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Technion researchers are part of an international team of scientists who discovered a swiftly moving gas streamer eclipsing a supermassive black hole

An international team of astronomers, including Prof. Ehud Behar and Dr. Shai Kaspi from the Technion’s Physics Department has discovered that the supermassive black hole at the heart of the galaxy NGC 5548 has recently undergone strange, unexpected behavior rarely seen in the heart of active galaxies. The researchers detected a clumpy gas stream flowing quickly outward and blocking 90 percent of the X-rays emitted by the supermassive black hole at the center of the galaxy.

This activity may provide new insights into the interaction of supermassive black holes and their host galaxies.

This discovery was accomplished through an intensive observing campaign with the major ESA and NASA space observatories: XMM-Newton, the Hubble Space Telescope, Swift, NuSTAR, Chandra, and INTEGRAL. An international team led by scientist Jelle Kaastra, of the SRON Netherlands Institute for Space Research conducted the most extensive monitoring campaign ever of an active galaxy in 2013 and 2014.

ציור של האזור המרכזי של NGC 5548 (לא בקנ”מ מדויק). הדיסקה סביב החור השחור מפיצה קרני X וקרינה אולטרה-סגולה, אופטית ואינפרה-אדומה ומוקפת בטבעת אבק. הקווים הקמורים מציינים את זרם הגז הנע לאורך קווי השדה המגנטי של הרוח של דיסקת הספיחה. האזור המעורפל עשוי מתערובת של גז מיונן ובתוכו חלקים צפופים וקרים יותר, והוא קרוב יותר לאזור הפנימי של פליטת קרינת אולטרה-סגול. אזור הקו הצר וקולט-החום נמצאים יותר בחוץ.

“We have been observing outflows from active galaxies in detail for over a decade, but have yet to crack their operating mechanism. The present observations are the first time we apparently caught the launch of such a wind and were able to measure its high velocity. ” said Ehud Behar a world renown expert on X-ray spectroscopy of outflows from active galaxies.

The researchers say that this is the first direct evidence for the long-predicted shielding process that is needed to accelerate powerful gas streams, or “winds,” to high speeds. The team reports that this is a milestone in understanding how supermassive black holes interact with their host galaxies.

These results are being published in the June issue of Science magazine.

Matter falling onto a black hole gets heated and emits X-rays and ultraviolet radiation. The ultraviolet radiation can launch winds outward. The winds may be so strong that they can blow off gas that otherwise would have fallen onto the black hole. Black hole winds can therefore regulate both the growth of the black hole and its galaxy. If the falling gas feeds the black hole, the newly discovered outflow is evidence for its eating disorder.

But the winds may only come into existence if their starting point is shielded from X-rays. The newly discovered gas stream in the archetypal Seyfert galaxy NGC 5548 — one of the best-studied sources of this type over the past half-century — provides this protection. It appears that the shielding has been going on for at least three years.

Right after the Hubble Space Telescope had observed NGC 5548 on June 22, 2013, the team discovered dramatic changes since the last observation with Hubble in 2011. They observed signatures of much colder gas than was present before, indicating that the wind had cooled down, due to a strong decrease of ionizing X-ray radiation from the nucleus.

After combining and analyzing data from the six observatories, the team was able to put the pieces of the puzzle together. Supermassive black holes in the nuclei of active galaxies, such as NGC 5548, expel large amounts of matter through powerful winds of ionized gas. For instance, the persistent wind of NGC 5548, known for two decades, reaches velocities exceeding 1000 km/s.

But now a new wind has arisen, much stronger and faster than the persistent wind. “The new wind reaches speeds of up to 5,000 kilometers per second but is much closer to the nucleus than the persistent wind,” Kaastra said. “The new gas outflow blocks 90 percent of the low-energy X-rays that come from very close to the black hole, and it obscures up to a third of the region that emits the ultraviolet radiation at a few light-days distance from the black hole.”

Further information

These results are published in Science:

http://www.sciencemag.org/content/early/2014/06/18/science.1253787.full

“A fast and long-lived outflow from the supermassive black hole in NGC 5548”, by Kaastra et al.

Team:

The team consists of Jelle Kaastra (SRON Utrecht, The Netherlands), Jerry Kriss (Space Telescope Science Institute, Baltimore, USA), Massimo Cappi (INAF-IASF Bologna, Italy), Missagh Mehdipour (SRON Utrecht, The Netherlands), Pierre-Olivier Petrucci (Univ. Grenoble Alpes, CNRS, France), Katrien Steenbrugge (Universidad Católica del Norte, Antofagasta, Chile), Nahum Arav (Virginia Tech, Blacksburg, USA), Ehud Behar (Technion-Israel Institute of Technology, Haifa, Israel), Stefano Bianchi (Università degli Studi Roma Tre, Italy), Rozenn Boissay (University of Geneva , Switzerland), Graziella Branduardi-Raymont (MSSL/UCL, Holmbury St. Mary, UK), Carter Chamberlain (Virginia Tech, Blacksburg, USA ), Elisa Costantini (SRON Utrecht, The Netherlands), Justin Ely (Space Telescope Science Institute, Baltimore, USA), Jacobo Ebrero (ESA, Spain), Laura Di Gesu (SRON Utrecht, The Netherlands), Fiona Harrison (California Institute of Technology, Pasadena, USA), Shai Kaspi (Technion-Israel Institute of Technology, Haifa, Israel), Julien Malzac (Université de Toulouse, France), Barbara De Marco (Max-Planck-Institut für extraterrestrische Physik, Garching, Germany), Giorgio Matt (Università degli Studi Roma Tre, Italy), Paul Nandra (Max-Planck-Institut für extraterrestrische Physik, Garching, Germany), Stéphane Paltani (University of Geneva , Switzerland), Renaud Person (St. Jorioz, France), Brad Peterson (Ohio State University, Columbus, USA), Ciro Pinto (University of Cambridge, UK), Gabriele Ponti (Max-Planck-Institut für extraterrestrische Physik, Garching, Germany), Francisco Pozo Nuñez (Ruhr-Universität Bochum, Gernmany), Alessandra De Rosa (INAF/IAPS, Roma, Italy), Hiromi Seta (Rikkyo University, Tokyo, Japan), Francesco Ursini (University of Grenoble, CNRS, France), Cor de Vries (SRON Utrecht, The Netherlands), Dom Walton (California Institute of Technology, Pasadena, USA), Megan Whewell (MSSL/UCL, Holmbury St. Mary, UK).

Movie:

A new creation by Renaud Person, one of the Worlds Director of the famous video game Assassin’s Creed © Ubisoft. The movie brings us in a journey to the inner regions of NGC5548, and helps us in visualizing the findings presented in this study.

www.sron.nl/~kaastra/press5548/NGC5548_Obscurer_H264.mov ‬‬

An animated journey through the active galaxy NGC 5548.

At its center is a supermassive black hole that is 40 million times heavier than our Sun, all concentrated in a region smaller than the Earth’s orbit around the Sun. Gas swirls around this black hole and is sucked into it, heating up its surroundings and producing strong energetic X-ray radiation. This X-ray hot corona is fuelled through a rapidly rotating accretion disk. The disk also produces strong patchy winds of warm gas that is thrown out into space. It contains denser parts that may obscure the X-rays emitted in the direction towards the Earth, shown by the green line. Further outwards we see the winds produced by the outer parts of the rotating disk, where the so-called broad line clouds are. At light years away from the black hole the warm winds also absorb some of the X-ray and ultraviolet light from the nucleus. These winds can cool down when the obscuring inner clouds block the light from the nucleus. The power emitted by the nucleus is so strong that it affects major parts of the host galaxy. The galaxy has a size of hundred thousand light years and is at a distance of 240 million light years away from us.

The work of assistant Professor Shelly Tzlil is an enlightening example of interdisciplinary research: in her undergrad degree she completed a dual major in chemistry and computer science, her graduate research (MSc and PhD) was in physical chemistry, and her postdoc focused on polymer chemistry. She is a biophysicist, who started off as a theoretician turned experimentalist and today study mechanical sensing in living cells at the Faculty of Mechanical Engineering.

What do biological cells have to do with mechanical engineering? “Typically when you think about communication of cells with their environment, you think about chemicals that cells release and absorb,” explains Tzlil. “But in recent years scientists realize that cells also respond to mechanical forces, such as flow or distortion (deformation) of material that they interact with. Cells bind to their environment, exert forces on it, and unravel its elastic properties by ‘measuring’ the deformations these forces induce. In the case of cultured stem cells, for example, something very surprising occurs – the cells attempt to match the degree of their intrinsic elasticity – their flexibility – to that of the environment and this ‘elastic-matching’ tendency dictates the cell type they will differentiate into. If the environmental elasticity is similar to brain tissue, it will differentiate into neuron, and if this elasticity is like that of a muscle, it will differentiate into muscle cell.”

“In light of this phenomenon, the identity of the investigator and his discipline, greatly affects the type of research questions raised. “While physicists and chemists will ask – ‘How do cells sense elasticity?’ biologists might ask – ‘What is the evolutionary advantage of such a mechanism?’ And medical doctors would want to know how such a mechanism will manifest itself in health and disease,” explains Assistant Professor Tzlil. “I am interested in exploring how cells are able to ‘feel’ the mechanics of their environment, and how they communicate by deforming their environment mechanically.”

“Mechanical engineers study the way material responds to mechanical forces, and how to measure and apply them. They view the cell as a machine with control mechanism and this drive them to ask different type of questions, such as ‘how does the cell ‘know’ how much force to apply?’ It’s a different way of thinking. In interdisciplinary work of this kind both sides have to make an effort to understand one another. I found this willingness in the Faculty of Mechanical Engineering.”

The Technion is a natural playground for this type of interdisciplinary work. “At the Technion the collaboration between medicine and engineering already exists, and I knew I’d be able to find a multidisciplinary working environment that would both suit me and enrich me. My research requires a continuous dialogue with engineers, biologists, medical doctors, theoreticians and experimentalists and the Technion is an ideal place for such integration. Theoretically, I could have found myself in biology, biotechnology engineering or biomedical engineering. The advantage of working in mechanical engineering for me is the toolbox I have here – and of course the excellent partners I’ve made in the fields of elasticity, dynamics and more. I bring to the mechanical engineering faculty the biological aspect, the study of soft matter and the focus on the cellular and molecular levels – aspects that do not belong to traditional areas of mechanical engineering. I came here because I thought that this interaction between the two worlds can lead to an interesting outcome.”

***

Shelly Tzlil was born in Rishon LeZion, and all of her degrees – her undergrad in chemistry and computer science, and her graduate degree in physical chemistry were completed at the Hebrew University in Jerusalem. In her doctoral studies she investigated processes such as the mechanics of DNA packaging in viruses, and protein adsorption on membranes. “My doctoral thesis was in theoretical biophysics – developing models that can explain biological processes. Over time, I realized that as a theoretician, I’m dependant on experimentalists to perform the experiments that interest me. As an experimentalist, I can design and conduct my own experiments to test our theories.”

Tzlil has done her postdoc at Caltech, working with Professor Dave Tirrell, a polymer chemist. “Tirrell knows how to “program” bacteria to operate as a polymer factory producing artificial proteins with unique functionalities.”

The research currently being conducted at Associate Professor Tzlil’s laboratory examines the implications of mechanical interactions between cells and the biological mechanism that enables it. Additionally, new biomaterials are designed that are able to increase the range of mechanical interaction between cells and simulate the physiological environment.

“Usually, biological interactions based on chemical or electrical signals are short range. Mechanical interactions can be felt in large distances. Cardiac cells, for example, can sense mechanical forces hundreds of microns away. It implies that cardiac cells can ‘feel’ each other and synchronize their beating without physical contact, especially when they are on an elastic substrate characteristic of a healthy tissue.”

Assistant Professor Shelly Tzlil believes that her research will enable the design of materials that will allow control over the rate and direction of nerve cell growth after injury. “As part of the research I’m developing bio-materials that increase the range of mechanical interactions between cells as well as materials that simulate the mechanical physiological environment,” explains Prof. Tzlil. “Materials that can effectively conduct mechanical deformations have the potential to control the rate and direction of nerve cell growth after injury.”

A warm welcome to our governors and friends from around the world who have joined us to celebrate Technion’s outstanding achievements and contributions on the national and global stages, and to look ahead to tomorrow’s challenges and promises.

The entire Technion community – faculty, students, staff and alumni – is grateful for the heartfelt generosity of our many supporters from Israel and across five continents.

תכנית מושב הקורטריון

BOG Meeting Program

MAP/מפה

Technion Scientists Develop ‘Test Tube Brain Tissue’ that Provides a 3-D View of Neural Activity

The new ‘Optonet’ cultures could enable a better understanding of complex activity within neural networks

Neural cells grown on laboratory plates (two-dimensional neural cultures) constitute a convenient model for many studies in the field of neuroscience and medicine. Their main advantage is the relative simplicity by which they can be used to examine physiological changes in neural cells’ activity patterns caused by changes in their environment. However, the shortcomings of these simple 2D cultures is that they contain only a single layer of cells, and do not exhibit the complex three-dimensional network connectivity found in real brains. Previous attempts to develop 3D models for studying the central nervous system have met with limited success, mainly due to the high complexity of developing a 3D culture capable of simulating brain tissue as well as challenges associated with developing methods for observing network activity in three dimensions. Technion researchers led by Professor Shy Shoham from the Department of Biomedical Engineering now report in Nature Communications that they were able to develop, for the first time, three dimensional cell networks that can simulate complex aspects of brain activity, which could provide a better access for understanding the physiology of the central nervous system.

המחשה של המיקרוסקופ אותו בנינו במעבדה. על ידי שימוש בטכניקה מתקדמת, הנקראת מיקוד זמני, ניתן לדמות ביעילות ובמהירות איזורים גדולים בתרבית. כל נקודה בתרבית מצולמת 10 פעמים בשניה, מהירות המאפשרת לזהות כל שינוי בפעילות התאים.

The Editors of Nature Communications note that three-dimensional neural networks represent a promising model of complex neural tissue, which may lead to a better understanding of the structure and function of the brain, and that the Technion researchers also present an advanced method for viewing the neural activity of the engineered culture using a fast microscopy system they developed.

Prof. Shoham and his research team, which included Dr. Hod Dana, Dr. Anat Marom, Shir Paluch, Roman Dvorkin and Dr. Inbar Brosh, explain that they grew the advanced culture in a clear gel that supports cellular growth and allows the cells to bind and form neural networks. “By optimizing the culturing conditions we achieved cellular density and composition similar to those found in the human brain, and were able to demonstrate the formation of connections between cells and of networks that maintain neural activity,” says Dr. Marom. To enable the study of network activity in 3D, optical tools were used: nerve cells in the cultures were genetically altered making it possible to view ongoing network activity through a fluorescence microscope, earning them the nickname “Optonets”.

To view cell activity in 3-D, the researchers developed an advanced imaging system that uses ‘temporal focusing’– a non-linear optical technique developed nearly a decade ago at the Weizmann Institute of Science. “The hybrid SLITE imaging system we developed is a significant step forward in improving research capabilities for viewing the activities of multiple brain cells in space and time through which we may be able to reach insights about brain activity,” explains Dr. Dana.

“Through complementary advances in microscopy and in neural tissue engineering we demonstrated an unprecedented ability to view more than a thousand cells within developing neural networks, exhibiting complex spontaneous activity patterns. These innovations open new windows of opportunity for further developments in the field of neural interfaces and other applications for 3-D engineered networks, ranging from basic brain research to the examination of the impact of neurological drugs on nerve cell activity”, summarizes Prof. Shoham.

In the photos:

Illustration of the Technion team’s SLITE microscope, which uses advanced optics to image the 3D culture at a rate of 10 images per second – fast enough to follow neural activity.
Optonets placed over text to illustrate their translucency; the images were taken on different days during the culture’s growth and development.

Clip:

The video shows activity imaged in a culture region containing approximately 1,000 cells, revealing synchronized spontaneous activity bursts in adjacent groups of cells. Neural activity is indicated by changes in the cells’ color.

“Space Elevators” to be Constructed as Part of the Technobrain Competition to be Held at Technion

Yuri Artsutanov, the Leningrad engineer who developed the idea of the ”space elevator,” will travel from Russia to Israel especially to judge the competition; among the competitors this year – three father-and-son teams of Technion graduates and students

Yuri Artsutanov, the engineer who developed the concept of the “space elevator,” will be the guest of honor and one of the judges in the traditional Technobrain Competition to be held at the Technion on June 18 as part of the Board of Governors meeting. Among the competitors this year – three father-and-son teams of Technion graduates (fathers) and students (sons).

The concept of the “space elevator” first appeared in 1895 when a Russian scientist by the name of Konstantin Tsiolkovsky, inspired by the newly constructed Eifel Tower in Paris, thought of a tower that reached all the way into space. In 1957 Yuri Artsutanov drew up a more feasible plan for building such a space tower. He proposed using a geostationary satellite as a base from which to build it. He suggested lowering a cable toward Earth while a counterweight was extended from Earth, keeping the cable’s center of gravity at the geosynchronous point. Artsutanov published his ideas in the Sunday supplement Komsomolskaya Pravda (a national newspaper) in 1960.

The challenge of this year’s Technobrain is to build a device capable of climbing in a nearly vertical manner (at an 80 degree angle to the ground), to a height of 25 meters (for this purpose the Technion has ordered a huge crane), and then slide down from this height while lifting a “space elevator” carrying practical cargo from the other side of the pulley (the position of the pulley will signify the location of the Space Station in space, while the mission course will emulate the movement of the space elevator).

Contestants will not be allowed to use energy sources of combustion or open flame of any kind. In addition, at the height of 12.5-17 meters, competing devices will release a flag or other visual signal to mark the point of no return.

Winners of the competition will be awarded 5,000 and 3,000 NIS cash prizes.

The Technobrain Competition is in its twelfth year, in memory of its promoter and founder Neev-Ya Durban, a student and outstanding Technion graduate. Neev-Ya was serving as an officer in the IDF when he was murdered during a mugging on a quiet street in Tel-Aviv in March 2003. The competition and the prizes are funded by Dr. Robert Shillman (who everyone knows as “Dr. Bob”), who did his graduate work at the Technion. Yuri Artsutanov’s visit to the Technion is supported through the Dean of Students Office, the Asher Space Research Institute (ASRI), and the foundation founded by family members of Norman and Helen Asher from Chicago.

Professor Peyman Milanfar from the University of California Santa Cruz, at the Technion Conference:

To improve the quality of digital photography in small cameras it will be necessary to take a number of pictures and merge them together into one good image – Google Glass are the first to do so.

“Those of you with a keen eye and even those of you without can distinguish between a photo taken with a high quality camera than from one taken with a cell phone, but this will not be the case for long,” asserted Professor Peyman Milanfar from the University of California Santa Cruz, an expert in image processing and artificial vision who has been working for Google over the past year. He spoke at the Fourth Annual International Conference held by TCE Technion Computer Engineering Center named after Henry Taub at the Technion. Professor Milanfar is working with the team developing the Google Glass software.

Professor Oded Shmueli, the Technion’s Executive Vice President for Research, said at the opening of the conference: “We are at the brink of a process which will usher in a new era. The areas of research discussed at the conference, such as artificial intelligence, computer vision and image processing, affect all aspects of our lives.

Within a decade from now cars will travel on roads equipped with computer, sensors and navigation and radar systems which will allow them to travel alone without the intervention of a driver.”

Prof. Oded Shmueli

The TCE Technion Computer Engineering Center was inaugurated three years ago and since then has become a leading center of excellence in groundbreaking research,” said Professor Assaf Schuster, the Head of TCE. “We have been successful at creating here a new model for collaboration between academia and industry.”

According to Professor Milanfar it will be hard and nearly impossible to achieve the level of next generation camera with the simple cameras installed today in cellular phones and tablets, and which in the near future may also be used as part of wearable computing devices. It is because they lack all the moving parts and the complex heavy lenses that professional cameras have. Even the need of not overburdening the user, which has prompted planners to make them lighter and smaller, doesn’t let them compete with the big cameras without encountering physical limitations. The

Professor Peyman Milanfar wearing the Google Glass

miniaturization of devices makes it very difficult to bring light into the device, so what remains is to use sophisticated algorithms to compensate for the size reduction.

“My job at Google is to develop the field of computerized photography that can merge a number of former disciplines such as image processing, photography, computer graphics and computer vision. It includes the development of algorithms, hardware Optics and image processing techniques (Rendering),” explained Professor Milanfar. “The principle is quite simple – instead of taking only one image you shoot a series of images and then merge them together into one image. This can be in the form of a high resolution picture, a trivial feature that allows intensified use of multiple photos, or making use of other ‘tricks’ such as shooting several pictures from different angles and calculating the distance to objects, so that you will be able to decide in which area of the picture to focus and what part of the image will remain vague to achieve a sense of depth. Another ‘trick’ that can be used is to capture images that cannot be detected by the naked eye, such as night vision (by using infra-red sensors),and the ability to detect changes that occur very quickly or very slowly, distinguishing fine details (for example, the motion of a baby’s breathing through cameras installed in a child’s bedroom).”

Scientists (and high school students alike) that use microscopes are surely aware of the phenomenon that occurs when looking at a sample – where only the central portion of the image appears very sharp while the rest of it remains vague. Merging the images will produce one photo where all of the parts of the specimen are sharp and clear. “Google Glass is the first device that contains a camera that at every snapshot photographs a series of pictures and merges them,” added Professor Milanfar.

Professor Amnon Shashua from the Hebrew University in Jerusalem, Co-founder, Chairman of the Board and CTO of Mobileye and the startup company OrCam, described another approach to wearable computing based cameras. OrCam developed a system that includes a camera and microphone that fasten onto regular eyeglasses. The system allows the visually impaired to point at bobjects such as street signs, traffic lights, buses or restaurant menus, and reads it back to them (the menu, color at traffic light, street sign, etc…).

“The OrCam concept differs from Google Glass – as it doesn’t shoot a photo each time the user requests a picture but rather shoots a continuous video and performs immediate processing. This requires a completely different deployment in terms of hardware and particularly with regards to energy consumption,” said Professor Shashua.

PTC signed an agreement with the Technion to establish a center for robotics and digital content

The agreement includes the option to expand the cooperation in the future to include the Technion institutions in the USA and China

The scope of the investment is 7 million dollars

X May, 2014 PTC Inc. signed an agreement with the Technion to support the establishment of a center for robotics and digital content in the department of Education in Science and Technology, investing 7 million dollars. Within the framework of this agreement, PTC will finance the creation of the center and its operational costs for the first 3 years. PTC has been operating in Israel for over 20 years. The Israeli branch is one of 3 worldwide development centers. PTC employees will take part in various activities of the Robotics Center. In addition, PTC will make its software available to Technion students in the new center. Both sides favorably view the possibility to expand the cooperation and include Technion institutions in the US and China.

PTC Inc. is an American company based in Boston (Needham, MA) and traded on the NASDAQ. The company has over 6,000 employees and sales in 2013 of a billion and three hundred million dollars. PTC customers are some of the largest manufacturers in the world, including: Toyota, Lockheed Martin, Boeing, Audi, Caterpillar, General Electric, Raytheon, EADS, Samsung, Dell, Toshiba, Motorola, and more.

PTC’s office in Israel was established in 1991 as the first development center outside of the US. Today this development center employs about 250 professionals in Haifa and Herzliya. Outside of the US, it is the second largest PTC development center in the world. In recent years, PTC has named the Israeli office a strategic development center and as a result the office has tripled in size in less than a decade. The Israel office is responsible for developing PTC’s leading products that are sold worldwide.

With PTC’s software clients can design products in 3D. They can manage all aspects of the product life cycle starting with concept and design and ending with production and support. The software allows PTC’s clients to digitally design the product, visualize it in three dimensions, and examine how each of its components fit together. Clients and vendors can test the product during the design and easily modify it before going to production.

Ziv Belfer, Manager of the PTC Israel development center states: “We are excited about signing the agreement with the Technion and about taking part in the establishment of the new center. As a company that develops new technologies, we value technological education. The Technion is considered one of the leading academic institutions in the fields

of engineering and technology and such cooperation is another step in the advancement of technological education in Israel and abroad.”

Prof. Boaz Golani, Vice President for External Relations and Resource Development at the Technion, stated that: “The Technion welcomes partnerships with technology companies that enrich the curriculum and contribute to the students learning experience. The agreement is a further step in an extensive range of existing connections between the Technion and educational institutions in the State of Massachusetts. PTC’s contribution is yet another evidence for the Technion’s reputation and international recognition as one of the leading institutions in the world in science and technology.”

For more information: Idit Rosenberg, Media-PR, 052-8527125

“Pharmacological Trojan Horse” Fighting Cancer and Resistance to Anticancer Drugs

Technion researchers develop a novel approach for potential treatment of cancer cells that are resistant to chemotherapy

Technion researchers have discovered that multidrug resistant cancer cells frequently produce a large number of lysosomes. Taking advantage of this unique feature of the production of multiple lysosomes and the dramatic irreversible accumulation of certain lipid-soluble drugs bearing light-sensitive properties in these lysosomes– a “Pharmacological Trojan Horse” has been developed that results in the destruction of drug resistant cancer cells.

For this groundbreaking research achievement, Professor Yehuda Assaraf, the Dean of the Faculty of Biology, will be awarded the Hilda and Hershel Rich Innovation and Entrepreneurship award in June 2014. This innovative new technology has been registered as an American patent, and has stirred a great deal of interest among major international pharmaceutical companies. Its potential therapeutic approach was published in the journal “Cell Death and Disease” and received wide coverage in a “Spotlight of Cell Press” article.

“Cancer cells acquire a wide range of sophisticated mechanisms to overcome cytotoxic drug therapy (i.e. chemotherapy) directed against them,” explains Professor Assaraf. “This phenomenon, known as ‘multidrug resistance’ (MDR) often stems from the fact that cancer cells possess an abundance of pump proteins, located in the membrane of cancer cells, that act as efficient pumps which expel a multitude of anticancer drugs from the cancer cells. This is an important mechanism by which malignant tumors become resistant to chemotherapy.”

Two types of MDR are known– inherent drug resistance that exists prior to drug therapy as well as acquired drug resistance that is provoked by drug treatment. Therefore, Professor Assaraf and members in his research team, including Dr. Michal Stark, Dr. Eran Bram and Yamit Adar, made it their primary goal to develop innovative therapeutic strategies in order to overcome the MDR phenomenon, which is a major hindrance to the development of curative drug therapies of cancer.

The researchers searched for the “Heel of Achilles” of MDR cancer cells which would constitute the weakest point through which these chemoresistant cancer cells could be defeated. They discovered that MDR cancer cells often contain a large number of microscopic intracellular organelles called lysosomes. Lysosomes were first discovered in 1974 by Nobel Laureate, Professor Christian de Duve. Lysosomes are intracellular acidic vesicles that contain dozens of hydrolytic enzymes capable of breaking down virtually all kinds of cell components, including proteins, fats, sugars, DNA and RNA. The role of lysosomes is to break down these cell components and other cells that have reached their end, to safeguard the proper physiological functioning of body cells.

The researchers discovered that light-sensitive, lipid-soluble drugs bearing weak basic features, selectively concentrate to very high levels within the multiple lysosomes present in MDR cancer cells. “MDR cancer cells are frequently equipped with two complementary defense systems,” explains Professor Assaraf. “One is the drug extrusion pump proteins located in the cell membrane that efficiently expels different anticancer drugs. The other is the multiplication of lysosomes; many anticancer drugs are lipid-soluble drugs with attributes bearing weak basic features. In other words, in an acidic environment such as inside lysosomes, these drugs become positively charged, get irreversible captured by lysosomes and accumulate to very high concentrations. Drugs capable of escaping one of the “guardians”- that is – the pumps that expel anticancer drugs, will be efficiently “vacuum-cleaned” by the numerous lysosomes found in the resistant cells and thereby prevent the drug from damaging its targeted site in the cancerous cell, resulting in high drug resistance.”

“We took advantage of this unique feature as an “Achilles Heel” and devised a “Pharmacological Trojan Horse” to kill MDR cancer cells,” explains Professor Assaraf. “When we illuminated light upon the MDR cells containing the light-sensitive drugs trapped in the lysosomes, it created oxygen free radicals that destroyed the lysosome membrane and as a result, all of the contents of the lysosomes was spilled into the cancerous cell. This resulted in a massive release of the above enzymes, and rapid digestion and destruction of MDR cancer cells.”

In collaborative efforts with other researchers, among them Professor Grifﬁoen, Dr. Nowak-Sliwinska, Professor van den Bergh, Professor Skladanowski, and Professor Sarna from Holland, Switzerland and Poland, it turned out that in live model experiments using multidrug resistant tumors of human ovarian cancer origin, the core of the tumor was destroyed upon exposure to light, after having accumulated vast amounts of anticancer drugs inside the lysosomes. Moreover, due to the free oxygen radicals that were created after light exposure, the blood vessels nourishing the tumor were destroyed and others were occluded (i.e. blocked). As a result, the blood supply to the remaining cells in the malignant tumor was cut off, and this led to the destruction of any malignant cells that remained.

Professor Assaraf and his research team are diligently working towards developing a second generation of “Pharmaceutical Trojan Horse” selectively targeting cancer cells only by homing protein receptors that are selectively present on the malignant cells without harming healthy body cells. These receptors will deliver the “Pharmacological Trojan Horse” into the lysosomes, which will then be activated by light irradiation from optic fibers. This and much more – the researchers are also developing an alternative “Trojan Horse” that will be activated by ultrasonic waves that would be possible to target any cancerous tissue or metastasis of cancerous cells in a patient’s body without using any invasive procedure.

However, Professor Assaraf emphasizes that the way to develop a “Pharmacological Trojan Horse” for the practical treatment of malignant tumors in humans is still a long way off.

In the image: MDR lung cancer cells containing large amounts of lysosomes (vesicles marked in red) shown on the bottom line of resistant cells as compared with the top line showing sensitive cancer cells with small amounts of intracellular lysosomes). The green fluorescent drugs which are sensitive to light accumulate to very high concentrations in the multiple lysosomes in multidrug resistant tumor cells (the vesicles marked in green) and after exposure to light the multiple lysosomes explode due to the abrupt formation of oxygen free radicals, and the lysosomes enzymes become released into the cells, hence digesting the contents of the cancer cells and killing them.

Technion Students Find a Loophole in Security in the World’s Most Popular Internet DNS Protocol

Following the discovery, algorithms will be replaced in the next software version release

Technion students, Roee Hay and Jonathan Kalechstein from the Faculty of Computer Science discovered a new weakness (loophole), which had not been previously documented in the world’s most widely used DNS software – BIND. “We were very surprised to find a loophole in the protocol,” said Kalechstein. “We reported it to the authorities responsible for its implementation, they responded that they were unaware of this problem, and added that they will replace the algorithms in the next software version release.”

רועי חי מציג את הפרויקט ביום המחקר בפקולטה למדעי המחשב בטכניון. צילום : שיצו שירותי צילום, דוברות הטכניון

Roee Hay presenting his research project on the day of the competition held by the Faculty of Computer Science at the Technion
Photograph: Shiatzo Photography Services, the Technion’s Spokesperson’s Office

The project was carried out at the Laboratory of Computer Communication & Networking in the Faculty of Computer Science at the Technion, and was led by Dr. Gabi Nakibly from Rafael (Rafael Advanced Defense Systems Ltd.). It won the faculty wide competition, the Amdocs Best Project Contest. In August 2013, the project was publicized at an academic conference on information security ‘Usenix WOOT,’ held in the US.

“We devised an attack on DNS, a protocol that is one of the cornerstones of the Internet, and we identified a weakness in one of its implementations,” explained Roee Hay. “The DNS protocol has been around for several years and has been investigated by researchers from all over the world. We knew in advance that the chances of finding a loophole in the software would be very small, but we like challenges.”

DNS (Domain Name System) is one of the most basic Internet protocols. It allows access to a decentralized database enabling computers to translate the names of websites to web addresses (IP addresses).

“During the resolution of name to IP address, DNS servers look for the server storing the corresponding IP address,” explains Dr. Gabi Nakibly. “The weakness that the students found allows hackers to compel a DNS server to connect with a specific server chosen out of a set of potential servers. If that server is controlled by the attacker, that DNS server will receive a false IP address. This type of cyber attack gives hackers an advantage, by causing computers to ‘talk’ with network stations that they alone control without being able to detect the occurrence of the fraud.”

Seeing by Hearing

Technion Students Develop Seeing Application for the Blind

The invention is based on a Kinect camera, mobile phone application and headphones

Three undergraduate students from the Faculty of Electrical Engineering at the Technion developed a seeing application for the blind, based on a Kinect camera, mobile phone application and headphones.

The application is based on images from the surrounding area obtained from the depth camera, which helps the blind navigate inside a building, warning them of obstacles through voice indication, while identifying and directing them to studied objects in the room.

The idea for the project was instigated by an undergraduate student, Tzahi Simkin. “The idea came to me while I was driving, where right before me I saw a blind man having trouble crossing the road. I thought to myself that if I could only describe to him, through technological means, a snapshot of the surrounding area, I would make it much easier for him and build his confidence in getting better oriented with his surroundings. I wanted to combine technological development with social assistance, and this is how this product was born; it connects a depth camera and cellular application, and integrates two different technological systems.”

Koby Kohai with students Tzahi Simkin and Gal Dalal

Tzahi partnered up with two undergrads, Gal Dalal and Danny Zilber, and together the trio began working on the project. “The technological advantage of the Kinect camera lies in its ability to take very good depth images and that it is relatively cheap,” added Tzahi. “This field is continually evolving, with cameras becoming smaller and less expensive all the time. Our project connected the depth images received from a smart phone application, to guide the blind within a given space.”

“The camera sits on a belt and takes depth images of the surrounding area,” explains Gal. “The wireless device processes the information received from the camera and gives a voice indication to the user through the application. The application we developed helps blind people navigate inside a building, warning them of obstacles through voice indication that identifies studies objects and directs the user to them. Studied objects refer to items such as keys or handbag that the application is previously programmed to recognize. In other words, there is an element of recognition and learning.”

“When there is an obstacle before someone who is blind, the application warns him/her to stop and directs them right or left to bypass the barrier,” says Tzahi.” We haven’t yet tested the product with blind people, but we tested it ourselves when blindfolded, and it worked. Recently, we contacted the Association for the Blind in Haifa, so that we could test the application on site from people who are blind, our end users, and obtain feedback for needed improvements.”

Koby Kohai, who heads the Control Robotics & Machine Learning Laboratory at the Faculty of Electrical Engineering, guided and mentored the students throughout the project. “The project received a grade of 100 and has been submitted for a competition for outstanding faculty projects,” said Kohai. “The project was initiated by students, and I instructed and steered them towards technologies currently available on the market. The concept of the project was to test a technological concept that could in the future integrate from a technological standpoint, developing hardware into something more advanced. Every year we suggest ideas for project development to our undergraduate students, coming from industry or research of graduate students at the Faculty. We do our best to provide students with a broad space with which to encourage their creativity and their ideas in their chosen projects.”

“From my point of view, we succeeded with this project,” summarizes Tzahi. “I am interested in continuing to develop the product, so that it can be used by the blind one day. Our motivation for the project was to help those who needed help. There are over 150 million blind and visually impaired people in the world, yet the number of technological solutions offered to them today is very limited. Despite advances in technology, the best means of guidance remains through a Seeing Eye cane or Guide Dog. Our product is not yet perfected, and we intend to continue to develop it.”

Pictures: Koby Kohai with students Tzahi Simkin and Gal Dalal.

Photographed by: Shiatzo Photography Services, Technion’s Spokesperson’s Office