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S.Korea seeks 4-year prison term for stem cell fraud

By Christine Kim
and Jon HerskovitzPosted 2009/08/24 at 5:31 am EDT

SEOUL, Aug. 24, 2009 (Reuters) — South Korean prosecutors told a Seoul court on Monday they wanted a four-year prison term for disgraced scientist Hwang Woo-suk, whose research team has been linked to major fraud in its once-celebrated stem cell studies.
Stem cell scientist Hwang Woo-suk arrives for his trial at a court in Seoul June 19, 2007. REUTERS/Jo Yong-Hak
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Hwang, once a scientist with rock-star like status in South Korea for his research that brought the country to the forefront of stem cell studies, is facing trial on charges of fraud, misusing 2.8 billion won ($2.25 million) in state funds and violating bioethics laws.

Prosecutors said Hwang brought shame to the country and harm to scientific research in South Korea.

"The disappointment felt by the (Korean) people is enormous," one of the team of prosecutors told the court.

Hwang, who has apologized for fraud in his team's work, has denied any wrongdoing and said he was duped by junior researchers into believing the landmark results

Lee Bong-gu, a lawyer for Hwang, said: "These people, including the prosecutors are trying to tear apart Hwang's precious scientific evidence."

Hwang's trial at a nondescript Seoul court has been going on for about three years, and could stretch into a fourth, legal experts said. It has been bogged down in the technical testimony from scores of scientists about the research done by his team.

His supporters have staged emotional rallies over the years and filled the court for each of what are typically monthly hearings, saying Hwang is a scientific savior who should be given a second chance.

Hwang's team was thought to have made two major breakthroughs in the field by cloning stem cells and tailoring them to a specific patient, which raised hopes of generating genetically specific tissue to repair damaged organs or treat diseases such as Alzheimer's.

Stem cells are the body's master cells, giving rise to all the tissues, organs and blood. Embryonic stem cells are considered the most powerful kinds of stem cells, as they have the potential to give rise to any type of tissue.

An investigation team at Seoul National University, where Hwang once worked, said in late 2005 that Hwang's team deliberately fabricated vital data in the two papers on human embryonic stem cells.

It did verify, however, that Hwang's team produced the world's first cloned dog, an Afghan hound named Snuppy.

"Hwang's fall discouraged the government from supporting stem cell studies. It also meant that researchers in the field were the objects of scorn," said Oh Il-hwan, a Catholic University Medical school professor specializing in bioethics.

With major financial backing from his supporters, Hwang went on to form Sooam Biotech Research Foundation in 2006, which specializes in animal cloning and has produced cloned dogs.

(Editing by Sanjeev Miglani)
Copyright Reuters 2008. See Restrictions for more details.
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* S.Korea Seeks 4-Year Prison Term for Stem Cell Fraud
Aug. 24, 2009 (ABC News) — South Korean prosecutors told a Seoul court on Monday they wanted a four year prison term for disgraced scientist Hwang Woo-suk, whose research ...
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Let There Be Light: Teaching Magnets To Do More Than Just Stick Around

ScienceDaily (Aug. 24, 2009) — That palm tree magnet commemorating your last vacation is programmed for a simple function – to stick to your refrigerator. Similarly, semiconductors are programmed to convey bits of information small and large, processing information on your computer or cell phone.
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Scientists are working to coax those semiconductors to be more than conveyers, to actually perform some functions like magnets, such as data recording and electronic control. So far most of those effects could only be achieved at very cold temperatures: minus 260 degrees Celsius or more than 400 below zero Fahrenheit, likely too cold for most computer users.

However, researchers led by a University of Washington chemist report on Aug. 21 in Science that they have been able to train tiny semiconductor crystals, called nanocrystals or quantum dots, to display new magnetic functions at room temperature using light as a trigger.

Silicon-based semiconductor chips incorporate tiny transistors that manipulate electrons based on their charges. Scientists also are working on ways to use electricity to manipulate the electrons' magnetism, referred to as "spin," but are still searching for the breakthrough that will allow "spintronics" to function at room temperature without losing large amounts of the capability they have at frigid temperatures.

The team led by Daniel Gamelin, a UW chemistry professor, has found a way to use photons – tiny light particles – to manipulate the magnetism of semiconductor nanocrystals efficiently, even up to room temperature.

"This provides a completely new approach to microelectronics, if you can use spin instead of charge to process information and use photons to manipulate that process," Gamelin said. "It opens the door to materials that store information and perform logic functions at the same time without the need for super cooling."

The team used nanocrystals of a cadmium-selenium semiconductor called cadmium selenide, but replaced some nonmagnetic cadmium ions with magnetic manganese ions. The crystals, smaller than 10 nanometers across (a nanometer is one-billionth of an inch), were then suspended in a colloid solution, like droplets of cream suspended in milk.

Beams of photons were used to align all of the manganese ions' spins, creating magnetic fields as much as 500 times more powerful than in the same semiconductor material without manganese. The magnetic effects were strongest at low temperatures, but remained remarkably strong up to room temperature, Gamelin said.

Besides Gamelin, authors of the Science paper are Rémi Beaulac and Paul Archer of the UW and Lars Schneider and Gerd Bacher of the University of Duisburg-Essen in Germany.

In a second paper published Sunday (Aug. 16) in the online edition of Nature Nanotechnology, Gamelin's group reported related effects in semiconductor nanocrystals made of zinc oxide but also containing small amounts of manganese impurities.

With zinc oxide, photons acted more as an on-off switch – once photons altered the zinc oxide's magnetism, the photon stream could be removed and the effect remained in place until another stimulus was applied to turn the effect off again.

Besides Gamelin, authors of the Nature Nanotechnology paper are Stefan Ochsenbein, Yong Feng, Kelly Whitaker, Ekaterina Badaeva, William Liu and Xiaosong Li, all of the UW.

Some behaviors described in the papers have been seen previously at very low temperatures, but in those cases the active materials were embedded in other crystals and so could not be isolated or processed. Suspending the nanocrystals in a colloid solution brings the magnetic effects into a new functional form that could be useful for integration with unconventional materials, Gamelin said. For example, the solution containing the crystals could be applied to a film using a device like an ink jet printer, or interfaced with carbon-based materials using techniques not typically practical for magnetic semiconductors.

"We've brought these spin effects into a processable form," he said. "I think both of these papers are converging on the same applications. We're exploring how to manipulate spins in these nanostructures and perhaps opening the door for some exciting new technologies."

Funding for the work in the two papers came from the U.S. National Science Foundation, the Dreyfus Foundation, the Sloan Foundation, the Natural Sciences and Engineering Research Council of Canada, the German Research Foundation, Gaussian Inc., the Research Corp., the Swiss National Science Foundation and the University of Washington.
Adapted from materials provided by University of Washington.
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Strong dopant-exciton magnetic exchange coupling in doped QDs can allow formation of magnetic polarons, where the spins of the dopants spontaneously align with the exciton spin. Key: Small green arrows: Mn2+ spins. Big yellow arrow: exciton spin. h½ = photoexcitation. EMP = excitonic magnetic polaron. rad = radiative decay. SLR = magnetic relaxation. Bext = external magnetic field. (Credit: Image courtesy of Daniel Gamelin/University of Washington)
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Math Model Accurately Mimics Cell Division In Carbon-cycling Bacterium

ScienceDaily (Aug. 22, 2009) — Scientists from the Department of Biological Sciences and the Virginia Bioinformatics Institute (VBI) at Virginia Tech have developed a quantitative, mathematical model of DNA replication and cell division for the bacterium Caulobacter crescentus. C. crescentus, an alpha-proteobacterium that inhabits freshwater, seawater and soils, is an ideal organism for genetic and computational biology studies due to the wealth of molecular information that has been accumulated by researchers. It also plays a key role in global carbon cycling in its natural environment.
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The researchers work will appear in the August 14 edition of PLoS Computational Biology. The article is by Genetics, Bioinformatics, and Computational Biology graduate student Shenghua Li, research scientist Paul Brazhnik, Professor and Director of VBI's Cyberinfrastructure Group Bruno Sobral, and University Distinguished Professor of Biological Sciences John Tyson.

The mathematical model described in the paper allows researchers to study and analyze the systems-level dynamics of the Caulobacter cell cycle, test hypotheses and suggest crucial new experiments. "By careful examination of the large amount of experimental information available about the genes, proteins and biochemical reactions involved in regulating the cell division of C. crescentus, we have developed a good understanding of the mechanism of cell division in this organism and a realistic, quantitative mathematical model of the molecular machinery that oversees Caulobacter's cell division cycle," said John Tyson.

Caulobacter normally undergoes a cell cycle that produces two different types of offspring: a motile "swarmer cell" with a flagellum, a slender thread-like structure that allows the bacterium to swim, and an immobile "sessile stalked cell" that lacks a flagellum. The two cell types undergo different development programs but share the same core molecular regulatory system that controls whether the cell commits to a new round of DNA synthesis and to the cell division process. This regulatory core comprises three key proteins – DnaA, GcrA, and CtrA – that act as control points or master switches for DNA replication and cell division. The new math model allows scientists to investigate how these proteins vary with time and their link to physiological events in both stalked and swarmer cells.

"Cells have some similarities to computers in the sense that they engage in information processing", said Tyson. "However, prokaryotic cells like Caulobacter have been somewhat neglected as information systems in studies by scientists. While computers are precise, digital processors, cells are analog systems that operate for the most part in sloppy, watery environments. Conveying instructions for DNA replication and cell division has profound consequences for a cell and needs to be done with considerable accuracy and precision and that's one of the reasons why we want to be able to model the process." Tyson added: "We have been able to establish a wiring diagram that maps the essential regulatory steps for DNA replication and cell division in Caulobacter in a way that is similar to how you would define a computer process. The model provides a rigorous account of the consequences of our hypotheses, which can be compared to experimental observations to test the model."

With the model in place, the researchers confirmed that it correctly represents the sequence of physiological events that take place during cell division. They were able to show in simulations that the model accurately describes how the different proteins change in quantity during the cell division cycle. Taking this one step further, they were also able to simulate the impact of specific known mutations on cell function.

Mutant cells provide valuable information about how individual components of the cell cycle control system affect the features (phenotype) of cells. Commented Tyson: "Our model allows you to perform quantitative predictions for novel mutants. We have performed simulations of some novel mutants that to our knowledge have not been described in the scientific literature. For example, the math model predicts that if the master regulator CtrA cannot be properly phosphorylated, which is a key step in the activation of CtrA, then the cell replicates its DNA but cannot divide. It will grow very long and eventually die. Specific predictions like this can test the reliability of the model. A validated model can then be used to design new experiments by in silico simulations."

The researchers have built a math model that allows for the study of how the protein components change with time. Future versions of the model will also take into account the spatial localization of the proteins. Said Bruno Sobral: "Caulobacter crescentus is a member of the alpha-proteobacteria, a group of diverse organisms whose members have successfully adopted different lifestyle and energy-yielding strategies over the course of evolution. Caulobacter was also recently detected as a human pathogen, which makes its study directly relevant to human health. Since many genes and mechanisms discovered in Caulobacter are evolutionarily conserved among the alpha-proteobacteria our computational model of cell replication may be applicable to other family members, in particular the causative agents of brucellosis in cattle and Rocky Mountain spotted fever in humans."

Journal reference:

1. Shenghua Li, Paul Brazhnik, Bruno Sobral, John J. Tyson. Temporal controls of the asymmetric cell division cycle in Caulobacter crescentus. PLoS Computational Biology, 2009; 5(8): e1000463 DOI: 10.1371/journal.pcbi.1000463

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Two cells of the aquatic bacterium Caulobacter crescentus attach to a surface, and each other, by their glue-secreting holdfasts. The holdfast is the structure at the tip of the stalk, a thin extension of the cell. The two cells in the picture are about to divide. (Credit: Yves V. Brun, Indiana University)
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Robot's Gentle Touch Aids Delicate Cancer Surgery

ScienceDaily (Aug. 24, 2009) — New, delicate surgery techniques to hunt for tumours could benefit from a lighter touch – but from a robot, rather than from a human hand. Canadian researchers have created a touchy-feely robot that detects tougher tumour tissue in half the time, and with 40% more accuracy than a human. The technique also minimises tissue damage.
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Reference

* Laparoscopic surgery
* Robotic surgery
* Interventional radiology
* Minimally invasive procedure

Surgeons have developed new minimally invasive surgery (MIS) techniques and instruments so that procedures that would previously have required a large incision can now be performed through a tiny 10mm cut. These new methods reduce tissue damage and infection compared with more traditional surgery, and can reduce recovery times and costs.

However, researchers from the University of Western Ontario and Canadian Surgical Technologies and Advanced Robotics (CSTAR) in London, Ontario identified an issue in MIS, and have come up with a robotic solution, which they detail in the International Journal of Robotics Research, published today by SAGE.

Malignant tissue is usually stiffer than the surrounding tissue. Oncologists use scanning techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) scanning pre-operatively to identify lesions. But tissues may shift during surgery, making it hard to rely on the position identified by the scan.

So instead surgeons use gentle pressure (palpation) to confirm where the tumour is, or to locate further tumours not picked up through scanning. But in MIS this can be very tricky due to access difficulties - as the surgeon must attempt to feel for harder tissue using long, slim instruments via a very small incision.

An alternative is to relay touch (haptic) cues via an instrument. Haptic cues include kinaesthetic information, relating to movement, which helps determine the shape and stiffness of an object, and tactile cues about surface textures. A variety of handheld sensors and grasping instruments have been developed since the mid 1990s for use in surgery, but these have the drawback that they do not in themselves control the amount of pressure used, nor do they position themselves correctly. Many are also too large for use in MIS.

Enter the robot-controlled palpating device: With cows' livers standing in for human tissue and 10mm and 5mm blobs of glue wrapped in wire representing tumours, the researchers compared palpation by surgeons, non-surgeons and the robot in the blinded trials. The researchers used a torque sensor to measure the force of the palpations.

Using tactile MIS sensing instruments under robotic control reduces the maximum force applied to the tissue by over 35% compared to a human controlling the same instrument. Accuracy in detecting the tumours was also far greater with the robot - between 59 and 90% depending on the robot control method used for palpation.

Unlike humans, the robot applies consistent force in each step, and moves over the tissue systematically. This produces a complete map, equivalent to one large pad applying ideal levels of force to the whole sample. (Similar to tactile sensors that have been developed to detect breast tumours.)

Humans do not know from one palpation to the next exactly how much force they are applying. This means some features are only highlighted because the surgeon is applying more force, or because the human user has changed the angle slightly between the instrument and the tissue. It is also easier to miss a tumour due to applying slightly lower force.

In fact both surgeons and non-surgeons were more likely to cause tissue damage than the robot. When a subject observed increased pressure on the visual display, they tended to focus on the area and apply even more force to see if what they had observed was a tumour. In the case of MIS, only a very small area can be palpated, which makes it challenging to compare adjacent areas and search for a tumour manually.

If developed further, the authors suggest that this type of instrument would particularly benefit surgeons performing lung tumour resection, where tissue often shifts significantly.

To develop the prototype robot for use in real MIS, the researchers plan to incorporate a design upgrade to include a flexible rotating head and a remote centre of motion. They would also add an improved interface to help surgeons overcome any fears about using robots in this type of surgery, and to allow them to increase the number of palpations around a suspicious area.

This means using robots during MIS to detect tumours is "not only feasible, but results in reduced tissue trauma and increased tumour detection," according to lead author Analuisa Trejos.

With one in eight deaths worldwide due to cancer, rising to one in four in North America, robots with a gentle touch may one day routinely offer a helping hand in cancer surgery.

Journal reference:

1. A.L. Trejos, J. Jayender, M.T. Perri, M.D. Naish, R.V. Patel and R.A. Malthaner. Robot-assisted Tactile Sensing for Minimally Invasive Tumor Localization. The International Journal of Robotics Research, 2009; 28 (9): 1118 DOI: 10.1177/0278364909101136

Adapted from materials provided by SAGE Publications UK, via EurekAlert!, a service of AAAS.
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Tiny Robots Get A Grip On Nanotubes

ScienceDaily (Aug. 24, 2009) — How do you handle the tiny components needed for constructing nanoscale devices? A European consortium has built two microrobotic demonstrators that can automatically pick up and install carbon nanotubes thousands of times thinner than a human hair.
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Matter & Energy

* Nanotechnology
* Materials Science
* Electronics

Computers & Math

* Mobile Computing
* Artificial Intelligence
* Robotics

Reference

* Nanorobotics
* Electron microscope
* Humanoid robot
* Scanning tunneling microscope

Carbon nanotubes, rolled up sheets of carbon only a few tens of nanometres in diameter, could become an essential part of the nanotechnologist’s construction kit. But there is a problem: how can you handle objects which are so thin that they cannot be seen at all with a normal optical microscope?

“The handling and characterisation of these objects has become more and more important in materials science and nanotechnology,” says Volkmar Eichhorn of the University of Oldenburg and its associated institute, OFFIS. “They have a huge application potential in various products.”

One solution, developed by the EU-funded NanoHand project, is to use mobile microrobots equipped with delicate handling tools. NanoHand builds on the work of ROBOSEM, an earlier EU project that developed the basic technologies that are now being put into effect.

The robots, about two centimetres in size, work inside a scanning electron microscope where their activities can be followed by an observer. “The whole set-up is integrated into the vacuum chamber of the microscope,” Eichhorn explains. “There is a glass plate where these mobile microrobots can walk around.”

Microgrippers

Each robot has a ‘microgripper’ that can make precise and delicate movements. It works on an electrothermal principle to open and close the jaws, much like a pair of tweezers.

The jaws open to about 2 micrometres and can pick up objects less than 100 nanometres in size. “[It is] really able to grip micro or even nano objects,” Eichhorn says. “We have handled objects down to tens of nanometres.”

At that scale, the intermolecular forces between objects are stronger than gravity. Once a nanotube has been picked up it will stick to the jaws of the gripper and cannot easily be dropped into position. The team have had to develop novel ‘pick-and-place’ techniques to get around this problem.

One approach is to glue the tube in its final position using electron beam-induced deposition. Another is to use geometrical principles to ensure that the intermolecular forces pulling the tube towards its intended location are greater than those holding it in the jaws of the gripper.

“Worldwide, we are the first project that has really realised the automated microgripper-based pick-and-place experiments,” Eichhorn notes. “The new thing is the high accuracy and the small scale of the objects – in the range of tens or hundreds of nanometres – and the excellent control and software architecture being built around this whole set-up facilitating a high degree of automation.”

Better microscope

An early success of the project was to improve the performance of an atomic force microscope, a workhorse of nanotechnology.

The microscope ‘feels’ a surface by dragging a fine probe over it. Individual atoms can be sensed and a picture built up. But conventional probes have a pyramid-shaped tip which cannot follow the hills and valleys of deeply corrugated surfaces. The NanoHand team used their microrobots to automatically pick up a carbon nanotube and attach it to the tip, so greatly improving the probe’s ability to sense deep valleys.

This achievement was made with the ‘NanoLab’ demonstrator, designed for use in experimental laboratory situations.

In parallel, the industrial partners have developed a more robust ‘NanoFab’ demonstrator, better suited to the needs of industry. They are exploring how the technology could be used for rapid prototyping of new designs for microchips. One idea is to use carbon nanotubes as ‘interconnects’, the fine wires that make the electrical connections to a chip. Because of their high electrical conductivity, carbon nanotubes dissipate less heat than copper and allow circuits to be packed more densely.

This application is of particular interest to STMicroelectronics, one of the project partners and a heavyweight maker of microchips. “They would like to have a nanorobotic system where they can do fast and rapid characterisation of these devices,” says Eichhorn. “Up to now, it was a manual, teleoperated characterisation which was very time consuming.”

Early exploitation

Many other industrial applications are possible, including novel devices that could not be constructed any other way. Applications in composite materials, displays and new kinds of transistors are all being talked about.

Other groups are working on methods of handling nanotubes, especially in the USA, Japan and China, but the NanoHand system of microrobots and microgrippers is proving effective and reliable. “It’s very promising for nanotechnology applications,” says Eichhorn.

From the start, the project has been run with commercialisation in mind and the first product is already on the market. Two of the industrial partners, Tescan and Klocke Nanotechnik, are collaborating to sell a scanning electron microscope equipped with a nanopositioning system based on NanoHand technology.

The Technical University of Denmark (DTU Nanotech) intends to set up a spin-off to market the microgrippers and the Ecoles Polytechniques Fédérale de Lausanne (EPFL) is seeking to further develop the microrobots to the point where they can be commercialised.

NanoHand received funding from the ICT strand of the EU’s Sixth Framework Programme for research.
Adapted from materials provided by ICT Results.
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