German Research Foundation grants new Collaborative Research Centre to the Goethe University – seven million Euros for historians, ethnologists, philosophers and historians of law
FRANKFURT. Humanities scholars in Frankfurt can begin a mammoth project on 1 January 2015: Between 2015 and 2018, historians, ethnologists, philosophers and law historians will be able to draw on more than 6 million Euros in an attempt to shed light on a global historical issue that stretches from ancient times to the present day. The German Research Foundation (DFG) yesterday granted a Collaborative Research Centre (CRC), currently the only one of its kind in the Humanities faculty of the Goethe University. It is entitled: "Discourses on weaknesses and resource regimes". Over the next three years, some 50 scientists will collaborate in this research association, among them about 40 junior researchers.
What is the purpose of this CRC? Here is an example: Contemporary historian Prof. Dr. Christoph Cornelißen intends to examine the debate involving the political, economic and cultural decline of Europe, which raged throughout the entire 20th century. A number of players – politicians, business representatives, publishers and scientists – feared for Europe's position in the world; Advancing Americanisation and the Yellow Peril are just two key phrases. Europe, they believed, was no longer a match for the growing pressure in world markets, and was also losing ground in international education rankings. The discourses on weaknesses were regularly interspersed with calls to mobilise all existing resources, from people and raw materials to organisations and ideas. The idea was to set up a new political, economic and societal order to prevent Europe's decline, galvanising ideas of a unified Europe. This is just a rough outline of the thesis; the work will now involve taking a closer look at the players and establishing with greater precision how resources can be developed from weaknesses.
"Discourses on weaknesses crop up everywhere. Examples that are often discussed include the Late Roman Empire and China in the 19th century. Yet rather different ones also come to mind, such as situations where weak areas of knowledge initially prevailed, as demonstrated by the budding material sciences of the early 20th century", explained the spokesperson of the new Collaborative Research Centre, Prof. Dr. Hartmut Leppin. "We anticipate a high potential of insight from being able to compare such seemingly disparate topics at an appropriate level of abstraction." When diagnosing the deficits, the scientists will always keep an eye on the self-perception of the players and how they are perceived from a distance.
The fact that weaknesses can develop into strengths is often demonstrated when the discourse on weaknesses mobilises the search for resources. It is this interplay that captures the scientists' interest. The humanities scholars in Frankfurt are fully aware that resources do not equate to raw materials: "Rather, we are interested in what it means to perceive a shortage of raw materials, which then develops into a discourse on weaknesses while the search goes on for other resources", Leppin says. This involves very diverse resources, depending on the sub-project: science, kinship, sanctity, nationalism, information, economic calculations, to name a few. "The wide range of resources can only be dealt with from contrasting disciplinary and temporal perspectives. Our aim is to compare cultures and epochs, in order to be able to provide highly generalised findings", the CRC spokesman explained. Ethnologists and law historians are grouped around a heavily historical nucleus, here in cooperation with the Max-Planck-Institute for European Legal History.
The cooperating scientists also intend to establish an approximation between European history and the history of East and South East Asia as well as Latin America. By way of example, ethnologist Prof. Dr. Susanne Schröter, like Leppin a principal investigator at the Frankfurt cluster of excellence "The Formation of Normative Order", intends to address the question of why it is almost impossible to assert Western models of organisation, such as a monopoly on the legitimate use of physical force, in many post-colonial countries. The particular focus here will fall on Indonesia and the Philippines. For instance, which resources do indigenous groups generate that elude state control? Are acephalous peoples with their egalitarian societies, which are oriented towards achieving political and social equality for their members, perhaps the ones who are truly strong, despite their political weaknesses? Is their conduct more reasonable than that of societies produced by state regulation or which have willingly integrated into such? These are the questions ethnologists seek answers to on the ground.
The participants at the Collaborative Research Centre wish to contribute a humanist perspective to our society's self-reflection. "The question of how to treat resources, their shortage and protection, is discussed in what are at times very heated and politically influential discourses on weaknesses. We have known this since the famous Club of Rome report of 1972, if not before", explains Leppin. "I believe the shortage of resources is one of the key challenges facing us today. However, we must avoid focussing on material resources to the exclusion of all else." Other acting CRC spokespeople besides Susanne Schröter are sinologist Prof. Dr. Iwo Amelung and science historian Prof. Dr. Moritz Epple.
The President of Goethe University, Prof. Dr. Werner Müller-Esterl, views the grant to the Collaborative Research Centre, the ninth at Goethe University, as further evidence of the influence of Frankfurt humanities scholars, and its historians in particular. "The grant is another highlight in a very successful year; back in March, the historians were awarded the DFG research group on "Personnel Decisions in Key Sociopolitical Positions". I would like to take this opportunity to congratulate Hartmut Leppin and his group on this successful application. It further underscores the profile of the Goethe University in the humanities."
Other projects of the historians and contributing humanities scholars are highly popular among sponsors.
The Volkswagen Foundation deemed the Research Centre for Historical Humanities at Goethe University to be "original, innovative and exemplary", and in July 2014 provided it with a grant of 826,000 Euros.
In total the German Research Foundation (DFG) will be establishing eight Collaborative Research Centres (CRC), the authorising committee decreed in Bonn at its Autumn meeting yesterday. The Frankfurt Collaborative Research Centre is the only one of the eight to involve the humanities. The new CRCs are being sponsored with a total of 62 million Euros. There is an additional 20 per cent programme allowance for indirect costs arising out of research projects. Two of the eight centres are CRC/Transregios (TRR), which are distributed across several research locations.
Prof. Dr. Hartmut Leppin, Faculty of History, Department of Ancient History, Campus Westend, Tel. (069) 798 32462, email@example.com
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Professor of Ancient History Dr. Hartmut Leppin is the spokesperson of the new Collaborative Research Centre "Discourse on weaknesses and resource regimes"
The new "L-CSC" supercomputer at the GSI Helmholtz Centre for Heavy Ion Research is ranked as the world's most energy-efficient supercomputer
FRANKFURT/NEW ORLEANS. The new "L-CSC" supercomputer at the GSI Helmholtz Centre for Heavy Ion Research is ranked as the world's most energy-efficient supercomputer. The new supercomputer reached first place on the "Green500" list published in New Orleans on Thursday, comparing the energy efficiency of the fastest supercomputers around the world. With a computing power of 5.27 gigaflops per watt, the "L-CSC" has also set a new world record for energy efficiency among supercomputers. Second and third place on the new list are held by two Japanese supercomputers (Suiren, Tsukuba and Tsubame-KFC, Tokyo).
"L-CSC" was developed at the Frankfurt Institute for Advanced Studies (FIAS) and the Goethe University Frankfurt. The supercomputer was financed by the GSI Helmholtz Centre for Heavy Ion Research in Darmstadt, where it is used for simulations and calculations in basic physics research. It is also slated to prepare experiments at the large international accelerator centre FAIR (Facility for Antiproton and Ion Research), which is currently under development in Darmstadt. The super-fast and energy-saving supercomputer was developed by the Frankfurt computer sciences professor Volker Lindenstruth and his team. It primarily uses efficient cooling and conventional graphics cards, in order to reduce the energy consumption and investment cost for the supercomputer.
Obtaining the world champion title for the "L-CSC" is already the third success for the FIAS scientists within four years on the worldwide who's-who list of green supercomputers: in 2010, the Frankfurt supercomputer "LOEWE-CSC" at Goethe University reached eighth place as Europe's most environmentally-friendly supercomputer. Two years later, the Saudi Arabian computer "SANAM", developed in Frankfurt and Darmstadt, reached second place on the "Green500" list. The world record crowns this series. The list is based on an assessment of how many floating point operations per second a supercomputer optimized for speed achieves with one watt of power.
"L-CSC" is still under construction. At the moment, 56 out of a total of 160 servers are installed. This already makes the computer in Darmstadt one of the world's fastest. On the worldwide "Top500" ranking – which is based purely on speed – it currently holds 168th place with 316.7 trillion floating point operations per second – about three thousand times faster than a normal office PC. And it will perform calculations about three times faster once it is completed in the coming weeks.
"L-CSC" was developed on the basis of the "LOEWE-CSC" and "SANAM" supercomputers, and relies even more heavily on graphics cards for its computing power. Its name is based on its predecessor. However, "L-CSC" performs computations considerably more quickly than its four-year-old predecessor "LOEWE-CSC" and achieves over seven times the computing power with the same amount of energy. This was achieved by using more optimized high speed graphics chips and improved software developed at the FIAS.
The investment costs for "L-CSC" are around two million Euros. When it comes to supercomputers, saving energy isn't just a question of protecting the environment, but is also important in saving on the electricity bill. Thus "L-CSC" runs with significantly lower operating costs than less energy-efficient supercomputers which are just as fast.
The person who developed the "L-CSC", Chairman of the Board at FIAS, IT Director at GSI and professor for high-performance computing architecture at the Goethe-Universität Frankfurt, Volker Lindenstruth, feels that the top ranking of his supercomputer confirms the long-standing energy efficiency efforts: "We are also making a contribution which will allow supercomputers to be used increasingly in industry, because society also requires more and more computing power, whether for technical developments, big data applications, cloud computing or other things."
From a technical point of view, "L-CSC" is a computing cluster, a network of connected computers. Upon completion, the computer is slated to consist of a total of 160 servers (ASUS ESC4000 G2S/FDR), with 1,600 processor cores, each of which contains two Intel-Ivy-Bridge processors and four AMD FirePro graphics cards. Every server has 256 Gigabytes of working memory. The servers are connected through an FDR Infiniband network. In theory, "L-CSC" is capable of providing a peak computing power of 1.7 petaflops with double precision, so 1.7 quadrillion
floating point operations per second in this configuration. This makes it the fourth-fastest supercomputer in Germany.
Information: FIAS Public Relations Office, Reiner Korbmann, c/o Science&Media, firstname.lastname@example.org; Phone ++49(0)89-642 17 50; Frankfurt Institute for Advanced Studies (FIAS), Ruth-Moufang-Str. 1, 60438 Frankfurt am Main, Phone ++49(0)69-798 44100; email@example.com.
Hypoxia protein also regulates growth factors
FRANKFURT/GIESSEN. Healthy cells reduce their growth when there is a lack of oxygen (hypoxia). This makes it even more surprising that hypoxia is a characteristic feature of malignant tumours. In two publications in the current edition of the "Nature Communications" journal, researchers from Goethe University and the Justus-Liebig-University of Giessen report on how cancer cells succeed at circumventing the genetic program of growth inhibition.
It has long been known that PHD proteins (prolyl-hydroxylase domain proteins) play a key role among the regulators of hypoxia. They control the stability of the hypoxia-induced transcription factors (HIFs) which govern the adaptation of cells to a lack of oxygen. The two teams led by Professor Amparo Acker-Palmer, Goethe University, and Professor Till Acker, Justus-Liebig-University, have now discovered that a special PHD protein, PHD3, also controls the epidermal growth factor receptor (EGFR).
In healthy cells, PHD3 responds to stressors such as a lack of oxygen by stimulating the uptake of EGF receptors into the cell interior. Growth signals are down-regulated by this internalisation. "We have discovered that PHD3 serves as a scaffolding protein, binding to central adapter proteins such as Eps15 and Epsin1 in order to promote the uptake of EGFR into the cells," says Acker-Palmer. This process is disrupted in tumour cells due to the loss of PHD3. As a result, the internalisation of EGFR is suppressed, which leads to overactivity of EGFR signals, and thus to uncontrolled cell growth.
The research team was able to show that the loss of PHD3 is a crucial step in the growth of human malignant brain tumours (glioblastomas). The tumour cells thus become refractory to the growth-inhibiting signals under hypoxia. "Clinically, this discovery is highly relevant, because it shows an alternative mechanism for the hyperactivation of the EGF receptor that is independent of its genetic amplification. It can be therapeutically suppressed by EGFR inhibitors," explains Till Acker, a neuropathologist at the University of Giessen.
"Our work shows an unexpected and new function of PHD3 on the interface of two currently red-hot research areas: Oxygen measurement and EGFR signalling," Acker-Palmer explains. "This once again proves how significant growth receptor internalisation is to the development of cancer." This connection was already shown by the research team in 2010 for tumour angiogenesis (Sawamiphak et al, Nature 2010).
Henze et al: Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR; Nature communications 25.11.2014; DOI 10.1038/ncomm6582
Garvalov et al.: PHD3 regulates EGFR internalization and signalling in tumours, Nature communications 25.11.2014, DOI: 10.1038/ncomms6577
Information: Prof. Amparo Acker-Palmer, Institute for Cell Biology and Neuroscience and the Buchmann Institute for Molecular Life Sciences, Campus Riedberg,Phone ++49(0)69 798- 42563, Acker-Palmer@bio.uni-frankfurt.de.Prof. Till Acker, Institute of Neuropathology, University Clinic Giessen and Marburg GmbH, Arndtstraße 16, 35392 Gießen, Phone ++49(0)641 99-41181, firstname.lastname@example.org
Structure of the ABC transporter, elucidated thanks to pioneering structure analysis/Publication in Nature
FRANKFURT. ABC-Transporters are proteins that are embedded in the cell membrane and facilitate the transport across cellular barriers not only of an almost unlimited variety of toxic substances, but also of substances that are essential for life. They also play a role in the development of antibiotic resistance. A research group at the Goethe University in Frankfurt am Main, in co-operation with American colleagues, has now succeeded in elucidating the detailed structure of this transporter.
"On the one hand, ABC transporters cause diseases such as cystic fibrosis, while on the other hand they are responsible for the immune system recognising infected cells or cancer cells," explains Professor Robert Tampé from the Institute for Biochemistry at the Goethe University. The considerable medical, industrial and economic significance of ABC transporters is also based on the fact that they cause bacteria and other pathogens to become resistant to antibiotics. Likewise, they can help cancer cells to defend themselves against cytostatic agents and thus determine whether chemotherapy will succeed.
For the first time, the group led by Robert Tampé, in collaboration with colleagues at the University of California in San Francisco, succeeded in determining the structure of an asymmetrical ABC transporter complex with the aid of a high-resolution cryo-electron microscope. "Over a period of five years, we have successfully implemented a number of innovative, methodological developments. These have enabled us to gain insights that previously were unimaginable," says Tampé.
The researchers report in the current issue of the renowned scientific journal, Nature that they have succeeded in investigating a single frozen ABC transport complex at a subnanometer resolution that has never before been achieved. For this purpose, they used a newly developed single electron camera, new imaging processes and specific antibody fragments in order to determine the structure and conformation of the dynamic transport machine.
"The combination of physical, biotechnological, biochemical and structural biological methods has led to a quantum leap in the elucidation of the structure of macromolecular complexes," says Tampé. The method facilitates the targeted development of a trend-setting therapeutic approach.
JungMin Kim et al.: Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter, nature 2.11.2014, doi:10.1038/nature13872
Biomarkers and target proteins identified in vulnerable neurons
FRANKFURT Parkinson's Disease is the second most common neurodegenerative disorder. In Germany alone, almost half a million people are affected. The focus of the disease is the progressive degeneration of dopamine-producing nerve cells in a certain region of the midbrain, the substantia nigra. Misfolded proteins are the cause. Until recently, it was unclear why damage is confined to specific nerve cells. A team or researchers led by Frankfurt neurophysiologists has now defined how this selective disease process begins using a genetic mouse model of Parkinson´s disease.
The progressive death of a certain type of nerve cells – dopaminergic neurons - in the substantia nigra causes dopamine deficiency, which is the major cause for the motor deficits in Parkinson patients. Although it is possible to therapeutically compensate the dopamine deficiency for a certain period of time, by e.g. administration of L-dopa or dopamine agonists, these therapies do not stop the progressive death of neurons.
In the last two decades, researchers have identified gene mutations and toxic protein aggregates to cause neurodegeneration, with the protein a-synuclein having an essential role. Until recently, it was unclear why only specific types of nerve cells, such as dopaninergic neurons in the substantia nigra, are affected by this process, while others, also expressing the mutant a-syncuclein such as dopaminergic neurons in the immediate vicinity, survive the disease process with little damage.
The research group led by Dr. Mahalakshmi Subramaniam and Prof. Jochen Roeper at the Institute for Neurophysiology at the Goethe University, in collaboration with researchers from Frankfurt's Experimental Neurology Group and from Freiburg University, demonstrated for the first time how sensitive dopaminergic substantia nigra neurons functionally respond to toxic proteins in a genetic mouse model. A mutated a-synculein gene (A53T), which causes Parkinson's Disease in humans, is expressed in the mouse model.
In the current issue of the Journal of Neuroscience, the researchers report that the sensitive dopaminergic substantia nigra neurons respond to the accumulation of toxic protein by significantly increasing the electric activity in the affected midbrain regions. In contrast, the less sensitive, neighboring dopaminergic neurons were not affected in their activity. "This process begins as early as one year before the first deficits appear in the dopamine system, and as such it presents an early functional biomarker that may have future potential for preclinical detection of impending Parkinson's Disease in humans," explains Prof. Jochen Roeper. "The potential for early preclinical detection of subjects at risk is essential for the development of neuroprotective therapies."
The Frankfurt group, also identified a regulatory protein, an ion channel, which is causes the increase in electric activity and the associated stress in nerve cells in response to oxidative damage. This channel provides a direct new target protein for the neuroprotection of dopaminergic neurons. In brain slices, the dysfunction of this ion channel acting as an "electric brake" for dopamine neurons was reversible just by adding redox buffers. If therapeutic drugs could reduce the channel´s redox sensitivity in future mouse models, the death of dopaminergic neurons in the substantia nigra might be prevented. Currently, the researchers are studying whether similar processes occur with other Parkinson genes and in aging itself. "The long-term objective is to investigate the extent to which these results from mice might be transferred to humans," says Roeper.
Publikation: Mahalakshmi Subramaniam et al.: Mutant a-Synuclein Enhances Firing Frequencies in Dopamine Substantia Nigra Neurons by Oxidative Impairment of A-Type Potassium Channels, The Journal of Neuroscience, October 8, 2014 • 34(41):13586 –13599. doi:10.1523/JNEUROSCI.5069-13.2014.
Information: Prof. Dr. med. Jochen Roeper, Institute of Neurophysiology Goethe University Frankfurt, Phone +49(0)69 6301–84091, email@example.com.