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1. Investigation of the Antiviral Activity of Experimental Samples Obtained from the Grass and Roots of Alchemilla vulgaris L. Against Vaccinia Virus and Ectromelia Virus

Author

N. A. Mazurkova, M. A. Protsenko, E. I. Filippova, T. A. Kukushkina, G. I. Vysochina, I. E. Lobanova, O. Yu. Mazurkov, L. N. Shishkina, and A. P. Agafonov

Subjects
alchemilla vulgaris, flavonoids, catechins, leucoanthocyanins, vaccinia virus, ectromelia virus, Pharmaceutical industry, HD9665-9675
Abstract

Introduction. The abolition of smallpox vaccination after its elimination in 1980 led to a decrease in the immunocompromised immunity in humans. Zoonotic monkeypox, camelpox, buffalopox and cowpox viruses that are close to the variola virus also pose a danger to humans. In Russia today there are no effective and safe medicines for the prevention and treatment of smallpox and other orthopoxvirus infections in humans and animals. The Lady's mantle (Alchemilla vulgaris) is a promising source for the development of new antiviral drugs. Previous studies have found that Alchemilla vulgaris shows activity against influenza virus and herpes simplex virus.Aim. The aim of this work was to study the chemical composition and antiviral activity of extracts from the roots and the grass of Alchemilla vulgaris against orthopoxviruses.Materials and methods. Qualitative analysis of the samples was performed by high performance liquid chromatography. Quantitative analysis was performed using a complex of spectrophotometric methods. To determine the toxicity and antiviral activity of experimental samples from Alchemilla vulgaris in vitro, a transplantable Vero cell culture was used. Antiviral activity of the obtained preparations was evaluated by reducing the infectivity (titer) of orthopoxviruses in the monolayer of Vero cells infected with orthopoxviruses in the presence of preparations with different concentrations relative to the cell culture infected with orthopoxviruses without the preparations.Results and discussion. It was shown that the experimental sample from Alchemilla vulgaris obtained by the method of ethyl acetate extraction from the roots of the studied plant and purified with chloroform contains mainly catechins and leucoanthocyanins (70 %). In parallel, extract from the raw mass of the grass of the plant purified with chloroform and ethanol contains the amount of flavonoids (71 %). Wherein the content of flavonoids in unpurified ethanol extracts from the roots and the grass of Alchemilla vulgaris composed 5 % and 6 %, respectively. It was revealed that purified preparations obtained from Alchemilla vulgaris roots when using ethyl acetate and ethanol as extractants showed antiviral activity against vaccinia virus and ectromelia virus, as well as preparations obtained from grass by ethanol extraction.Conclusion. Thus, purified ethyl acetate extracts from the roots and ethanol extracts from the wet grass mass of Alchemilla vulgaris exhibit antiviral activity against orthopoxviruses in vitro.

Published
2019
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2. STUDY OF ANTIHERPETIC ACTIVITY OF LADY'S MANTLE (ALCHEMILLA VULGARIS L.) EXTRACTS

Author

N. A. Mazurkova, T. A. Kukushkina, G. I. Vysochina, Z. B. Ibragimova, I. E. Lobanova, E. I. Filippova, O. Yu. Mazurkov, E. V. Makarevich, L. N. Shishkina, and A. P. Agafonov

Subjects
extracts of lady's mantle (alchemilla vulgaris l.), antiviral activity, herpes simplex virus, Pharmaceutical industry, HD9665-9675
Abstract

The article presents information on the distribution, on the use in traditional medicine, the chemical composition of plant material, pharmacological study of lady's mantle (Alchemilla vulgaris L.), as well as the results of a study in culture Vero cell toxicity and antiviral properties of aqueous solutions of dry ethanol extract of the aerial parts and the ethyl acetate extract of the roots of lady's mantle, growing in Western Siberia, in respect of the herpes simplex virus. It is shown that the extracts derived from both aerial parts and roots of plants have on the Vero cell culture antiviral activity against herpes simplex virus of 1 and 2-type.

Published
2019

4. RADIATION SAFETY PROVISIONS AT THE OCTOBER RAILWAY FACILITIES

Author

N. E. Lobanova, M. V. Obukhova, N. N. Artemyeva, T. B. Baltrukova, and V. I. Kuzin

Subjects
радиационная безопасность, октябрьская железная дорога, радиационная обстановка, Medical physics. Medical radiology. Nuclear medicine, R895-920, Radioactivity and radioactive substances, QC794.95-798
Abstract

The article presents analysis of radiation situation at the October railway. Main directions of radiation safety provisions on the railway, ways of its achievement are envisaged.

Published
2015

5. Interaction System of the State and Business in the Regime of Public-Private Partnership in the Pharmaceutical Complex of the Russian Federation

Author

Anastasia E. Lobanova and Natalia S. Klunko

Subjects
Public–private partnership, State (polity), business.industry, Financial risk, General partnership, media_common.quotation_subject, Health care, Quality (business), Public administration, Private sector, business, Modernization theory, media_common
Abstract

The issue of interaction between the state and business in the mode of public-private partnership in the pharmaceutical complex of the Russian Federation is investigated. The concept of "state" and "business" is defined, the forms of interaction between the state and business are considered, the concept of "public-private partnership" is defined, the main features of public-private partnership in general and in the pharmaceutical complex in particular are identified, the goals and investments of partners in public-private partnership in the pharmaceutical sector, studied the prospects for the development of public-private partnership in the pharmaceutical sector of the country as a form of interaction between the state and business. The researcher also researched economic, legal and organizational partnership. One of the types of economic partnership in this area of activity is а public-private partnership. Public-private partnership in the pharmaceutical sector of the Russian Federation is а cooperation for a specified period between the state and the private sector on the basis of which, by combining the experience and expertise of the state and business, sharing financial risks and benefits, socially significant programs and projects in the pharmaceutical sector is implemented. It has been established that the subjects of interaction between business and the state in the form of public-private partnership are public and private partners, who, when participating in this type of interaction, set different goals and play different roles. It has been revealed that this type of partnership has great development prospects, which will contribute to increasing the competitiveness of the pharmaceutical sector, modernizing the health care system, improving the quality of health services delivery and access to medicines. The development of public-private partnerships as a form of interaction between the state and business in the pharmaceutical sector is an effective mechanism for the modernization of the industrial national sector.

Published
2021

7. MECHANISM OF REGULATION OF PUBLIC-PRIVATE PARTNERSHIP IN THE PHARMACEUTICAL COMPLEX OF THE RUSSIAN FEDERATION

Author

Anastasia E. Lobanova and Natalia S. Klunko

Subjects
Public–private partnership, Russian federation, Business, Public administration, Mechanism (sociology)
Abstract

This study examines the mechanism of regulation of public-private partnership in the pharmaceutical complex of the Russian Federation as a fundamental principle of public-private partnership in general. The features of the two main national regulations that regulate public-private partnership in this area of the economy are studied, and their features are determined. The features of international regulation of public-private partnerships on a national scale, as well as in the commercial sector of the pharmaceutical complex, are studied. A number of industry standards of the pharmaceutical complex of the Russian Federation are considered, their main tasks are highlighted. The analysis of the subject composition of public-private partnerships in the pharmaceutical complex is carried out, their main differences and features are formed. Based on the results of the study of national and international standards, tools are proposed for the development and improvement of international and Russian legislation regulating public-private partnership relations in the pharmaceutical sector.

Published
2020

9. PUBLIC-PRIVATE PARTNERSHIP: WORLD EXPERIENCE AND PROSPECTS OF DEVELOPMENT IN RUSSIA

Author

Anastasia E. Lobanova

Subjects
Public–private partnership, Political science, Public administration
Abstract

The article examines the nature and world experience of public-private partnership (PPP). The advantages of PPP for the state and for private business, types of contacts and the most popular spheres of application of public-private partnership are considered. The essence of concession is considered as one of the most widespread types of public-private partnership, as well as features of concession contracts. Prospects of application of concession relations in Russia are analyzed. The article analyzes the conditions of occurrence and the main stages of development of partnerships between the state and the private sector. The features of functioning of public-private partnership (PPP) in developed and developing countries are investigated. The world experience of PPP projects implementation is summarized and practical recommendations on the establishment and development of the public-private partnership institute in Russia are presented.

Published
2019

10. Prevalence of BRCA1 and BRCA2 genes promoter hypermethylation in breast cancer tissue

Author

N L Medvedieva, O E Lobanova, N.G. Gorovenko, Viktoriia Vershyhora, Z.I. Rossokha, R. Vereshchako, V. Cheshuk, L Ye Fishchuk, and L M Zakhartseva

Subjects
Adult, Cancer Research, endocrine system diseases, Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, Disease, law.invention, Breast cancer, law, medicine, Humans, Genetic Predisposition to Disease, Family history, Promoter Regions, Genetic, skin and connective tissue diseases, Gene, Aged, BRCA2 Protein, BRCA1 Protein, business.industry, Promoter, Methylation, DNA Methylation, Middle Aged, medicine.disease, Oncology, DNA methylation, Cancer research, Suppressor, Female, business
Abstract

Background Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. Aim To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. Materials and methods Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. Results Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region - in 50% of cases, and hypermethylation of the promoter region of both genes - in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. Conclusions The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.

Published
2021

11. Public and Private Partnership: Updating New Forms of Interaction Between the State and Business

Author

Anastasiia E. Lobanova

Subjects
форма собственности, частный сектор, форма взаимодействия, промышленная политика, государственно-частное партнерство, инвестиция
Abstract

Рассмотрены сущность и особенности механизма государственно-частного партнерства (ГЧП). Автор пришел к выводу, что в условиях санкций и ограничений на ввоз ряда товаров первой необходимости, фармацевтических продуктов, импорт которых ограничен из-за санкций, руководству департаментов, агентств, комитетов различного уровня необходимо внедрять новые формы взаимодействия между госсектором и компаниями, с представительствами за рубежом, чтобы наладить идеальный объем импорта в сферы Минздрава, социальной защиты, чтобы избежать зависимости России от внешних условий санкций, которые ставят наше государство в состояние заложника геополитических решений.

Published
2020

12. Evaluation Transaction Costs For The State 'Start' Young Professionals In The Workplace

Author

E. V. Demidova, T. V. Shendel, and E. E. Lobanova

Subjects
Estimation, Transaction cost, Labour economics, Government, Young professional, ComputingMilieux_THECOMPUTINGPROFESSION, Process (engineering), Internship, Reproduction (economics), Business, Human capital
Abstract

The article outlines the problems of employment of young specialists in the labor market, including those related to the specifics of the formation and demand for human capital in this category of labor. The significance of accounting of transaction costs of various subjects of this process by the stages of reproduction of young specialists has been determined. A personal approach to assessment of the state transaction costs on the “entry” of young specialists into the labor sphere through the development of internships is proposed. A model for the assessment of these costs is based on a total accounting of both state losses from unemployed young professionals and government expenses to “advance” them into the labor sector. A dynamic model for the estimation of these costs for university graduates in Russia as a whole, as well as for one of the largest territorial entities of the country, the Krasnoyarsk Territory, has been built. The results of testing time-series model allow us to confirm the hypotheses formulated in the article and come to the conclusion that the state expenses to support unemployed graduates through internships give a tangible result for society in the form of reduced losses from unemployed young specialists and generally reduces the total transaction costs of the state Thus, the proposed model for assessment of the transaction costs of the state for the “entry” of young specialists into the labor sphere can serve as a tool for modeling costs in the designated area.

Published
2020

14. FEATURES OF CORRELATION OF ELECTROMYOGRAPHICAND AXIOGRAPHIC STUDIES IN PATIENTSWITH INCREASED ERASURE OF HARD DENTAL TISSUES

Author

E. E Lobanova, S D Arutyunov, M. M Antonik, and Lilith Avagovna Brutyan

Subjects
Correlation, Orthodontics, stomatognathic diseases, Rehabilitation, business.industry, Tooth wear, medicine.medical_treatment, Correlation analysis, General Engineering, Energy Engineering and Power Technology, Erasure, Medicine, business
Abstract

Clinical and instrumental diagnostics, including electromyographic (EMG) and axiographic (EA) study of 24 patients to improve the efficiency of planning and predicting the results of their dental treatment was carried out. Correlation links were studied both within EMG and EA studies, and between them. There were no significant correlations between the parameters of EMG and EA of the methods of investigation. Therefore, for full dental rehabilitation ofpatients with tooth wear in the diagnosis and monitoring of the stages and results of treatment, it is necessary to carry out both methods, since they do not exclude each other, but supplement

Published
2017

15. ASSESSMENT OF THE POTENTIAL OF THE REGIONAL VOCATIONAL EDUCATION SECTOR ACCORDING TO THE IMPLEMENTATION OF THE EFFECTIVE TRAINING OF LABOUR FORCES FOR THE INDUSTRY BRANCH: THE CASE OF SIBERIAN STATE TECHNOLOGICAL UNIVERSITY, KRASNOYARSK REGION

Author

V. A. Prigozhikh, M. V. Tayurskaya, P. M. Vcherashniy, O. E. Podverbnykh, E. E. Lobanova, and A. I. Tayurskiy

Subjects
State (polity), Vocational education, media_common.quotation_subject, Political science, Regional science, Training (civil), media_common
Published
2017

16. CBM Collaboration

Author

T. Ablyazimov, R.P. Adak, A. Adler, A. Agarwal, K. Agarwal, Z. Ahammed, A. Ahmad, F. Ahmad, N. Ahmad, A. Akindinov, P. Akishin, V. Akishina, M. Al-Turany, I. Alekseev, E. Alexandrov, I. Alexandrov, A. Andronic, H. Appelshäuser, D. Argintaru, B. Arnoldi-Meadows, E. Atkin, M.D. Azmi, V. Baban, S. Bähr, M. Bajdel, G. Balassa, M. Balzer, N. Baranova, S. Bashir, M. Baszczyk, E. Bechtel, J. Becker, K.-H. Becker, M. Becker, J. Beckhoff, S. Belogurov, A. Belousov, J. Bendarouach, A. Bercuci, R. Berendes, D. Bertini, O. Bertini, O. Bezshyyko, P.P. Bhaduri, A. Bhasin, S.A. Bhat, W.A. Bhat, B. Bhattacharjee, A. Bhattacharyya, T.K. Bhattacharyya, S. Biswas, T. Blank, D. Blau, C. Blume, J. Brzychczyk, T. Bus, A. Bychkov, M. Cãlin, M. Caselle, A. Chakrabarti, S. Chatterjee, S. Chattopadhyay, A. Chaus, H. Cherif, P. Chudoba, E. Clerkin, M. Csanád, P. Dahm, Supriya Das, Das Susovan, J. de Cuveland, A. Demanov, D. Dementiev, Wendi Deng, Zhi Deng, H. Deppe, I. Deppner, O. Derenovskaya, M. Deveaux, Zhiguo Ding, Sheng Dong, E. Dorenskaya, P. Dorosz, A.K. Dubey, A. Dubla, M. Dürr, V.V. Elsha, D. Emschermann, H. Engel, T. Eşanu, J. Eschke, M. Esen, Xingming Fan, O. Fateev, C. Feier-Riesen, Sheng-Qin Feng, F. Fidorra, S.P.D. Figuli, D. Finogeev, P. Fischer, H. Flemming, J. Förtsch, P. Foka, U. Frankenfeld, V. Friese, E. Friske, I. Fröhlich, J. Frühauf, T. Galatyuk, R. Ganai, G. Gangopadhyay, Xin Gao, P. Gasik, T. Geßler, C. Ghosh, S.K. Ghosh, D. Giang, S. Gläßel, L. Golinka-Bezshyyko, O. Golosov, S. Golovnya, M. Golubeva, D. Golubkov, S. Gope, S. Gorbunov, S. Gorokhov, D. Gottschalk, P. Gryboś, F. Guber, M. Gumiński, A. Gupta, Yu. Gusakov, R. Haas, Dong Han, H. Hartmann, Shu He, J. Hehner, N. Heine, N. Herrmann, J.M. Heuser, C. Höhne, R. Holzmann, Dongdong Hu, Guangming Huang, Xinjie Huang, D. Hutter, M. Irfan, D. Ivanishchev, P. Ivanov, Victor Ivanov, Vladimir Ivanov, A. Ivashkin, A. Izvestnyy, H. Jahan, T. Janson, A. Jash, A. Jipa, I. Kadenko, P. Kähler, B. Kämpfer, K.-H. Kampert, R. Kapell, R. Karabowicz, N. Kargin, D. Karmanov, N. Karpushkin, E. Kashirin, V.K.S. Kashyap, K. Kasiński, G. Kasprowicz, A. Kazantsev, U. Kebschull, G. Kekelidze, M.M. Khan, S. Khan, A. Khanzadeev, F. Khasanov, A. Kiryakov, M. Kiš, I. Kisel, P. Kisel, S. Kiselev, T. Kiss, P. Klaus, R. Kłeczek, Ch. Klein-Bösing, V. Klochkov, P. Kmon, K. Koch, L. Kochenda, P. Koczoń, M. Kohn, R. Kolb, A. Kolozhvari, B. Komkov, M. Korolev, I. Korolko, O. Kot, R. Kotte, O. Kovalchuk, M. Koziel, G. Kozlov, V. Kozlov, P. Kravtsov, I. Kres, D. Kresan, M. Kruszewski, A.V. Kryanev, E. Kryshen, A. Krzyżanowska, W. Kucewicz, L. Kudin, I. Kudryashov, A. Kugler, P. Kuhl, Ajay Kumar, Ajit Kumar, L. Kumar, S.K. Kundu, A. Kurepin, N. Kurepin, P. Kurilkin, S. Kuznetsov, V. Kyva, V. Ladygin, C. Lara, E. Lavrik, I. Lazanu, A. Lebedev, S. Lebedev, E. Lebedeva, J. Lehnert, Y. Leifels, Chao Li, Yuanjing Li, V. Lindenstruth, Feng Liu, I. Lobanov, E. Lobanova, S. Löchner, P.-A. Loizeau, K. Łojek, O. Lubynets, J.A. Lucio Martínez, Xiaofeng Luo, A. Lymanets, Pengfei Lyu, N. Lyublev, Jian-Hao Ma, A. Maevskaya, S. Mahajan, P. Maj, Z. Majka, A. Malakhov, E. Malankin, D. Malkevich, B. Mallick, O. Malyatina, M. Mandal, V. Manko, O. Maragoto Rodriguez, A.M. Marin Garcia, J. Markert, T. Matulewicz, S. Mehta, M. Merkin, A. Meyer-Ahrens, J. Michel, P. Miedzik, L. Mik, K. Mikhailov, V. Mikhaylov, V. Militsija, M.F. Mir, D. Miskowiec, B. Mohanty, I. Momot, H. Morgenweck, T. Morhardt, S. Morozov, D. Mühlheim, W.F.J. Müller, C. Müntz, S. Mukherjee, P. Munkes, Yu. Murin, E. Nandy, L. Naumann, T. Nayak, F. Nickels, W. Niebur, V. Nikulin, D. Normanov, A. Olar, P. Otfinowski, J.H. Otto, E. Ovcharenko, Liang-ming Pan, I. Panasenko, S. Pandey, P. Parfenov, S. Parzhitskiy, V. Patel, C. Pauly, V. Petráček, M. Petri, M. Petriş, M. Petrovici, O. Petukhov, D. Pfeifer, P. Pfistner, K. Piasecki, J. Pietraszko, G. Pitsch, R. Płaneta, V. Plotnikov, V. Plujko, J. Pluta, K. Poźniak, S.K. Prasad, M. Prokudin, A. Prozorov, M. Pugach, V. Pugatch, A. Puntke, S. Querchfeld, L. Radulescu, S. Raha, P. Raisig, W. Raja, D. Ramazanov, J. Rautenberg, R. Ray, A. Redelbach, T. Rehman, A. Reinefeld, A. Reshetin, C. Ristea, O. Ristea, A. Rodriguez Rodriguez, F. Roether, R. Romaniuk, A. Rost, E. Rostchin, A. Roy, D. Roy, S. Roy, E. Rubio, A. Rustamov, Yu. Ryabov, R. Sahoo, P.K. Sahu, S.K. Sahu, J. Saini, F. Salem, S. Samanta, S.S. Sambyal, V. Samsonov, O. Sander, S. Sarangi, S. Sau, C. Schiaua, F. Schintke, C.J. Schmidt, D. Schmidt, H.R. Schmidt, P.M. Schneider, T. Schütt, F. Seck, I. Segal, I. Selyuzhenkov, A. Semennikov, A. Sen, A. Senger, P. Senger, A. Shabanov, A. Shabunov, N. Sharma, A.D. Sheremetiev, Shusu Shi, S. Shirinkin, M. Shiroya, M. Shitenkow, V. Shumikhin, I. Sibiryak, V. Sidorenko, C. Simon, C. Simons, A.K. Singh, B.K. Singh, C.P. Singh, O. Singh, R. Singh, V. Singhal, L. Škoda, D. Smith, Y. Söhngen, I. Som, D. Spicker, D. Stach, P. Staszel, D. Storozhyk, M. Strikhanov, J. Stroth, C. Stüllein, C. Sturm, Yuan Su, N. Sukhov, R. Sultanov, Yongjie Sun, Zhengyang Sun, D. Svirida, R. Szczygieł, A. Taranenko, O. Tarassenkova, T. Tölyhi, A. Toia, N. Topil'skaya, M. Träger, M. Traxler, E. Trifonova, Yu. Tsyupa, N.G. Tuturas, F. Uhlig, K.L. Unger, E. Usenko, D. Varga, I. Vassiliev, O. Vasylyev, R. Visinka, M. Völkl, E. Volkova, A. Vorobiev, A. Voronin, L. Wahmes, Botan Wang, Dong Wang, Tianxing Wang, Xinjian Wang, Yi Wang, A.A. Weber, M. Weber, P. Weidenkaff, F. Weiglhofer, J.P. Wessels, D. Wielanek, A. Wieloch, A. Wilms, D. Wójcik, Gy. Wolf, Ke-Jun Wu, Qiqi Wu, Junfeng Yang, Rongxing Yang, Zhongbao Yin, In-Kwon Yoo, Jianhui Yuan, I. Yushmanov, W. Zabołotny, Yu. Zaitsev, N.I. Zamiatin, H. Zbroszczyk, M. Zhalov, Qiunan Zhang, Xiaoming Zhang, Yu Zhang, Yan-Qing Zhao, Sheng Zheng, Daicui Zhou, Jian Zhou, Wenxiong Zhou, Xianglei Zhu, A. Zinchenko, I. Zivko, M. Żoładź, F. Zorn, W. Zubrzycka, P. Zumbruch, and M. Zyzak

Subjects
Nuclear and High Energy Physics
Published
2021

17. Challenges in QCD matter physics --The scientific programme of the Compressed Baryonic Matter experiment at FAIR

Author

V. Jakovlev, R. Talukdar, Alberica Toia, V.M. Golovatyuk, P. Ivanov, Abhijit Bhattacharyya, M. Kohn, Yu. Onishchuk, M. Tanha, Suman Sau, E. Friske, L. Kumar, A. Roy, Valerica Baban, Yaping Wang, V. Blinov, D. Svirida, Pradip Kumar Sahu, D. Dementiev, A. Gomez Ramirez, M. Petris, Ming Shao, D. Blau, Yu. P. Tsyupa, A. Rost, D. P. Mahapatra, Y. F. Ryabov, D. Wielanek, Anju Bhasin, C. Lara, Saikat Biswas, Shusu Shi, E. P. Akishina, F. Seck, V. Jain, Hongfang Chen, O. Malyatina, B. Komkov, I. Carevic, V. Baublis, Raghunath Sahoo, D. Normanov, Tetyana Galatyuk, S. Amar-Youcef, Cristian Andrei, Yu. I. Bocharov, A. Vorobiev, M. Strikhanov, Y. Leifels, O. Petukhov, A. Petrovici, Dezso Varga, Oana Ristea, W. Verhoeven, J. Sánchez Rosado, Victor Golovtsov, S. Belogurov, E. Kryshen, M. Dey, Johannes Lehrbach, Y. P. Viyogi, A. V. Kazantsev, A. Himmi, M. Anđelić, Oleg Bezshyyko, Cheng Li, A. Raportirenko, Xu Cai, C. Kreidl, Daniela Bartos, T. Balog, Volker Lindenstruth, A. Chaus, M. Mohisin Khan, Mate Csanad, J. Pluta, A. Senger, Matthias Balzer, Christoph Blume, H. Appelshäuser, Di Jiang, B. Kämpfer, A. Lymanets, I. Berceanu, S. Gorbunov, S. Sarangi, V. Pospíšil, N. Heine, A. Veshikov, Yuanjing Li, V. Kushpil, Ch. Klein-Bösing, I. Selyuzhenkov, S. Razin, Guofeng Song, D. Belyakov, G. Berezin, V. Kyva, Andrei Ionut Herghelegiu, Heiko Engel, K. Schmidt, V. Klochkov, Alla Maevskaya, P.-A. Loizeau, L. Golinka-Bezshyyko, V.A. Karnaukhov, J. Bendarouach, C. Xiang, A.D. Sheremetiev, V. F. Chepurnov, Hr Schmidt, Zbigniew Sosin, M. Singla, I. Momot, O. Andreeva, I. Alexandrov, R. N. Singaraju, S. Avdeev, Evgeny Alexandrov, R. Płaneta, Gennady Ososkov, D. Hutter, A. Reinefeld, C.J. Schmidt, Andrei Dorokhov, Vikram Patel, K.-H. Becker, N. Kurepin, E. Lebedeva, C. P. Singh, Y. K. Sun, K. Jaaskelainen, Andras Szabo, J. Rożynek, Sanjeev Singh Sambyal, V. S. Negi, Krzysztof Piasecki, W. F. J. Müller, M. Baznat, N. Miftakhov, Feng Liu, N. Ahmad, L. Skoda, G. D. Kekelidze, Vladimir Ivanov, Krzysztof Kasinski, Xi-Wei Wang, D. Miskowiec, Serguei Volkov, Sudhir Raniwala, I. Tsakov, A. Nedosekin, Peter Senger, T. Barczyk, S. Dubnichka, C. Ristea, N.G. Tuturas, E. V. Atkin, D. Karmanov, W. Zabolotny, Tatiana Karavicheva, Subhasis Samanta, Yu.V. Zanevsky, S. Bähr, O. Batenkov, M. Petrovici, B. Milanovic, Muhammad Farooq, R. Karabowicz, I. Vassiliev, P. Staszel, Sheng Dong, Udo Wolfgang Kebschull, P. Koczon, Goutam Gangopadhyay, P. Zumbruch, Vladimir Plujko, Y. Berdnikov, Shue He, Volodymyr Vovchenko, V. Mialkovski, W. Zipper, T. Bus, O. Tarassenkova, S. K. Sahu, V. Militsija, Yu. Zaitsev, C. Müntz, S. K. Ghosh, Sushanta Tripathy, E. Rostchin, V. Shumikhin, I. Fröhlich, I. Panasenko, A. Laso Garcia, L. Dutka, Yu.S. Anisimov, B. Linnik, T. Tischler, A. Ivashkin, R. Kotte, Calin Besliu, T. Akishina, Rashmi Raniwala, Sheng Zheng, K. Koch, J. Kunkel, A. Shabunov, E. Lobanova, Wojciech Kucewicz, T. Breitner, M. Al-Turany, R. P. Adak, Claudiu Cornel Schiaua, S. Masciocchi, Zhongbao Yin, Xinjie Huang, Jens Wiechula, Nu Xu, I. Kisel, Christian Sturm, T. Mahmoud, V. Kalinin, A. Abuhoza, Mohd Danish Azmi, P. Zrelov, Jing Zhou, M. Dželalija, C. Deveaux, M. Goffe, Ke-Jun Wu, S. Strohauer, S. Bashir, D. Argintaru, B. Heß, A. Turowiecki, M. B. Golubeva, F. Ahmad, S. Gläßel, V. Plotnikov, Manuel Penschuck, Supriya Das, Grzegorz Kasprowicz, Vladislav Manko, O. Vasylyev, D. Kresan, L. Kudin, Yu. V. Gusakov, Dongdong Hu, Vladimir Nikulin, M. Ivanov, D. Gottschalk, Karl-Heinz Kampert, A. Kolosova, G. Caragheorgheopol, K. Dey, K. Mikhailov, Anand Kumar Dubey, J. Scholten, S. P. D. Figuli, T. Blank, Ajit Kumar, Vladimir Peshekhonov, Igor Pshenichnov, E. Badura, Michael Deveaux, I. Rostovtseva, M. Kiš, Jürgen Becker, Evgeny Karpechev, B. W. Kolb, Valery Pugatch, Xiaofeng Luo, I. Som, E. Ovcharenko, F.F. Guber, H. Büsching, H. Cherif, N. R. Panda, Zubayer Ahammed, R. Najman, Fouad Rami, M. Gumiński, J. Pieper, Jerzy Gajda, G. Kozlov, H. Jahan, A. Drozd, V. Butuzov, Joachim Stroth, I. K. Yoo, Thomas Janson, M. Petri, R. Holzmann, D. Finogeev, S. Golovnya, Ping Cao, E. Malankin, Buddhadeb Bhattacharjee, L. Meder, Junfeng Yang, Lei Zhao, C. Simon, S. Kuznetsov, I. Valin, M. Zyzak, H. Hartmann, T. Satława, Yi Wang, Anton Andronic, Daicui Zhou, Zebo Tang, M. Prokudin, V. Saveliev, Qiyan Li, I. M. Deppner, Mahitosh Mandal, F. Uhlig, J. A. Lucio Martínez, J. Book, L. Mik, S. Schatral, S. K. Pal, A. Petrovskiy, J. Pietraszko, B. Debnath, E. Usenko, O. Svoboda, Gy. Wolf, V.V. Elsha, J. Lehnert, Pengfei Lyu, S. Seddiki, Peter Fischer, Huanhuan Fan, D. Doering, J. Frühauf, C. Wendisch, Yu Zhang, V. Kozlov, P. Tlustý, Piotr Otfinowski, N. Baranova, Sergey Kiselev, J. Rautenberg, Dmitry Mal'kevich, I. Kadenko, I. Lobanov, Mikhail Zhalov, A. Rodriguez Rodriguez, D. Emschermann, Vikas Singhal, Pavel Akishin, M. Bach, P. Kravtsov, X. Zhu, C. Nandi, I. Korolko, Rongxing Yang, E. Nandy, D. Ivanischev, Anil Prakash, A. Semennikov, I. E. Yushmanov, S. Parzhitskiy, M. Vznuzdaev, A. Khvorostukhin, A. Kiryakov, Soma Mukherjee, LuYao Chen, M. Pugach, Piotr Kmon, J. Gebelein, V. Kleipa, C. Bergmann, Kai Schweda, S. Rabtsun, Victor Ivanov, Tivadar Kiss, M. Dreschmann, I. G. Alekseev, A. K. Kurilkin, A. Volochniuk, E. Krebs, A. Lebedev, V. Kramarenko, N. Topil'skaya, S. Das, S. Lebedev, S. Querchfeld, Madan M. Aggarwal, N.I. Zamiatin, Amrendra K. Singh, Swagata Mandal, A. Khanzadeev, C. Simons, Gilles Claus, U. Frankenfeld, V.V. Ivanov, A. Chernogorov, Pascal Dillenseger, V. Dobyrn, Z. Dubnichkova, S. Löchner, Bhartendu K. Singh, S. Ahmad, Rishat Sultanov, J. Kallunkathariyil, A. Wieloch, T. Matulewicz, R. Berendes, A. Shabanov, Saniya Khan, V. Friese, Anik Gupta, L. Kochenda, M. Kirejczyk, Pavel Kisel, Amlan Chakrabarti, Ashwini Kumar, Michal Koziel, A. Berdnikov, A. Sadovsky, T. O. Ablyazimov, S. Mahajan, M. Merkin, Robert Szczygiel, C. Pauly, Krzysztof Poźniak, F. Roether, Alexey Kurepin, Alexander Voronin, A. Bubak, Nikolai Shumeiko, Nicolas Winckler, A. V. Kryanev, Andrey Reshetin, A. Simakov, Sukalyan Chattopadhyay, E. M. Ilgenfritz, B. Sikora, Jihye Song, J. Hehner, Zhi Deng, M. Irfan, J. Saini, S. A. Lone, L. Naumann, D. Eschweiler, A. M. Marin Garcia, P. Kähler, O. Derenovskaya, A.P. Ierusalimov, Alexandru Jipa, K. Agarwal, T. Tolyhi, H. Malygina, Xingming Fan, Amalia Pop, Dmitry Golubkov, E. M. Verbitskaya, L. Radulescu, Ryszard S. Romaniuk, D. Pfeifer, Yifei Zhang, Rajarshi Ray, V. Zryuev, M. Teklishyn, M. Träger, S. Morozov, H. Flemming, A. Oancea, A. Wilms, P. Ghosh, A. Grzeszczuk, V. Mikhaylov, Patrick Simon Reichelt, Ankhi Roy, Sanguk Won, Vladimir Samsonov, T. Esanu, V. Akishina, D.V. Peshekhonov, A.I. Zinchenko, M. Żoładź, Xin Li, I. Sibiryak, J. Wüstenfeld, Aleksey Voronin, M. Korolev, Guangming Huang, A. Kugler, E. Kaptur, J. Michel, J. Tarasiuk, Manjit Kaur, A. Bychkov, F. Lemke, Bekhzod S Yuldashev, T. K. Bhattacharyya, S. Gorokhov, F. Schintke, P. Klaus, Adrian Byszuk, Ionel Lazanu, Dong Wang, Michael Dürr, M. Krieger, H. Deppe, Sibaji Raha, O. Sander, S. Kowalski, K. Wiśniewski, Alexander Malakhov, I. Filozova, Shengqin Feng, M. Calin, S. Reinecke, V. Kucher, M. Weber, A. Kovalchuk, V. Petráček, M. Adamczyk, K.K. Gudima, Johannes Peter Wessels, P. Sitzmann, J. Markert, V. K. Eremin, Alexandru Bercuci, Marc Winter, Mateusz Baszczyk, M.I. Ciobanu, E. Bao, M. Kuc, U. Brüning, O. V. Fateev, Piotr Maj, J. de Cuveland, M. G. Târzilă, Pavel Larionov, R. Averbeck, Jianping Cheng, Jacek Rauza, C. E. Muñoz Castillo, N. D'Ascenzo, O. Bertini, Wendi Deng, G. Kretschmar, I. Skwira-Chalot, W. Niebur, K. Oh, V. P. Ladygin, T. Morhardt, C. Höhne, M. G. Wiebusch, Partha Pratim Bhaduri, Dong Han, Oleg Karavichev, N. Herrmann, R. Visinka, F. Constantin, C. García Chávez, J. Brzychczyk, Sidharth Kumar Prasad, D. Soyk, V. V. Kirakosyan, W. Koenig, D. Bertini, Z. Majka, F. Khasanov, J. Eschke, P. Gryboś, E. Lavrik, V. Cătănescu, K. Siwek-Wilczyńska, P. K. Kurilkin, J.M. Heuser, Adeel Akram, Yu. Murin, Alexander Akindinov, A. K. Bhati, I. Kres, J. Förtsch, Rafal Kleczek, Jiajun Zheng, S. Manz, T. K. Nayak, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CBM, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
J/psi(3100), Phase transition, matter: interaction, Hadron, Nuclear Theory, hypernucleus, 7. Clean energy, 01 natural sciences, Critical point (thermodynamics), transport theory, hadron: gas, Nuclear Experiment, neutron star, QCD matter, Brookhaven RHIC Coll, quark gluon: plasma, Physics, Large Hadron Collider, fireball, elliptic flow, strong interaction, Observable, heavy ion, CERN LHC Coll, QCD matter, Quark-Gluon-Plasma (QGP), QCD phase diagram, strong interaction, hadronic matter, partonic matte, heavy-ion, 2-4.9 GeV/nucleon, Nuclear and High Energy Physics, Particle physics, CBM, charmonium, [PHYS.NUCL]Physics [physics]/Nuclear Theory [nucl-th], Strong interaction, review, nonperturbative, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], symmetry: chiral, quantum chromodynamics: critical phenomena, strangeness, 0103 physical sciences, density: high, Darmstadt GSI FAIR, structure, 010306 general physics, equation of state, quantum chromodynamics: matter, 010308 nuclear & particles physics, High Energy Physics::Phenomenology, nucleus, temperature: high, baryon, Neutron star, Automatic Keywords, HADES, charm
Abstract

International audience; Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 ( $\sqrt{s_{NN}}=$ 2.7--4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials ( $\mu_B > 500$ MeV), effects of chiral symmetry, and the equation of state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2024, in the context of the worldwide efforts to explore high-density QCD matter.

Published
2017

18. CBM Collaboration

Author

T. Ablyazimov, A. Abuhoza, R. Adak, J. Adamczewski-Musch, M. Adamczyk, M.M. Aggarwal, Z. Ahammed, F. Ahmad, N. Ahmad, S. Ahmad, A. Akindinov, P. Akishin, E. Akishina, T. Akishina, V. Akishina, M. Al-Turany, E. Alexandrov, I. Alexandrov, S. Amar-Youcef, M. Anđelić, O. Andreeva, C. Andrei, A. Andronic, Yu. Anisimov, H. Appelshäuser, A. Arend, D. Argintaru, E. Atkin, S. Avdeev, R. Averbeck, M.D. Azmi, V. Baban, M. Bach, E. Badura, S. Baginyan, T. Balle, T. Balog, S. Bandyopadhyay, P. Banerjee, N. Baranova, T. Barczyk, D. Bartoş, S. Bashir, Z. Basrak, M. Baszczyk, O. Batenkov, V. Baublis, C. Baumann, M. Baznat, K.-H. Becker, T. Bel, S. Belogurov, J. Bendarouach, I. Berceanu, A. Bercuci, E. Berdermann, A. Berdnikov, Y. Berdnikov, R. Berendes, C. Bergmann, D. Bertini, O. Bertini, C. Beşliu, O. Bezshyyko, P.P. Bhaduri, A. Bhasin, A.K. Bhati, B. Bhattacharjee, A. Bhattacharyya, T.K. Bhattacharyya, S. Biswas, D. Blau, C. Blume, Yu. Bocharov, S. Böttger, M. Borysova, T. Breitner, U. Brüning, J. Brzychczyk, A. Bubak, H. Büsching, A. Bychkov, A. Byszuk, Xu Cai, M. Cãlin, Ping Cao, R. Čaplar, G. Caragheorgheopol, I. Carević, V. Cătănescu, A. Chakrabarti, S. Chatterji, Sanatan Chattopadhyay, Subhasis Chattopadhyay, Hongfang Chen, Jianping Cheng, V. Chepurnov, S. Chernenko, A. Chernogorov, Kyung-Eon Choi, M.I. Ciobanu, G. Claus, F. Constantin, V. Covlea, M. Csanád, N. D'Ascenzo, S. Das, K. Davkov, V. Davkov, J. de Cuveland, B. Debnath, D. Dementiev, Zhi Deng, H. Deppe, I. Deppner, O. Derenovskaya, C.A. Deveaux, M. Deveaux, K. Dey, M. Dey, P. Dillenseger, V. Dobyrn, D. Doering, A. Dorokhov, A. Drozd, A.K. Dubey, S. Dubnichka, A. Dubnichkova, M. Dürr, W. Dulinski, L. Dutka, M. Dželalija, D. Emschermann, H. Engel, V. Eremin, T. Eşanu, J. Eschke, D. Eschweiler, Jongsik Eum, Huanhuan Fan, O. Fateev, I. Filozova, D. Finogeev, P. Fischer, H. Flemming, U. Frankenfeld, V. Friese, E. Friske, I. Fröhlich, J. Frühauf, Á. Fülöp, J. Gajda, T. Galatyuk, A. Galkin, V. Galkin, G. Gangopadhyay, C. García Chávez, I. Gašparić, J. Gebelein, P. Ghosh, S.K. Ghosh, M. Goffe, L. Golinka-Bezshyyko, V. Golovatyuk, S. Golovnya, V. Golovtsov, M. Golubeva, D. Golubkov, A. Gómez Ramírez, S. Gorbunov, S. Gorokhov, D. Gottschalk, P. Gryboś, A. Grzeszczuk, F. Guber, K. Gudima, A. Gupta, Yu. Gusakov, A. Haldar, S. Haldar, H. Hartmann, J. Hehner, K. Heidel, N. Heine, E. Hellbär, A. Herghelegiu, N. Herrmann, B. Heß, J.M. Heuser, A. Himmi, C. Höhne, R. Holzmann, Guangming Huang, Xinjie Huang, J. Hutsch, D. Hutter, E. Iakovleva, A. Ierusalimov, E.-M. Ilgenfritz, M. Irfan, M. Ivanov, Valery Ivanov, Victor Ivanov, Vladimir Ivanov, A. Ivashkin, K. Jaaskelainen, H. Jahan, V. Jain, V. Jakovlev, T. Janson, A. Jipa, I. Kadenko, B. Kämpfer, S. Kalcher, V. Kalinin, K.-H. Kampert, Tae Im Kang, E. Kaptur, R. Karabowicz, O. Karavichev, T. Karavicheva, D. Karmanov, V. Karnaukhov, E. Karpechev, K. Kasiński, G. Kasprowicz, M. Kaur, A. Kazantsev, U. Kebschull, G. Kekelidze, M.M. Khan, S.A. Khan, A. Khanzadeev, F. Khasanov, A. Khvorostukhin, V. Kirakosyan, M. Kirejczyk, A. Kiryakov, M. Kiš, I. Kisel, P. Kisel, S. Kiselev, A. Kiss, T. Kiss, P. Klaus, R. Kłeczek, Ch. Klein-Bösing, V. Kleipa, P. Kmon, K. Koch, L. Kochenda, P. Koczoń, W. König, M. Kohn, B.W. Kolb, A. Kolosova, B. Komkov, J.M. Kopfer, M. Korolev, I. Korolko, R. Kotte, A. Kotynia, A. Kovalchuk, S. Kowalski, M. Koziel, G. Kozlov, P. Kravtsov, E. Krebs, C. Kreidl, D. Kresan, G. Kretschmar, M. Kretz, M. Krieger, E. Kryshen, W. Kucewicz, L. Kudin, A. Kugler, I. Kulakov, J. Kunkel, A. Kurepin, P. Kurilkin, V. Kushpil, V. Kyva, V. Ladygin, C. Lara, P. Larionov, A. Laso Garcia, E. Lavrik, I. Lazanu, A. Lebedev, S. Lebedev, E. Lebedeva, J. Lehnert, J. Lehrbach, F. Lemke, Cheng Li, Jin Li, Qiyan Li, Yuanjing Li, Yulan Li, V. Lindenstruth, S. Linev, B. Linnik, E. Litvinenko, Feng Liu, I. Lobanov, E. Lobanova, S. Löchner, P.-A. Loizeau, J.A. Lucio Martínez, A. Lymanets, A. Maevskaya, S. Mahajan, D.P. Mahapatra, T. Mahmoud, P. Maj, Z. Majka, A. Malakhov, E. Malankin, D. Malkevich, O. Malyatina, H. Malygina, S. Mandal, V. Manko, S. Manz, V. Marin, A.M. Marin Garcia, J. Markert, S. Masciocchi, T. Matulewicz, M. Merkin, V. Mialkovski, J. Michel, N. Miftakhov, K. Mikhailov, V. Mikhaylov, B. Milanović, V. Militsija, M.F. Mir, D. Miskowiec, T. Morhardt, W.F.J. Müller, C. Müntz, Yu. Murin, R. Najman, L. Naumann, T. Nayak, A. Nedosekin, B. Neumann, W. Niebur, V. Nikulin, D. Normanov, M. Nüssle, A. Oancea, Kunsu Oh, Y. Onishchuk, D. Osipov, G. Ososkov, D. Ossetski, P. Otfinowski, E. Ovcharenko, S. Pal, I. Panasenko, N.R. Panda, S. Parzhitskiy, C. Pauly, Haiping Peng, I. Peric, D. Peshekhonov, V. Peshekhonov, V. Petráček, M. Petriş, A. Petrovici, M. Petrovici, A. Petrovskiy, O. Petukhov, K. Piasecki, J. Pieper, J. Pietraszko, R. Płaneta, E. Plekhanov, V. Plotnikov, V. Plujko, J. Pluta, V. Poliakov, P. Polozov, A. Pop, V. Popov, V. Pospisil, B.V.K.S. Potukuchi, J. Pouryamout, K. Poźniak, A. Prakash, M. Prokudin, I. Pshenichnov, M. Pugach, V. Pugatch, S. Querchfeld, L. Radulescu, S. Raha, W. Raja, F. Rami, R. Raniwala, S. Raniwala, A. Raportirenko, J. Rautenberg, J. Rauza, R. Ray, S. Razin, P. Reichelt, S. Reinecke, A. Reshetin, C. Ristea, O. Ristea, F. Roether, R. Romaniuk, A. Rost, E. Rostchin, I. Rostovtseva, A. Roy, J. Rożynek, Yu. Ryabov, V. Rykalin, A. Sadovsky, S. Sadovsky, R. Sahoo, P.K. Sahu, J. Saini, S. Samanta, S.S. Sambyal, V. Samsonov, J. Sánchez Rosado, S. Sau, V. Saveliev, S. Schatral, C. Schiaua, C.J. Schmidt, H.R. Schmidt, K. Schmidt, K. Schweda, A. Scurtu, F. Seck, S. Seddiki, I. Selyuzhenkov, A. Semennikov, A. Senger, P. Senger, A. Shabunov, Ming Shao, M.K. Sharma, N. Shumeiko, V. Shumikhin, B. Sikora, A. Simakov, C. Simon, C. Simons, R.N. Singaraju, A.K. Singh, B.K. Singh, C.P. Singh, V. Singhal, K. Siwek-Wilczyńska, L. Škoda, I. Skwira-Chalot, I. Som, Jihye Song, I. Sorokin, Z. Sosin, D. Soyk, P. Staszel, A. Stavinskiy, E. Stephan, D. Storozhyk, M. Strikhanov, S. Strohauer, J. Stroth, C. Sturm, R. Sultanov, Yongjie Sun, O. Svoboda, R. Szczygieł, R. Talukdar, Zebo Tang, M. Tanha, J. Tarasiuk, O. Tarassenkova, M.-G. Târzilă, V. Tiflov, T. Tischler, P. Tlustý, A. Toia, T. Tolyhi, N. Topil'skaya, C. Trageser, P. Trivedy, I. Tsakov, Yu. Tsyupa, A. Turowiecki, F. Uhlig, E. Usenko, I. Valin, T. Vasiliev, I. Vassiliev, E. Verbitskaya, W. Verhoeven, A. Veshikov, R. Visinka, Y.P. Viyogi, S. Volkov, Yu. Volkov, A. Vorobiev, A. Voronin, V. Vovchenko, E. Vznuzdaev, M. Vznuzdaev, Dong Wang, Yaping Wang, Wang Yi, C. Wendisch, J.P. Wessels, M. Wiebusch, J. Wiechula, B. Wiedemann, D. Wielanek, A. Wieloch, N. Winckler, M. Winter, K. Wiśniewski, D. Wohlfeld, Gy. Wolf, Won Sanguk, J. Wüstenfeld, Changzhou Xiang, Xu Nu, Jun-Gyu Yi, Zhongbao Yin, In-Kwon Yoo, Qian Yue, B. Yuldashev, I. Yushmanov, W. Zabołotny, Yu. Zaitsev, Yu. Zanevsky, M. Zhalov, Ya Peng Zhang, Yifei Zhang, Daicui Zhou, Xianglei Zhu, A. Zinchenko, W. Zipper, M. Żoładź, P. Zrelov, V. Zryuev, P. Zumbruch, and M. Zyzak

Subjects
Nuclear and High Energy Physics
Published
2014

19. The CBM Collaboration

Author

A. Abuhoza, J. Adamczewski-Musch, M.M. Aggarwal, Z. Ahammed, F. Ahmad, N. Ahmad, S. Ahmad, A. Akindinov, P. Akishin, E. Akishina, T. Akishina, V. Akishina, M. Al-Turany, S. Amar-Youcef, M. Anđelić, C. Andrei, A. Andronic, Yu. Anisimov, H. Appelshäuser, A. Arend, D. Argintaru, T. Armbruster, E. Atkin, S. Avdeyev, M.D. Azmi, V. Baban, M. Bach, E. Badura, S. Baginyan, T. Balog, S. Bandyopadhyay, P. Banerjee, N. Baranova, D. Bartoş, S. Bashir, Z. Basrak, M. Baszczyk, O. Batenkov, V. Baublis, C. Baumann, K.-H. Becker, T. Bel, S. Belogurov, I. Berceanu, E. Berdermann, A. Berdnikov, Y. Berdnikov, R. Berendes, C. Bergmann, D. Bertini, C. Beşliu, O. Bezshyyko, P.P. Bhaduri, A. Bhasin, A.K. Bhati, B. Bhattacharjee, A. Bhattacharyya, T.K. Bhattacharyya, S. Biswas, D. Blau, C. Blume, Yu. Bocharov, S. Böttger, M. Borysova, B. Bozsogi, T. Breitner, U. Brüning, J. Brzychczyk, A. Bubak, A. Bychkov, Xu Cai, M. Cãlin, R. Čaplar, G. Caragheorgheopol, I. Carević, V. Cătănescu, A. Chakrabarti, S. Chatterji, Sanatan Chattopadhyay, Subhasis Chattopadhyay, Hongfang Chen, Jianping Cheng, V. Chepurnov, S. Chernenko, A. Chernogorov, M.I. Ciobanu, G. Claus, F. Constantin, V. Covlea, M. Csanád, N. DʼAscenzo, S. Das, K. Davkov, V. Davkov, J. de Cuveland, B. Debnath, Zhi Deng, H. Deppe, I. Deppner, O. Derenovskaya, M. Deveaux, K. Dey, M. Dey, P. Dillenseger, V. Dobyrn, D. Doering, M. Domachowski, A. Dorokhov, C.A. Dritsa, A.K. Dubey, S. Dubnichka, A. Dubnichkova, W. Dulinski, M. Dželalija, D. Emschermann, H. Engel, V. Eremin, T. Eşanu, J. Eschke, O. Fateev, P. Fischer, H. Flemming, U. Frankenfeld, V. Friese, I. Fröhlich, J. Frühauf, Á. Fülöp, J. Gajda, T. Galatyuk, A. Galkin, V. Galkin, G. Gangopadhyay, M.S. Ganti, C. García Chávez, I. Gašparić, J. Gebelein, P. Ghosh, S.K. Ghosh, M. Goffe, V. Golovatyuk, S. Golovnya, V. Golovtsov, M. Golubeva, D. Golubkov, S. Gorbunov, D. Gottschalk, P. Gryboś, A. Grzeszczuk, F. Guber, A. Gupta, Yu. Gusakov, A. Haldar, S. Haldar, M. Hartig, J. Hehner, K. Heidel, N. Heine, A. Herghelegiu, N. Herrmann, B. Heß, J.M. Heuser, A. Himmi, C. Höhne, R. Holzmann, Guangming Huang, J. Hutsch, D. Hutter, A. Ierusalimov, E.-M. Ilgenfritz, M. Irfan, Valery Ivanov, Victor Ivanov, Vladimir Ivanov, A. Ivashkin, K. Jaaskelainen, V. Jakovlev, T. Janson, A. Jipa, I. Kadenko, B. Kämpfer, S. Kalcher, V. Kalinin, K.-H. Kampert, Tae Im Kang, E. Kaptur, R. Karabowicz, O. Karavichev, T. Karavicheva, D. Karmanov, V. Karnaukhov, E. Karpechev, K. Kasiński, M. Kaur, A. Kazantsev, U. Kebschull, G. Kekelidze, M.M. Khan, S.A. Khan, A. Khanzadeev, F. Khasanov, V. Kirakosyan, M. Kirejczyk, M. Kiš, I. Kisel, P. Kisel, S. Kiselev, A. Kiss, T. Kiss, R. Kłeczek, Ch. Klein-Bösing, V. Kleipa, K. Koch, L. Kochenda, P. Koczoń, B. Kolb, B. Komkov, J.M. Kopfer, M. Korolev, I. Korolko, R. Kotte, A. Kotynia, A. Kovalchuk, S. Kowalski, M. Koziel, G. Kozlov, P. Kravtsov, C. Kreidl, D. Kresan, M. Kretz, M. Krieger, E. Kryshen, W. Kucewicz, L. Kudin, A. Kugler, I. Kulakov, J. Kunkel, A. Kurepin, V. Kyva, V. Ladygin, C. Lara, P. Larionov, A. Laso Garcia, E. Lavrik, I. Lazanu, A. Lebedev, S. Lebedev, E. Lebedeva, J. Lehrbach, F. Lemke, Cheng Li, Jin Li, Li Qyian, Yuanjing Li, Yulan Li, V. Lindenstruth, S. Linev, E. Litvinenko, Feng Liu, I. Lobanov, E. Lobanova, S. Löchner, P.-A. Loizeau, A. Lymanets, A. Maevskaya, S. Mahajan, D.P. Mahapatra, T. Mahmoud, P. Maj, Z. Majka, A. Malakhov, O. Malyatina, H. Malygina, J. Manjavidze, V. Manko, S. Manz, V. Marin, T. Matulewicz, M. Merkin, V. Mialkovski, N. Miftakhov, K. Mikhailov, B. Milanovic, V. Militsija, F. Mir, W.F.J. Müller, C. Müntz, Yu. Murin, L. Naumann, T. Nayak, B. Neumann, W. Niebur, V. Nikulin, M. Nüssle, A. Oancea, Oh Kunsu, Y. Onishchuk, G. Ososkov, D. Ossetski, P. Otfinowski, E. Ovcharenko, Pal Susanta, I. Panasenko, S. Parzhitskiy, C. Pauly, Haiping Peng, I. Peric, D. Peshekhonov, V. Peshekhonov, V. Petráček, M. Petriş, A. Petrovici, M. Petrovici, A. Petrovskiy, O. Petukhov, K. Piasecki, J. Pietraszko, E. Plekhanov, V. Plujko, V. Poliakov, P. Polozov, A. Pop, V. Popov, V. Pospisil, B.V.K.S. Potukuchi, J. Pouryamout, A. Prakash, M. Prokudin, I. Pshenichnov, V. Pugatch, S. Querchfeld, S. Raha, W. Raja, F. Rami, R. Raniwala, S. Raniwala, A. Raportirenko, J. Rautenberg, R. Ray, S. Razin, P. Reichelt, S. Reinecke, A. Reshetin, C. Ristea, O. Ristea, E. Rostchin, I. Rostovtseva, A. Roy, J. Rożynek, Yu. Ryabov, V. Rykalin, A. Sadovsky, S. Sadovsky, P.K. Sahu, J. Saini, S.S. Sambyal, V. Samsonov, J. Sanchez Rosado, V. Saveliev, S. Schatral, C. Schiaua, C.J. Schmidt, H.R. Schmidt, C. Schrader, K. Schweda, A. Scurtu, S. Seddiki, A. Semennikov, A. Senger, P. Senger, A. Shabunov, Ming Shao, M.K. Sharma, V. Shumikhin, B. Sikora, A. Simakov, C. Simon, C. Simons, R.N. Singaraju, A.K. Singh, B.K. Singh, C.P. Singh, V. Singhal, M. Singla, K. Siwek-Wilczynska, L. Škoda, Song Jihye, I. Sorokin, D. Soyk, P. Staszel, A. Stavinskiy, E. Stephan, D. Storozhyk, M. Strikhanov, J. Stroth, C. Sturm, Yongjie Sun, O. Svoboda, R. Szczygieł, R. Talukdar, Zebo Tang, O. Tarassenkova, M. Târzilă, V. Tiflov, T. Tischler, P. Tlustý, T. Tolyhi, N. Topilʼskaya, C. Trageser, P. Trivedy, I. Tsakov, Yu. Tsyupa, F. Uhlig, E. Usenko, I. Valin, T. Vasiliev, I. Vassiliev, E. Verbitskaya, W. Verhoeven, A. Veshikov, Y. Viyogi, S. Volkov, Yu. Volkov, A. Vorobiev, A. Voronin, E. Vznuzdaev, M. Vznuzdaev, Dong Wang, Yaping Wang, Yi Wang, C. Wendisch, J.P. Wessels, J. Wiechula, B. Wiedemann, M. Winter, K. Wisniewski, D. Wohlfeld, Gy. Wolf, J. Wüstenfeld, Changzhou Xiang, Xu Nu, Jun-Gyu Yi, Yin Zhongbao, In-Kwon Yoo, Qian Yue, I. Yushmanov, Yu. Zaitsev, Yu. Zanevsky, M. Zhalov, Ya Peng Zhang, Yifei Zhang, Zhou Daicui, Xianglei Zhu, A. Zinchenko, W. Zipper, M. Żoładź, P. Zrelov, V. Zryuev, P. Zumbruch, and M. Zyzak

Subjects
Nuclear and High Energy Physics
Published
2013

20. [Local hyperthermia by means of ballon-type electrodes in combined therapy of patients with locally spread cancer of the mouth mucosa and lower lip]

Author

V E, Cheshuk, A V, Kravchenko, O E, Lobanova, Iu R, Medinets, and L G, Maloed

Subjects
Adult, Male, Antimetabolites, Antineoplastic, Mouth Mucosa, Hyperthermia, Induced, Middle Aged, Combined Modality Therapy, Methotrexate, Treatment Outcome, Lip Neoplasms, Carcinoma, Squamous Cell, Humans, Female, Mouth Neoplasms, Electrodes
Abstract

Modification of the standard chemo- and radiotherapy with local hyperthermia gives evident positive results in treatment of patients with local cancer of tunica mucosa of mouth and lower lip. Since this area having uneven complex surface needs to develop radiofrequency emitting special applicators. We have used catheters with ballons filled with hypertonic solution as electrodes to adapt the mouth cavity. An electric field creating between these ballons and high surface adjustability makes this system come in useful.

Published
2006

21. [Clinical effectiveness of nadroparin calcium in the surgical treatment of breast cancer]

Author

A Ia, Iaremchuk, A S, Zotov, V E, Cheshuk, N F, Anikuc'ko, L M, Zakhartseva, M V, Diatel, A V, Kravchenko, O E, Lobanova, and O I, Sidorchuk

Subjects
Treatment Outcome, Thromboembolism, Anticoagulants, Humans, Breast Neoplasms, Female, Nadroparin, Mastectomy, Retrospective Studies
Abstract

The report deals with an assessment of frequency of fatal thromboembolic complications after surgery for breast cancer, in particular, frequency and severity of the side-effects of calcium nadroparin treatment as a component of surgical preparation. Considering the low incidence of thromboembolic complications in such patients and the side-effects of anti-coagulant therapy, it is suggested that decisions be made on a strictly individual basis under stringent clinical control.

Published
2003

22. [Galactomannan from ambiguous Crazyweed (Oxytropis ambigua (Pall) DC)]

Author

N M, Mestechkina, I E, Lobanova, O V, Anulov, and V D, Shcherbukhin

Subjects
Mannans, Magnetic Resonance Spectroscopy, Galactose, Fabaceae
Abstract

A galactomannan with a molecular weight of 735 kDa was first isolated and purified from seeds of ambiguous crazyweed Oxytropis ambigua (Pall) DC. (family Leguminosae) with a yield of 3.6%. Its aqueous solutions displayed an optical activity ([alpha]D = 73.32 degrees) and high viscosity ([eta] = 644 ml g-1). Chemical analysis and 13C-NMR spectroscopy revealed the presence in the heteropolysaccharide of D-mannopyranose and D-glucopyranose at a molar ratio of 1.39:1. The linear backbone of its macromolecule consists of 1.4-beta-D-mannopyranose residues. Single beta-D-galactose residues substitute 72% of mannoses to form branches.

Published
2001

24. [Development of a method for the quantitative assessment of the microorganism sensitivity to antibiotics by using discs. A study of the patterns of doxycycline diffusion from discs into the nutrient agar]

Author

S M, Navashin, S M, Chaĭkovskaia, S P, Raezvan, A S, Rabinovich, and E E, Lobanova

Subjects
Diffusion, Agar, Staphylococcus aureus, Dose-Response Relationship, Drug, Doxycycline, Escherichia coli, Microbial Sensitivity Tests, Anti-Bacterial Agents, Culture Media
Abstract

Doxycycline concentrations provided by the antibiotic diffusion from paper discs into sterile agarized medium and the medium plated with staphylococci and Coli bacteria were studied at different distances from the disc center. Infection of the nutrient medium with the test cultures had no effect on the antibiotic diffusion rate. A linear relation between the logarithm of the antibiotic concentration in the agar and distance from the disc centre were found. Probably it is possible to determine the MIC of the antibiotic with respect to various microorganisms by the value of the radius of the growth inhibition zone around the disc using diagrams expressing such a relation.

Published
1977

25. [Some characteristics and the pathogenesis of functional disorders in chronic pneumonia]

Author

I V, Landysheva, E E, Lobanova, V M, Nosyrev, V N, Katiukhin, and V A, Bashkatov

Subjects
Adult, Male, Blood Volume, Adolescent, Respiratory System, Stomach, Hemodynamics, Pneumonia, Middle Aged, Kidney, Cardiovascular System, Liver, Adrenal Glands, Chronic Disease, Humans, Female, Vascular Resistance, Hypoxia, Blood Coagulation, Blood Flow Velocity, Aged
Published
1975

27. Improved Imaging Surface for Quantitative Single-Molecule Microscopy.

Author

Zhang YP, Lobanova E, Dworkin A, Furlepa M, Yang WS, Burke M, Meng JX, Potter N, Sala RL, Kahanawita L, Layburn F, Scherman OA, Williams-Gray CH, and Klenerman D

Subjects
Humans, Surface Properties, Polyethylene Glycols chemistry, Protein Aggregates, alpha-Synuclein metabolism, alpha-Synuclein chemistry, tau Proteins metabolism, tau Proteins chemistry, Single Molecule Imaging methods
Abstract

Preventing nonspecific binding is essential for sensitive surface-based quantitative single-molecule microscopy. Here we report a much-simplified RainX-F127 (RF-127) surface with improved passivation. This surface achieves up to 100-fold less nonspecific binding from protein aggregates compared to commonly used polyethylene glycol (PEG) surfaces. The method is compatible with common single-molecule techniques including single-molecule pull-down (SiMPull), super-resolution imaging, antibody-binding screening and single exosome visualization. This method is also able to specifically detect alpha-synuclein (α-syn) and tau aggregates from a wide range of biofluids including human serum, brain extracts, cerebrospinal fluid (CSF) and saliva. The simplicity of this method further allows the functionalization of microplates for robot-assisted high-throughput single-molecule experiments. Overall, this simple but improved surface offers a versatile platform for quantitative single-molecule microscopy without the need for specialized equipment or personnel.

Published
2024
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28. Single-molecule characterization of salivary protein aggregates from Parkinson's disease patients: a pilot study.

Author

Furlepa M, Zhang YP, Lobanova E, Kahanawita L, Vivacqua G, Williams-Gray CH, and Klenerman D

Abstract

Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson's disease. Candidate diagnostic tests for Parkinson's disease to date have predominantly focused on measurements of α-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary α-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of α-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary α-synuclein and amyloid-β peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary α-synuclein aggregate/amyloid-β aggregate ratio is increased almost 2-fold in patients with Parkinson's disease ( n = 20) compared with controls ( n = 20, P < 0.05). Morphological information also provides insight, with saliva from patients with Parkinson's disease containing a greater proportion of larger and more fibrillar amyloid-β aggregates than control saliva ( P < 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson's disease ( n = 17) and controls ( n = 18) with a high degree of accuracy (area under the curve = 0.87, P < 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2024
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29. Cerebral organoids with chromosome 21 trisomy secrete Alzheimer's disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy.

Author

Fertan E, Böken D, Murray A, Danial JSH, Lam JYL, Wu Y, Goh PA, Alić I, Cheetham MR, Lobanova E, Zhang YP, Nižetić D, and Klenerman D

Subjects
Humans, Amyloid beta-Protein Precursor genetics, Amyloid beta-Protein Precursor metabolism, Neurons metabolism, Brain metabolism, Brain pathology, Carrier Proteins metabolism, Carrier Proteins genetics, Trisomy genetics, Oxidative Stress, Plaque, Amyloid metabolism, Plaque, Amyloid pathology, Culture Media, Conditioned, Microscopy, Fluorescence methods, Organoids metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, Alzheimer Disease genetics, tau Proteins metabolism, Down Syndrome metabolism, Down Syndrome genetics, Down Syndrome pathology, Induced Pluripotent Stem Cells metabolism, Amyloid beta-Peptides metabolism
Abstract

Understanding the role of small, soluble aggregates of beta-amyloid (Aβ) and tau in Alzheimer's disease (AD) is of great importance for the rational design of preventative therapies. Here we report a set of methods for the detection, quantification, and characterisation of soluble aggregates in conditioned media of cerebral organoids derived from human iPSCs with trisomy 21, thus containing an extra copy of the amyloid precursor protein (APP) gene. We detected soluble beta-amyloid (Aβ) and tau aggregates secreted by cerebral organoids from both control and the isogenic trisomy 21 (T21) genotype. We developed a novel method to normalise measurements to the number of live neurons within organoid-conditioned media based on glucose consumption. Thus normalised, T21 organoids produced 2.5-fold more Aβ aggregates with a higher proportion of larger (300-2000 nm 2 ) and more fibrillary-shaped aggregates than controls, along with 1.3-fold more soluble phosphorylated tau (pTau) aggregates, increased inflammasome ASC-specks, and a higher level of oxidative stress inducing thioredoxin-interacting protein (TXNIP). Importantly, all this was detectable prior to the appearance of histological amyloid plaques or intraneuronal tau-pathology in organoid slices, demonstrating the feasibility to model the initial pathogenic mechanisms for AD in-vitro using cells from live genetically pre-disposed donors before the onset of clinical disease. Then, using different iPSC clones generated from the same donor at different times in two independent experiments, we tested the reproducibility of findings in organoids. While there were differences in rates of disease progression between the experiments, the disease mechanisms were conserved. Overall, our results show that it is possible to non-invasively follow the development of pathology in organoid models of AD over time, by monitoring changes in the aggregates and proteins in the conditioned media, and open possibilities to study the time-course of the key pathogenic processes taking place., (© 2023. The Author(s).)

Published
2024
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31. Imaging Protein Aggregates in Parkinson's Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down.

Author

Zhang YP, Lobanova E, Emin D, Lobanov SV, Kouli A, Williams-Gray CH, and Klenerman D

Subjects
Humans, Protein Aggregates, alpha-Synuclein metabolism, Amyloid beta-Peptides metabolism, Parkinson Disease diagnostic imaging, Parkinson Disease metabolism
Abstract

The formation of soluble α-synuclein (α-syn) and amyloid-β (Aβ) aggregates is associated with the development of Parkinson's disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aβ aggregates in human serum from early PD patients and age-matched controls. Our diffraction-limited imaging results indicate that the proportion of α-syn aggregates (α-syn/(α-syn+Aβ)) can be used to distinguish PD and control groups with an area under the curve (AUC) of 0.85. Further, super resolution fluorescence imaging reveals that PD serums have a higher portion of larger and rounder α-syn aggregates than controls. Little difference was observed for Aβ aggregates. Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis.

Published
2023
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32. An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients.

Author

Kulenkampff K, Emin D, Staats R, Zhang YP, Sakhnini L, Kouli A, Rimon O, Lobanova E, Williams-Gray CH, Aprile FA, Sormanni P, Klenerman D, and Vendruscolo M

Abstract

Misfolded α-synuclein oligomers are closely implicated in the pathology of Parkinson's disease and related synucleinopathies. The elusive nature of these aberrant assemblies makes it challenging to develop quantitative methods to detect them and modify their behavior. Existing detection methods use antibodies to bind α-synuclein aggregates in biofluids, although it remains challenging to raise antibodies against α-synuclein oligomers. To address this problem, we used an antibody scanning approach in which we designed a panel of 9 single-domain epitope-specific antibodies against α-synuclein. We screened these antibodies for their ability to inhibit the aggregation process of α-synuclein, finding that they affected the generation of α-synuclein oligomers to different extents. We then used these antibodies to investigate the size distribution and morphology of soluble α-synuclein aggregates in serum and cerebrospinal fluid samples from Parkinson's disease patients. Our results indicate that the approach that we present offers a promising route for the development of antibodies to characterize soluble α-synuclein aggregates in biofluids., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Published
2022
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33. Small soluble α-synuclein aggregates are the toxic species in Parkinson's disease.

Author

Emin D, Zhang YP, Lobanova E, Miller A, Li X, Xia Z, Dakin H, Sideris DI, Lam JYL, Ranasinghe RT, Kouli A, Zhao Y, De S, Knowles TPJ, Vendruscolo M, Ruggeri FS, Aigbirhio FI, Williams-Gray CH, and Klenerman D

Subjects
Brain metabolism, Humans, Liposomes metabolism, Protein Aggregates, Parkinson Disease metabolism, alpha-Synuclein metabolism
Abstract

Soluble α-synuclein aggregates varying in size, structure, and morphology have been closely linked to neuronal death in Parkinson's disease. However, the heterogeneity of different co-existing aggregate species makes it hard to isolate and study their individual toxic properties. Here, we show a reliable non-perturbative method to separate a heterogeneous mixture of protein aggregates by size. We find that aggregates of wild-type α-synuclein smaller than 200 nm in length, formed during an in vitro aggregation reaction, cause inflammation and permeabilization of single-liposome membranes and that larger aggregates are less toxic. Studying soluble aggregates extracted from post-mortem human brains also reveals that these aggregates are similar in size and structure to the smaller aggregates formed in aggregation reactions in the test tube. Furthermore, we find that the soluble aggregates present in Parkinson's disease brains are smaller, largely less than 100 nm, and more inflammatory compared to the larger aggregates present in control brains. This study suggests that the small non-fibrillar α-synuclein aggregates are the critical species driving neuroinflammation and disease progression., (© 2022. The Author(s).)

Published
2022
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34. Gene Therapy in Opn1mw -/- /Opn1sw -/- Mice and Implications for Blue Cone Monochromacy Patients with Deletion Mutations.

Author

Ma X, Sechrest ER, Fajardo D, Zhu P, Dyka F, Wang Y, Lobanova E, Boye SE, Baehr W, and Deng WT

Subjects
Animals, Disease Models, Animal, Genetic Therapy methods, Humans, Mice, Opsins genetics, Opsins metabolism, Retinal Cone Photoreceptor Cells metabolism, Rod Opsins genetics, Sequence Deletion, Color Vision Defects genetics, Color Vision Defects therapy
Abstract

Blue cone monochromacy (BCM) is a congenital vision disorder affecting both middle-wavelength (M) and long-wavelength (L) cone photoreceptors of the human retina. BCM results from abolished expression of green and red light-sensitive visual pigments expressed in M- and L-cones, respectively. Previously, we showed that gene augmentation therapy to deliver either human L- or M-opsin rescues dorsal M-opsin dominant cone photoreceptors structurally and functionally in treated M-opsin knockout ( Opn1mw -/- ) mice. Although Opn1mw -/- mice represent a disease model for BCM patients with deletion mutations, at the cellular level, dorsal cones of Opn1mw -/- mice still express low levels of S-opsin, which are different from L- and M-cones of BCM patients carrying a congenital opsin deletion. To determine whether BCM cones lacking complete opsin expression from birth would benefit from AAV-mediated gene therapy, we evaluated the outcome of gene therapy, and determined the therapeutic window and longevity of rescue in a mouse model lacking both M- and S-opsin ( Opn1mw -/- /Opn1sw -/- ). Our data show that cones of Opn1mw -/- /Opn1sw -/- mice are viable at younger ages but undergo rapid degeneration. AAV-mediated expression of human L-opsin promoted cone outer segment regeneration and rescued cone-mediated function when mice were injected subretinally at 2 months of age or younger. Cone-mediated function and visually guided behavior were maintained for at least 8 months post-treatment. However, when mice were treated at 5 and 7 months of age, the chance and effectiveness of rescue was significantly reduced, although cones were still present in the retina. Crossing Opn1mw -/- /Opn1sw -/- mice with proteasomal activity reporter mice (Ub G76V -GFP) did not reveal GFP accumulation in Opn1mw -/- /Opn1sw -/- cones eliminating impaired degradation of ubiquitinated proteins as stress factor contributing to cone loss. Our results demonstrate that AAV-mediated gene augmentation therapy can rescue cone structure and function in a mouse model with a congenital opsin deletion, but also emphasize the importance that early intervention is crucial for successful therapy.

Published
2022
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35. Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson's disease.

Author

Lobanova E, Whiten D, Ruggeri FS, Taylor CG, Kouli A, Xia Z, Emin D, Zhang YP, Lam JYL, Williams-Gray CH, and Klenerman D

Subjects
Amyloid beta-Peptides metabolism, Biomarkers metabolism, Brain metabolism, Humans, Protein Aggregates, Parkinson Disease metabolism, alpha-Synuclein metabolism
Abstract

Aggregation of α-synuclein plays a key role in the development of Parkinson's disease. Soluble aggregates are present not only within human brain but also the CSF and blood. Characterizing the aggregates present in these biofluids may provide insights into disease mechanisms and also have potential for aiding diagnosis. We used two optical single-molecule imaging methods called aptamer DNA-PAINT and single-aggregate confocal fluorescence, together with high-resolution atomic force microscopy for specific detection and characterization of individual aggregates with intermolecular β-sheet structure, present in the CSF and serum of 15 early stage Parkinson's disease patients compared to 10 healthy age-matched controls. We found aggregates ranging in size from 20 nm to 200 nm, in both CSF and serum. There was a difference in aggregate size distribution between Parkinson's disease and control groups with a significantly increased number of larger aggregates (longer than 150 nm) in the serum of patients with Parkinson's disease. To determine the chemical composition of the aggregates, we performed aptamer DNA-PAINT on serum following α-synuclein and amyloid-β immunodepletion in an independent cohort of 11 patients with early stage Parkinson's disease and 10 control subjects. β-Sheet aggregates in the serum of Parkinson's disease patients were found to consist of, on average, 50% α-synuclein and 50% amyloid-β in contrast to 30% α-synuclein and 70% amyloid-β in control serum [the differences in the proportion of these aggregates were statistically significant between diseased and control groups (P = 1.7 × 10-5 for each species)]. The ratio of the number of β-sheet α-synuclein aggregates to β-sheet amyloid-β aggregates in serum extracted using our super-resolution method discriminated Parkinson's disease cases from controls with an accuracy of 98.2% (AUC = 98.2%, P = 4.3 × 10-5). Our data suggest that studying the protein aggregates present in serum can provide information about the disruption of protein homeostasis occurring in Parkinson's disease and warrants further investigation as a potential biomarker of disease., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2022
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36. Soluble amyloid beta-containing aggregates are present throughout the brain at early stages of Alzheimer's disease.

Author

Sideris DI, Danial JSH, Emin D, Ruggeri FS, Xia Z, Zhang YP, Lobanova E, Dakin H, De S, Miller A, Sang JC, Knowles TPJ, Vendruscolo M, Fraser G, Crowther D, and Klenerman D

Abstract

Protein aggregation likely plays a key role in the initiation and spreading of Alzheimer's disease pathology through the brain. Soluble aggregates of amyloid beta are believed to play a key role in this process. However, the aggregates present in humans are still poorly characterized due to a lack of suitable methods required for characterizing the low concentration of heterogeneous aggregates present. We have used a variety of biophysical methods to characterize the aggregates present in human Alzheimer's disease brains at Braak stage III. We find soluble amyloid beta-containing aggregates in all regions of the brain up to 200 nm in length, capable of causing an inflammatory response. Rather than aggregates spreading through the brain as disease progresses, it appears that aggregation occurs all over the brain and that different brain regions are at earlier or later stages of the same process, with the later stages causing increased inflammation., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2021
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37. Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals.

Author

Blinova E, Pakhomov D, Shimanovsky D, Kilmyashkina M, Mazov Y, Demura T, Drozdov V, Blinov D, Deryabina O, Samishina E, Butenko A, Skachilova S, Sokolov A, Vasilkina O, Alkhatatneh BA, Vavilova O, Sukhov A, Shmatok D, Sorokvasha I, Tumutolova O, and Lobanova E

Subjects
Administration, Topical, Aminocaproates metabolism, Animals, Cerium metabolism, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Experimental pathology, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 1 pathology, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 pathology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Rats, Wound Healing physiology, Aminocaproates administration & dosage, Cerium administration & dosage, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 2 drug therapy, Wound Healing drug effects
Abstract

Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals., Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl 6 mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db / db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA., Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties., Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.

Published
2021
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38. Retinal homeostasis and metformin-induced protection are not affected by retina-specific Pparδ knockout.

Author

Xu L, Brown EE, Santiago CP, Keuthan CJ, Lobanova E, and Ash JD

Subjects
Animals, Homeostasis, Mice, PPAR gamma, Retina, Metformin pharmacology, PPAR delta genetics
Abstract

Peroxisome proliferator-activated receptors (PPARs) are a family of three nuclear hormone receptors (PPARα, PPARδ, and PPARγ) that are known to regulate expression of lipid metabolism and oxidative stress genes. Given their role in reducing oxidative stress in a variety of tissues, these genes are likely important for retinal homeostasis. This hypothesis has been further supported by recent studies suggesting that PPAR-activating drugs are protective against retinal degenerations. The objective of the present study was to determine the role of PPARδ in the neuroretina. RNA-seq data show that Pparα and Pparδ are both expressed in the retina, but that Pparδ is expressed at 4-fold higher levels. Single-cell RNAseq data show that Pparδ is broadly expressed in all retinal cell types. To determine the importance of Pparδ to the retina, we generated retina-specific Pparδ knockout mice. We found that deletion of Pparδ had a minimal effect on retinal function or morphology out to 12 months of age and did not increase retinal sensitivity to oxidative stress induced by exposure to bright light. While data show that PPARδ levels were increased by the drug metformin, PPARδ was not necessary for metformin-induced protection from light damage. These data suggest that Pparδ either has a redundant function with Pparα or is not essential for normal neuroretina function or resistance to oxidative stress., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2020
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