancer cells differ from normal cells, which do not need this enzyme.

"The concept is built on that cancer cells have an altered metabolism, resulting in oxidation of nucleotide building blocks," says Thomas Helleday."MTH1 sanitises the oxidized building blocks, preventing the oxidative stress to be incorporated into DNA and becoming DNA damage. This allows replication in cancer cells so they can divide and multiply. With an MTH1 inhibitor, the enzyme is blocked and damaged nucleotides enter DNA, causing damage and kill cancer cells. Normal cells do not need MTH1 as they have regulated metabolism preventing damage of nucleotide building blocks. Finding a general enzymatic activity required only for cancer cells to survive opens up a whole new way of treating cancer,"

To take the treatment concept to towards a clinical application, the scientists have taken a multidisciplinary collaboration strategy with researchers from five Swedish universities. They have produced a potent MTH1 inhibitor that selectively kills cancer cells in the tumours that have been surgically removed from skin cancer patients. Dr Roger Olofsson Bagge is a surgeon at Sahlgrenska University Hospital, and also affiliated with the Sahlgrenska Academy at the University of Gothenburg:

"When we saw that the tumour from one of my melanoma patients who has developed resistance to all the current treatment actually responded very well to the treatment, we were extremely happy. It's rare that you get to experience and witness such a breakthrough," he says.

However, a lot of work remains to be done before it is time for clinical trials, which is likely to take at least one or two years, according to Thomas Helleday. In another article published in the same issue of Nature parts of the Swedish research team, together with collaborators in Austria and the UK present results showing that even previously identified substances that kill cancer cells work by inhibiting the MTH1 enzyme, something which has not been realised until now.

"That existing anticancer agents hit the MTH1 shows that the concept really works. Now that we understand the mechanism, we can develop very selective inhibitors," says Thomas Helleday

 

pRADEEP SHUKLA

PGDM 2 SEM

Story

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Bharti Airtel renews IBM outsourcing contract for five years

Bangalore/Singapore: Bharti Airtel Ltd, India’s largest telecom services provider, has renewed its outsourcing contract with International Business Machines Corp. (IBM) for five years, reducing the order by more than half the size of the one that expired at the end of MarchAlthough neither US-based IBM nor Bharti Airtel disclosed the financial terms, the deal is estimated to be valued at around $500 million, according to three people familiar with the development. One of them is a Bharti Airtel executive.IBM is the sole vendor on this contract and the final terms of the deal were signed late on Tuesday night, the people said, requesting anonymity. IBM will manage Bharti Airtel’s infrastructure and application services in India for the next five years.

IBM’s share of business from the Bharti Airtel contract will fall to roughly $100 million a year, down from the $250-300 million it was generating from the original $2.5-3 billion, 10-year agreement it had signed in 2004. The earlier contract ended on 31 March.

pratima kumari

pgdm 2nd sem

 

 

New Land Rover Discovery family previewed with Vision concept

Official images give the closest look yet at Land Rover's new Discovery family, which will launch next year

These latest images preview a new Land Rover Discovery concept car

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by Hilton Holloway

3 April 2014 12:02am

Land Rover has release new preview images of the upcoming Discovery Vision Concept, which will be revealed at the New York motor show on 16 April.
The company says the new car is a “bold new concept that will showcase Land Rover’s design vision for a new family of Discovery vehicles.”
Described as “premium leisure SUVs”, the company says that the new Discovery line-up will be “built on Land Rover’s key principles of emotive design, unrivalled capability and ultimate versatility…taken to new levels using customer-focused advanced technologies.”
Even at this stage of the reveal process, it is clear that the design language established with the Discovery 3 and 4 has been completely abandoned. These pictures of the concept's interior show a much more sophisticated approach, with what appears to be a touch screen centre console and minimalistic controls and lots of jewel-like detailing, right down to the faceting of the sides of the rotary controller. The accent on luxury seems to extend to individually-reclining seats front and rear.
Shots of the exterior show that the Discovery family will have much slicker, more aerodynamic lines than the current model. The first model to use this new look will be the Freelander replacement, which is expected to appear in showroom guise before the end of the year.
Gerry McGovern, Land Rover’s design boss and chief creative officer, said that the Discovery has been “pivotal in helping to build the foundations of the Land Rover brand.  It is admired all over the world and loved by its strong customer base. We have created the Vision Concept to…debut a new, compelling, relevant design direction that connects on an emotional level with customers of today and tomorrow.”
See 25 years of the Land Rover Discovery in our picture special.

SHYAM KISHOR SINGH
PGDM - 2SEM

Chile's coast evacuated again after second strong earthquake

Tsunami alert issued for coast of Chile and Peru

Sunken fishing boats are seen on April 2, 2014 at the Riquelme Cove, in Iquique, northern Chile, after a powerful 8.2-magnitude earthquake hit off Chile's Pacific coast Photo: AFP

Bonnie Malkin and agencies 

 5:05AM BST 03 Apr 2014

 

A strong 7.8 magnitude earthquake has struck off northern Chile, prompting authorities to again order the evacuation of large swaths of the coastline.

The quake, the largest of a series of aftershocks following a powerful and deadly 8.2 magnitude quake that hit a day earlier, was located 12 miles (19 km) south of the port of Iquique at a relatively shallow depth of 12.4 miles (20 km), the USGS said. It was earlier reported as a 7.4 magnitude quake.

The Pacific Tsunami Warning Center said there was no widespread tsunami threat, but that the latest tremor could generate a local tsunami.

Chile's emergency office said it had ordered a preventative evacuation of the northern coastal area and declared a tsunami alert. Peru also issued a tsunami warning for its southern coast.

Chile's president Michele Bachelet was among the hundreds evacuated from the coast. She had been visiting the region to survey the damage wrought by the earlier earthquake and tsunami

shailendar kumar
pgdm 2nd sem
hindustan time

2G scam accused Raja declares Rs 3.16cr wealth

3 April 14

 A Raja, considered the architect and prime beneficiary of the Rs 1.72 lakh crore 2G spectrum scam, is worth Rs 3.16 crore, (including his dependents' assets), going by an poll affidavit he filed before the returning officer in Nilgiris, on Wednesday. Raja is the sitting MP in Nilgiris.

The value of his immovable assets have registered a 34% increase, but value of movable assets like jewellery and bank deposits have increased by 219% in the last five years. He has liabilities of Rs 39.65 lakh. All in all, in real terms, his assets have increased by Rs 1.9 crore between 2009 and 2014 when he spent much of his time battling cases.

The affidavit also provides a status report on all cases pending against him. CBI filed an FIR against him in the 2G scam on 21 October 2009. In comparison, the former telecom minister, who is the most prominent dalit face of DMK, had no case pending against him when he contested the 2009 polls, after he shifted his constituency from Perambalur, his hometown, to Nilgiris.

After filing the nomination, he told mediapersons, "I revolutionized the telecom sector in India by making mobile connectivity cheap. I have been wrongly implicated in the case and branded a criminal. I have filed a 102-page reply to the court. I will prove my innocence."

In the affidavit, he has included the assets in his name and those in his wife's and daughter's names and his share of family assets. Total moveable assets are valued at Rs 2.55 crore now, compared to Rs 80 lakh shown in the 2009 affidavit. This includes bank deposits which have increased from Rs 23.81 lakh to Rs 71.92 lakh and investment in bonds which have gone up from 27.69 lakh to Rs 59.15 lakh. During the same period,

Raja also bought a Toyota Corolla car worth Rs 13.81 lakh and gifted a diamond studded necklace worth Rs 12 lakh to his daughter. Gold and silver jewellery, which were valued at Rs 25.26 lakh in 2009 are worth Rs 94.45 lakh in the new affidavit. His share of gold alone is worth Rs 26.5 lakh. Raja also owns a computer worth Rs 97,965.

There has been no addition to fixed assets like land and buildings in the last five years. But the value of these assets like agricultural land and houses in and around Trichy and Perambalur have gone up from Rs 45.98 lakh to 61.5 lakh.

As per income tax returns filed last year, he paid tax of Rs 8.09 lakh and his wife Parameswari paid Rs 5.24 lakh tax. His minor daughter is also an income tax assessee.  AJAY SINGH THAKUR  PGDM 2nd sem 

Featured Research

from universities, journals, and other organizations

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EEG study shows how brain infers structure, rules when learning

Date:

3, 4 , 2014

Source:

Brown University

Summary:

A new study documents the brain activity underlying our strong tendency to infer a structure of context and rules when learning new tasks (even when a structure isn't valid). The findings, which revealed individual differences, shows how we try to apply task knowledge to similar situations and could inform future research on learning disabilities.

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“It is efficient to generalize if there is structure," one researcher said, “and there usually is structure.” The frontal cortex, it turns out, learns or infers rules and structure that may help with subsequent tasks.

Credit: Frank lab/Brown University

[Click to enlarge image]

In life, many tasks have a context that dictates the right actions, so when people learn to do something new, they'll often infer cues of context and rules. In a new study, Brown University brain scientists took advantage of that tendency to track the emergence of such rule structures in the frontal cortex -- even when such structure was not necessary or even helpful to learn -- and to predict from EEG readings how people would apply them to learn new tasks speedily.

Context and rule structures are everywhere. They allow an iPhone user who switches to an Android phone, for example, to reason that dimming the screen would involve finding a "settings" icon that will probably lead to a slider control for "brightness." But when the context changes, inflexible generalization can lead a person temporarily astray -- like a small-town tourist who greets strangers on the streets of New York City. In some developmental learning disabilities, the whole process of inferring abstract structures may be impaired.
"The world tends to be organized, and so we probably develop prior [notions] over time that there is going to be a structure," said Anne Collins, a postdoctoral scholar in the Department of Cognitive, Linguistic, and Psychological Sciences at Brown and lead author of the study published March 25 in the Journal of Neuroscience. "When the world is organized, you just reduce the size of what you have to learn about by being able to generalize across situations in which the same things usually happen together. It is efficient to generalize if there is structure, and there usually is structure."
Imagined rules
To measure how the phenomenon plays out in the brain, Collins and her colleagues used arrays of EEG electrodes to record the frontal cortex activity of 35 volunteers while they learned and performed some seemingly simple tasks. All subjects had to do was look at some shapes of different colors and learn the correct buttons to punch in response. Then they moved on to two similar tasks with new sets of colors or shapes.
The experimental trick was that there was no actual structure of context and rules to the original task: People could have just learned which button to press for each unique combination of color and shape. People were free, however, to assume instead that either the dimension of color or shape would signify a particular context for indicating how to act in response to the other dimension. This invented hierarchical structure would allow them to learn the initial task, but the experiment was designed so that learning it in this way would help make learning subsequent tasks easier in some conditions (those that shared the same structure as seen previously) and harder in others.
On the whole, participants tended to infer a rule structure, with about half of them (18 of 35) imagining rules dictated by the context of color, while the other half assumed rules based on the context of shape.
Tangible signals
With these behavioral results, the researchers could then look at the EEG data recorded at the same time and search for activity related to the formation of these rule structures in regions of the frontal cortex. They informed their investigation with a computational model of cognition that predicted the following pattern: Subjects will first formulate their idea of the task's structure in the prefrontal cortex (closer to the forehead), and later formulate the movement plan to press the presumed correct button in a part of the brain a little further back (the premotor cortex).
The EEG readings confirmed this prediction with precise correlations between the timing (and less precisely the locations) of the brain activity and behavior.
The researchers were able to determine from the EEG readings -- not just from the behavioral results -- which context subjects were imagining: shape or color.
Individual variation
Not everyone was the same. People showed significant individual variation. The extent of structure forming activity in the brain correlated with the extent to which people applied the structure they imagined to the subsequent tasks.
"There are predictable signatures in the neural data that showed if their brains seemed to be representing the structure in the way that we would predict from our models and the behavioral experiments, then they were more likely to be able to use that when it's helpful afterwards in novel environments," said Michael Frank, associate professor of cognitive, linguistic, and psychological sciences and the paper's corresponding author. "There is something to the organization of the prefrontal cortex that facilitates looking for those structures and the ability to generalize them."
The study offers new information about the basic neuroscience of cognition and learning, but Frank also hypothesizes that the findings could be valuable if applied to the study of learning disabilities.
"So far we've only studied young, healthy people, but there is some potential for using the variance across individuals in the tendency to discover structure and for their brains to be looking for that -- [the potential] to understand what happens in some disorders where people often won't think in more abstract ways that allow them to generalize their behaviors," Frank said

NARESH KR PG SEM

New iPhone 6 screens to enter production as early as May: sources

Tokyo: Apple Inc. suppliers will begin mass producing displays as early as May for the next iPhone, expected to be launched this autumn, with a 4.7-inch screen likely to be produced first while a 5.5-inch version could be delayed, supply chain sources said.

Japan Display Inc., Sharp Corp. and South Korea’s LG Display Co. Ltd have all been tapped to make the screens, said the sources, who asked not to be identified.

Representatives for the three suppliers and for Apple declined to comment.

Both iPhone 6 screens will be larger than the 4-inch panels on Apple’s existing iPhone 5S and 5C models.

Larger iPhones, the subject of months of speculation, would mark yet another incremental tweak to the popular smartphone line and an attempt to catch up to rivals like Samsung Electronics Co. Ltd.

The company that helped to define American technology innovation is under increasing pressure to once again revolutionise the gadget industry, but CEO Tim Cook, while promising only “new product categories” for 2014, has played his cards close to his chest.

Apple’s shares have languished below $600 since November 2012, in part because of worries about smartphone market saturation and its ability to stay at the forefront of tech innovation.

Both iPhone 6 screens are expected to use in-cell touch panel technology—built into the screen and allowing for thinner construction than with standard touch panel films—that was introduced with the iPhone 5, the sources said.

But due to difficulties with in-cell production technology for the larger 5.5-inch size, one of the sources said, a decision was made to begin mass production with the 4.7-inch version alone.

Production of 5.5-inch screens is expected to start several months later, with the possibility of a shift to a film sensor instead of in-cell technology for that size, the source said.

 

 Japan Display will be the first supplier to start production, at its flagship plant at Mobara, east of Tokyo, as early as May, the sources said. The others are due to begin output around June. Reuters

 

PRAVEEN SHARMA

PGDM 2ND SEM