Newly developed a method for the detection of amyloid fibers
The breakthrough will help in the diagnostic of neurodegenerative diseases as Alzheimer’s and Parkinson’s disease
This discovery makes possible to study the rate and conditions of fiber growth
A team of researchers, with participation of CIC biomaGUNE, CIC bioGUNE, University of Antwerp, University of Extremadura and University of Vigo, has developed a new method for the detection of amyloid fibers from proteins that are usually implicated in Parkinson’s disease and other neurodegenerative diseases such as Alzheimer’s or those from prions.
Amyloid fibers are structures based on misfolded proteins that become organised as helicoidal fiber suprastructures. The misfolded proteins constituting the fibers are characterized by a strong interaction between each other, creating structures extraordinarily resistant to elimination. These fibers are observed in the encephalon of people affected by various neurodegenerative diseases such as Alzheimer’s, Parkinson’s or prionic diseases (mad cow disease, Kuru, etc.), in which neuronal death occurs because of the presence of the fibers. One of the features that these diseases have in common is the accumulation and propagation of an incorrectly folded protein, that builds up precisely in the form of such amyloid fibers.
Healthy brain. Upon disease proggression, neurons die out gradually, generating cavities and atrophy of certain brain regions
“Although the damage is done in the brain, it is believed that fibers also form in other parts of the body. Therefore, we can think of an analysis system to complement currently existing tests. From a more fundamental perspective, this technique allows us to carry out kinetic studies. This means we can investigate the rate of formation of the fibers under different conditions and, perhaps, understand which are the parameters that can accelerate the process or even those that can stop it”, explains Luis Liz-Marzán, scientific director of CIC biomaGUNE, where he also works as a researcher of the Ikerbasque program, and coordinator of the work entitled “Detection of Amyloid Fibrils in Parkinson´s Disease Using Plasmonic Chirality”.
The results of this work, published by the Proceedings of the National Academy of Sciences of the USA, open the door to new diagnostic methods for these neurodegenerative diseases, and perhaps to deeper insights into the factors influencing amyloid fiber formation. Deeper and deeper insights into this family of diseases are developed, casting increasing hopes for the future of many patients of neurodegenerative diseases.
Image credits:
Healthy brain image in the public domain, downloaded from Wikimedia Commons.
Aged stem cells conserve circadian rhythm but now perform another set of functions to tackle the problems that arise with age,” explains ICREA researcher Salvador Aznar Benitah, leader of two studies published in Cell Press by scientists at IRB Barcelona, the Universitat Pompeu Fabra and the University of California, Irvine (US). Rejecting the scientific dogma associating ageing with the loss of stem cell circadian rhythm, the researchers show that, with age, stem cells promote a greater functional decline in tissues due to an alteration of their rhythmic activity. The study also demonstrates that a low-calorie diet keeps the circadian rhythm young. Read the press release, and an interview with first authors of the two studies, research associate Guiomar Solanas and “la Caixa” PhD student Francisca Oliveira Peixoto, both at IRB Barcelona.
Novel contribution for the development of high-capacity rechargeable calcium batteries
Electrochemical extraction of calcium proven: a step towards high-performance calcium rechargeable batteries
The study was carried out at the Institute of Materials Science of Barcelona (ICMAB) in collaboration with Toyota Motor Europe
A group of researchers of the Institute of Materials Science of Barcelona (ICMAB – CSIC) has made a discovery that could entail the replacement in the future of the currently omnipresent Lithium–ion batteries. From mobiles to laptops, drills to hedge trimmers, or electric bicycles and cars, these batteries are used in countless devices, small and large. Now, building on top of their previous discoveries in this field, the research group of M. Rosa Palacín has proven the feasibility of electrochemically extracting calcium from a calcium containing oxide. This opens the possibility for developing cathodes and giving proof-of-concept for calcium-based batteries, something previously considered unfeasible. These batteries may outperform Li-ion batteries in terms of energy density in the future.
Calcium and Lithium
Calcium, in its many forms, has applications in industries ranging from the construction and the manufacturing industry to the chemical, pharmaceutical or the food industry. With the discovery by ICMAB scientists, a new application could enlarge the repertoire: the design and construction of rechargeable batteries using calcium-based electrodes.
Are modern Lithium-ion batteries perhaps unsatisfactory? Certainly a common complaint in (intensive) mobile phone users is about the duration of their battery. Battery duration is related to its energy density, and is a key characteristic in any hand-held battery-powered device. Owing to the divalent nature of calcium ions (Ca2+), if compared to the monovalent lithium ions (Li+), batteries based on the first could be designed to have considerably higher energy. Result: batteries could last considerably longer.
In addition to this, Lithium ranks as the 33th most abundant element on the Earth crust, while calcium is the fifth. Being close to two-thousand fold more abundant than Lithium, the economic impact of switching to Calcium-based batteries could be enormous. Moreover, lithium is relatively scarce and potentially subject to future demand and supply issues.
The sources or processes to obtain Lithium and Calcium share similarities. Both can be obtained from ore materials, or also by means of brine mining. Regarding the first method, the most abundant mineral source of calcium is limestone, a sedimentary rock naturally rich in calcium carbonate. This mineral is the direct or indirect source of diverse calcium salts of industrial application. Remarkably, a process invented in the 1860s in Belgium, the notorious “Solvay process” for soda ash production, still significantly contributes today to global calcium chloride production.
Lime Kiln Building at the Solvay Process Company at the town of Solvay, Onondaga County, New York, circa 1968
In addition to its extraction from ore, calcium can also be obtained industrially by the more cost- and energy-effective brine mining method. In this process, dissolved salts are precipitated by evaporation. The precipitated salts may contain different proportions of ions of interest, components that can be purified later on. Whether from ore or brine, finally a stable calcium product is obtained, from which downstream uses will stem. The abundance of calcium will, in the long run, ensure that its price and supply remain stable, to the benefit of present and future industries relying on it.
Batteries, a simple view
One can consider, simplifiedly, that a battery has two main components: the electrolyte and the electrodes (the cathode and the anode). These electrodes correspond to the positive, and negative poles, respectively. Each electrode is host to a chemical reaction: the one releasing electrons; the other one, taking them up. The flow of electrons through the circuit from the anode towards the cathode is, ultimately, what generates the electric current our devices can use.
Another component is necessary, as the course of the reduction and oxidation reactions taking place at the electrodes would generate a charge imbalance blocking the operation of the battery. The charge is compensated by the use of a “salt bridge”. This, in practice, is a semipermeable membrane or separator disk, soaked in the electrolytic solution, allowing ion transport, in turn allowing the battery to avoid that charge imbalance, and keep operating.
Galvanic cell: zinc oxidises, releasing zinc ions and electrons. Copper ions take up the electrons, generating metallic copper
If the battery needs to be rechargeable, the reactions in the cathode and anode have to be reversible. This allows that, upon application of an opposing external voltage, the electron current runs in the opposite direction. This allows to restore the electrodes to their initial state. If during operation or recharge some end-product products form that cannot be transformed back into the original elements of the battery, the battery will not be decreasingly rechargeable. The maximization of the reversibility of reactions inside the battery is a key: it ensures that it can be re-charged numerous times and extends its operation life.
The discovery: a new calcium-based cathode
Two years ago, unlike previously thought, the group of Prof. Palacín proved that metallic calcium could be used as an anode for batteries. The study was published in Nature Materials in 2016. Now, their discovery of a potential calcium cathode adds to this previous research, even if reversibility needs to be improved. Once this is achieved, a full calcium-based rechargeable battery will be feasible.
In the recent study, published in the journal Dalton Transactions, the electrochemical extraction of calcium from a metallic oxide has been achieved, proving that this oxide could be used as a cathode for calcium rechargeable batteries if reversibility was possible. M. Rosa Palacín, the ICMAB researcher leading the study, further explains that, in this case, a calcium-cobalt oxide was used.
Calcium ions (Ca2+) are divalent cations, meaning they have a double positive charge. Lithium ions (Li+), by comparison, have only one. Divalent charge carriers, as Ca2+, need only half the number of ions to achieve a certain electrochemical capacity if compared with lithium. The direct consequence of this is the possibility for the design of higher energy density batteries.
The experiments by the Palacín team were performed in conventional organic electrolytes and moderate operating conditions. The electrolytes used were similar to those used in the Li-ion battery technology and thus enable high cell potential. These findings are the first step to solve one of the main problems facing calcium-based batteries: to find cathodes able to incorporate and release calcium ions in a reversible way. This enables not only battery operation, but also re-charge and re-use.
Proposed battery using the anode and cathode by Palacín and coworkers. A prototype will become a reality in the future
Similar developments have been proposed using other divalent metal ions, as magnesium (Mg2+). However, amongst divalent electropositive ions, calcium ion (Ca2+) remains especially attractive due to its abundance. Another advantage in the context of the design of rechargeable batteries is that it has a standard reduction potential very close to that of lithium, which again enables high cell voltage. Using calcium, cells with voltages of up to 4 or 4.5 volt could be attained (similar to that of Lithium), making them suited for use in power-hungry devices and applications. Using magnesium, on the other hand, would allow at most voltages of only around 3 volt.
In addition to the previous, the higher charge to radius ratio of magnesium ions suggests that the reaction kinetics (the speed or reactions, hence the responsiveness of the battery) would be higher in the case of a calcium battery. In other words: calcium batteries would have a higher performance than their equivalent magnesium counterparts.
The structure of the calcium-cobalt oxide used modifies upon electrochemical extraction of calcium, explains M. Rosa Palacín
These results represent a crucial step towards the development of enhanced alternatives to the current Li-ion batteries. The development has resulted in a patent together with Toyota Motor Europe, the company partnering in the research. In order to bring rechargeable calcium batteries to the market, however, some hurdles have to be overcome. Firstly, a working prototype of rechargeable calcium battery needs to be developed. In addition, the reversibility of the cathode must be achieved, and all the components of the battery, optimized.
The story of calcium batteries is still to be continued. To support in the challenges ahead, the acquired experience with lithium batteries will be of inestimable help, as lithium batteries have been on the market for nearly 30 years. The calcium relief to the already veteran lithium-ion batteries is under way.
Image credits:
Frontpage image of a Smartphone taken from the public domain (Pixabay).
100xCiencia.2 conclusions on knowledge and technology transfer (KTT) released on new position paper
SOMMa institutions are active participants and generators of KTT, in collaboration with multiple collaborating actors
Stability, investment and a supportive environment: requirements for successful KTT
100xCiencia is a forum where Severo Ochoa (SO) and María de Maeztu (MM) research centres and units gather, addressing topics related to Spanish research and its impact. The first edition took place in La Palma (Canary Islands) in 2015, and put an emphasis on the communication of science. The next edition, 100xCiencia.3, will take place next November in Madrid, where expectedly close to 50 SOMMa institutions will gather.
Previous 100xCiencia.2 meeting: “Co-creating Value in Scientific Research”.
The previous edition, 100xCiencia.2: Co-Creating Value in Scientific Research, was hosted by the Instituto de Neurociencias (IN), in Alicante (Spain). Discussions took place about knowledge and technology transfer, its requirements, implications for society, and what is the state of the matter at SO and MM institutions. From their conclusions, the position paper “La investigación científica como palanca hacia una economía del conocimiento” is here presented (text in Spanish). The main points of the text are extracted, from which the resulting adaptation follows next.
Knowledge and technology transfer
Knowledge and technology transfer (KTT) comprises a range of collaboration activities beneficial to the actors involved: the transfer of experience and know-how, of physical and intellectual property, the exchange of good practice, or even the more spectacular transfer of game-changing breakthroughs. This often includes an exchange of economic resources, further supporting new developments. In fact, a multidirectional exchange or co-creation is to be the core of a successful and sustainable collaboration. Technological advances become more widely distributed, and available for further development. Ultimately, those translate into business ideas eventually reaching the marked.
The involved parties include universities, research institutions and hospitals, as well as technological and industrial companies. KTT originates a driving force supporting economic growth and generating tangible benefits for society. For businesses, it can become a profitable –albeit often risky- venture. For researchers, it can provide new perspectives, leading to new research approaches, as well as some welcome extra resources. For society, it should become a source of increased development and well-being. To this regard, 100xCiencia.2 participants attest that they are net contributors indeed.
KTT and the SO-MM centres and units
KTT is a relevant aspect in all of the SO and MM research institutions. Collaborations with businesses and hospitals are ongoing, as well as the creation of spin-offs, the patenting of inventions and patent licensing, or the establishment of personnel exchanges for training purposes.
Different approaches and emphasis points characterise the KTT activities of each particular institution. The dominant activities, to that regard, depend heavily on the main scientific area, and the approach to research of the institution. What is the drive behind projects and activities? Does it develop challenge-driven, or rather curiosity-driven research? Is it mainly an applied research institution, or, on the contrary, a more basic-research-oriented institution?
Whatever the case, KTT is an eminently long-term activity that starts with fundamental research. From it, building blocks for increasingly applied advances become available. Basic research remains, without a shade of doubt, the foundation of future technologies to come.
Starting from basic research, knowledge generated ultimately results in new patents, licenses, and spin-offs. With favourable luck, thorough planning and a good business idea, eventually investors flock towards the nascent companies with the largest potential. Finally, new goods and services may reach the market, to the benefit of society at large.
Recommendations and conclusions arising from 100xCiencia.2
The process of research and its translation to services and products is long and arduous. 100xCiencia.2 participants stressed that, during that process, the context in which the value chain develops should remain as stable and predictable as possible. Such conditions are needed to favour not only research itself, but also the transfer of the generated knowledge. Failing to provide stability will fall short of generating the confidence required for investors to risk their capital in possibly fruitful, but still uncertain initiatives.
As the position paper raises, the measure of the success of an institution in KTT should focus on the impact it generates, rather than on the revenues from royalties. This stems partly from the fact that direct economic returns are only a marginal part of the income of research institutions. In addition, royalty revenues tend to come from only a small portion of all patents held. The social return, however, is immense: thousands of companies founded and many more highly qualified jobs created.
As concluded from the analysis of notorious cases of success, a number of conditions need to be met to develop a favourable, healthy KTT environment:
-Firstly, most of the research in the academia should be financed via public funding, obtained through competitive calls.
-Next, there is a need for the inflow of high-risk investment from the industry, which should be stimulated.
-Third, for spin-offs to successfully bridge the gap between academia and business, a dedicated support environment for KTT needs to be in place. Such a support network would offer resources, training and the possibility to establish relevant connections or find funding.
As stressed in the paper, an increase in Spain from the currently modest investment of 1.19 % of GDP in science to 2.03 % (the average in Europe) would be clearly beneficial. Increased scientific output and more synergies would arise, particularly if the KTT ecosystem is stimulated.
In addition to the previous, research institutions need the resolute support of government institutions, and an appropriate regulatory framework. Legislation considering the particularities of research is needed, as was outlined in previous actions by SOMMa, resulting yet in some legislative successes.
Group picture of participants in 100xCiencia.2 in front of the host institution, the Instituto de Neurociencias de Alicante.
Failing to translate research into benefits for society owing to an inappropriate transfer environment risks making the existing investment less relevant. In the current international context, in which the centre of gravity of world economy is moving away from Western countries, Spain and Europe can hardly afford this. As a result, investing into a healthy and dynamic research and KTT ecosystem would be a strategically sound decision in favour of a better future for science, economy and society in Spain.
CNB pioneered in Spain the biomedical public-private partnership with the foundation of its Department of Immunology and Oncology (DIO)
Genetrix, a Spin-off started at the DIO, 18 years after its foundation lands its largest success
Tigenix, a company born from Genetrix subsidiaries and external partners, sold for over 500 million Euro
Genetrix: a successful umbrella business strategy
Since its foundation 18 years ago, Genetrix has carried out an ambitious business development strategy that includes a fruitful policy of acquisitions and sales with other pharmaceutical companies. In January 2018 the multinational Takeda presented a public offer for share acquisition for the prize of 520 million Euro. This operation, which ends by start July 2018, culminates the activity of Genetrix as a private promoter of biomedicine in Spain. It represents a milestone of the success of the company and its subsidiary projects.
Venus Genetrix, goddess of motherhood in ancient Rome. To the right, Temple of Venus Genetrix in the Forum of Caesar, Rome
Genetrix has been one of the scarce Spanish examples of successful basic-clinical collaboration. Paired with an adequate business development, it has managed to successfully re-invent itself, adapting to the needs and mechanisms to access the market. This is its story.
Origin
Genetrix SL was constituted in November 2000 as a spin-off of the Department of Immunology and Oncology (DIO) of the Spanish National Center for Biotechnology of CSIC (CNB-CSIC), in Madrid. Founded by Prof. Carlos Martínez-Alonso in November 1996, the department came into being as a pioneering initiative between CSIC and the multinational Pharmacia-Upjohn, establishing a prominent case of public-private research collaboration in Spain.
The three founding members of Genetrix were Carlos Martínez Alonso himself, together with Cristina Garmendia and Antonio Bernad. Garmendia and Bernad met during their Ph.D. in the laboratory of Prof. Margarita Salas, a recognized Spanish biochemist (and former pupil of Severo Ochoa). Numerous conversations during that period hinted about their mutual interest to get involved into the biotech business. Eventually, they and their colleagues decided to start a company further deepening into the collaboration already running between the public and private sectors at the DIO.
The development
Genetrix, in which the CSIC was also invited to participate, was initially conceived as a company dedicated to the development and commercialization of intellectual property of the know-how emerging from the DIO not prioritized by Pharmacia-Upjohn. As a safeguard of the commercial interests of the multinational, Pharmacia-Upjohn would retain a first-refusal option in later stages of development; that is, the priority of purchase in sales offered to third parties.
Of the three founder members, Garmendia, having completed an MBA, took responsibility for the financial design and selection of the initial investors. For their part, Martínez-Alonso and Bernad selected the initial projects and were architects of the strategy for the R+D Department, as well as liaison contacts with the DIO. A first financial round was executed and Garmendia was designated as President and CEO of Genetrix SL. The inestimable support of the director of the CNB at that time, Mariano Esteban contributed towards finding a physical location at CNB, where temporary laboratories would be located at the so-called Pilot Plant. The offices of Genetrix were established at the Madrid Technological Park, in front of the CNB. Their adventure had started.
Once it had sprung into existence, the company structured in two main areas: Molecular Therapy, and Cellular Therapy. The Molecular Therapy Area focused on the development of humanized antibodies for intervention in human pathological conditions, particularly in connection to inflammatory processes. For its part, the Cellular Therapy Area concentrated on the use of mesenchymal stem cells derived from adipose tissue (ASC), for the treatment of conditions with exacerbated inflammation and impaired healing capacity.
Finance-driven adjustments
The needs associated to the following higher-level financial rounds, pushed towards a modification of the business strategy. The implemented changes would entail the development of more advanced projects in subsidiary companies. The required flexibilization resulted in the creation of a new company, from the Cellular Therapy Area, in 2004. The newly created company, Cellerix SA, continued its focus on developing human ASC for disease treatment, as the Cellular Therapy Area had done before.
The company ecosystem around Genetrix has substantially grown since its foundation in the year 2000
Valuable new financial partners were incorporated by the creation of Cellerix. These included Ventech, LSP, Ysios, Roche Genera, AyG and Novartis. Finally, in February 2011, Cellerix SA announced positive results in the phase II clinical trial ADMIRE-CO. This project addressed the treatment of Crohn’s disease patients suffering from complex perianal fistulas. The condition it focused on, while not life-threatening, substantially reduces patient quality of life. No adequate treatment was available, making this a virgin market to be exploited.
Not long after this advance, in June 2011, Cellerix SA merged with TiGenix NV, a Belgian company listed on the Brussels stock market (NYSE Euronext Brussels: TIG). Together, they constituted TiGenix Living Medicines. The merger process valued yet Cellerix SA at 58 million Euro, even before the decisive phase III of ADMIRE-CO launch in 2012.
In July 2015, Genetrix, the original parent company, strengthened the alliance constituted four years before: it reached an agreement for the acquisition by TiGenix of its subsidiary company CoreTherapix, a Cell Therapy Cardiovascular Company. Genetrix would receive a total of 267 million Euro, conditioned to the fulfilment of several clinical and commercial accomplishments. In addition, Genetrix would receive a direct full down payment of 25 million Euro for each ongoing pipeline product that reached the market.
Touching the market
In July 2016, The Lancet published the early (24-week post-treatment) positive results of ADMIRE-CO (phase III). An exhaustive follow-up of the patients to 104 weeks post-treatment confirmed the stability and safety of the treatment, paving its way towards the market. At that time, TiGenix initiated an official application to commercialize Cx601, which would receive the denomination Alofisel (Darvadstrocel). TiGenix signed an agreement with the multinational Takeda Pharmaceutical Company Limited to transfer all exclusive rights of Cx601 for worldwide commercialization, except in the USA. Thereafter, in December 2016, TiGenix was incorporated into the Nasdaq index.
In December 2017, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), in conjunction with the Committee for Advanced Therapies (CAT), adopted a positive opinion recommending the authorization of the compound Cx601 (Alofisel). Definitive authorization ensued in March 2018. In January 2018, Takeda presented a public offer for share acquisition (OPA) of TiGenix. The offer valued TiGenix at 520 million Euro.
Take-home message
Over its 18 years of life, Genetrix has carried out an ambitious project to promote and reinforce the private-public interface in Spanish biomedicine. On the way, Genetrix has created, directly and indirectly, more than 200 specialized jobs. Genetrix will continue to participate in decisions regarding the projects in which it still participates, and which are in expansion, as are Tigenix-Takeda and Sygnis-Expedeon.
Genetrix team in the year 2005, with the largest successes still to come
The success of projects like the Genetrix Spin-off depends on many factors, and doubtlessly the selection of the initial investors was key. The previous public-private collaboration at CNB, the reputation of the founding members and a solid financial plan were essential to the success of this venture. All this together, allowed translating research results into drugs making it to the market. In the process, the story of the company and its success was written. Genetrix has been part of the successful avant-garde of companies populating an area almost non-existent in Spain at its time.
Founding members:
Carlos Martínez Alonso
Prof. Carlos Martínez Alonso (Villasimpliz, 1950), is a chemist and researcher in immunology with a long national and international career in the study of lymphocyte biology and its implications in cell migration and autoimmunity. He is awarded with the DuPont Prize for Science; the Carmen y Severo Ochoa; the Rey Jaime I Award for Scientific Research; the Lilly de Investigación Preclínica; the Spanish National Award of Medicine “Gregorio Marañon”, and The International Award to Science and Technology of the Government of Mexico among others. He has presided the European Molecular Biology Organization (EMBO), the Spanish National Research Council (CSIC) and been Secretary of State for Research in the Ministry of Science and Innovation, among other relevant positions. He is a member of the European Molecular Biology Organization (EMBO) and was a member of its Scientific Council, of the Academia Europaea, Dr. Honoris Causa by several universities and member of the editorial committee of various international prestigious journals.
Cristina Garmendia
Dr. Cristina Garmendia (San Sebastián, 1962), is a biologist and businessperson, notorious for her nomination in the year 2008 as Minister of Science and Innovation of the Spanish Government, under President José Luis Rodríguez Zapatero. After the end of her Ministry, Garmendia returned to her entrepreneurial activities in the private sector. Dr. Garmendia has participated as member of multiple business associations and scientific/advisory boards. She currently presides over the Fundación Cotec para la Innovación, a private foundation promoting innovation as an engine for economic and social improvement.
Antonio Bernad
Prof. Antonio Bernad (Zaragoza 1961), is a biochemist and researcher in the field of stem cells. He has researched at institutions of excellence including CIEMAT, CNB, CNIC and the Harvard Medical School. At the CNB, he built a research team focused on the biology of hematopoietic and mesenchymal stem cells and their use in tissue engineering. While at the CNIC, he has addressed the field of adult cardiac progenitor cells (CPC) and their regulation, homeostasis, and biosafety in cell therapy. He was Director of the Regenerative Cardiology Department, and coordinated the European project CARE-MI for clinical evaluation of CPC in allogeneic transplant. Since 2013, he is back at DIO (CNB-CSIC) as group leader of the Adult Stem Cell team.
Genetrix founders: Carlos Martínez Alonso, Cristina Garmendia and Antonio Bernad
Acknowledgements
We thank sincerely Prof. Antonio Bernad for the original text on which this article was closely based, and for the help during the review and correction process. Images were kindly provided by Prof. Antonio Bernad himself, via the CNB.
BCAM supports the INSPIRA project to promote STEM education among young girls
Amaia Abanda, a researcher from the Basque Center for Applied Mathematics, collaborates as a mentor in this initiative promoted by the University of Deusto
The number of students that choose scientific or technological studies is dropping every year, with a decrease that is even larger among girls: even though 54,3% of the students in the Spanish University System are women, their presence in STEM degrees amounts only to 26,4%.
INSPIRA is a project that was born by the urgent need to promote scientific and technological degrees among Basque students, especially among girls. Its goal is to encourage young students to pursue STEM degrees by raising awareness of the situation and by providing guidance sessions from professional women in the area of research, science or technology. The initiative is promoted by the University of Deusto in collaboration with Innobasque and the Elhuyar Foundation and financed by the Regional Governments of Araba,Bizkaia and Gipuzkoa, and BBK.
More than 100 volunteer women are giving mentoring sessions in schools in Araba, Bizkaia, and Gipuzkoa in order to raise awareness around gender stereotypes and occupation. The main purpose is to make young girls reflect on prejudices by bringing science closer to them and by giving visibility to the important duty scientist women have had throughout history. The program also aims to provide them with a close female referent working in these areas.
In line with BCAM’s strong commitment to the promotion of scientific vocations among young girls and boys, the center signed a partnership agreement with the project last June and has joined the INSPIRA MANIFEST to actively work towards gender equality in scientific and technological careers. As part of this collaboration BCAM researcher Amaia Abanda has been working as a mentor for young girls during the second edition of INSPIRA, giving 6 mentoring sessions to girls from Bilbao’s La Salle school.
Amaia Abanda, a researcher from the Basque Center for Applied Mathematics, collaborates as a mentor in this initiative promoted
Amaia graduated in Mathematics at the Universitat Autònoma de Barcelona and has a Master in Computational Engineering and Intelligent Systems from the University of the Basque Country. She is currently a Ph.D. student in Data Science at the Basque Center for Applied Mathematics’ Machine Learning department. Regarding her time as a mentor as part of INSPIRA she says the experience was “extremely gratifying” and that the students “really enjoyed learning”.
The particle accelerator SuperKEKB, in Japan will break the world record of particle accelerator luminosity and particle collision rate
The Spanish contributors IFIC, IFCA and ITAINNOVA have developed a new detector for Belle II: DEPFET
These joint efforts will contribute data to answer fundamental questions about the Cosmos
A few words about elementary particle physics
In particle physics, an elementary particle is one without any further sub-structure. The particles currently considered to be elementary are the fermions and bosons. Of those, fermions include quarks, leptons, antiquarks and antileptons, and are considered to be the constituent elements of matter and antimatter. Bosons include gauge bosons and the notorious Higgs boson, and are considered to be “force particles”, mediating interactions between fermions. Collisions between elementary particles by means of particle accelerators constitute invaluable means of studying these particles, and more widely, matter and the Universe.
The Standard Model is a theory in particle physics, which describes the elementary particles composing the invisible matter of the Universe and their interactions. It describes three of the four known fundamental forces operating in the Universe: the electromagnetic, weak, and strong interactions (hence, gravitational forces are not included).
Diagram of interactions between elementary particles
The Belle II experiment was launched in the pursuit of data to support the elaboration of the theory beyond the Standard Model, Belle II will, to that aim, be measuring unusual disintegrations of elementary particles, corpuscles displaying names as curious to the non-specialist as the tau leptons (particles related to electrons), the “beauty quark” or the “charm quark”.
During its time in operation, Belle II will be looking for evidence of new particles helping to solve pressing questions about the Cosmos. For instance: why is the Universe dominated by matter and not by antimatter, if they must have been formed in equal amounts after the Big Bang?
SuperKEKB and Belle II
SuperKEKB is a particle accelerator with a perimeter of 3 km, located at the facilities of the High Energy Accelerator Research Organization in Tsukuba (prefecture of Ibaraki, Japan). It consists of two rings: one for the high-energy electron beam (HER), and one of lower energy for the positron beam (LER). It is a “B Meson Factory”, specialized in producing these particles.
Unlike the largest, most powerful, proton accelerator of the World, the Large Hadron Collider of CERN, in Geneva (Switzerland), the SuperKEKB is designed to be the accelerator with the strongest luminosity. Luminosity is a measure of the number of potential collisions in an accelerator per unit of surface over a given time period. SuperKEKB leads the way moving the so-called “frontier of luminosity” forward. It will expectedly break the current World Record of luminosity held by its predecessor KEKB since year 2009.
Belle II is, in essence, a detector module located at one of the four experimental zones of the SuperKEKB accelerator. It has a 10×10 metre height and width, and a weight of 1,500 tonnes and is equipped with a set of different subdetectors. Those detectors, located around the tube where collisions take place in SuperKEKB, take measurements to characterise and identify the particles formed from collisions.
The newly operating SuperKEKB accelerator and the Belle II detector module, in Tsukuba (Japan), are designed to search for a new physics theory, going further ahead of the Standard Model. Spanish participants have contributed to the design, construction, installation and operation of DEPFET, a new detector for the Belle II experiment.
Start of the Belle II experiment
The first electron beam was stored in the main high-energy ring of the SuperKEKB accelerator on March the 21st, 2018. Ten days later, on March the 31st the first positron beam was stored. Adjustment and fine-tuning followed to ensure beam collision at the centre of the Belle II detector, before any data collection would take place.
Electrons and their counterpart antiparticles, positrons, were accelerated and accumulated by the SuperKEKB accelerator. They were collided on past April the 26th at 00:38, with the first collisions registered in the accelerator of the High Energy Accelerator Research Organization (KEK) in Japan since its predecessor, KEKB, finished operation in 2010.
Collision location of elementary particles, around which, the detector module Belle II.
Belle II registered the mutual annihilation of particle and anti-particle, the collision of these electrons and positrons generating new matter elements: quark pairs and “b” quarks and antiquarks (“b” for “bottom” or “beauty”), of which the latter are amongst the heaviest of all quarks.
The project
An international team of collaborators from more than 750 researchers from 25 countries designed and built the Belle II detector module. It has enormously improved capabilities over its predecessor, and is able to detect and reconstruct events far faster. It does so by leveraging the 40-fold higher luminosity of SuperKEKB if compared to KEKB.
In the Spanish contribution to Belle II, a new detector was developed, called DEPFET. The Spanish partnership joined the expertise and know-how of the Institute for Corpuscular Physics (IFIC, joint institute of CSIC and Universitat de València), the Instituto de Física de Cantabria (IFCA, centro mixto CSIC-Universidad de Cantabria), the Instituto Tecnológico de Aragón (ITAINNOVA) and the Instituto Nacional de Técnica Aeroespacial (INTA). In addition, international collaborating partners encompass the Max Planck Institute of Physics in Munich, the Vienna Institute of High-energy Physics (HEPHY) and the European project AIDA2020 on Advanced Infrastructures for Accelerators and Detectors.
The newly developed DEPFET active pixel detectors are composed of a single silicon piece integrating the sensor with the physical support, onto which reading chips are welded. The result is a pixel detector of extreme thinness (75 microns at the active area). This reduces the alteration of particle trajectory resulting from the interaction with detector materials. IFCA and INTA contributed to the in-built Pixel Vertex Detector (PXD), a component designed to collect information about particles coming from the collision location. ITAINNOVA contributed towards keeping electromagnetic noise (EMC) under control, allowing to ensure correct functioning of experiment electrical systems.
Different components of the Belle II detector module
IFIC has been for more than a decade one of the participants in the development of DEPFET. Firstly, coordinating the tests with particle beams, and later on, working on the detector refrigeration strategy, result of the Ph.D. thesis of Carlos Mariñas. IFIC has, moreover, designed and produced the electronics to check the correct working of the different modules of DEPFET once assembled on Belle II.
Hear the voices of some participants
To the director of KEK, Masanori Yamauchi, “it is with great pleasure that we confirm the first collisions in the SuperKEKB accelerator, and we are glad to celebrate the start of the Belle II experiment after more than 7 years of improvements. I am eager to see how the results of Belle II will help us understand the nature of the Universe. We give thanks to all those who have supported this project. Regardless of any difficulties which may eventually arise before SuperKEKB reaches the planned luminosity, 40 times the record marked by KEKB, we will uphold our efforts to succeed in this, in collaboration with researchers from the whole World”.
Tom Browder, professor of the University of Hawaii and spokesperson of the Belle II team, declared that “after more than 7 years of construction and preparations by numerous researchers, engineers and by talented, dedicated students, the Belle II experiment has begun. It is a really rewarding moment for us to be part of this international collaboration. We now eagerly await for the start of the research programme of the first super-factory of B mesons [producing them] from electrons and positrons”.
Participants of SuperKEKB celebrating this collective success
Carlos Mariñas, doctorate from the Institute of Corpuscular Physics (IFIC, CSIC-Universitat de València) is currently in the University of Bonn as an assistant coordinator for the operation of Belle II. “Detecting the first collisions is a great breakthrough for the teams involved, during the process of beam fine-tuning of the previous months. The experience of the Japanese particle acceleration scientists has led us to this point in a very short time, allowing to progressively turn Belle II on, without any risks to the experiment. Now, getting the most out of this exceptional machine rests on the hands of all of us, physicists working with the detector. And we accept the challenge indeed.”
FP9 will be yet another stepping-stone for Europe’s future as an innovation and economic growth pole
Public consultations take place during the year 2018 to contribute to the design of the successor of H2020
Framework Programmes and Horizon 2020
The Framework Programmes (FPs) are funding plans created by the EU/EC to support research in the European Research Area, with objectives varying between different FPs. The FP ongoing during the 2014-2020 period is Horizon 2020 (abbreviated as H2020, or FP8), and focuses on innovation, on the faster delivery of resulting economic growth, and on the provision of outcome developments and solutions to end users.
A goal of H2020 is to ensure that Europe produces world-class science, removes barriers to innovation and makes it easier for the public and private sectors to work together in delivering innovation. Horizon 2020 is, to date, the largest EU Research and Innovation programme, with a total of €80 billion in investment over the 2014 to 2020 period, an investment also considered to be a tool in favour of sustainable and inclusive economic growth and job creation in the EU.
A hallmark of H2020 is the coupling of research and innovation. This helps it to achieve its goals with an emphasis on excellent science, industrial leadership and the tackling of societal challenges. Through H2020, the European Commission has also taken steps towards promoting and implementing Open Science, aiming at accomplishing a transparent, open and inclusive R+D+i and education landscape.
Edifice Berlaymont, location of the European Commission headquarters in Brussels.
The way to ensure success of the future FP9, is to build on top of previous experience and achievements, and to allow excellent research to flourish by implementing effective supportive policies. This entails, among other things, significantly increasing the budget for groundbreaking research in the forthcoming framework programme.
During the year 2018, the European Commission (EC) is consulting different stakeholders in order to support the elaboration of a comprehensive proposal for the design of the post-Horizon 2020 Framework programmes.
SOMMa recommendations:
SOMMa, in line with its mission and objectives, is a strong supporter of the European Framework Programmes for R&D. SOMMa members are particularly active and successful in H2020, substantially contribute to the European excellence in research, participate in numerous international initiatives, and hold relevant positions in important scientific societies, committees, platforms and networks, which together allow for the mobilisation of additional stakeholders. Thus, the alliance can offer valuable insights for the design of the upcoming FP9.
The recommendations proposed by SOMMa have been included into a position paper describing suggestions and recommendations which are generally outlined next.
From the point of view of budget allocation, SOMMa encourages decision makers to seriously consider the recommendations of the Independent High-Level Group Chaired by Pascal Lamy and endorse an FP9 budget that nearly doubles the H2020 budget, to up to 150 Billion Euros. SOMMa also strongly supports the ERC Scientific Council in its recommendation for a minimum annual budget allocation for the ERC of 4 Billion Euros.
As well, SOMMa recommends doubling the budget of Marie Skłodowska-Curie actions with particular emphasis on Individual Fellowships and Innovative Training Networks. A budget increase for Future and Emerging Technologies programmes, FET Open and FET Proactive, is also proposed, in order to enhance these initiatives, as tools to boost innovative research and disruptive technologies.
Regarding project evaluation, SOMMa calls on the EC to alleviate a certain existing bias towards favouring short-term impact projects. Failing to do so potentially impairs the funding of basic research, on which applied research ultimately lays its foundations. SOMMa asks for a stronger commitment towards frontier research and bottom-up calls, covering the whole Technology Readiness Level spectrum, including calls under Societal Challenges.
Excellence should be the key evaluation criterion to allocate budgets, as it is the strongest indicator for impactful research. SOMMa also urges the EC to create a broader definition of impact, and to use a diversity of metrics to evaluate more adequately a project’s potential and outcomes.
An additional aspect that has the potential to release research resources, in the form of research labour, would be to favour the wider implementation of two-stage project application calls, which SOMMa strongly encourages. If successfully implemented, this would allow numerous researchers to decrease time spent applying for projects, allowing them to turn more of their efforts towards research itself.
Finally, SOMMa strongly supports the policy that European framework programmes should not substitute national or regional investment. Relatedly, measures should be adopted to incentivise R&I investment from Member States (MS) budgets aiming at least to investment ratios of 3% of GDP. This, both necessary and ambitious, is far from the current state of things, regarding research investment in most EU states.
The proposals and suggestions developed over the Position Paper aim at making FP9 a pivotal instrument to expand the frontiers of knowledge, European leadership and competitiveness via research and innovation (R&I).
In the framework of an ERC proof-of-concept European Project, Magnetic Supercapacitors, new hybrid materials for energy storage based on graphene and magnetic nanoparticles, have been developed.
The rapid increase in energy demand in recent years has accelerated the search for low-cost alternatives for energy storage and conversion. Currently, batteries are still considered as the dominating energy storage devices, but they have a low power density and lose their ability to retain energy throughout their lifetime due to material damage.
Supercapacitors store the energy electrostatically on the surface of the material. They are able to store high amounts of energy and can release them very quickly when needed, leading to a very high power density. Furthermore, they have the ability to repeat many charge-discharge cycles without losing efficiency, as chemical reactions are not involved in the process. While batteries can supply energy in a sustained release, supercapacitors can deliver high power bursts so they perfectly fit the current market needs (recovery of energy derived from braking (trains, tramways), source of energy for the starting of electric motors…).
The magnetic supercapacitors developed at ICMol are formed by a graphene based nanocomposite together with FeNi3 nanoparticles. These supercapacitors show a huge increase of their features after being subjected to a series of galvanostaic cycles in the presence of a magnetic field, improving the characteristics of the original material, from a capacitance of 100 Fg-1 to 1000 Fg-1, which is, altogether superior if compared to current commercial materials. These properties make them attractive for the industry, having caught already the attention of several companies in the energy sector.
Wearables will benefit greatly from the autonomy provided by supercapacitors
This discovery has led to three patents and, at this moment, ICMol is carrying further developments in this field addressed to integrate the electroactive material in the so-called Systems in a Chip (SoCs). The integration of ultra-small, flexible and compact components that act on the chip as energy storage units is a key factor to the power autonomy of remote sensors, small robots, medical devices or wearable devices. This involves the replacement of their traditional design with new architectures and processes. Particular attention will have to be paid to energy and economic costs, and to the possibility for automation and reuse of the materials. This innovative concept will contribute as well to the boost of the industrial use of SoCs.
Business organizations, and associations connected to R+D+i express their support towards research, backing the petition of the Severo Ochoa and María de Maeztu alliance (SOMMa).
SOMMa advocates in favour of the political class acting to clear the administrative problems currently affecting science in Spain.
SOMMa and the organizations supporting this initiative represent close to 6,800 businesses, societies, centres and research units, which employ more than 500,000 people in Spain, and have an economic activity equivalent to 10,53 % of the GDP.
Now, for the first time, business organizations and associations linked to R+D+I in Spain express their support towards Spanish research, and towards the initiative promoted by SOMMa. In particular, they stress the need for adequate, specific regulations within the framework of the European regulations, safeguarding the competitiveness of the research sector, as happens in other countries. As well, they insist on the need to make science a priority, and to promote innovation, allowing knowledge to translate into tangible benefits for society.
Support of business and the industry will strengthen the position of SOMMa in defence of science and research
All these entities, together with the members of SOMMa, represent close to 6,800 companies, centres and research units that employ more than 500,000 people, and which have an economic activity equivalent to 10.53 % of Spanish gross domestic product.
“It is not only a matter of defending science from the point of view of research institutions. Science is crucial to boost economy and the business sector is convinced about it. So they support us in this call for all political parties to decisively support research,” expresses Luis Serrano, director of the Centre for Genomic Regulation (CRG), and president of SOMMa. “It is urgent that steps are taken to safeguard the competitiveness of science, and by extension, of the Spanish economy. For that, we need to unlock the resolution of the administrative problems currently affecting R+D entities, and to increase the investment in R+D+i”, he finishes.
“Without science it is impossible for our country to be competitive, and for our companies to innovate. ASEBIO wants to support all initiatives focusing on bringing science to public and political debate, and from that stems our commitment and support to SOMMa. We consider that the moment has come to lay the foundations of a new model of public financing for R+D+i and for a stable regulatory framework reflecting a decided strategic support for R+D, with a mid- and long-term vision, and a wide political consensus,” explains Ion Arocena, general director of ASEBIO.
From the ICT sector, Pedro Mier, president of AMETIC, said “the IT sector, in our country but also internationally, is one of the most relevant actors regarding R+D+i, which is key for the productivity and competitiveness of industry. Any country aiming at promoting high added-value employment and at bolstering salary growth must invest into knowledge generation”. He continued stating that, “technology-based innovation, so relevant in this new industrial revolution, requires of a strong scientific system which is well-connected to business. Such a system is not improvised, and is the result of a sustained effort which reflects a long-term political commitment, and a shared, common project for our country, something which we do support.”
The associations Feique and Farmaindustria also shared the concerns expressed by SOMMa regarding the problems that R+D+i faces in Spain. In a joint statement made public some weeks ago, they explicited their commitment towards R+D -hence with the centres devoted to research, and with the public-private collaborations in that field-. In that statement, they joined the appeal to facilitate a discussion by politicians and officials. This, to allow for the taking of structural measures to promote research in Spain, with a strategic and long-term vision, and particularly, in the biomedical, pharmaceutical, chemical and biotechnological fields.
The prestigious journal Nature Structural and Molecular Biology has published a piece of research conducted by CIC nanoGUNE researchers. They have experimentally reconstructed titin fragments from their common ancestors and measured their mechanochemical properties. They have discovered a correlation between the properties of the protein measured on a nanoscale and animal size.
The Ikerbasque researcher Raúl Pérez-Jiménez of nanoGUNE’s Nanobiomechanics group has led a piece of research in which, starting from the sequences of the titin protein of a selection of modern day animals, they inferred the phylogenetic tree of tetrapods (all animals with four limbs including mammals, birds, reptiles and amphibians), and reconstructed the sequence that this protein would have had in the common ancestors of these animal groups. After obtaining their sequences, they synthesised a part of the ancestral proteins and studied their mechanical and chemical properties in the laboratory. This has enabled them to find a link between the properties of the protein and the body mass of the animals, which they have been able to confirm in the fossil record of each epoch. The scientific journal Nature Structural & Molecular Biologyhas just published the results of the research carried out by the nanoGUNE researchers in collaboration with the CNIC.
David De Sancho, Raul Perez-Jimenez, and Aitor Manteca, three of the scientists that carried out the research
Titin is one of the proteins that make up the muscles of all vertebrates; it is an elastic protein that acts as a spring by refolding and returning to its original state. “Protein evolution has been studied from many points of view: its thermal stability, function and structure, but no one had ever studied the evolution of the mechanical properties of a protein. For titin this is a particularly appropriate approach given its function,” said Pérez-Jiménez.
For this research, they selected over thirty animals from different taxonomic groups and of different sizes. “The complete genome of many animals was already available, so the first thing we did was to build a phylogenetic tree with the titin sequences of around thirty tetrapods. This tree enabled us to calculate the most probable sequences of the protein titin of four common ancestors of the taxonomic groups to which these animals belong: placental mammals, dating back about 100 million years; all mammals, dating back 170-180 million years; the common ancestor of the sauropsids, including all birds, reptiles and also dinosaurs, and which lived about 280 million years ago; and the common ancestor of all the animals we have studied, which would be the common ancestor of the tetrapods, dating back about 350 million years,” specified Pérez-Jiménez.
Once they had the sequences, they synthesised the most elastic fragment of the proteins in the laboratory, and using an atomic force microscope available at nanoGUNE they were able to measure the mechanical resistance of each of the proteins. This instrument “allows one, literally, to take a protein and stretch it, unfold it mechanically using force, which is something similar to what happens to titin in the muscle,” remarked the researcher. That way they were able to compare the resistance or stability of all the titins being studied. In this study “we realised that the mechanochemical stability of the proteins depended on the number of disulphide bridges displayed by the titin, which are sulphur-sulphur bonds between two cysteine residues.
They were able to see that “the ancestral proteins were more resistant than those of today’s animals, and they had more disulfide bridges than the modern ones. Yet this difference was not so big compared with a small animal such as a finch”. This fact led them to think that there could be a link between the mechanochemical properties of titin and the size of the animals. “We saw a pretty good correlation: the larger animals had less stable proteins and the smaller ones more stable proteins. And that enabled us to predict the size of the ancestral animals”.
Once they had inferred the size of the common ancestors, the group led by Pérez-Jiménez compared them with fossil records and the scientific literature available in this respect. “We were able to see that there was substantial agreement; the ancestors of mammals, birds and tetrapods in general were really small, weighing less than 100 g; although we do of course have a margin of error inherent in the techniques themselves. This may not be surprising because one could consider that it is information that was already known, but what is new here is that we did not use a fossil, but started from a reconstructed protein, a purely molecular piece of information,” pointed out the researcher.
Pérez-Jiménez believes that “the interesting thing is that we have seen that mechanochemical evolution, how the titin gradually changed throughout evolution, and we have been able to reconstruct it”. These results will lead to pursuing the research further. “We would like to see, for example, whether this correlation with size is truly global, whether it exists in all animal groups,” he concluded.
Further information:
Mechanochemical evolution of the giant muscle protein titin as inferred from resurrected proteins A. Manteca, J. Schönfelder, A. Alonso-Caballero, M. J. Fertin, N. Barruetabeña, B. F. Faria , E. Herrero-Galán, J. Alegre-Cebollada, D. De Sancho, and R. Perez-Jimenez. Nature Structural & Molecular Biology, July 2017. DOI: 10.1038/nsmb.3426
A new artificial intelligence-based method to diagnose breast cancer is developed in an international partnership featuring IFIC
A team of researchers from the Instituto de Física Corpuscular (IFIC), has participated in the development of a system to help in the diagnosis of breast cancer. The development, which will be of great help in clinical practice, is capable of reducing the number of false positives. It has a detection accuracy of 90 %, one of the highest in this kind of screening systems. In addition to IFIC, which is a joint institute of the Sspanish Consejo Superior de Investigaciones Científicas (CSIC) and the Universitat de València, the Universitat Politècnica de València and research groups from seven other international institutions participate of this work.
As the researchers point out, current methods of diagnostic support employed by radiologists are most often limited to only observing and detecting potentially suspicious areas in tests obtained by imaging techniques. The developed device, for its part, is capable of reducing the number of false positives, and to give more reliable information on the likelihood of cancer presence. This is attained on basis of AI techniques as neural networks, and the use of predictive algorithms.
Breast cancer is one of the types of cancer with the highest incidence in developed countries. Mamographies are diagnostic techniques for its early detection which have proven their efficacy over the years. Complementarily, the new system will be able to decrease the number of false positives in all age ranges, and will minimise false alarms, avoiding the unnecessary use of more aggressive diagnostic tests. It allows, as well, for a reduction of clinical costs, which could help to include new risk populations into screening campaigns.
Several phases of lesion detection using the new diagnostic test
“In addition, if other clinical evidence hints the professional on the possibility of non-evident positive diagnostic, he or she can amplify image regions which are cause of higher concern, surpassing the capabilities of an expert human eye. Also, this could help to determine future biopsy locations.”, says Dr. Francisco Albiol, CSIC researcher at IFIC, a Severo Ochoa centre of excellence.
“For each year a developing breast cancer is diagnosed earlier, a 20 % increase in the 5-year survival rate results increase a 20 %. The algorithm we have developed can be a great tool towards early diagnosis of this type of cancer, offering clinicians an additional advanced diagnosis tool”, says Francisco Albiol.
The participants in this project currently study how to translate the method into clinical practice. “One of the simplest possibilities would be its application to reduce the fatigue of radiologists, by screening the easiest cases”, adds Alberto Albiol, researcher from the Universitat Politècnica de València.
Digital Mammography DREAM Challenge
DREAM Challenges pose problems relating to the fields of biology or medical research. Participant researchers present their projects, which have to positively impact society, and which are subject to evaluation.
The development is a result of the Digital Mammograpy DREAM Challenge, a world project driven by the main American institutions fighting against breast cancer, hand in hand with multinationals as IBM and Amazon. The aim is to improve the detection of breast cancer by the interpretation of mammographies by artificial intelligence. 120 multidisciplinary teams participated of this challenge, of which the Instituto de Física Corpuscular – Universitat Politècnica de Valencia team was the only Spanish participant.
“To be able to generalize large-scale use of these kinds of technologies, it is of utter importance to generate and maintain local collections of patient data representing the general ethnical, [social] and economic state of a public health system” stresses Francisco Albiol.
Image:
“Several phases of lesion detection using the new diagnostic test” by IFIC / CSIC / UV / UPV.
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