Статті в журналах: "Green biotechnologies"

1

Fenyvesi, Éva, and Tamás Sohajda. "Cyclodextrin-enabled green environmental biotechnologies." Environmental Science and Pollution Research 29, no. 14 (January 22, 2022): 20085–97. http://dx.doi.org/10.1007/s11356-021-18176-w.

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El Amrani, Abdelhak, Anne-Sophie Dumas, Lukas Y. Wick, Etienne Yergeau, and Richard Berthomé. "“Omics” Insights into PAH Degradation toward Improved Green Remediation Biotechnologies." Environmental Science & Technology 49, no. 19 (September 17, 2015): 11281–91. http://dx.doi.org/10.1021/acs.est.5b01740.

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3

Ricroch, Agnès, Jean-Marc Boussard, Yvette Dattée, André Gallais, Philippe Gate, Louis-Marie Houdebine, Gil Kressmann, et al. "Green biotechnologies: a strategic issue for the future of the French seed industry." Notes Académiques de l'Académie d'agriculture de France / Academic Notes of the French Academy of Agriculture 5 (2018): 1–20. http://dx.doi.org/10.58630/pubac.not.a551012.

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Since man has domesticated plants and improved them, he has used every means at his disposal to do so. During the last 60 years, with the progress of knowledge in biology, especially in genetics, new tools, called "green biotechnologies", have appeared and are increasingly used. A working group of the French Academy of Agriculture has evaluated the use of green biotechnologies and identified their development potential by 2030 to meet the triple challenge of agriculture: coping with food security, respecting the environment and adapting to climate change. This report presents original information from a 2016 survey of 79 French plant breeding centres including 23 private companies and three public research centres of INRA (Institut National de la Recherche Agronomique; French National Institute for Agricultural Research), who were asked about the use of these tools.

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Valieva, Olga. "INSTITUTIONAL FEATURES OF CREATING GLOBAL VALUE CHAINS: AN EXAMPLE OF SIBERIAN BIOTECHNOLOGY COMPANIES." Interexpo GEO-Siberia 3, no. 1 (2019): 55–63. http://dx.doi.org/10.33764/2618-981x-2019-3-1-55-63.

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In accordance with the European concept of GVC, the study identified key players in the biotechnology market and attempted to analyze the degree of incorporation of Siberian biotechnology companies into global value chains. Preliminary results showed that domestic companies are poorly embedded in global value chains. In the markets of “red” biotechnologies, this is the import of primary highly purified / low-purified substances, depending on the scope of use in the final product and the export of high-tech R & D services. The weak link of our market in GVC is engineering and distribution. In the markets of "green" biotechnology, in which segments of genetic engineering can be distinguished (breeding new plant varieties, GM crops), biotechnologies for livestock and plant growing, high competitiveness and export potential have so far formed only in the market of biological plant protection products.

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Stucki, Tobias, and Martin Woerter. "The private returns to knowledge: A comparison of ICT, biotechnologies, nanotechnologies, and green technologies." Technological Forecasting and Social Change 145 (August 2019): 62–81. http://dx.doi.org/10.1016/j.techfore.2019.05.011.

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Cecchi, Grazia, Laura Cutroneo, Simone Di Piazza, Giovanni Besio, Marco Capello, and Mirca Zotti. "Port Sediments: Problem or Resource? A Review Concerning the Treatment and Decontamination of Port Sediments by Fungi and Bacteria." Microorganisms 9, no. 6 (June 11, 2021): 1279. http://dx.doi.org/10.3390/microorganisms9061279.

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Contamination of marine sediments by organic and/or inorganic compounds represents one of the most critical problems in marine environments. This issue affects not only biodiversity but also ecosystems, with negative impacts on sea water quality. The scientific community and the European Commission have recently discussed marine environment and ecosystem protection and restoration by sustainable green technologies among the main objectives of their scientific programmes. One of the primary goals of sustainable restoration and remediation of contaminated marine sediments is research regarding new biotechnologies employable in the decontamination of marine sediments, to consider sediments as a resource in many fields such as industry. In this context, microorganisms—in particular, fungi and bacteria—play a central and crucial role as the best tools of sustainable and green remediation processes. This review, carried out in the framework of the Interreg IT-FR Maritime GEREMIA Project, collects and shows the bioremediation and mycoremediation studies carried out on marine sediments contaminated with ecotoxic metals and organic pollutants. This work evidences the potentialities and limiting factors of these biotechnologies and outlines the possible future scenarios of the bioremediation of marine sediments, and also highlights the opportunities of an integrated approach that involves fungi and bacteria together.

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Yarkova, Y., and P. Atanasova. "LEADING INNOVATIVE PRACTICES IN THE THEMATIC AREA “HEALTHY LIVING INDUSTRY AND BIOTECHNOLOGIES” AT A REGIONAL LEVEL." Trakia Journal of Sciences 18, Suppl.1 (2020): 451–59. http://dx.doi.org/10.15547/tjs.2020.s.01.074.

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The regional context of smart specialization continues to be in the focus of academic discussions as the innovative potential of regions in Bulgaria is being determined. The aim of the present work is to identify innovative practices in one of the leading thematic areas – “Healthy living industry and biotechnologies” during the period of 2014-2019 in a selected region. The object of research is the region of Yambol listed in the National Strategy for Smart Specialization in the Republic of Bulgaria as a promising region in the thematic area “Healthy living industry and biotechnologies”. We have applied methods of regional economic analysis based on objective statistical data. Regional analysis has been complemented with a survey to reflect the subjective viewpoint of stakeholder representatives. The survey and the analysis of the collected information prove the presence of potential in the region of Yambol for expanding organic production in the food industry and generating “green energy” in the energetics sector.

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Capozzi, Vittorio, Mariagiovanna Fragasso, and Francesco Bimbo. "Microbial Resources, Fermentation and Reduction of Negative Externalities in Food Systems: Patterns toward Sustainability and Resilience." Fermentation 7, no. 2 (April 6, 2021): 54. http://dx.doi.org/10.3390/fermentation7020054.

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One of the main targets of sustainable development is the reduction of environmental, social, and economic negative externalities associated with the production of foods and beverages. Those externalities occur at different stages of food chains, from the farm to the fork, with deleterious impacts to different extents. Increasing evidence testifies to the potential of microbial-based solutions and fermentative processes as mitigating strategies to reduce negative externalities in food systems. In several cases, innovative solutions might find in situ applications from the farm to the fork, including advances in food matrices by means of tailored fermentative processes. This viewpoint recalls the attention on microbial biotechnologies as a field of bioeconomy and of ‘green’ innovations to improve sustainability and resilience of agri-food systems alleviating environmental, economic, and social undesired externalities. We argue that food scientists could systematically consider the potential of microbes as ‘mitigating agents’ in all research and development activities dealing with fermentation and microbial-based biotechnologies in the agri-food sector. This aims to conciliate process and product innovations with a development respectful of future generations’ needs and with the aptitude of the systems to overcome global challenges.

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Melnyk, Maryana, Svitlana Shchehlyuk, Iryna Leshchukh, and Roman Yaremchuk. "EU regional policy in the context of smart-specialization: efficiency of priority directions’ funding." Regional Economy, no. 1(95) (2020): 172–83. http://dx.doi.org/10.36818/1562-0905-2020-1-19.

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The paper provides the evaluation of the efficiency of financing the regional policy promotion activities from the EU structural funds and efficiency of funding of national and regional smart specialization strategies’ priorities in 2014-2020. It determines 6 key smart specialization domains among 216 RIS3 of national and regional (NUTS 2) levels: agriculture, food, and biotechnologies; green technologies, energy; transport, mobility, logistics; ICT; life sciences, biotechnologies, pharmacy, biotechnologies; material sciences and intellectual production. Four hypotheses on the close relationship between the investment volumes, directions, and results of their use are empirically verified. The results of the applied correlation analysis show the close relationship between the volumes of funding of the smart-specialization activities and the paces of agricultural output per capita with three clusters of countries by the distribution of funding by the strategic priorities. Regarding the other smart specialization priorities – “environmental technologies, energy efficiency” and “transport, mobility, logistics”, the dependence between the funding from the European Structural and Investment Funds and reducing CO2 emissions from new vehicles is proven. Support of strategic priorities “material science” and “smart production” by European Structural and Investment Funds in 2014-2020 is characterized by growing GRP volumes per capita with clear differences between the developed and average-level EU countries. The reasonability of supporting the implementation of the smart-priority “medicine, pharmacy, healthcare” in most RIS3 of EU countries and the substantial correlation of financial support from EU funds with the paces of state expenses on healthcare increase is substantiated. The conclusions about the efficiency of selected priorities, their high convergence ability, and the capacity to form transnational cooperation are made.

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10

Albert, Hovsepyan, Mayrapetyan Khachatur, Poghosyan Gnel, Eloyan Silva, and Eghiazaryan Anna. "The Efficiency of Planting Stock of Some Tree-Shrubs in Armenia in Open-Air Hydroponics Conditions." Academic Journal of Life Sciences, no. 56 (June 20, 2019): 38–42. http://dx.doi.org/10.32861/ajls.56.38.42.

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The question of nature conservation became one of the most important in the world. It especially concerns to the countries with dry climate, such as Armenia, where auto recovery possibility of forests is excessively low. Gradual disappearance of forests, green areas is due to human non-competent acting, climate change, which aggravates present ecological crisis. One of the important steps for solution of this problem is the recovery of forests, green areas that requires the existence of huge amount of saplings. The use of open-air hydroponics is one of the best versions to receive healthy, qualify saplings. We studied and developed open-air hydroponic methods and biotechnologies of cultivation of 25 species of tree-shrubs important for the landscaping and forest recovery. There was studied the influence of nutrition solution offered by Davtyan G.S. and used in our Institute many years and its modified variants with the changes of main nutrients elements ratio on the biometric parameters of plants. Received results showed that saplings grown in open-air hydroponics conditions have strong root system, provide high rooting, which is very important in the recovery of forests, green areas, especially today’s ecological critical conditions of forest zones.

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11

Chang, Liou, and Lo. "A Hybrid MCDM Model for Evaluating Strategic Alliance Partners in the Green Biopharmaceutical Industry." Sustainability 11, no. 15 (July 27, 2019): 4065. http://dx.doi.org/10.3390/su11154065.

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Since the rise of strategic alliances which play such an important role in industry today, the biopharmaceutical industry worldwide has entered an era of rapid change and collaborative thinking. The strategic alliance is one of the most important strategies for the green biopharmaceutical industry. Member organizations in these alliances work together to create more advantageous biotechnologies based on environmental protection to achieve mutual benefits. In the past, there have been only a few studies discussing partner evaluations and the selection process for the green biopharmaceutical industry, so the criteria or indicators are still not complete. Therefore, this study proposes a novel multi-criteria decision-making (MCDM) framework for strategic alliance partner evaluation that combines the best-worst method (BWM) and the fuzzy TOPSIS technique based on the concept of aspiration level (called fuzzy TOPSIS-AL) to evaluate the performance and priority rankings of strategic alliance partners. The BWM overcomes the shortcomings of small sample sizes and streamlines the number of conventional pairwise comparisons needed. The fuzzy TOPSIS-AL technique introduces the concept of the aspiration level, thereby leading to more reasonable suggestions for improvement. In addition, data from a multinational green biopharmaceutical company survey are utilized to demonstrate the validity and applicability of the proposed model.

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12

Gotovtsev, Pavel. "How IoT Can Integrate Biotechnological Approaches for City Applications—Review of Recent Advancements, Issues, and Perspectives." Applied Sciences 10, no. 11 (June 9, 2020): 3990. http://dx.doi.org/10.3390/app10113990.

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There are a number of significant changes taking place in modern city development and most of them are based on the number of recent technological progress. This paper provides a review and analysis of recent approaches of biotechnology that can find a place in today’s cities and discusses how those technologies can be integrated into a city’s Internet of Things (IoT). Firstly, several biotechnologies that focus on rain gardens, urban vertical farming systems, and city photobioreactors are discussed in the context of their integration in a city’s IoT. The next possible application of biofuel cells to the sensor network’s energy supply is discussed. It is shown that such devices can influence the low-power sensor network structure as an additional energy source for transmitters. This paper shows the possibility of bioelectrochemical biosensor applications, discusses self-powered biosensors, and shows that such a system can be widely applied to rainwater monitoring in rain gardens and green streets. Significant attention is paid to recent approaches in synthetic biology. Both cell-based biosensors and bioactuators with synthetic genetic circuits are discussed. The development of cell-based biosensors can significantly enhance the sensing possibilities of a city’s IoT. We show the possible ways to develop cyber-physical systems (CPSs) with the systems mentioned above. Aspects of data handling for the discussed biotechnologies and the methods of intelligent systems, including those that are machine learning-based, applied to the IoT in a city are presented.

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13

Tagliabue, Giovanni. "The necessary "GMO" denialism and scientific consensus." Journal of Science Communication 15, no. 04 (June 7, 2016): Y01. http://dx.doi.org/10.22323/2.15040401.

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"Genetically Modified Organisms" are not a consistent category: it is impossible to discuss such a miscellaneous bunch of products, deriving from various biotech methods, as if they had a common denominator. Critics are too often pre-emptively suspicious of peculiar risks for health or the environment linked to this ill-assorted ensemble of microorganisms, plants or animals: yet, even before being unscientific, the expression "GMO(s)" has very poor semantic value. Similarly, claims that recombinant DNA technology is always safe are a misjudgement: many unsatisfactory "GMOs" have been discarded, as has happened also for innumerable agri-food outcomes, obtained via more or less traditional field and lab methods. The scientific consensus, i.e. the widespread accord among geneticists, biologists and agriculturalists, maintains that every biotech invention has to be examined case by case, evaluating the unique profile of each new organism ("GMO" or otherwise): to assess its safety, the technique(s) used to produce it are irrelevant. Therefore, in considering "green" biotechnologies, a triple mantra should be kept in mind: 1. product, not process; 2. singular, not plural; 3. a posteriori, not a priori. Both people's and law-makers' attitude to agricultural biotechnologies should be reoriented, and this is an interesting task for science communicators: they should explain how meaningless and misleading the "GMO" frame is, debunking a historical, ongoing socio-political blunder, clarifying to the public what most life scientists have been recommending for several decades.

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Molina, Lázaro, Regina-Michaela Wittich, Pieter van Dillewijn, and Ana Segura. "Plant-Bacteria Interactions for the Elimination of Atmospheric Contaminants in Cities." Agronomy 11, no. 3 (March 6, 2021): 493. http://dx.doi.org/10.3390/agronomy11030493.

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One of the major health risks for humans, especially for those living in large cities, is air pollution. Air pollution consists mainly of emissions of particulate matter (PM), nitrogen oxides, sulphur dioxide, ammonia and volatile organic compounds (VOCs). The organic carbon fraction of particulate matter is a mixture of hundreds of organic compounds, such as polycyclic aromatic hydrocarbons (PAHs), or polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), some of which are mutagenic and/or carcinogenic. Because this particulate matter represents a serious threat for human health, measures to reduce emissions and to eliminate contaminants need to be strongly reinforced, with a focus on novel biotechnologies. In this review, we will explore the possibilities that bacteria associated with plants may offer the amelioration of atmospheric contaminants in cities, and we will discuss this strategy in the context of “Green Architecture”.

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15

Santi, Micol, Luca Sancineto, Vanessa Nascimento, Juliano Braun Azeredo, Erika V. M. Orozco, Leandro H. Andrade, Harald Gröger, and Claudio Santi. "Flow Biocatalysis: A Challenging Alternative for the Synthesis of APIs and Natural Compounds." International Journal of Molecular Sciences 22, no. 3 (January 20, 2021): 990. http://dx.doi.org/10.3390/ijms22030990.

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Biocatalysts represent an efficient, highly selective and greener alternative to metal catalysts in both industry and academia. In the last two decades, the interest in biocatalytic transformations has increased due to an urgent need for more sustainable industrial processes that comply with the principles of green chemistry. Thanks to the recent advances in biotechnologies, protein engineering and the Nobel prize awarded concept of direct enzymatic evolution, the synthetic enzymatic toolbox has expanded significantly. In particular, the implementation of biocatalysts in continuous flow systems has attracted much attention, especially from industry. The advantages of flow chemistry enable biosynthesis to overcome well-known limitations of “classic” enzymatic catalysis, such as time-consuming work-ups and enzyme inhibition, as well as difficult scale-up and process intensifications. Moreover, continuous flow biocatalysis provides access to practical, economical and more sustainable synthetic pathways, an important aspect for the future of pharmaceutical companies if they want to compete in the market while complying with European Medicines Agency (EMA), Food and Drug Administration (FDA) and green chemistry requirements. This review focuses on the most recent advances in the use of flow biocatalysis for the synthesis of active pharmaceutical ingredients (APIs), pharmaceuticals and natural products, and the advantages and limitations are discussed.

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MA, R., and S. PULLI. "Factors influencing somatic embryogenesis and regeneration ability in somatic tissue culture of spring and winter rye." Agricultural and Food Science 13, no. 4 (December 4, 2008): 363. http://dx.doi.org/10.2137/1239099043633305.

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Rye is an important crop in Northern and Eastern Europe. However, the application of various biotechnologies in rye breeding has been limited duo to its recalcitrant in tissue culture. In order to improve somatic tissue effi ciency, key factors affecting somatic embryogenesis and reproducible green plant regeneration of rye (Secale cereale L.) were evaluated and optimised. In this study, a total 27 rye genotypes including 10 spring and 17 winter genotypes were involved in the investigation. Genotype, culture medium, sugar, gel agent and auxin infl uenced somatic embryogenesis of immature embryo signifi cantly. One-two weeks cold pretreatment of young embryo enhanced somatic embryogenesis and green plant regeneration. In culture of immature embryos, infl orescences and leaf segments of the seedlings, explants signifi cantly infl uenced the culture effi ciency. Highest embryogenic callus yield resulted from rye immature embryo as explant compared to young infl orescence and leaf segment of seedling. Developmental stage of embryo played an important role in somatic embryogenesis. Late spherical coleoptile stage (embryo size 0.51mm in length) was optimal developmental stage of immature embryo for culture. Morphogenetic potential of embryogenic callus decreased with an increasing number of subcultures, and this ability could be maintained in vitro for a maximum of 8 months of culturing.;

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Miroshnichenko, Dmitry, Anna Klementyeva, and Sergey Dolgov. "The Effect of Daminozide, Dark/Light Schedule and Copper Sulphate in Tissue Culture of Triticum timopheevii." Plants 10, no. 12 (November 29, 2021): 2620. http://dx.doi.org/10.3390/plants10122620.

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Triticum timopheevii Zhuk. is a tetraploid wheat that is utilized worldwide as a valuable breeding source for wheat improvement. Gene-based biotechnologies can contribute to this field; however, T. timopheevii exhibits recalcitrance and albinism in tissue cultures, making this species of little use for manipulation through genetic engineering and genome editing. This study tested various approaches to increasing in vitro somatic embryogenesis and plant regeneration, while reducing the portion of albinos in cultures derived from immature embryos (IEs) of T. timopheevii. They included (i) adjusting the balance between 2,4-D and daminozide in callus induction medium; (ii) cultivation using various darkness/illumination schedules; and (iii) inclusion of additional concentrations of copper ions in the tissue culture medium. We achieved a 2.5-fold increase in somatic embryogenesis (up to 80%) when 50 mg L−1 daminozide was included in the callus induction medium together with 3 mg L−1 2,4-D. It was found that the dark cultivation for 20–30 days was superior in terms of achieving maximum culture efficiency; moreover, switching to light in under 2 weeks from culture initiation significantly increased the number of albino plants, suppressed somatic embryogenesis, and decreased the regeneration of green plants. Media containing higher levels of copper ions did not have a positive effect on the regeneration of green plants; contrarily, the elevated concentrations caused albinism in plantlets. The results and relevant conclusions of the present study might be valuable for establishing an improved protocol for the regeneration of green plants in tissue cultures of T. timopheevii.

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Perra, Matteo, Gianluigi Bacchetta, Aldo Muntoni, Giorgia De Gioannis, Ines Castangia, Hiba N. Rajha, Maria Letizia Manca, and Maria Manconi. "An outlook on modern and sustainable approaches to the management of grape pomace by integrating green processes, biotechnologies and advanced biomedical approaches." Journal of Functional Foods 98 (November 2022): 105276. http://dx.doi.org/10.1016/j.jff.2022.105276.

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Voronina, Natalia, and Zhanna Shnorr. "Legal regulation of “green” agriculture in Russia: current state and prospects of development." E3S Web of Conferences 291 (2021): 03011. http://dx.doi.org/10.1051/e3sconf/202129103011.

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According to the Millennium Development Goals, approved by the UN in 2000, it is necessary to eradicate hunger in the 21st century, while solving the environmental problems that have accumulated over the past hundred years. The international community sees a way out in the development of a “green” economy, an integral part of which is agriculture. The current state of technology development enables the use of innovative methods of agricultural activities, including biotechnology. However, the consequences of their use for humans and the environment are completely unknown. Biotechnologies make it possible to obtain agricultural products with pre-defined characteristics, adapt their cultivation and production to unfavorable natural conditions, and increase labor productivity. But at the same time, the UN and FAO strategic planning documents note that produced agricultural products shall be safe for human health, and agricultural activities shall have a minimal impact on the environment. Therefore, the need for the formation and development of a model of “green” agriculture is justified at the international level. In Russia, attention is also paid to the production of products that are as safe as possible for both humans and the environment. At the same time, the current state of legal regulation of “green” agriculture does not allow us to speak about the formed effective model of legal regulation of the production of environmentally safe agricultural products. Legal problems and conflicts of the current legislation do not allow our country to take a competitive position in the international market of agricultural products. The purpose of this article is to provide a legal analysis of the current legislation and identify possible solutions to the legal problems of “green” agriculture, as well as to form a conceptual model of its legal regulation. Using the methods of comparative analysis, legal hermeneutics, and legal modeling, a legal analysis of the modern legal regulation of “green” agriculture is carried out and a conceptual model of its legal regulation is determined, based on which proposals for improving legislation in the considered sphere of public relations are formulated.

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Tlais, Ali Zein Alabiden, Giuseppina Maria Fiorino, Andrea Polo, Pasquale Filannino, and Raffaella Di Cagno. "High-Value Compounds in Fruit, Vegetable and Cereal Byproducts: An Overview of Potential Sustainable Reuse and Exploitation." Molecules 25, no. 13 (June 30, 2020): 2987. http://dx.doi.org/10.3390/molecules25132987.

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Food waste (FW) represents a global and ever-growing issue that is attracting more attention due to its environmental, ethical, social and economic implications. Although a valuable quantity of bioactive components is still present in the residuals, nowadays most FW is destined for animal feeding, landfill disposal, composting and incineration. Aiming to valorize and recycle food byproducts, the development of novel and sustainable strategies to reduce the annual food loss appears an urgent need. In particular, plant byproducts are a plentiful source of high-value compounds that may be exploited as natural antioxidants, preservatives and supplements in the food industry, pharmaceuticals and cosmetics. In this review, a comprehensive overview of the main bioactive compounds in fruit, vegetable and cereal byproducts is provided. Additionally, the natural and suitable application of tailored enzymatic treatments and fermentation to recover high-value compounds from plant byproducts is discussed. Based on these promising strategies, a future expansion of green biotechnologies to revalorize the high quantity of byproducts is highly encouraging to reduce the food waste/losses and promote benefits on human health.

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Banner, Alec, Helen S. Toogood, and Nigel S. Scrutton. "Consolidated Bioprocessing: Synthetic Biology Routes to Fuels and Fine Chemicals." Microorganisms 9, no. 5 (May 18, 2021): 1079. http://dx.doi.org/10.3390/microorganisms9051079.

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The long road from emerging biotechnologies to commercial “green” biosynthetic routes for chemical production relies in part on efficient microbial use of sustainable and renewable waste biomass feedstocks. One solution is to apply the consolidated bioprocessing approach, whereby microorganisms convert lignocellulose waste into advanced fuels and other chemicals. As lignocellulose is a highly complex network of polymers, enzymatic degradation or “saccharification” requires a range of cellulolytic enzymes acting synergistically to release the abundant sugars contained within. Complications arise from the need for extracellular localisation of cellulolytic enzymes, whether they be free or cell-associated. This review highlights the current progress in the consolidated bioprocessing approach, whereby microbial chassis are engineered to grow on lignocellulose as sole carbon sources whilst generating commercially useful chemicals. Future perspectives in the emerging biofoundry approach with bacterial hosts are discussed, where solutions to existing bottlenecks could potentially be overcome though the application of high throughput and iterative Design-Build-Test-Learn methodologies. These rapid automated pathway building infrastructures could be adapted for addressing the challenges of increasing cellulolytic capabilities of microorganisms to commercially viable levels.

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Hori, Katsutoshi, Hisami Watanabe, Shun'ichi Ishii, Yasunori Tanji, and Hajime Unno. "Monolayer Adsorption of a “Bald” Mutant of the Highly Adhesive and Hydrophobic Bacterium Acinetobacter sp. Strain Tol 5 to a Hydrocarbon Surface." Applied and Environmental Microbiology 74, no. 8 (February 29, 2008): 2511–17. http://dx.doi.org/10.1128/aem.02229-07.

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ABSTRACT The affinity of microbial cells for hydrophobic interfaces is important because it directly affects the efficiency of various bioprocesses, including green biotechnologies. The toluene-degrading bacterium Acinetobacter sp. strain Tol 5 has filamentous appendages and a hydrophobic cell surface, shows high adhesiveness to solid surfaces, and self-agglutinates. A “bald” mutant of this bacterium, strain T1, lacks the filamentous appendages and has decreased adhesiveness but retains a hydrophobic cell surface. We investigated the interaction between T1 cells and an organic solvent dispersed in an aqueous matrix. During a microbial-adhesion-to-hydrocarbon (MATH) test, which is frequently used to measure cell surface hydrophobicity, T1 cells adhered to hexadecane droplet surfaces in a monolayer, whereas wild-type cells aggregated on the droplet surfaces. The adsorbed T1 cells on the hexadecane surfaces hindered the coalescence of the droplets formed by vortexing, stabilizing the emulsion phase. Following the replacement of the aqueous phase with fresh pure water after the MATH test, a proportion of the T1 cells that had adsorbed to the hydrocarbon surface detached during further vortexing, suggesting a reversible adsorption of T1 cells. The final ratio of the adhering cells to the total cells in the detachment test coincided with that in the MATH test. The adhesion of T1 cells to the hydrocarbon surface conformed to the Langmuir adsorption isotherm, which describes reversible monolayer adsorption. Reversible monolayer adsorption should be useful for green technologies employing two-liquid-phase partitioning systems and for bioremediation because it allows effective reaction and transport of hydrophobic substrates at oil-water interfaces.

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23

Nevo, Eviatar. "Genome evolution of wild cereal diversity and prospects for crop improvement." Plant Genetic Resources 4, no. 1 (April 2006): 36–46. http://dx.doi.org/10.1079/pgr2006108.

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Genomic and proteomic diversity provide the basis of evolutionary change by natural selection under abiotic and biotic stresses, and the human-driven evolutionary process of domestication by artificial selection. Described here are some of the regional and local genomic and proteomic long-term multidisciplinary studies conducted at the Institute of Evolution, University of Haifa, Israel, during 1975–2005 (see publications at http://evolution.haifa.ac.il), involving both wild barley, Hordeum spontaneum, the progenitor of cultivated barley and wild emmer sheat, Triticum dicoccoides, the progenitor of modern tetraploid and hexaploid cultivated wheat. Wild cereals harbour large amounts of as yet untapped adaptive genetic resources for crop improvement (resistances against abiotic and biotic stresses, micronutrient metal deficiencies, storage proteins, amylases and photosynthetic yield, among others). The adaptive genomic diversity of wild cereals, including cryptic beneficial alleles at specific quantitative trait loci of T. dicoccoides and H. spontaneum is the best genomic resource to be conserved in situ and ex situ for utilization by classical and modern biotechnologies, to enrich the genetically impoverished and stress-vulnerable food cultivars, advance crop improvement, and thereby increase and optimize world food production in a second genetic green revolution.

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Popa, Olga, Ana-Maria Rosu, Daniela Nicuta, Roxana Elena Voicu, Valentin Zichil, and Ileana Denisa Nistor. "Factorial Design to Stimulate Biomass Development with Chemically Modified Starch." Applied Sciences 12, no. 19 (October 7, 2022): 10069. http://dx.doi.org/10.3390/app121910069.

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The present study is focused on mathematical modeling by testing the benefits of modified potato starch in the biomass production of microorganisms, such as the fungus type. Microorganisms need a carbon source for the biomass development. In different industries, microorganisms, such as the Penicillium type, are used for the extraction of different important compounds utilized in biotechnologies. The aim of this study is to establish some important parameters in order to stimulate the biomass production in the presence of chemically modified starch. The carbon sources used in this research are glucose, native potato starch, and chemically modified potato starch. The chemical modification of potato starch was realized with green chemical compounds in order to not influence biomass development. The chemical characterization of starch and modified starch was important in order to confirm the chemical modification of starch. The response function in mathematical modeling is the amount of biomass developed when there are varied parameters. The varied parameters for the factorial design are as follows: time of biomass development, mass report of glucose:starch (G:S), and mass report of glucose:modified starch (G:MS). The results obtained for the optimal values are as follows: 6 days for the biomass development, 1:1.35 for the mass report of G:S, and 1:1.27 for the report of G:MS.

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Ďuračka, Michal. "The in vitro effect of kanamycin on the behaviour of bovine spermatozoa." Archives of Ecotoxicology 1, no. 4 (December 20, 2019): 36–40. http://dx.doi.org/10.36547/ae.2019.1.4.36-40.

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The use of antibiotics is a common part of animal biotechnologies. Especially, the use of antibiotics in semen extenders is necessary. However, the effect of antibiotics on the spermatozoa structure and function is still not completely examined. Therefore, the aim of our study was to investigate the effect of kanamycin on bovine spermatozoa at concentrations of 80 and 160 µg/mL during the 24 h in vitro cultivation. Semen samples were collected from clinically healthy Holstein-Friesian bulls. At times of 0, 2 and 24 h the motility assessment, mitochondrial activity, acrosomal and membrane integrity evaluation were performed. The sperm motility was measured using the Computer-assisted sperm analysis (CASA). Mitochondrial activity was evaluated through the Mitochondrial Toxicity Test (MTT). The acrosomal status was determined using the fast green/rose bengal staining on slides. Similarly, the membrane integrity was analysed using the eosin-nigrosin staining. Our results revealed the dose- and time-dependent effect of kanamycin under the in vitro conditions. In conclusion, the selected concentrations of kanamycin may have adverse effects on the motility, mitochondrial activity, acrosomal and membrane integrity during semen processing. Considering the relatively low concentrations used, we do not recommend to use kanamycin as a supplement in bovine semen extenders.

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26

Luchko, I. A., M. S. Arzhatkina, and A. A. Stelmakhov. "Safety of repeated use of deep-level openings in Norilsk mines." Mining informational and analytical bulletin, no. 6-1 (May 20, 2020): 119–27. http://dx.doi.org/10.25018/0236-1493-2020-61-0-119-127.

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The article discusses safe repeated use of deep-level openings in Norilsk mine for vegetable production and herb cultivation in special facilities. Farming on the field in the north and east of Russia either is restricted by a short warm period suitable for vegetation, or is impossible due to climate, while the glasshouse industry bears losses because of the power cost and other expenses. At the actual depth of mining in the Talnakh ore cluster, the mine air temperature may reach 40 Celsius degrees and higher, which offers comfortable condition for the implementation of R&D projects in biotechnologies. One the other hand, the ore bodies in the cluster are rockburst-hazardous, which means high probability of dynamic events with deformation and destruction of underground excavations. It is necessary to undertake the elaborated studies into geodynamic safety to select and validate installation sites for biotechnology objects. It is suggested to select deep-level installation sites for the production of vegetable crops AVK-15 with regard to the geodynamic zoning of the Norilsk ore cluster. Deeplevel vegetation production will become safe as a result, and new eco-friendly and adaptable technologies will be developed for the year-round cultivation of fresh vegetables and green at the low material inputs and power consumption per unit product.

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Smirnov, H. A., C. N. Ladyzhenko, and V. L. Polunin. "Clean technologies in the angaro-yenisei macro-region." Bulletin of the Academy 1, no. 68 (2022): 98–104. http://dx.doi.org/10.36871/v.a.2022.03.01.012.

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Purpose of the article. The main hopes in solving the most acute environmental problems (including resource ones) are pinned today on technological breakthroughs. In recent years, developed countries have reoriented their development towards the implementation of a strategy of environmentally oriented growth, one of the main components of which is «clean technologies». The development of environmental technologies in Russia has great prospects if the plans are implemented, especially given the Russian potential in the development of macro technologies (nuclear power, power equipment, communications, etc.), laser, nano-, biotechnologies, etc. Investments in environmental innovations are growing, including on the part of the Russian business, «development institutions» of the innovative economy are being created. Materials and methods. The article considers the Angara-Yenisei macroregion in more detail, including innovative projects being developed on its territory, as well as the most promising areas for the development of «clean technologies» that contribute to improving the environmental situation in the region. Results. Among the most promising areas for the development of «clean technologies» in the Angara-Yenisei macroregion, contributing to the improvement of the environmental situation in the region, are the following: restoration of the activities of environmental authorities: the federal Environmental Fund and environmental funds of the subjects of the Russian Federation; development of scientific and innovative infrastructure of the macroregion; improvement of the mechanism of payments for negative impact on the environment environment; implementation of the practice of financial stimulation of the eco-innovation process; accelerated depreciation of fixed assets of «green» purpose; development of «green» financing instruments; development of highly competitive areas with the use of clean technologies. Conclusion. It is necessary not only to focus on reducing the dependence of the macroregion on the resource economy, but also to promote the development of highly competitive areas with the use of clean technologies.

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Jelev, Viorica. "Future Economy and Touristic Entrepreneurship." Journal of Economic Development, Environment and People 5, no. 3 (September 30, 2016): 29. http://dx.doi.org/10.26458/jedep.v5i3.502.

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Specialists claim that Eco-Bio-economy or social economy is the economy of future, in the service of human life by the rational use of environmental resources. The concept brings together in an integrated manner, according to the researchers, economy, ecology, biodiversity, biotechnologies and focuses on integrated sustainable development of the world. The new social economy, together with the corporate social responsibility joins a new multipolar world to a healthy environment by creative and innovative concepts that will ensure the sustainability of living in a sustainable manner. Doctors have added to thisEco-Bio-Economy concept a new one called One Health - a new integrated approach for human, animals and environment health state to that they should emphasize the importance of human behavior upon the planet biodiversity. Economer agents have mostly understood the importance of alarm signals drawn up by researchers on the destruction of the resources of the planet and adapted their business sites to the requirements of the green economy. A responsible business is also ecotourism that promotes a favourable travel for the surrounding environment. It requires accommodation on farms, in peasant houses, small rural hotels. The educational environment contributes to the trend planetary tourism, with the formation of new specialists with new knowledge, behaviors and consumers use formation of new characters, sensitive to environmental issues. This educational model is also promoted by Spiru Haret University, by creating the Master degree in tourism but also in environmental protection.

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Scavo, Aurelio, and Giovanni Mauromicale. "Crop Allelopathy for Sustainable Weed Management in Agroecosystems: Knowing the Present with a View to the Future." Agronomy 11, no. 11 (October 20, 2021): 2104. http://dx.doi.org/10.3390/agronomy11112104.

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In the face of yield losses caused by weeds, especially in low-input agricultural systems, and environmental pollution due to the excessive use of synthetic herbicides, sustainable weed management has become mandatory. To address these issues, allelopathy, i.e., the biochemical phenomenon of chemical interactions between plants through the release of secondary metabolites into the environment, is gaining popularity. Although many important crops are known for their allelopathic potential, farmers are still reluctant to use such knowledge practically. It is therefore important to assist advisors and farmers in assessing whether allelopathy can be effectively implemented into an eco-friendly weed management strategy. Here, we aim to give a comprehensive and updated review on the herbicidal potential of allelopathy. The major findings are the following: (1) Crops from different botanical families show allelopathic properties and can be cultivated alone or in combination with other non-allelopathic crops. (2) Many allelopathic tools can be adopted (crop rotation, intercropping, cover cropping as living or dead mulches, green manuring, use of allelochemical-based bioherbicides). (3) These methods are highly flexible and feature increased efficiency when combined into an integrated weed management strategy. (4) Recent advances in the chemistry of allelopathy are facilitating the use of allelochemicals for bioherbicide production. (5) Several biotechnologies, such as stress induction and genetic engineering techniques, can enhance the allelopathic potential of crops or introduce allelopathic traits de novo. This review shows how important the role of allelopathy for sustainable weed management is and, at the same time, indicates the need for field experiments, mainly under an integrated approach. Finally, we recommend the combination of transgenic allelopathy with the aforementioned allelopathic tools to increase the weed-suppressive efficacy of allelopathy.

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Kingwell, Ross, and David Pannell. "Economic trends and drivers affecting the Wheatbelt of Western Australia to 2030." Australian Journal of Agricultural Research 56, no. 6 (2005): 553. http://dx.doi.org/10.1071/ar04196.

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Most of the farm businesses in Western Australia remain profitable, with rates of return comparable with non-farming sectors. However, there is continuing pressure on poor-performing farms, as well as a range of social pressures, which mean that there will continue to be a steady fall in the number of farms in the Wheatbelt of Western Australia. Most remaining farms will continue to be profitable, due in significant part to successful research and development (R&D). Farms will continue to be highly diversified. We expect the real prices of most agricultural commodities to continue to fall, although we note predictions for meat prices to rise in the medium to long-term. Key uncertainties about price trends include: future levels of agricultural protection in developed counties; the levels of price premia for ‘green’ products; the rates of productivity improvement for agriculture in developing countries; and energy prices. Key uncertainties about R&D/technology include the availability of funds for R&D, and the contributions of biotechnologies. Use of information technologies will increase, although not as much as some expect, and in some cases driven by shortages of skilled farm labour rather than production advantages. The fundamental elements of managing a farm have altered little, and we do not expect them to change in the next 30 years. Successful farm management will continue to depend largely on good decisions about the farm’s enterprise mix, machinery replacement, land leasing or purchase, labour hiring, and off-farm investments. Agricultural R&D should continue to address a diversified portfolio of issues, including attention to environmental issues, but not neglecting the need for ongoing productivity improvements in agriculture.

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Dalmazzo, A., P. A. A. Góes, M. Nichi, R. O. C. Silva, J. R. C. Gurgel, E. G. A. Perez, C. C. Rocha, et al. "232 INFLUENCE OF SEMINAL PLASMA ON THE SUSCEPTIBILITY OF DOG SPERM AGAINST DIFFERENT REACTIVE OXYGEN SPECIES." Reproduction, Fertility and Development 23, no. 1 (2011): 215. http://dx.doi.org/10.1071/rdv23n1ab232.

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Due to the importance of dogs to humans, there is increasing interest in breeders in the use of reproductive biotechnologies. However, most of the biotechnologies would require the removal or dilution of the seminal plasma, which is known to exert both beneficial and deleterious effects on sperm quality. One of the beneficial effects of seminal plasma would be the antioxidant protection because sperm are particularly susceptible to oxidative stress, mainly due to the reduced cytoplasm and the high content of polyunsaturated fatty acids in their membrane. An alternative to overcome the injuries caused by oxidative stress is the antioxidant treatment, which requires the identification of those reactive oxygen species (ROS) that are the most deleterious. The aim of this study was to identify the most harmful ROS to dog semen. Semen samples from 6 adult dogs were collected and centrifuged. Seminal plasma (SP) was removed and samples were incubated (1 h, 37°C) with 4 ROS-inducing mechanisms: xanthine/xanthine oxidase (produces superoxide anion), hydrogen peroxide (4 mM), ascorbate and ferrous sulfate (4 mM; produces hydroxyl radical) alone or with additional SP. Samples were analysed for motility by computer assisted sperm analysis (CASA). The 3-3′ diaminobenzidine stain was used as an index of mitochondrial activity, the eosin nigrosin stain as an index of membrane integrity, the simple stain (fast green/Bengal rose) as an index of acrosome integrity, sperm chromatin structure assay (SCSA) as an index of DNA fragmentation, and measurement of thiobarbituric acid reactive substances (TBARS) as an index of lipid peroxidation. Statistical analysis was performed using the SAS System for Windows (SAS Institute Inc., Cary, NC, USA; least significant differences test and Spearman correlation; P < 0.05). Results showed that dog sperm is differentially modulated depending on the presence of SP. In addition, damage to the different sperm structures depended on the different ROS. Samples incubated with SP showed no differences concerning TBARS (1 233 in SP, 1 260 in Tris; P = 0.99). On the other hand, samples incubated without SP showed higher lipid peroxidation when treated with hydroxyl radical compared with the other ROS. Furthermore, although hydroxyl radical mostly altered mitochondrial activity in samples incubated with SP (DAB IV = 4.3%; P < 0.05 against all other ROS), the most significant ROS in samples incubated without SP was hydrogen peroxide (DAB IV = 4.7%; P < 0.05 against all other ROS). Superoxide anion was less harmful to acrosome integrity in samples incubated with SP and to motility in samples incubated without SP. The present results suggest that seminal plasma may play an important role in the susceptibility of dog sperm to oxidative stress. Moreover, the results indicate that different sperm compartments are susceptible to different ROS. It is concluded that the quality of frozen–thawed dog semen may be improved by treating with a combination of different antioxidants to destroy the chain reaction causing the oxidative stress. FAPESP is acknowledged for financial support.

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Fedyna, Svitlana M. "Forming the System of Sustainable Development Indicators for Biosocial Economy Assessment." Mechanism of an Economic Regulation, no. 4 (2020): 129–37. http://dx.doi.org/10.21272/mer.2019.86.13.

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The paper compares frequently used methods for sustainable development assessing. We studied the systems of sustainable development indicators for assessing its individual areas (in particular, economic, environmental and social), and also analyzed aggregate indices designed for a comprehensive assessment of development both at the macro level and at the level of specific individual territorial units. For each methodology, the structures of index systems were presented with their breakdown into spheres and blocks / categories, and the main disadvantages of each methodology were determined. Among the methodologies considered are the following: the methodology proposed by the Global Biopact, indicator systems from the OECD Green Growth Strategy and World Bank indicators. The work carried out a structural analysis and explored the content of aggregated indices: Social Progress Index, Environmental Efficiency Index, Global Climate Change Adaptation Index and Human Development Index. The listed systems of indicators and indices are used at the global level, their use for Ukraine needs to be adapted. The adaptation of such techniques to the Ukrainian realities was shown on the example of a system of indicators based on the goals of sustainable development. Each goal has a number of tasks, the implementation of which is necessary to achieve it. For each task, several indicators are proposed for assessing the level of their implementation, an analysis of these indicators showed that for Ukraine, metadata has not been defined for indicators for most of the goals. In the above methods, indicators for assessing the bioeconomic direction (with the exception of biodiversity) are almost not presented, therefore, the development of a model for assessing the biosocial economy requires the inclusion of indicators characterizing bioresources, biotechnologies, and bioenergy. Key words: index, indicator, sustainable development, biosocial economy, bioeconomics, biodiversity, sustainable development goals.

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Seidel, J., F. Krujatz, T. Walther, M. Gelinsky, A. Lode, and J. Steingroewer. "Green Bioprinting - 3D-Druck mit pflanzlichen Zellen für die Biotechnologie." Chemie Ingenieur Technik 90, no. 9 (August 24, 2018): 1343. http://dx.doi.org/10.1002/cite.201855454.

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Silva, R. O. C., E. G. A. Perez, R. P. Cabral, D. G. Silva, C. H. C. Viana, M. Nichi, P. A. A. Goes, et al. "320 SUSCEPTIBILITY OF GOAT SPERM TO DIFFERENT REACTIVE OXYGEN SPECIES." Reproduction, Fertility and Development 22, no. 1 (2010): 316. http://dx.doi.org/10.1071/rdv22n1ab320.

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Semen quality is one of the main limiting factors for the success of artificial insemination in goats. It is well known that reactive oxygen species (ROS) lead to structural and functional damages to sperm, impairing or avoiding fecundation. The understanding of sperm oxidative mechanisms in goats may provide information on possible treatments to improve semen quality and fertility rates. The aim of the present study was to verify the resistance of goat spermatozoa to different reactive oxygen species. Sperm samples from 4 goats were collected using an artificial vagina. Sperm samples were then incubated (1 h, 37°C) with 4 ROS inducer mechanisms: xanthine/xanthine oxidase (produces superoxide anion), hydrogen peroxide (4 mM), ascorbate/ferrous sulfate (4 mM; produces hydroxyl radical), and malondialdehyde (MDA, lipid peroxidation product). Samples were analyzed for mitochondrial activity using the 3,3′ diaminobenzidine stain, for membrane integrity using the eosin/nigrosin staining, for acrosome integrity using the simple stain (fast green/Bengal rose), and for lipid peroxidation by dosing thiobarbituric acid reactive substances (TBARS). Results showed that goat sperm is more sensitive to hydrogen peroxide, when compared to superoxide anion, hydroxyl radical, and MDA, when considering acrosome integrity, membrane integrity, and mitochondrial potential (Table 1). On the other hand, TBARS production was increased in samples submitted to hydroxyl radical incubation. Strong negative correlations were found between sperm samples showing impaired mitochondrial potential and both membrane and acrosome integrity (r = -0.97, P < 0.0001 and r = -0.91, P < 0.0001, respectively). The concentration of TBARS correlated negatively with the percentage of sperm showing intact membranes (r = -0.53, P = 0.06), and the later correlated negatively with sperm showing no mitochondrial activity (r = -0.78, P = 0.0006). Results of the present experiment suggest that goat sperm are extremely susceptible to the attack of hydrogen peroxide, being resistant to other ROS. Therefore, an alternative to improve the use of goat semen in reproductive biotechnologies would be the treatment with catalase or glutathione peroxidase, important hydrogen peroxide scavengers. Table 1.Effect of different ROS on goat sperm The authors thank Nutricell for the media used in this experiment.

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von Wulffen, Caroline. "Forschungsergebnisse schneller in den Markt." UmweltMagazin 50, no. 10-11 (2020): 26–27. http://dx.doi.org/10.37544/0173-363x-2020-10-11-26.

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Nachhaltigkeit, Kreislaufwirtschaft, Green Deal – die Richtung, in die sich Wirtschaft und industrielle Produktion bewegen soll, ist eindeutig. Die industrielle Biotechnologie hätte dazu viel beizutragen. Dennoch finden viele Forschungsergebnisse nur sehr langsam oder gar nicht in den Markt. Woran liegt das, und wie kann man Abhilfe schaffen?

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Perez, E. G. A., M. Nichi, C. A. Baptista Sobrinho, P. A. A. Góes, A. Dalmazzo, J. R. Gurgel, C. C. Rocha, R. O. C. Silva, R. C. Barnabe, and V. H. Barnabe. "240 FUNCTIONAL TRAITS OF CAT SPERM DURING DISTINCT MATURATION STATUS." Reproduction, Fertility and Development 23, no. 1 (2011): 218. http://dx.doi.org/10.1071/rdv23n1ab240.

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Sperm recovery from the caudae epididymides can be advantageous for preserving semen of endangered animal species. In this context, the domestic cat is a suitable model for the study of sperm physiology in endangered feline species and the research on epididymal sperm preservation combined with the use of reproductive biotechnologies including intracytoplasmic sperm injection (ICSI). The aim of the present study was to examine the sperm collected from the cauda and caput of the cat epididymis using functional tests. Testicles and epididymides from 5 adult tomcats were collected by orchiectomy and maintained at 4°C for 4 h, until semen collection. Semen samples were collected from the epididymal tail and head by careful dissection. Samples were then analysed for motility by computer assisted sperm analysis (CASA; only for the caudal sperm). The 3-3′ diaminobenzidine stain was used as an index of mitochondrial activity, the eosin nigrosin stain as an index of membrane integrity, the simple stain (fast green/Bengal rose) as an index of acrosome integrity, and the measurement of thiobarbituric acid reactive substances (TBARS) as an index of lipid peroxidation. Statistical analysis was performed using the SAS System for Windows (SAS Institute Inc., Cary, NC, USA; least significant differences test and Spearman correlation; P < 0.05). No motility was observed in samples collected from the epididymal head, whereas samples from the tail showed 50.0 ± 4.2% motile spermatozoa. Surprisingly, more spermatozoa with high mitochondrial activity were found in the epididymal head than in samples from the tail (74.0 ± 3.5 v. 50.0 ± 4.3%, respectively). Similarly, samples collected from the head showed a higher susceptibility against the attack of ROS (31.9 ± 5.5 v. 16.3 ± 7.1 ng of TBARS/106 sperm, respectively). Furthermore, epididymal head sperm showed a lower percentage of sperm with intact membrane and a higher percentage of sperm with intact acrosome (44.9 ± 3.3 and 78.4 ± 1.8 v. 66.4 ± 4.2 and 56.7 ± 4.4%, respectively). Our results demonstrate that, during maturation, feline sperm are subjected to high oxidative stress, as shown by the lipid peroxidation assay, which would lead to structural damage to biomolecules, DNA, lipids, carbohydrates and proteins, as well as other cellular components, such as mitochondria, and acrosomal impairment. Similar results were found in humans, in which higher levels of oxidative stress occurred in the post-testicular environment. The plasma membrane seems to be more resistant to damages. This may be due to the described rearrangement in the lipid profile occurring during maturation, but studies to test this hypothesis are still underway.

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Gurgel, J. R. C., M. Nichi, E. G. A. Perez, P. A. A. Góes, A. Dalmazzo, R. O. C. Silva, C. C. Rocha, et al. "235 MANGALARGA STALLION SPERM IS HIGHLY SUSCEPTIBLE TO THE HYDROXYL RADICAL." Reproduction, Fertility and Development 23, no. 1 (2011): 216. http://dx.doi.org/10.1071/rdv23n1ab235.

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Анотація:

Mangalarga, due to its marching abilities, is the mostly widespread and numerous equine breed in Brazil. Furthermore, previous studies indicate that the semen of these horses is particularly susceptible to cryo-injuries. Therefore, the use of chilled semen is crucial when employing reproductive biotechnologies. However, previous studies indicate that chilled semen is highly impaired by the oxidative stress, which is caused by reactive oxygen species (ROS). An alternative to overcome the injuries caused by oxidative stress is antioxidant treatment, which requires the identification of those ROS that are the most deleterious. The aim of this study was to identify the most harmful ROS to Mangalarga sperm. Semen samples from 4 horses were collected, mixed with chilling media (Equimix®, Nutricell) and transported to the laboratory at 15°C. Samples were then incubated (1 h, 37°C) with 4 ROS inducing mechanisms: xanthine/xanthine oxidase (produces superoxide anion), hydrogen peroxide (4 mM), ascorbate and ferrous sulfate (4 mM; produces hydroxyl radical). Samples were analysed for motility using computer assisted sperm analysis (CASA). The 3-3′ diaminobenzidine stain was used as an index of mitochondrial activity, the eosin nigrosin stain as an index of membrane integrity, the simple stain (fast green/Bengal rose) as an index of acrosome integrity, sperm chromatin structure assay (SCSA) as an index of DNA fragmentation, and the measurement of thiobarbituric acid reactive substances (TBARS) an index of lipid peroxidation. Statistical analysis was performed using the SAS System for Windows (SAS Institute Inc., Cary, NC, USA; least significant differences test and Spearman correlation; P < 0.05). Results showed that Mangalarga sperm is highly susceptible to the hydroxyl radical. Samples treated with this ROS showed a lower percentage of sperm with high mitochondrial activity then samples treated with hydrogen peroxide (24.6 ± 5.9 v. 43.7 ± 6.8%, respectively). Similarly, lipid peroxidation (TBARS) was higher in samples treated with hydroxyl radical when compared with those treated with both superoxide anion and hydrogen peroxide (2037.7 ± 154.8, 681.2 ± 170.1, and 789.4 ± 124.5 ng/106 sperm). In addition, for all variables analysed using CASA except for ALH and BCF, samples treated with hydroxyl radical showed decreased quality when compared with the other samples. A positive correlation was found between TBARS and mitochondrial activity, indicating that the higher the sperm susceptibility of sperm against oxidative stress, the lower the mitochondrial activity. Level of TBARS also correlated negatively with most of the variables evaluated by CASA. The present results suggest that Mangalarga sperm is highly susceptible to the hydroxyl radical, a mechanism apparently related to the mitochondrial activity. Therefore, an alternative to overcome the deleterious influence of oxidative stress in semen of Mangalarga stallions would be the treatment with hydroxyl radical scavengers such as vitamins C and E, reduced glutathione, and other nonenzymatic antioxidants. The authors acknowledge Nutricell for the media used and CAPES for financial support.

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Silva, R. O. C., M. Nichi, E. G. A. Perez, P. A. A. Góes, A. Dalmazzo, J. R. C. Gurgel, C. C. Rocha, et al. "91 TREATMENT OF GOAT SPERM WITH CATALASE TO IMPROVE POST-THAW QUALITY." Reproduction, Fertility and Development 23, no. 1 (2011): 151. http://dx.doi.org/10.1071/rdv23n1ab91.

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Анотація:

Semen cryopreservation is extremely important to the use of reproductive biotechnologies in goats. However, studies indicate that cryopreservation may lead to increased oxidative stress which may cause structural damage to biomolecules, DNA, lipids, carbohydrates, and proteins, as well as other cellular components. Previous studies performed by our group indicate fresh goat sperm is highly susceptible to the attack of hydrogen peroxide. Therefore, the treatment with hydrogen peroxide scavengers would be an alternative to improve post-thaw sperm quality in goats. The aim of the present study was to evaluate the efficiency of catalase, an important hydrogen peroxide scavenger, to improve post-thaw quality in cryopreserved goat semen samples. Semen samples from 5 adult goats were collected and cryopreserved (Botu-Bov®, Biotech Ltda.). After thawing, samples were incubated (2 h, 37°C) with 0, 60, 120, and 240 UI mL–1 of catalase. Samples were then analysed for motility using the computer assisted sperm analysis (CASA); the 3–3′ diaminobenzidine stain, as an index of mitochondrial activity; the eosin nigrosin stain, as an index of membrane integrity; the simple stain (Fast green/Bengal rose), as an index of acrosome integrity; sperm chromatin structure assay, as an index of DNA fragmentation; and the measurement of thiobarbituric acid reactive substances (TBARS), as an index of lipid peroxidation. Statistical analysis was performed using the SAS System for Windows (SAS Institute Inc., Cary, NC, USA; least significant differences test and Spearman correlation; P < 0.05). Results showed that catalase treatment after thawing played a role on improving mitochondrial activity. Samples treated with 240 UI mL–1 showed lower percentage of sperm showing low mitochondrial activity when compared with samples treated with 0 and 120 UI mL–1 of catalase (6.5 ± 2.3, 17.2 ± 3.5, and 10.0 ± 1.3%, respectively). However, no effect of catalase was observed on any of the other variables studied. Results indicate that catalase, despite its beneficial effect on mitochondrial activity, does not influence positively on sperm quality after thawing. A hypothesis to explain such results would be that because of seminal plasma dilution with the extender, the antioxidants were also diluted. Therefore, the antioxidant protection would be impaired and the most deleterious reactive oxygen species, as observed in fresh semen, would also be different depending on the semen extender used because sperm are extremely dependent on the extracellular environment due to the reduced cytoplasm and the high content of polyunsaturated fatty acids in the membrane. A study performed by our group confirms such a hypothesis. Possibly, the treatment with catalase would be more effective if performed before cryopreservation. Also, it is possible that the use of different antioxidants would provide better results. Thanks to Nutricell for the media used and CAPES for financial support.

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Green, Damian J., Margot Pont, Blythe Duke Sather, Andrew J. Cowan, Cameron J. Turtle, Brian G. Till, Anne M. Nagengast, et al. "Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 1011. http://dx.doi.org/10.1182/blood-2018-99-117729.

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Abstract Background: Despite advances in the treatment of multiple myeloma (MM) almost all patients relapse and high risk features continue to portend a short median survival. The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in MM, but the durability of response has not been established. The infusion of genetically modified CD8+ and CD4+ T cells of a defined composition facilitates the evaluation of each subset's function and has contributed to reproducible efficacy and safety in clinical trials with CD19-specific CAR T cells. In this phase I first-in-human study employing a human scFv containing BCMA CAR T cell construct, we report rapid and deep objective responses at a low CAR T cell dose level (5 x 107) suggesting that construct specific features and differences in product formulation may substantially impact efficacy. Methods: Eligible patients had relapsed or treatment refractory MM, ≥10% CD138+ bone marrow (BM) plasma cells (PC), and ≥5% BCMA expression by flow cytometry (FC). Patients were stratified by tumor burden (CD138+ IHC) into two cohorts; 10-30% MM cells [cohort A] or >30% BM involvement [cohort B] to facilitate assessment of impact of disease burden on outcome. Eligible patient's CD8+ and CD4+ T cells were isolated via positive selection, enriched separately by immunomagnetic selection and cryopreserved. The CD8+ and CD4+ T cells were stimulated in independent cultures with anti-CD3/anti-CD28 paramagnetic beads and transduced with a 3rd generation lentiviral vector encoding a fully human BCMA scFv and 4-1BB and CD3 zeta signaling domains. After in vitro expansion, the cell product for infusion was formulated in a 1:1 ratio of CD4+:CD8+ BCMA CAR T cells. A truncated non-functional human epidermal growth factor receptor (EGFRt) was encoded in the transgene cassette to identify transduced T cells. Lymphodepleting chemotherapy preceded infusion of EGFRt+ CAR T cells at a starting dose of 5 x 107 EGFRt+ cells (n=5) for each cohort. Results: Seven patients (median age of 63 years; range 49 to 76) with a median of 8 prior regimens (range 6 to 11) have received treatment. The median %PC in BM (IHC) at enrollment was 58% (range 20% to >80%). In cohort B the dose has been escalated to 15 x107 EGFRt+ cells (n=2). All patients (7/7) had at least one high risk cytogenetic feature (17p- [n=4], t(4;14) [n=2], t(14;16) [n=1]), 71% had ≥ 2 high risk cytogenetic features, 71% had prior autologous stem cell transplant, 43% had prior allogeneic transplant, and one patient (14%) had PCL. The median involved free light chain (FLC) at enrollment was 180 mg/dL (range 40.37 to 502.96 mg/dL; n=5) and the median monoclonal protein was 3.8 g/dL (range 1.6 to 6.5 g/dL; n=5). The overall response rate at 28 days was 100%; at this time all evaluable patients (n=6) had no detectable abnormal BM PC clone by both IHC and high sensitivity FC. Within 28 days of treatment the involved FLC was normal or sub-normal in all patients and the M-protein had decreased by a median of 73% (range 56.25 to 83% reduction). BCMA CAR T cells remained detectable 90 days after infusion, representing up to 41.5 percent of CD3+ lymphocytes. All patients were surviving at a median of 16 wks (range 2 to 26 wks). One patient relapsed (day +60) and a tumor biopsy demonstrated the presence of a BCMAneg PC population, a 70% reduction in the fraction of MM cells expressing BCMA by FC and a fivefold reduction in BCMA antigen binding capacity on MM cells retaining target expression. A cytotoxic T lymphocyte response to the trans-gene product was not identified in this patient. No dose limiting toxicity has been observed during the 28 day monitoring window and treatment has been well tolerated with no cytokine release syndrome (CRS) observed in one patient and grade 2 or lower CRS (Lee Criteria) for all other patients. No neurological toxicity has been observed. Conclusion: BCMA CAR T cells harboring a fully human scFv with a defined composition of CD4+:CD8+ T cells were well tolerated and potent, demonstrating complete objective responses in heavily pretreated high-risk MM at total cell doses as low as 5 x 107. Next generation sequencing and multiparameter high sensitivity flow cytometry studies to evaluate for minimal residual disease are ongoing. Peak expansion levels and persistence of the CAR T cells are being monitored with early findings suggesting an absence of transgene product immunogenicity. Disclosures Green: Juno Therapeutics: Patents & Royalties, Research Funding. Sather:Juno Therapeutics: Employment. Cowan:Janssen: Research Funding; Abbvie: Research Funding; Juno Therapeutics: Research Funding; Sanofi: Research Funding. Turtle:Caribou Biosciences: Consultancy; Gilead: Consultancy; Bluebird Bio: Consultancy; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptevo: Consultancy; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Consultancy, Research Funding; Juno Therapeutics / Celgene: Consultancy, Patents & Royalties, Research Funding; Adaptive Biotechnologies: Consultancy. Till:Mustang Bio: Patents & Royalties, Research Funding. Becker:GlycoMimetics: Research Funding. Blake:Celgene: Employment, Equity Ownership. Works:Juno Therapeutics: Employment. Maloney:GlaxoSmithKline: Research Funding; Juno Therapeutics: Research Funding; Seattle Genetics: Honoraria; Roche/Genentech: Honoraria; Janssen Scientific Affairs: Honoraria. Riddell:Cell Medica: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Adaptive Biotechnologies: Consultancy; NOHLA: Consultancy.

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Montalban Bravo, Guillermo, Elias Jabbour, Tapan M. Kadia, Farhad Ravandi, Zeev E. Estrov, Kiran Naqvi, Koji Sasaki, et al. "Initial Results of a Phase 1 Dose Escalation Study of CPX-351 for Patients with Int-2 or High Risk IPSS Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) after Failure to Hypomethylating Agents." Blood 136, Supplement 1 (November 5, 2020): 1–3. http://dx.doi.org/10.1182/blood-2020-139942.

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INTRODUCTION: Hypomethylating agents (HMAs) are the standard of care of patients (pts) with higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). HMA failure is associated with poor outcomes, with a median survival of only 4 to 6 months. There are currently no effective standard therapies for these patients. Prior studies have shown that different combinations of purine analogues and cytarabine can be effective in patients with higher-risk MDS and CMML after HMA failure (HMA-F). CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of pts with newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with MDS related changes. Here we present the initial results of a phase I/II study of CPX-351 for high-risk MDS and CMML after HMA-F. METHODS: We designed a phase I/II clinical trial of CPX-351 for pts with MDS or CMML after HMA-F with Int-2 or High risk by IPSS, or Int-1 with >10% bone marrow blasts. The study included an initial phase 1 dose escalation portion, following a 3+3 design, followed by a phase 2 dose expansion portion. Dose escalation included 4 dose levels of CPX-351: 10 units/m2 (daunorubicin 4.4mg/m2 and cytarabine 10mg/m2), 25 units/m2 (daunorubicin 11mg/m2 and cytarabine 25mg/m2), 50 units/m2 (daunorubicin 22mg/m2 and cytarabine 50mg/m2) and 75 units/m2 (daunorubicin 33mg/m2 and cytarabine 75mg/m2). Therapy was administered intravenously on days 1, 3 and 5 of 28-day cycles during induction and on days 1 and 3 of re-induction or consolidation. In pts not achieving response after induction, the study allowed re-induction. The primary end point was to evaluate the safety and determine the maximum tolerated dose of CPX-351. Responses were evaluated following 2006 IWG criteria. The study included stopping rules for toxicity and futility. The Kaplan-Meir product-limit method was used to estimate survival. Overall survival was calculated from time of treatment start to last follow up or death. RESULTS: At the current data cut off of July 16th 2020 a total of 11 pts have been treated: 6 with MDS and 5 with CMML. Four (36%), 6 (55%) and 1 (9%) pts had Int-1 risk by IPSS with >10%, Int-2 or High risk by IPSS, respectively. Median age was 71 years (range 59-87) and 72% pts were male. Six (55%) pts had normal karyotype and 8 (72%) had high-risk mutations including ASXL1, RUNX1, EZH2 or RAS pathway mutations. Characteristics of pts are detailed in Figure 1A. The median number of prior therapies was 1 (range 1-4) with a median of 13 (range 5-26) cycles of prior HMA. Two patients had received prior therapy with venetoclax. No DLTs have been observed to date up to the maximum dose of 75 units/m2 of CPX-351. Median number of administered cycles of therapy is 1 (range 1-7). A total of 5 (45%) pts had non-hematological adverse events as detailed in Figure 1B. Eight-week mortality was 0%. All patients are evaluable for response with an overall response rate of 64% (n=7). Responses included mCR in all pts (Figure 1C) with one pt having achieved HI for <8 weeks. Two pts required re-induction prior to achieving mCR. The median response duration is 1.3 months (0-7.8 months). Two pts proceeded to allogeneic-stem-cell transplantation after achieving response to therapy. Three patients experienced transformation to AML: 2 after cycle 1 of therapy without prior response, and 1 after 1 month of having achieved mCR. Patient disposition is detailed in Figure 1D with time during study showed in green and continued follow up once off study in orange. With a median follow up of 3.8 months the median event-free survival is 2.4 months (range 0.9-3.9) and the median overall survival has not been reached. CONCLUSIONS: Preliminary data suggests lower doses of CPX-351 in higher-risk MDS and CMML after HMA failure can induce marrow responses with acceptable toxicity profile. Further follow up is required to determine response duration and survival benefit and to determine its potential role in HMA failure. Figure Disclosures Jabbour: Amgen: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding. Kadia:Pfizer: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Cellenkos: Research Funding; Amgen: Research Funding; Astra Zeneca: Research Funding; Incyte: Research Funding; Abbvie: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Astellas: Research Funding; Pulmotec: Research Funding; Ascentage: Research Funding; Cyclacel: Research Funding; Celgene: Research Funding; Novartis: Honoraria; BMS: Honoraria, Research Funding. Ravandi:BMS: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Orsenix: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding. Sasaki:Pfizer Japan: Consultancy; Otsuka: Honoraria; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Kantarjian:Novartis: Honoraria, Research Funding; Jazz: Research Funding; Immunogen: Research Funding; Aptitute Health: Honoraria; Pfizer: Honoraria, Research Funding; Ascentage: Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; BMS: Research Funding; Delta Fly: Honoraria; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Research Funding; Janssen: Honoraria; Oxford Biomedical: Honoraria; Sanofi: Research Funding; BioAscend: Honoraria; Amgen: Honoraria, Research Funding; Adaptive biotechnologies: Honoraria. Garcia-Manero:Merck: Research Funding; Jazz Pharmaceuticals: Consultancy; AbbVie: Honoraria, Research Funding; Novartis: Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Amphivena Therapeutics: Research Funding; H3 Biomedicine: Research Funding; Onconova: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria.

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Shadman, Mazyar, Cecilia Yeung, Mary Redman, Sang Yun Lee, Dong Hoon Lee, Susan Ra, Chaitra S. Ujjani, et al. "Safety and Efficacy of Third Generation CD20 Targeted CAR-T (MB-106) for Treatment of Relapsed/Refractory B-NHL and CLL." Blood 138, Supplement 1 (November 5, 2021): 3872. http://dx.doi.org/10.1182/blood-2021-149181.

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Abstract Background: Autologous CD19-targeting chimeric antigen receptor T cell (CAR-T) products are approved as standard treatment options for patients (pts) with relapsed diffuse large cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). Their long-term efficacy for DLBCL is ~40% and is unknown for other histologies. Additionally, associated toxicities including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain a challenge. CD20 is a proven target for treatment of B-NHLs/CLL with demonstrated high clinical efficacy of unmodified, radiolabeled, and bispecific antibodies. Therefore, CD20-targeted CAR-T represents a promising adoptive immunotherapy option that could be utilized to treat relapsed/refractory (R/R) B-NHLs and CLL. MB-106 is a fully human 3rd-generation CD20-targeted CAR-T product with both 4-1BB and CD28 costimulatory domains. We present results of our ongoing phase I/II clinical trial investigating safety and efficacy of CD20 CAR-T for high-risk B-NHLs and CLL (NCT03277729). Methods: Pts with R/R CD20+ B-cell malignancies are eligible, including but not limited to DLBCL, FL, MCL, and CLL. Prior treatment with CD19 CAR-T is permitted. Lymphodepletion (LD) consists of cyclophosphamide (Cy) ± fludarabine (Flu). CAR-T cells are administered at one of 4 dose levels (DL): DL1: 3.3x10 5, DL2: 1x10 6, DL3: 3.3x10 6, DL4: 1x10 7 CAR T cells/kg. A continual reassessment method dose escalation design was used to find the maximally tolerated dose. CAR-T is infused in the outpatient setting except for the first pt of each dose cohort (overnight observation). Treatment response is assessed on day 28. CRS and ICANS are graded per ASTCT consensus grading. The study underwent a major cell manufacturing modification after treating 7 pts with no objective responses as previously reported (Shadman, ASH 2020, #1443). This abstract includes pts who were treated under the modified process. Results: Between Dec 2019 and July 2021, 16 pts (12 FL, 2 MCL, 1 CLL, 1 DLBCL) were treated after LD with Cy-Flu and had day 28 assessment. All DLs were reached (see table), with no dose-limiting toxicities to date. CRS occurred in 7 pts (44%): 4 pts with grade (Gr) 1 and 3 with Gr 2. ICANS was observed in 1 pt (6.2%) at Gr 2. There were no Gr 3 or Gr 4 CRS or ICANS. Median time to CRS was 6.5 days (range, 0-12); the 1 ICANS event occurred on day 12. One pt (CLL) developed Gr 3 temporary neuropathic pain which, in the absence of other explanation, was attributed to the CAR-T. No pts had tumor lysis syndrome or Gr 3-4 infections. Thrombocytopenia (Gr 3-4: 19%) and neutropenia (Gr 3-4: 94%) were common but there were no bleeding complications, and the rate of febrile neutropenia was 19%. Overall response (ORR) was 94% (15/16) with complete response (CR) rate of 62% (10/16). In FL pts (n =12), ORR was 92% (11/12) and CR rate was 75% (9/12). Among FL pts who received DL 3 or 4, the CR rate was 86%. The CLL pt had a PET-negative CR and undetectable measurable residual disease in peripheral blood and bone marrow by flow cytometry (10 -4) (uMRD4) on day 28. The pt with DLBCL achieved a partial response (PR) on day 28 and a repeat PET on day ~ 90 showed continued improvement but still indicating a PR. Among pts who achieved a CR, only one pt (FL) relapsed after 9 months. All other CRs are ongoing (range: 3-18 months). CAR-T persistence was lost at day 95 in 1 pt who had progression and proceeded to other anti-lymphoma treatment; 2 other patients lost CAR-T engraftment by day 181 and 201 with B cell recovery. All other patients continue to have detectable CAR-T cells as of last follow-up (max 13 months post-infusion). Conclusion: Treatment with MB-106 shows a favorable safety profile with no Gr 3 or Gr 4 CRS or ICANS. In addition, we observed a high rate of ORR and CR with ongoing CRs and high rate of CAR-T persistence. Enrollment is currently ongoing; data will be updated at the time of presentation. Figure 1 Figure 1. Disclosures Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy. Yeung: Merck,Celgene: Consultancy. Ujjani: ACDT: Honoraria; Gilead: Honoraria; TG Therapeutics: Honoraria; Janssen: Consultancy; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Atara Bio: Consultancy; Loxo: Research Funding; Adaptive Biotechnologies: Research Funding; Kite, a Gilead Company: Honoraria; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Dezube: Mustang Bio: Current Employment, Current holder of individual stocks in a privately-held company. Poh: Acrotech: Honoraria; Incyte: Research Funding; Morphosys: Consultancy. Chapuis: Karkinos Therapeutics: Other: Ownership; Lonza: Other: Intellectual Property; Cullian: Other: Intellectual Property; TScan Therapeutics, Inc.: Consultancy, Other: Ownership; SignalOne Bio: Consultancy, Other: Ownership; Bluebird bio: Other: Intellectual Property; Juno therapeutics: Other: Intellectual Property; Adapyive Biotechnologies Corporation: Other: Ownership/Intellectual Property; Pfizer: Other: Intellectual Property; Affini-T: Other: Ownership; Ridgeline: Consultancy; BioNTech: Consultancy. Green: Seagen Inc.: Research Funding; bristol myers squibb: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Cellectar Biosciences: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen Biotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Patents & Royalties, Research Funding; Legend Biotech: Consultancy; Neoleukin Therapeutics: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SpringWorks Therapeutics: Research Funding. Cowan: Abbvie: Consultancy, Research Funding; Harpoon: Research Funding; Janssen: Consultancy, Research Funding; Sanofi Aventis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Nektar: Research Funding; GSK: Consultancy; Secura Bio: Consultancy; Cellectar: Consultancy. Cassaday: Amgen: Consultancy, Research Funding; Servier: Research Funding; Vanda Pharmaceuticals: Research Funding; Pfizer: Consultancy, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Pepromene Bio: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding. Kiem: Homology Medicines: Consultancy; VOR Biopharma: Consultancy; Ensoma Inc.: Consultancy, Current holder of individual stocks in a privately-held company. Gauthier: Janssen: Membership on an entity's Board of Directors or advisory committees; Multerra Bio: Consultancy; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Larvol: Consultancy; JMP: Consultancy; Eusapharma: Consultancy. Turtle: T-CURX: Other: Scientific Advisory Board; Century Therapeutics: Consultancy, Other: Scientific Advisory Board; Arsenal Bio: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Eureka Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Nektar Therapeutics: Consultancy, Research Funding; Precision Biosciences: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Caribou Biosciences: Consultancy, Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Juno Therapeutics/BMS: Patents & Royalties: Right to receive royalties from Fred Hutch for patents licensed to Juno Therapeutics, Research Funding; AstraZeneca: Consultancy, Research Funding; Myeloid Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Asher Bio: Consultancy; Amgen: Consultancy; PACT Pharma: Consultancy; TCR2 Therapeutics: Research Funding; Allogene: Consultancy. Lynch: TG Therapeutics: Research Funding; Bayer: Research Funding; Incyte: Research Funding; Juno Therapetics: Research Funding; Morphosys: Consultancy; Genentech: Research Funding; SeaGen: Research Funding; Cyteir: Research Funding. Smith: Portola Pharmaceuticals: Research Funding; Acerta Pharma BV: Research Funding; ADC Therapeutics: Consultancy; Incyte Corporation: Research Funding; AstraZeneca: Consultancy, Research Funding; Incyte: Consultancy; Ayala (spouse): Research Funding; Merck Sharp & Dohme Corp: Research Funding; Bristol Myers Squibb (spouse): Research Funding; De Novo Biopharma: Research Funding; Ignyta (spouse): Research Funding; KITE pharm: Consultancy; Millenium/Takeda: Consultancy; Bayer: Research Funding; Karyopharm: Consultancy; Beigene: Consultancy, Research Funding; Genentech: Research Funding. Gopal: Gilead: Consultancy, Honoraria, Research Funding; Genetech: Consultancy, Honoraria, Research Funding; SeaGen: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Research Funding; Bristol Meyers Squibb: Research Funding; Agios: Research Funding; MorphoSys: Honoraria; IGM Biosciences: Research Funding; ADC Therapeutics: Consultancy, Honoraria; Acrotech: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Nurix Inc: Consultancy, Honoraria; Takeda: Research Funding; Teva: Research Funding; I-Mab bio: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Incyte: Honoraria; Beigene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Cellectar: Consultancy, Honoraria. Maloney: BioLineRx, Juno, Celgene, Kite, a Gilead Company, Gilead, Novartis, and Pharmacyclics: Honoraria; A2 Biotherapeutics: Consultancy; Kite, a Gilead Company, Juno, and Celgene: Research Funding; Juno: Patents & Royalties; A2 Biotherapeutics: Divested equity in a private or publicly-traded company in the past 24 months. Till: Mustang Bio: Consultancy, Patents & Royalties, Research Funding.

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Gavrilov, V., T. Antipova, Y. Vlasov, S. Ardatov, and A. Ardatova. "METHOD OF TELEPORTATION BASED ON NATURE-LIKE USING OF BIOLOGICAL OBJECTS." ASJ 1, no. 48 (May 14, 2021): 4–17. http://dx.doi.org/10.31618/asj.2707-9864.2021.1.48.93.

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SEFER hA MINAGIM, p. 574 (photo 1), on behalf of an older book, writes that according to Jewish tradition, the navel does not close completely after childbirth, but remains partially open to extract various infections from the body. "From the "greenness" called "gable- zaht" (דזשאָנדַאַס איז קרענק די – disease jaundice), he will take a male pigeon for a man, and a dove for a woman; and put it on the navel, and the pigeon (dove), having drained all the infection from it (the patient), will die. Well-known veterinarian, Dr. Yekutiel Sharabi, owner of an elite veterinary clinic in Northern Tel Aviv, studied the causes of pigeon death after such a session. He found that immediately after treatment with pigeons, the patient's blood bilirubin level decreases by 25%, and recovery lasts an average of 3 days (as opposed to 28 days with conventional treatment). Autopsies of pigeons that died after the session showed liver enlargement and dysfunction. If the session was applied to a healthy person, not a single pigeon died. [1] In this paper, we consider a heuristic method for using quantum teleportation protocols in convergent dualuse biotechnologies based on new physical principles of operation [1-80]. The features of these biotechnologies will be considered within the framework of the possibilities of convalescence of pathological conditions (for example, nosological form: liver damage (lat. jecur, jecor, hepar, etc. - Greek ἧπαρ) by the hepatitis "C" virus (non-A, non-B hepatitis, or NANBH, or HCV infection). A hypothetical convalescence technology can be implemented by preparing cascades of entangled states of biological objects. In fact, this paper implies a certain information exchange in the planet's biogeosphere, hypotheses, protocols, and schemes for implementing these mechanisms based on new physical principles of action (NFP) [1-80].

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Cairns, Timothy C., Xiaomei Zheng, Ping Zheng, Jibin Sun, and Vera Meyer. "Turning Inside Out: Filamentous Fungal Secretion and Its Applications in Biotechnology, Agriculture, and the Clinic." Journal of Fungi 7, no. 7 (July 2, 2021): 535. http://dx.doi.org/10.3390/jof7070535.

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Filamentous fungi are found in virtually every marine and terrestrial habitat. Vital to this success is their ability to secrete a diverse range of molecules, including hydrolytic enzymes, organic acids, and small molecular weight natural products. Industrial biotechnologists have successfully harnessed and re-engineered the secretory capacity of dozens of filamentous fungal species to make a diverse portfolio of useful molecules. The study of fungal secretion outside fermenters, e.g., during host infection or in mixed microbial communities, has also led to the development of novel and emerging technological breakthroughs, ranging from ultra-sensitive biosensors of fungal disease to the efficient bioremediation of polluted environments. In this review, we consider filamentous fungal secretion across multiple disciplinary boundaries (e.g., white, green, and red biotechnology) and product classes (protein, organic acid, and secondary metabolite). We summarize the mechanistic understanding for how various molecules are secreted and present numerous applications for extracellular products. Additionally, we discuss how the control of secretory pathways and the polar growth of filamentous hyphae can be utilized in diverse settings, including industrial biotechnology, agriculture, and the clinic.

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Cowan, Andrew J., Margot Pont, Blythe Duke Sather, Cameron J. Turtle, Brian G. Till, Edward Libby, David G. Coffey, et al. "Safety and Efficacy of Fully Human BCMA CAR T Cells in Combination with a Gamma Secretase Inhibitor to Increase BCMA Surface Expression in Patients with Relapsed or Refractory Multiple Myeloma." Blood 138, Supplement 1 (November 5, 2021): 551. http://dx.doi.org/10.1182/blood-2021-154170.

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Abstract Background: Chimeric antigen receptor T cells (CAR T cells) targeting B cell maturation antigen (BCMA) have demonstrated rapid and deep responses among patients with multi-agent refractory multiple myeloma (MM). BCMA is shed from tumor cells mediated through enzymatic cleavage by the gamma secretase complex, and tumor cells with low levels of BCMA could potentially escape CAR T recognition. We showed previously that gamma secretase inhibitors (GSI) increase BCMA surface density on tumor cells, decrease soluble BCMA levels, and enhance efficacy of BCMA CAR T cells in an immunodeficient mouse model. We have completed accrual to a phase 1 first-in-human trial of escalating doses of BCMA targeted CAR T cells in combination with a GSI (JSMD194) for patients with relapsed or refractory multiple myeloma, and herein report results on the 18 patients accrued to this trial. Methods: Eligible patients had relapsed/refractory MM, with ≥ 10% plasma cells in the bone marrow by CD138 IHC, and measurable disease. CD8+ and CD4+ T cells were enriched by To assess the discrete impact of the GSI on plasma cell BCMA expression, patients received a GSI (JSMD194) monotherapy "run-in" consisting of three oral doses (25 mg) administered 48 hours apart over 5 days. A bone marrow sample was obtained on day 5 and BCMA expression was compared to baseline. Following lymphodepleting chemotherapy, BCMA CAR T cells were infused at a starting dose of 5 x 10 7 CAR+ cells, in combination with JSMD194 dosed orally at 25 mg thrice weekly for three weeks, starting on the day of CAR infusion. Results: From June 2018 to March 2021, 18 patients underwent leukapheresis, run-in with JSMD194, and treatment with BCMA CAR T cells. The median age was 65 years, and patients had received a median of 10 prior lines of therapy (range, 4-19). 67% of patients were refractory to lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab, 72% had high-risk cytogenetic features, and 28% had extramedullary disease. 7/18 (39%) had prior BCMA targeted therapy; other BCMA targeted CAR T cell products had previously been administered to 4/18 patients (22%). All 18 treated patients completed the 5-day run-in with JSMD194. After three oral doses of GSI, increased from a median of 610 to 9563 receptors per cell, or a median of 12-fold (range, 0.2-fold to 157-fold; Figure 1). The only patient that did not demonstrate an increase in BCMA ABC after GSI run-in had previously received BCMA targeted therapy and BCMA expression at screening was virtually absent. 5 patients were treated at 5x10 7 CAR+ cells, 3 were treated at 15x10 7 CAR+ cells, 3 were treated at 30x10 7 CAR+ cells, and 7 were treated at 45x10 7 CAR+ cells dose levels. Treatment was consistent with other BCMA CAR T therapy, with manageable toxicities. One patient experienced a DLT. 95% of patients experienced cytokine release syndrome (CRS), mostly grade 1-2 (83%), and 66% of patients experienced ICANS, predominantly grades 1-2. The overall response rate was 89%, with 14 patients achieving ≥ VGPR, and 8 patients achieving CR (including 5 with sCR). Deep responses were observed at all dose levels; including the first patient treated on trial at (dose level 1) who has maintained a stringent CR (sCR) for over 35 months and 3 of 5 patients at dose level 1 had no evidence of progressive disease for >18 months. With a median follow-up of 20 months, the median PFS is 11 months (95% CI, 6 mos to not reached). Amongst patients without prior exposure to BCMA targeted therapy (n=11), the median PFS has not been reached, while amongst those previously exposed to BCMA targeted therapy (n=7), the median PFS was 2 months. Discussion: In this study combining a GSI with BCMA CAR T cells, we have demonstrated that the combination is safe and tolerable. GSI administration routinely increased BCMA surface density on plasma cells. Further, we have observed durable, rapid responses in a heavily pretreated refractory population of MM patients, of whom a significant proportion had prior treatment with BCMA targeted therapy and CAR T therapy. The combination of BCMA CAR T and GSI may augment anti-tumor activity, even when very low doses of BCMA CAR T cells are administered. Figure 1 Figure 1. Disclosures Cowan: Harpoon: Research Funding; Secura Bio: Consultancy; Sanofi Aventis: Consultancy, Research Funding; GSK: Consultancy; Abbvie: Consultancy, Research Funding; Nektar: Research Funding; Cellectar: Consultancy; Bristol Myers Squibb: Research Funding; Janssen: Consultancy, Research Funding. Pont: Lyell Immunopharma: Other: Has equity interest; SpringWorks Therapeutics: Other: Received consulting income; CellPoint B.V.: Current Employment. Sather: Lyell Immunopharma: Current Employment. Turtle: Arsenal Bio: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; PACT Pharma: Consultancy; Amgen: Consultancy; Eureka Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; AstraZeneca: Consultancy, Research Funding; Juno Therapeutics/BMS: Patents & Royalties: Right to receive royalties from Fred Hutch for patents licensed to Juno Therapeutics, Research Funding; Myeloid Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; TCR2 Therapeutics: Research Funding; T-CURX: Other: Scientific Advisory Board; Asher Bio: Consultancy; Allogene: Consultancy; Century Therapeutics: Consultancy, Other: Scientific Advisory Board; Nektar Therapeutics: Consultancy, Research Funding; Precision Biosciences: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Caribou Biosciences: Consultancy, Current holder of stock options in a privately-held company, Other: Scientific Advisory Board. Till: Mustang Bio: Consultancy, Patents & Royalties, Research Funding. Libby: GSK: Research Funding; Janssen: Consultancy, Research Funding; BMS: Research Funding; Genentech: Research Funding. Tuazon: BMS: Current Employment. Shadman: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding. Chapuis: Karkinos Therapeutics: Other: Ownership; Lonza: Other: Intellectual Property; Cullian: Other: Intellectual Property; TScan Therapeutics, Inc.: Consultancy, Other: Ownership; SignalOne Bio: Consultancy, Other: Ownership; Bluebird bio: Other: Intellectual Property; Juno therapeutics: Other: Intellectual Property; Adapyive Biotechnologies Corporation: Other: Ownership/Intellectual Property; Pfizer: Other: Intellectual Property; Affini-T: Other: Ownership; Ridgeline: Consultancy; BioNTech: Consultancy. Maloney: MorphoSys: Honoraria; Genentech: Honoraria; Navan Technologies: Honoraria, Other: Stock options; Celgene: Honoraria, Other: Rights to royalties from Fred Hutchinson Cancer Research Center for patents licensed to Juno Therapeutics/Bristol Myers Squibb; Novartis: Honoraria; Kite Pharma: Honoraria, Other: Research funding was paid to my institution, Research Funding; Juno therapeutics: Other: Research funding was paid to my institution, Research Funding; Celgene: Other: Research funding was paid to my institution, Research Funding; Amgen: Honoraria; BMS: Honoraria, Other: Rights to royalties from Fred Hutchinson Cancer Research Center for patents licensed to Juno Therapeutics/Bristol Myers Squibb; Juno Therapeutics: Honoraria, Other: Rights to royalties from Fred Hutchinson Cancer Research Center for patents licensed to Juno Therapeutics/Bristol Myers Squibb; Umoja: Honoraria; Legend Biotech: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options; Janssen: Honoraria. Riddell: Lyell Immunopharma: Other. Green: Seagen Inc.: Research Funding; bristol myers squibb: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Cellectar Biosciences: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen Biotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Patents & Royalties, Research Funding; Legend Biotech: Consultancy; Neoleukin Therapeutics: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SpringWorks Therapeutics: Research Funding. OffLabel Disclosure: JSMD194 - an oral gamma secretase inhibitor

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Zielińska, Elżbieta, Krystyna Matusiak-Mikulin, Krzysztof Grabski, Anna Heda, Aleksandra Krzykowska, and Zbigniew Tukaj. "Growth Improvement of Nicotiana and Arabidopsis In Vitro by Microalgal Conditioned Media." Acta Biologica Cracoviensia s. Botanica 56, no. 2 (March 1, 2015): 91–97. http://dx.doi.org/10.2478/abcsb-2014-0029.

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Abstract Conditioned medium (CM) is a general term describing media in which cells have already been cultivated for some time. Such media, usually clarified by filtration, have been used by plant biotechnologists as additives sup-porting the growth of cell suspensions, organs and whole plants. This study examined the effect of CM obtained from green alga Desmodesmus subspicatus on the growth and functioning of the photosynthetic apparatus of Nicotiana tabacum and Arabidopsis thaliana in culture in vitro. Plants where cultured on CM diluted 1.25-, 2-and 5-fold with MS medium. The increase in fresh and dry weight was highest in tobacco and Arabidopsis cultured on CM/2 and CM/1.25 media. Those two concentrations also increased the amount of chlorophylls in both plants tested. CM improved parameter PI (reflecting the photosynthetic “vitality” of the organism) and electron transport efficiency, and increased the fraction of active reaction centers. Analysis of chlorophyll fluorescence in vivo suggests that the improvement of these plants grown in the presence of algal CM may result from stimulation of photosynthesis. Algal CM offers a convenient, cheap, universal supplement for stimulating the growth of higher plants in vitro.

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46

Green, Damian J., Margot Pont, Andrew J. Cowan, Gabriel O. Cole, Blythe Duke Sather, Anne M. Nagengast, Xaoling Song, et al. "Response to Bcma CAR-T Cells Correlates with Pretreatment Target Antigen Density and Is Improved By Small Molecule Inhibition of Gamma Secretase." Blood 134, Supplement_1 (November 13, 2019): 1856. http://dx.doi.org/10.1182/blood-2019-129582.

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Introduction: The adoptive transfer of B-Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T cells is demonstrating early promise in multiple myeloma [MM], however durable responses remain elusive and most studies report >50% of patients relapsing within 18 months of receiving CAR-T cell therapy. The mechanism of relapse is likely the consequence of multiple factors including the variable distribution of BCMA on tumor cells, allowing cells with low antigen density to escape. Initial target density, receptor downregulation and the emergence of antigen loss variants have all been implicated in relapse following CAR-T cells directed against CD22 and CD19. Reduced or absent BCMA expression may similarly be linked to relapse in MM. We have previously demonstrated that BCMA cleavage by the γ-secretase complex reduces ligand density for CAR-T cell recognition, and that a small molecule γ-secretase inhibitor (GSI) markedly increases surface BCMA levels in a dose-dependent fashion while improving CAR-T cell recognition in preclinical models. Methods and Results: In a phase I first-in-human study (NCT03338972) employing a CAR-T cell construct encoding a fully human BCMA scFv and 4-1BB/CD3z, rapid and deep objective responses at CAR-T cell doses starting at 5 x 107 have been observed. All patients had bone marrow (BM) involvement at baseline (mean 42.5 % CD138+ by IHC) and 14/15 had no detectable disease in the BM 28 days after therapy. One patient with comparatively very low BCMA expression (BCMA antibody binding capacity [ABC; QuantiBRITE] = 269; 16.9% of the malignant plasma cells (PCs) BCMA+ by flow cytometry) was the only subject with persistent tumor cells in the BM 28 days after therapy. Despite complete BM responses in all remaining patients, late relapses have occurred. Differences in the BCMA expression level on tumor cells prior to CAR-T cells between long term responders and those with relapse are evident. Among the 12 subjects with at least 3 months of follow up, those remaining in remission (median 12 months, range 3-16; data cut off 7/15/19) demonstrated a median pre-treatment BCMA ABC of 1761 (range 781-2922, n=5), in contrast patients with relapse (mean of 7.3 months, range 2-12) had a median pre-treatment BCMA ABC of 920 (range 260-1540, n=7). Six patients with a pretreatment mean ABC of 919 (range 260-1540) had BM evaluable for BCMA expression at relapse and the mean ABC decreased to 304 (range 121-519). The percent PCs expressing BCMA decreased from 77.5% (range 13 - 99.8) to 30% (range 10.4-60.4). The impact of gamma secretase inhibition on BCMA expression was assessed on BM cells obtained from a patient relapsing after BCMA CAR-T cells. At relapse a 9.5-fold decrease in ABC from baseline was observed. The cells were cultured for 5 hours in the presence of GSI (JSMD194) at a concentration of 1mM, which is readily achievable by oral administration. A significant increase in BCMA antigen expression was observed (ABC=917). The impact of modulating BCMA expression on tumor cells by concurrently administering an oral GSI with CAR-T cells is being explored in a phase one clinical trial (NCT03502577). In this setting, the GSI has increased BCMA expression when low level residual BCMA was observed following relapse after prior BCMA therapy failure. Two patients have been evaluated for response to an JSMD194 after failing other BCMA targeted agents. One received a prior BCMA CAR-T cell product and after relapse demonstrated a BCMA ABC of 769. Target expression increased in this patient almost nine-fold to 6828 (ABC) after three oral doses of JSMD194. A second patient had a BCMA ABC of 666 after failing a BCMA bispecific T cell engager. BCMA density increased over 14-fold to 9583 after GSI. Comprehensive data from the combination GSI and BCMA CAR-T cell trial are being reported separately. Conclusion: Pretreatment BCMA target density quantified with a uniform flow cytometry method of measurement and performed on all patients enrolled on a single center BCMA CAR-T cell clinical trial is associated with the durability of response. Further, BCMA expression can be significantly increased following GSI exposure in patients evidencing low BCMA ABC at baseline or when downregulation is the consequence of prior BCMA targeting therapy. The capacity for GSIs to increase BCMA target density and decrease soluble BCMA levels is a promising approach to be exploited in clinical trials. Disclosures Green: Juno Therapeutics: Consultancy, Patents & Royalties, Research Funding; Celgene: Consultancy; GSK: Consultancy; Seattle Genetics: Research Funding; Cellectar: Research Funding. Pont:Fred Hutchinson Cancer Research Center: Other: Inventor on a patent. Cowan:Sanofi: Consultancy; Juno: Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellectar: Consultancy. Sather:Lyell Immunopharma: Employment, Equity Ownership. Blake:Celgene: Employment, Equity Ownership. Works:Celgene: Employment, Equity Ownership. Maloney:Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; A2 Biotherapeutics: Honoraria, Other: Stock options ; BioLine RX, Gilead,Genentech,Novartis: Honoraria; Celgene,Kite Pharma: Honoraria, Research Funding. Riddell:Juno Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Adaptive Biotechnologies: Consultancy; Lyell Immunopharma: Equity Ownership, Patents & Royalties, Research Funding. OffLabel Disclosure: Oral Gamma Secretase Inhibitor. Purpose is to increase expression of B Cell Maturation Antigen

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47

Gensheimer, Kathleen F. "A Public Health Perspective on Child Care." Pediatrics 94, no. 6 (December 1, 1994): 1116–18. http://dx.doi.org/10.1542/peds.94.6.1116.

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A child care provider is the mother of young life. She nourishes the children, brings them up—gives them energy, her resources, her nerve and all the possibilities to come true—when needed or ready. To not pay her a decent wage is undervaluing the care. To over-regulate her can decrease the supply and raise the cost. To under-regulate her can harm the quality. To zone her out of residential neighborhoods does not fit in a society that "values" children. And yet, all these misdeeds are committed state-wide. Nobody is made really and effectively responsible. Yet we all are! That's why the misdeeds can go on and even increase. Collective responsibility is hidden by our ignorance and greed. At present we live in a world out of balance. We work with no support for family and child care needs. We live lives of turmoil because of a system unable to care. We live lives that call for another way of living. Can biotechnologists build a child who requires less nurturing, less loving? or Can we foster conditions that help, rather than hurt, families using child care? It will oblige all of us to assign a new value to families, children and child care. It will oblige us to establish a strong public policy so that children and child care are valued as more than a mere "life style" option.1 On a personal level, as a mother of four young children and as a consumer of child-care services, I can well relate to the issue of child care.

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48

Smadbeck, James B., Neeraj Sharma, Nadine Abdallah, Hongwei Tang, Moritz Binder, Rafael Fonseca, P. Leif Bergsagel, et al. "Characterization of Atypical t(11;14) CCND1/IGH Translocations in Multiple Myeloma." Blood 138, Supplement 1 (November 5, 2021): 3771. http://dx.doi.org/10.1182/blood-2021-150569.

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Abstract Purpose: Multiple myeloma (MM) is a plasma cell malignancy characterized by a collection of cytogenetic abnormalities that drive clinical presentation, response to treatment, and prognosis. The most common immunoglobulin heavy chain (IGH) translocation found in MM, t(11;14), results in CCND1 overexpression. Although t(11;14) is considered a standard risk cytogenetic abnormality, heterogeneity in patient outcomes and response to therapy within the t(11;14) group has been reported. In contrast to t(11;14) mantle cell lymphoma, where most cases (73%) have a typical, balanced t(11;14) rearrangement, only 47% of t(11;14) MM have a typical, balanced t(11;14) FISH pattern; the remaining 53% of MM are characterized by an atypical t(11;14) FISH result (Dalland, Genes Chromosomes Cancer, 2021). Here, we compared the genetic characteristics of typical vs. atypical t(11;14) MM and the association with other genomic abnormalities, CCND1 expression, IGH breakpoint location and patient outcomes. Methods: We performed a retrospective study of newly diagnosed t(11;14) MM patients seen at Mayo Clinic (N=411) or enrolled in the MMRF CoMMpass trial (N=167). The t(11;14) FISH results of the Mayo Clinic samples were segmented into two groups: typical CCND1/IGH signal pattern (n=179, 3 red, 3 green, 2 fusion signals) and atypical CCND1/IGH signal pattern (n=232, any FISH pattern deviating from typical). The CoMMpass cases had both RNAseq and long-insert WGS data and were analyzed to detect gene expression, structural and copy number variants and IGH breakpoint locations. These data were used to classify the t(11;14) as typical (n=63) or atypical (n=104) and whether there was a single t(11;14) fusion (n=107) or a gain of the t(11;14) fusion (n=60), and whether these cases were associated with changes in gene expression or breakpoint location. Differences between the groups were measured using χ2 and Wilcoxon tests. Survival curves were estimated using Kaplan Meier and compared using the Log-Rank test. Statistical significance was determined at p<0.05. Results: Of the Mayo t(11;14) cohort, 232/411 (56%) had an atypical t(11;14) FISH pattern and 179/411 (44%) had a typical t(11;14) FISH pattern. Although an atypical t(11;14) FISH pattern was not significantly associated with monosomy 17/17p deletion, MYC rearrangements, 1q gain or ISS stage III, it was significantly associated with the presence of any trisomy in comparison to typical t(11;14) cases (40/222=18% vs.12/166=7%, p=0.002). Atypical t(11;14) cases had an increase in CCND1 gene expression compared to typical t(11;14) cases (median 375.0 RPKM vs. 266.4 RPKM, p<0.0001) and cases with a gain of the t(11;14) fusion were associated with even greater CCND1 expression compared to cases with a single t(11;14) fusion (median 459.4 RPKM vs. 263.2 RPKM, p<0.0001). We next evaluated whether the t(11:14) FISH pattern was associated with differences in IGH breakpoint locations. Nearly 80.0% of atypical t(11;14) cases had a breakpoint within the constant region of the IGH locus commonly reported for MM, while only 61.0% of the typical cases had constant region breakpoints (p=0.035); the remaining cases had breakpoints involving the VDJ region. We next evaluated the impact of atypical t(11;14) FISH on OS. In Mayo cases, OS was significantly shorter in patients with atypical FISH patterns compared to typical t(11;14) FISH patterns (6.9 years [95% CI: 5.1-7.8] vs. 9.0 years [95% CI: 7.0-11.6], p=0.019). Although atypical t(11;14) was associated with increased risk of death (RR 1.45, p=0.021), this finding was not retained in a multivariate model including high risk abnormalities such as age, ISS stage, 17p deletion and 1q gain demonstrating atypical t(11;14) is not an independent predictor of poor outcome when treated with standard therapies. Conclusions: Atypical t(11;14) FISH in MM is found in approximately half of t(11;14) cases, is associated with trisomies, higher CCND1 expression and is more likely to have a breakpoint involving the constant region of the IGH locus. The enrichment of VDJ breakpoints within typical t(11;14) MM is consistent with enrichment of VDJ IGH breakpoints in MCL, which are mostly characterized by typical t(11;14) FISH patterns. While not an independent predictor of outcome with standard therapies, it remains to be evaluated whether patients with typical or atypical t(11;14) have a differential response to novel agents, such as venetoclax. Disclosures Fonseca: Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; AbbVie: Consultancy; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; Mayo Clinic in Arizona: Current Employment; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Bergsagel: Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Genetech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: human CRBN mouse. Kumar: Merck: Research Funding; Carsgen: Research Funding; Roche-Genentech: Consultancy, Research Funding; Beigene: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Sanofi: Research Funding.

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49

Alimuddin, G. Yoshizaki, and O. Carman. "Rapid method for identification of transgenic fish zygosity." Jurnal Akuakultur Indonesia 6, no. 2 (July 1, 2007): 177. http://dx.doi.org/10.19027/jai.6.177-182.

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Identification of zygosity in transgenik fish is normally achieved by PCR analysis with genomic DNA template extracted from the tissue of progenies which are derived by mating the transgenic fish and wild-type counterpart. This method needs relatively large amounts of fish material and is time- and labor-intensive. New approaches addressing this problem could be of great help for fish biotechnologists. In this experiment, we applied a quantitative real-time PCR (qr-PCR) method to analyze zygosity in a stable line of transgenic zebrafish (Danio rerio) carrying masu salmon, Oncorhynchus masou D6-desaturase-like gene. The qr-PCR was performed using iQ SYBR Green Supermix in the iCycler iQ Real-time PCR Detection System (Bio-Rad Laboratories, USA). Data were analyzed using the comparative cycle threshold method. The results demonstrated a clear-cut identification of all transgenic fish (n=20) classified as a homozygous or heterozygous. Mating of those fish with wild-type had revealed transgene transmission to the offspring following expected Mendelian laws. Thus, we found that the qTR-PCR to be effective for a rapid and precise determination of zygosity in transgenic fish. This technique could be useful in the establishment of breeding programs for mass transgenic fish production and in experiments in which zygosity effect could have a functional impact. Keywords: quantitative real-time PCR; zygosity; transgenic fish; mass production ABSTRAK Identifikasi sigositas ikan transgenik biasanya dilakukan menggunakan analisa PCR dengan cetakan DNA genomik yang diekstraksi dari jaringan ikan hasil persilangan antara ikan transgenik dan ikan normal. Metode ini memerlukan ikan dalam jumlah yang banyak, dan juga waktu serta tenaga. Pendekatan baru untuk mengatasi masalah tersebut akan memberikan manfaat besar kepada peneliti bioteknologi perikanan. Pada penelitian ini, kami menggunakan metode PCR real-time kuantitatif (krt-PCR) untuk menganalisa sigositas pada satu strain ikan zebra (Danio rerio) transgenik yang membawa gen D6-desaturase-like dari ikan salmon masu, Oncorhynchus masou. krt-PCR dilakukan menggunakan iQ SYBR Green Supermix pada mesin iCycler iQ Real-time PCR Detection system (Bio-Rad Laboratories, USA). Data dianalisis menggunakan metode pembandingan nilai cycle threshold. Hasil penelitian menunjukkan bahwa semua ikan transgenik (n=20) yang diidentifikasi dapat diklasifikasikan secara jelas sebagai ikan homosigot atau heterosigot. Persilangan antara ikan transgenik tersebut dengan ikan normal menunjukkan transmisi transgen ke keturunannya mengikuti hukum segregasi Mendel. Dengan demikian, metode krt-PCR adalah efektif untuk penentuan sigositas secara cepat dan tepat pada ikan transgenik. Teknik ini dapat berguna dalam program produksi ikan transgenik secara massal dan dalam percobaan dimana faktor sigositas memberikan pengaruh nyata. Kata kunci: kuantitatif real-time PCR; sigositas, ikan transgenik; produksi massal

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50

Gazeau, Nicolas, Pere Barba, Gloria Iacoboni, Mi Kwon, Rebeca Bailen, Juan Luis Reguera, Lucía López Corral, et al. "Safety and Efficacy of Two Anakinra Dose Regimens for Refractory CRS or Icans after CAR T-Cell Therapy." Blood 138, Supplement 1 (November 5, 2021): 2816. http://dx.doi.org/10.1182/blood-2021-147454.

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Abstract Background: Chimeric antigen receptor-engineered (CAR) T-cell therapy remains associated with significant toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Recently, the recombinant IL-1 receptor antagonist anakinra has emerged as a promising approach after failure of tocilizumab and corticosteroids to treat CRS/ICANS (Norelli, Nat Med 2018; Giavridis, Nat Med 2018). Here, we describe the safety and efficacy of two anakinra dose regimens to treat refractory CRS and/or ICANS after CAR T-cell therapy. Methods: We retrospectively analyzed data from 26 patients with B-cell or plasma cell malignancies treated at 9 institutions with anakinra for CRS and/or ICANS after CAR T-cell therapy. Details regarding CAR T-cell product and disease type are shown in the Table. CRS/ICANS grade was determined by applying the ASTCT criteria at the time of peak symptom severity. We defined response to anakinra as an improvement in CRS and/or ICANS symptoms per the attending physician's evaluation. Results: Patients, disease, and CAR T-cell product are shown in the Table. Anakinra was administered at 100-200mg/day subcutaneously (SC) in 13 patients (pts) (50%; low-dose), or at 8mg/kg/day SC or intravenously (IV) in 13 pts (50%; high-dose). Most pts were treated with anakinra for steroid-refractory ICANS (n=23); two pts were treated for tocilizumab-refractory CRS (n=2) and one for both (n=1). All but one patient received anakinra concurrently with corticosteroids. Median peak CRS and ICANS grade by ASTCT criteria was 2 (range, 1-4), and 4 (range, 0-5), respectively. Median CRS and ICANS duration was 5 days (range, 1-10) and 15.5 days (range, 1-38), respectively. Median time from CAR T-cell infusion to anakinra initiation was 9 days (range, 5-31). The median duration of anakinra treatment was 8.5 days (range, 1-47). The median time to anakinra initiation from CRS or ICANS onset was comparable in pts receiving high-dose compared to low-dose anakinra (4 versus 4 days, respectively; p=0.8). Comparable peak CRS (median grade, 2 versus 2, p=0.9) and ICANS (median grade, 4 versus 4, p=0.2) were measured in both groups. Other toxicity-directed therapies were administered in 8 pts receiving low-dose anakinra (siltuximab, n=8; intrathecal chemotherapy, n=2, etoposide n=1). The only infectious event reported after anakinra initiation was HHV6 encephalitis (n=1). Two pts with infections confirmed prior to anakinra initiation died after anakinra treatment: CMV pneumonia (n=1), Escherichia coli bacteremia (n=1). In one patient the anakinra administration route was changed from SC to IV due to a subcutaneous hematoma; in one patient anakinra was discontinued due to elevated liver enzymes. We observed anti-tumor responses (partial or complete) to CAR T-cell therapy in 15 pts (58%; B-ALL, n=1/1; DLBCL, n=9/15; MCL, n=3/4; MM; n=1/1; PMBCL, n=1/3), including complete responses in 11 pts (42%). In high-dose anakinra pts, the ORR was 77% (complete response, 53%). CRS/ICANS improvement was observed after anakinra initiation in 73% of pts with a median duration of treatment of 3 days (range 1-7). Higher response rates were seen in pts who received high-dose compared to low-dose anakinra (100% versus 46%, respectively; p=0.005) and the non-relapse mortality rate at day 30 was significantly lower in pts treated with high-dose anakinra compared to low-dose anakinra (0% versus 69%; p=0.001%). In addition, a shorter time to anakinra initiation from CRS or ICANS onset was associated with CRS/ICANS improvement (median, 2 versus 5 days in responders versus non-responders, respectively; p=0.04). Conclusion After failure of tocilizumab and/or corticosteroids, early administration of high-dose anakinra (8mg/kg/day IV or SC) was associated with rapid resolution of CRS/ICANS symptoms after use of tocilizumab and/or corticosteroids, with a manageable toxicity profile, and with a non-relapse mortality rate at day 30 of 0%. In contrast, 38% of patients treated with low-dose anakinra died from infections. We observed complete responses to CAR T-cell therapy in pts treated with high-dose anakinra, suggesting limited impact on in vivo CAR-T cell function. In summary, high-dose anakinra is a feasible and promising approach after failure of conventional CRS and ICANS-directed therapies. Prospective trials of anakinra to prevent or treat CRS and ICANS are ongoing. Figure 1 Figure 1. Disclosures Barba: Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, Jazz Phar,aceuticals: Honoraria; Cqrlos III heqlth Institute, aSOCIACION espanola contra el cancer, PERIS: Research Funding. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Bailen: Gilead, Pfizer: Speakers Bureau. Reguera: Janssen, Kite/Gilead, Novartis: Speakers Bureau; BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees. Corral: Gilead: Consultancy; Novartis: Consultancy; Gileqd: Honoraria. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Maziarz: Allovir: Consultancy, Research Funding; Novartis: Consultancy, Other: Data and Safety Monitoring board, Research Funding; Vor Pharma: Other: Data and Safety Monitoring Board; Incyte Corporation: Consultancy, Honoraria; Bristol-Myers, Squibb/Celgene,, Intellia, Kite: Honoraria; Artiva Therapeutics: Consultancy; CRISPR Therapeutics: Consultancy; Omeros: Research Funding; Intellia: Honoraria; Athersys: Other: Data and Safety Monitoring Board, Patents & Royalties. Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy. Green: Seagen Inc.: Research Funding; bristol myers squibb: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Cellectar Biosciences: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen Biotech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Patents & Royalties, Research Funding; Legend Biotech: Consultancy; Neoleukin Therapeutics: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; SpringWorks Therapeutics: Research Funding. Chow: ADC Therapeutics: Current holder of individual stocks in a privately-held company, Research Funding; AstraZeneca: Research Funding. Hirayama: Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Maloney: Kite, a Gilead Company, Juno, and Celgene: Research Funding; A2 Biotherapeutics: Consultancy; BioLineRx, Juno, Celgene, Kite, a Gilead Company, Gilead, Novartis, and Pharmacyclics: Honoraria; A2 Biotherapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Juno: Patents & Royalties. Turtle: AstraZeneca: Consultancy, Research Funding; Nektar Therapeutics: Consultancy, Research Funding; Precision Biosciences: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Caribou Biosciences: Consultancy, Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Eureka Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Arsenal Bio: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Century Therapeutics: Consultancy, Other: Scientific Advisory Board; T-CURX: Other: Scientific Advisory Board; Myeloid Therapeutics: Current holder of stock options in a privately-held company, Other: Scientific Advisory Board; Asher Bio: Consultancy; Amgen: Consultancy; PACT Pharma: Consultancy; TCR2 Therapeutics: Research Funding; Juno Therapeutics/BMS: Patents & Royalties: Right to receive royalties from Fred Hutch for patents licensed to Juno Therapeutics, Research Funding; Allogene: Consultancy. Gauthier: Janssen: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Multerra Bio: Consultancy; Larvol: Consultancy; JMP: Consultancy; Eusapharma: Consultancy.

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