For the first time scientists at the Technion have succeeded in taking skin cells from heart failure patients and reprogramming them to transform into healthy, new heart muscle cells that are capable of integrating with existing heart tissue.

The research, which is published online today (Wednesday) in the European Heart Journal, opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to repair their damaged hearts. As the reprogrammed cells would be derived from the patients themselves, this could avoid the problem of the patients’ immune systems rejecting the cells as “foreign”. However, the researchers warn that there are a number of obstacles to overcome before it would be possible to use hiPSCs in humans in this way, and it could take at least five to ten years before clinical trials could start.

Recent advances in stem cell biology and tissue engineering have enabled researchers to consider ways of restoring and repairing damaged heart muscle with new cells, but a major problem has been the lack of good sources of human heart muscle cells and the problem of rejection by the immune system. Recent studies have shown that it is possible to derive hiPSCs from young and healthy people and that these are capable of transforming into heart cells. However, it has not been shown that hiPSCs could be obtained from elderly and diseased patients. In addition, until now researchers have not been able to show that heart cells created from hiPSCs could integrate with existing heart tissue.

Professor Lior Gepstein, Professor of Medicine (Cardiology) and Physiology at the Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel, who led the research, said: “What is new and exciting about our research is that we have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young – the equivalent to the stage of his heart cells when he was just born.”

Ms Limor Zwi-Dantsis, who is a PhD student in the Sohnis Research Laboratory, Prof Gepstein and their colleagues took skin cells from two male heart failure patients (aged 51 and 61) and reprogrammed them by delivering three genes or “transcription factors” (Sox2, Klf4 and Oct4), followed by a small molecule called valproic acid, to the cell nucleus. Crucially, this reprogramming cocktail did not include a transcription factor called c-Myc, which has been used for creating stem cells but which is a known cancer-causing gene.

“One of the obstacles to using hiPSCs clinically in humans is the potential for the cells to develop out of control and become tumours,” explained Prof Gepstein. “This potential risk may stem from several reasons, including the oncogenic factor c-Myc, and the random integration into the cell’s DNA of the virus that is used to carry the transcription factors – a process known as insertional oncogenesis.”

The researchers also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterwards so as to avoid insertional oncogenesis.

The resulting hiPSCs were able to differentiate to become heart muscle cells (cardiomyocytes) just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for this study. Then the researchers were able to make the cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. Within 24-48 hours the tissues were beating together. “The tissue was behaving like a tiny microscopic cardiac tissue comprised of approximately 1000 cells in each beating area,” said Prof Gepstein.

Finally, the new tissue was transplanted into healthy rat hearts and the researchers found that the grafted tissue started to establish connections with the cells in the host tissue.

“In this study we have shown for the first time that it’s possible to establish hiPSCs from heart failure patients – who represent the target patient population for future cell therapy strategies using these cells – and coax them to differentiate into heart muscle cells that can integrate with host cardiac tissue,” said Prof Gepstein.

“We hope that hiPSCs derived cardiomyocytes will not be rejected following transplantation into the same patients from which they were derived. Whether this will be the case or not is the focus of active investigation. One of the obstacles in dealing with this issue is that, at this stage, we can only transplant human cells into animal models and so we have to treat the animals with immunosuppressive drugs so the cells won’t be rejected.”

Much research has to be conducted before these results could be translated into treatment for heart failure patients in the clinic. “There are several obstacles to clinical translation,” said Prof Gepstein. “These include: scaling up to derive a clinically relevant number of cells; developing transplantation strategies that will increase cell graft survival, maturation, integration and regenerative potential; developing safe procedures to eliminate the risks for causing cancer or problems with the heart’s normal rhythm; further tests in animals; and large industry funding since it is likely to be a very expensive endeavour. I assume it will take at least five to ten years to clinical trials if one can overcome these problems.”

Prof Gepstein and his colleagues will be carrying out further research into some of these areas, including evaluating using hiPSCs in cell therapy and tissue engineering strategies for repairing damaged hearts in various animal models, investigating inherited cardiac disorders, and drug development and testing.

Editor-in-Chief of the European Heart Journal, Professor Thomas Lüscher, who is Professor and Chairman of Cardiology at the University Hospital Zurich and Director of Cardiovascular Research at the Institute of Physiology of the University Zurich, Switzerland, commented: “The European Heart journal is proud to publish this exciting study which opens the door for a novel approach in regenerative medicine.”

The European Heart Journal is the flagship journal of the European Society of Cardiology (http://www.escardio.org). It is published on behalf of the ESC by Oxford Journals, a division of Oxford University Press. Please acknowledge the journal as a source in any articles.

NEW YORK–(BUSINESS WIRE)–Google Inc. CEO Larry Page announced today that Google will allocate 22,000 square feet of its New York headquarters to CornellNYC Tech, while the university completes its campus on Roosevelt Island. He was joined by New York City Mayor Michael R. Bloomberg, Cornell President David Skorton and Technion’s Director Craig Gotsman at a press conference this morning at Google New York. The space will allow Cornell to build its presence in New York in close proximity to the tech companies and entrepreneurs with whom it will collaborate. This arrangement represents Google, Cornell, Technion and the City of New York’s commitment to educating and developing tech talent in New York City.

“We are proud to be launching CornellNYC Tech in what is becoming the center of the tech world”

Google will initially provide Cornell with 22,000 square feet of office space on July 1, 2012, free of charge for 5 years and 6 months or until the completion of Cornell’s campus on Roosevelt Island—whichever occurs first. Additionally, Cornell will be able to expand to 58,000 square feet over five years as it builds its presence in New York City.

“I’m passionate about breaking ground in science and engineering because technology has driven many of the advances humankind has made,” said Google CEO Larry Page. “But we still don’t have enough people working in these areas. It’s why I am tremendously pleased that Google is giving Cornell the office space to get their new engineering university up and running in New York City.”

“We’re about to find out what happens when you marry one of the world’s most innovative companies with one of the most innovative economic development strategies any city has undertaken,” said Mayor Bloomberg. “When we first envisioned the Applied Sciences initiative, we hoped the winning school would establish strong relationships with the tech sector. But this kind of synergy is beyond anything we could have imagined. CornellNYC Tech is well on its way to being fully integrated into New York City’s vibrant tech industry, and Google’s support is another huge vote of confidence for that industry. Just a few years ago, our tech sector was barely on anyone’s radar screen – now, it’s creating jobs and becoming a major player in our diversified economy.”

“We are proud to be launching CornellNYC Tech in what is becoming the center of the tech world,” said Cornell President David J. Skorton. “The one missing ingredient has been a pipeline of top-level tech talent, and that is what the tech campus will provide. Building on Mayor Bloomberg’s vision, we are creating a new academic model for this time, this place and this industry. The key is engagement between world class academics, companies and early-stage investors to catalyze innovation. That’s what we’ll be creating on Roosevelt Island, and thanks to Google it’s what will be happening here starting this fall.”

“We are delighted to launch our exciting programs with Cornell University in the Google building. This space provides the optimal environment for the education and nurturing of technical talent. This is a major step towards the fulfillment of Mayor Bloomberg’s vision to seed the city with entrepreneurs and start-ups. We at Technion are confident that our academic partnership with Cornell University will help build the city’s tech ecosystem and boost this sector of the economy,” said Technion President Peretz Lavie.

Technion researchers have demonstrated an innovative method that substantially improves the resolution (the ability to distinguish between details) of microscopes. This was reported by the prestigious scientific journal Nature Materials. The method is based on innovative concepts, and scientists hail it as being a “breakthrough with the potential to change the world of microscopy, imaging systems, and other optical measurement systems”. The method is attracting great interest, both in the scientific world and in industry.

“When you look through an optical microscope at an object with features (optical information) smaller than one half the wavelength of light – you necessarily see a blurred image”, explains Distinguished Prof. Mordechai (Moti) Segev of the Technion’s Department of Physics. “The reason for this is that the information about the structure of very small features does not propagate through space and thus does not reach the eye or the microscope camera. Today, a number of methods are used to achieve a resolution under one half of the wavelength of light, but they all require point-by-point scanning of the object. Hence, these methods may be used only for a static object, which does not change during the scan”.

Scientists have attempted for many years to find algorithms to reconstruct the sub-wavelength information lost between the object and the microscope camera. But thus far all such attempts were largely unsuccessful. The main reason is noise: random scattering of light (for example, from reflections off non-ideal surfaces), which is inevitable in optical systems, has thus far prevented algorithmic reconstruction of features smaller than one half the wavelength of light from measurements of the blurred image.

Now a team of Technion researchers presented a breakthrough algorithmic method for improving the resolution of microscopes to considerably under one half the wavelength of light. To a great extent, the project was successful thanks to the collaboration between several research groups from four different Technion faculties (the groups of Prof. Moti Segev and of Dr. Oren Cohen of the Department of Physics, Prof. Yonina Eldar of the Department of Electrical Engineering, Prof. Irad Yavneh and Dr. Michael Zibulevsky of the Computer Science Department, and Prof. Shy Shoham of the Department of Biomedical Engineering).

“The algorithmic method relies on finding the most suitable reconstruction that meets two criteria: the reconstructed high-resolution image must conform to the blurred image, and it must minimize of the number of the degrees of freedom”, explains Prof. Segev. “The second criterion has to do with understanding compact (sparse) representation of information and with the effect caused by noise in the measurement system. Random noise occupies all degrees of freedom, whereas information has some structure, hence it occupies a given number of degrees of freedom and never all of them. In many cases, there is some sort of a priori knowledge about the information. In principle, in such a case the information may be presented compactly, such that mathematically it is represented by a small number of projections onto basis functions that cover all the possibilities of spatial information. It is then said that the information is sparsely represented, and the number of degrees of freedom it occupies is small. In general, there are many cases where information can be represented compactly. A well known example is file compression using JPEG, a method of compact representation through projection onto a basis where the information in the file is represented sparsely (compactly)”.

This innovative concept of improving resolution in microscopy through representation of the image in the correct basis in which the image is sparse, was developed by Prof. Moti Segev of the Department of Physics and Prof. Yonina Eldar of the Department of Electrical Engineering, graduate students Snir Gazit and Yoav Shechtman and postdoctoral researcher Alex Szameit, currently a professor at the University of Jena, Germany. The idea was initially demonstrated in 2009. However, exhausting the full potential of the resolution improvement necessitated measuring the phase of the light reaching the microscope camera. Phase measurement requires interference-based methods (interferometric methods) which increase the complexity of the system substantially and limit the applications of this method.

About two years ago, Dr. Oren Cohen proposed adding an important layer to the algorithm, which in effect replaces the need for phase measurement, and to thus obtain image reconstruction at a higher resolution than one half the wavelength of light, through intensity measurement only (using a regular camera). In fact, Dr. Cohen proposed that two research directions be combined – Profs. Segev and Eldar’s idea of sub-wavelength imaging and “lensless imaging”, in which images are algorithmically (computationally) reconstructed from measurements of the intensity of the light at a very far distance from the image. This area – of lensless imaging – has recently become an extremely important field of science. On completion of the construction of three short pulse X-ray lasers (in the USA, Germany and Japan) at a cost of one billion dollars per laser, researchers intend to use lensless imaging to measure the structure of hundreds of thousands of single molecules (molecules that cannot be assembled into a crystallized structure). Understanding the structure of these molecules will pave the way for chemists, biologists and doctors to understand many biological processes at the molecular level. Until now, the resolution of all “lensless imaging” methods has been limited to features bigger than a wavelength. However, the methods developed by the Technion researchers could bring about a revolutionary improvement of the entire “lensless imaging” field, and allow measurement of dynamically changing molecules.

The Technion research team has demonstrated in experiments the reconstruction of details at least five times smaller than the wavelength of light, in a single-shot measurement of the light intensity at the focal plane of the microscope lens. The research work was published in the prestigious journal Nature Materials. The majority of the research work was done by postdoctoral researcher Alex Szameit and graduate students Yoav Shechtman and Eli Osherovich. The experiments, conducted by Alex Szameit and Hod Dana (graduate student at the Department of Biomedical Engineering), demonstrated reconstructions of objects with optical features 100 nanometers in size using radiation with a wavelength of 530 nanometers. In comparison, without using the new method, the resolution of this microscope is limited to features bigger than 300 nanometers.

As described above, the main part of the research is the development of the algorithm for the reconstruction of missing information: (a) reconstruction of the phase of light measured by the camera and (b) reconstruction of the part of the optical information which never reached the camera (information on features smaller than one half the wavelength of light). The initial algorithm, developed by Elad Bullkich, an undergraduate student at the time the research was conducted, and Yoav Shechtman, was based on performing the phase reconstruction algorithm followed by the algorithm for the reconstruction of sub-wavelength information. Some time later, Eli Osherovich developed a far better algorithm that reconstructs both types of “missing information” concurrently, thereby substantially increasing performance and allowing handling a wide range of images.

Technion researchers are now working on the development of similar methods for improving the resolution of other measurement systems. For example, graduate student Pavel Sidorenko has recently demonstrated breaking the resolution barrier of spectroscopic resolution: he has reconstructed spectral information at a higher resolution than the fundamental limit on spectroscopy (the time duration a photon spends in the measuring instrument). The researchers hope that these developments will lead to the improvement of spectral systems used, as an example, for the measurement of pollutants in the air of in water, detection of explosives, etc.

A robot waiter developed by middle school students of Haifa Municipal School C under the guidance of researchers from the Technion Department of Education in Technology and Science, has won the “Best Humanoid Robot” title in an international contest which took place in Connecticut, USA.

The project took place as part of the doctorate of Dan Cuperman, who enlisted also the help of his son, Amit. Dan began his professional path as a practical electronics engineer, graduate of the Bosmat Technical High School. He served for five years in MAMRAM, IDF’s Computing and Information Systems Center, and has worked since in the computer company Memorex. At the age of 33 he began studying at the Technion’s Faculty of Mechanical Engineering. When he presented his final project at the MadaTech Museum of Science, he met Prof. Igor Verner of the Technion Department of Education in Technology and Science. Prof. Verner saw his intense desire to teach, and proposed that he join the Department. Dan began his graduate studies in the Department of Education in Technology and Science two years later. “I did it for the soul, and to contribute to the community, not jut to make a living”, he says.

His grade average was 97, and so he accepted the suggestion of his advisor, Prof. Verner, that he proceed to do a doctorate on the subject: “Use of Robotic Models in Technology and Science Education”. He then presented a challenge to his students in Municipal School C in Naveh Shaanan, Haifa: “build a system which mimics one that exists in nature”.

“Since the year 2000, the Roboner contest has been taking place in Israel – a fire-fighting home robots contest”, says Prof Verner. “The contest was the initiative of a former student of mine, today a Ph.D., Eli Kolberg. The winners of this contest participate in the international contest in Connecticut, USA. Three years ago, the RoboWaiter competition was added to the contest in the USA, the object of which is to create a robot that will serve a disabled person at his home, will go to the refrigerator, take food and carry it to that person. It is required to overcome obstacles in its way. To date the participants were robots on wheels, but the user accepts a humanoid robot better, and so we developed a ‘human’ robot waiter, which is a far more difficult challenge than a robot on wheels. The robot developed by Dan, Amit and the students has 18 motors, it is not as stable as the robot on wheels and is difficult to steer, and has to maintain its orientation in space so that it would walk straight. This is a project for excellent students, one which brings out the creativity in them”.

When Amit joined he added to the robot some sensors, a compass and a camera that can identify colors (the table on which the plate is placed in the contest is marked with red lights).

“The walk through open space is a complex challenge, so we added the compass”, explains Amit, who worked on the robot with six 9^th grade students.

In the contest itself, “ED” (the robot was named Technion Ed, short for Education) encountered several surprises, such as a floor that was painted only two hours before the contest, which made it difficult for “ED” to walk on it, or electromagnetic disturbances which interfered with the compass, so “ED” walked along the walls.

Prof. Verner adds that the emotional aspect was well felt in the contest. The spectators loved “ED” and said that he is “cute”, something they did not do when a robot on wheels appeared before them. When “ED” dropped the plate he carried, a great sigh was heard from the audience.

“ED” won a special prize – “Best Humanoid Robot”, and even received an especially fat “tip” – 1000 dollars.

Above: Dan Cuperman, the robot “ED” and the students (from right to left) Yarin Frenkel, Omer Shoshan and Omer Zamir. Photo: Technion Spokesman

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New York City Mayor Bloomberg’s special message (HTIA).

In a message to The High Tech Industry Association (HTIA) 2012 Annual conference on Sept. 11, 2012 Bloomberg included a direct address to Technion, a partner in establishing the Technion Cornell Institute of Innovation on Roosevelt Island in New York City.

The HTIA conference is an important Technology conference and event that takes place in Israel every year.The association brings together Israeli start-ups, venture capital firms, entrepreneurs, large Israeli technology companies and multi-national companies.

This year, the conference joined forces with the Technion which is celebrating its cornerstone centennial, and honored the outstanding contribution of the Technion to the high-tech industry worldwide. Israel is the second largest innovative technology hub after Silicon Valley, with over 4000 startups, about 300 multinational companies with R&D centers, and a venture capital market investing over US$ 2.0 Billion per year in technology companies.

The HTIA’s goal is to develop and enhance a highly innovative competitive global technology industry, by merging both technology and business innovation. The annual conference is the highlight of the association’s activity throughout the year. With over 3,500 participants each year, this annual event has become the largest conference of its kind in Israel.

Dr. Avital Stein opens the tournament. Photo: Roy Tal, One Frame, Technion Spokesman

Technion Challenge – The first international beach volleyball tournament of its kind in Israel opened yesterday at the Technion, as it celebrates the centennial of the cornerstone laying for its historical building.

The tournament will be divided into two parts: an Israel State Cup and the international tournament. The competitors in the Israel State Cup will be students from various academic institutions in Israel, among them the Technion, Tel Aviv University and Ben Gurion University, and the winning  pair will participate in the international tournament, which opens today.

Fourteen pairs of men and women from abroad will take part in the international tournament. Among the pairs are top ranking players from all over the world: the Brazilian pair Benjamin-Harley, who won first place in the 2011 World Championship as well as 12 gold medals over the years, and Pablo Herrera from Spain, who won a silver medal in the Athens Olympics together with his partner Adrian Gavira, who finished fifth in the two last world championships and who won a bronze medal in the European championship. The women’s tournament will be attended by Hana Klapalova and Lenka Hájec(ková from the Czech Republic, who finished fourth in the last world championship, one place before the Americans Lauren Fendrick and Brooke Hanson, who will also participate in the tournament.

During the tournament days, the Technion students will enjoy a performance by the Technion Salsa and Dance Group, a pool party and an earphone party. In addition, players from abroad will enjoy tours to Nazareth and Caesarea.

The Technion Executive Vice President and Director General, Dr. Avital Stein, said in the opening ceremony: “As someone who came from the world of sports, I am thrilled to open this unique international sports event, which is being held in the Technion at the initiative of the Student Association. This is a wonderful way to commemorate the cornerstone centennial of the Technion, a leader not only in academics and research but also in scores of sports, culture and art activities.”

Chairman of the Student Association Asaf Zinger said: “I am the first student to bring 650 tons of sand into the Technion and not be punished for it.” He wished success to all competitors, from Israel and abroad.

Chairman of the Israel Volleyball Association Jacob Shtofman said that the Technion could bring world dignitaries to celebrate with it the historical date, but has instead chosen to hold a first sports event of its kind in Israel as part of its centennial events. “We are proud to be here,” he emphasized.

The tournament finals will be held on Wednesday.

Beach volleyball is usually played by two players in each group, and most of the game rules resemble regular volleyball rules. The first beach volleyball game was played in 1920 in California. It was introduced in the Olympic Games in 1996 and today there are the beach volleyball leagues in most countries.

The tournament is held in collaboration with the Israel Volleyball Association and the Municipality of Haifa.

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