8,855 research outputs found
KYT2022 Finnish Research Programme on Nuclear Waste Management 2019–2022 : Final Report
KYT2022 (Finnish Research Programme on Nuclear Waste Management 2019–2022), organised by the Ministry of Economic Affairs and Employment, was a national research programme with the objective to ensure that the authorities have sufficient levels of nuclear expertise and preparedness that are needed for safety of nuclear waste management.
The starting point for public research programs on nuclear safety is that they create the conditions for maintaining the knowledge required for the continued safe and economic use of nuclear energy, developing new know-how and participating in international collaboration.
The content of the KYT2022 research programme was composed of nationally important research topics, which are the safety, feasibility and acceptability of nuclear waste management.
KYT2022 research programme also functioned as a discussion and information-sharing forum for the authorities, those responsible for nuclear waste management and the research organizations, which helped to make use of the limited research resources. The programme aimed to develop national research infrastructure, ensure the continuing availability of expertise, produce high-level scientific research and increase general knowledge of nuclear waste management
Translational Genomics for Alfalfa Varietal Improvement
Key points Medicago truncatula is a model legume with available mapping, genome, and RNA, protein and metabolite profiling databases and genetically diverse populations. Genomics resources developed for M. truncatula have application in the study and improvement of alfalfa making it an excellent model for this forage legume
Anuário científico da Escola Superior de Tecnologia da Saúde de Lisboa - 2021
É com grande prazer que apresentamos a mais recente edição (a 11.ª) do Anuário Científico da Escola Superior de Tecnologia da Saúde de Lisboa. Como instituição de ensino superior, temos o compromisso de promover e incentivar a pesquisa científica em todas as áreas do conhecimento que contemplam a nossa missão. Esta publicação tem como objetivo divulgar toda a produção científica desenvolvida pelos Professores, Investigadores, Estudantes e Pessoal não Docente da ESTeSL durante 2021. Este Anuário é, assim, o reflexo do trabalho árduo e dedicado da nossa comunidade, que se empenhou na produção de conteúdo científico de elevada qualidade e partilhada com a Sociedade na forma de livros, capítulos de livros, artigos publicados em revistas nacionais e internacionais, resumos de comunicações orais e pósteres, bem como resultado dos trabalhos de 1º e 2º ciclo. Com isto, o conteúdo desta publicação abrange uma ampla variedade de tópicos, desde temas mais fundamentais até estudos de aplicação prática em contextos específicos de Saúde, refletindo desta forma a pluralidade e diversidade de áreas que definem, e tornam única, a ESTeSL. Acreditamos que a investigação e pesquisa científica é um eixo fundamental para o desenvolvimento da sociedade e é por isso que incentivamos os nossos estudantes a envolverem-se em atividades de pesquisa e prática baseada na evidência desde o início dos seus estudos na ESTeSL. Esta publicação é um exemplo do sucesso desses esforços, sendo a maior de sempre, o que faz com que estejamos muito orgulhosos em partilhar os resultados e descobertas dos nossos investigadores com a comunidade científica e o público em geral. Esperamos que este Anuário inspire e motive outros estudantes, profissionais de saúde, professores e outros colaboradores a continuarem a explorar novas ideias e contribuir para o avanço da ciência e da tecnologia no corpo de conhecimento próprio das áreas que compõe a ESTeSL. Agradecemos a todos os envolvidos na produção deste anuário e desejamos uma leitura inspiradora e agradável.info:eu-repo/semantics/publishedVersio
Towards personalized immunotherapy : development of in vitro models for imaging natural killer cell behavior in the tumor microenvironment
Tremendous advances in the tumor immunology field have transformed immunotherapy
from a promising approach to a standard clinical practice. However, a subset of cancer
patients is non-responsive to immunotherapy. More research is therefore needed to
understand the mechanisms underlying tumor resistance to immunotherapeutic treatments.
The aim of this doctoral work was to develop new tools to study the mechanisms of cancer
immunosurveillance and to test immunotherapeutic treatments in vitro. In this thesis, I
describe the methods developed, and I discuss the main biological findings obtained by
using these methods.
The thesis is organized as follows. A short historical background of immunotherapy is
provided in Chapter 1. Chapter 2 describes the principles of NK cell-mediated cancer
immunosurveillance, and provides an overview on rare cancers, mainly focusing on
sarcoma. The research aims are listed in Chapter 3. In Chapter 4, I describe the cell culture
methods and cell analysis techniques relevant for my doctoral work. In Chapter 5, I
describe the methods we developed to culture tumor spheroids in vitro using ultrasonic
standing waves in microwell chips, focusing on the theory, design, and applications.
Chapter 6 and Chapter 7 focus on the biological findings obtained using our platform in
combination with traditional immunological methods, followed by future implementations
discussed in Chapter 8. The constituent papers are provided at the end of the thesis.
In Paper I, we combined the use of the microwell chip, ultrasonic standing waves and a
protein-repellent polymer coating to enable the production of spheroids from multiple cell
types. In absence of cell adhesion to the chip, spheroids could be collected and further
analyzed by off-the-chip techniques.
In Paper II, we designed a novel multichambered microwell chip to perform multiplexed
fluorescence screening of two- or three-dimensional cell cultures. The platform allows the
direct assessment of drug or immune cell cytotoxic efficacy, making it a promising tool for
individualized cytotoxicity tests for personalized medicine.
In Paper III, we investigate the function of PVR receptors in NK cells interacting with
renal carcinoma spheroids, and the impact of PVR in NK cell-based cellular
immunotherapy. We demonstrated that variations in PVR expression are primarily
recognized by the inhibitory receptor TIGIT, while DNAM-1 strongly contributes to NK
cell activation mainly through PVR-independent mechanisms. We performed NK
cell-based cytotoxicity assays against renal carcinoma spheroids in the microwell chip.
Anti-TIGIT treatment was effective only for TIGIThigh NK cells both when used as
monotherapy or in combination with other drugs, suggesting that only a fraction of patients
might respond to anti-TIGIT therapy.
In Paper IV, a similar approach was used with primary sarcomas. We cultured
patient-derived sarcoma spheroids and tested NK cell-based immunotherapy in the
microwell chip, either alone or in combination with antibody therapy, and we identified
promising treatment combinations.
In Paper V, we applied the use of expansion microscopy to visualize NK cells infiltrating
renal carcinoma spheroids. In conclusion, our multi-disciplinary work shows the
development of new imaging-based platform and its use to study the mechanisms of NK
cell-mediated tumor surveillance and for personalized therapy
TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH
Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on people’s lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)
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After Creation: Intergovernmental Organizations and Member State Governments as Co-Participants in an Authority Relationship
This is a re-amalgamation of what started as one manuscript and became two when the length proved to be more than any publisher wanted to consider. The splitting consisted of removing what are now Parts 3, 4, and 5 so that the manuscript focused on the outcome-related shared beliefs holding an authority relationship together. Those parts were last worked on in 2018. The rest were last worked on in late 2021 but also remain incomplete.
The relational approach adopted in this study treats intergovernmental organizations and the governments of member states as co-participants in an authority relationship with the governments of their member states. Authority relationships link two types of actor, defined by their authority-holder or addressee role in the relationship, through a set of shared beliefs about why the relationship exists and how the participants should fulfill their respective roles. The IGO as authority holder has a role that includes a right to instruct other actors about what they should or should not do; the governments of member states as addressees are expected to comply with the instructions. Three sets of shared beliefs provide the conceptual “glue” holding the relationship together. The first defines the goal of the collective effort, providing both the rationale for having the authority relationship and providing a lode star for assessments of the collective effort’s success or lack of success. The second set defines the shared understanding about allocation of roles and the process of interaction by establishing shared expectations about a) the selection process by which particular actors acquire authority holder roles, b) the definitions identifying one or more categories of addressees expected to follow instructions, and c) the procedures through which the authority holder issues instructions. The third set focus on the outcomes of cooperation through the relationship by defining a) the substantive areas in which the authority holder may issue instructions, b) the bases for assessing the relevance actions mandated in instructions for reaching the goal, and c) the relative efficacy of action paths chosen for reaching the goal as compared to other possible action paths.
Using an authority relationship framework for analyzing cooperation through IGOs highlights the inherently bi-directional nature of IGO-member government activity by viewing their interaction as involving a three-step process in which the IGO as authority holder decides when to issue what instruction, the member state governments as followers react to the instruction with anything from prompt and full compliance through various forms of pushback to outright rejection, and the IGO as authority holder responds to how the followers react with efforts to increase individual compliance with instructions and reinforce continuing acceptance of the authority relationship. Foregrounding the dynamics produced by the interaction of these two streams of perception and action reveals more clearly how far intergovernmental organizations acquire capacity to operate as independent actors, the dynamic ways they maintain that capacity, and how much they influence member governments’ beliefs and actions at different times. The approach fosters better understanding of why, when, and for how long governments choose cooperation through an IGO even in periods of rising unilateralism
Human induced pluripotent stem cell-derived kidney organoids toward clinical implementations
The generation of kidney organoids from human pluripotent stem cells (hPSCs) has represented a relevant scientific achievement in the organoid field. Importantly, hPSC-derived kidney organoids contain multiple nephron-like structures that exhibit some renal functional characteristics and have the capacity to respond to nephrotoxic agents. In this review, we first discuss how bioengineering approaches can help overcome current kidney organoid challenges. Next, we focus on recent works exploiting kidney organoids for drug screening and disease modeling applications. Finally, we provide a state of the art on current research toward the potential application of kidney organoids and renal cells derived from hPSCs for future renal replacement therapies
QAnon Propaganda on Twitter as Information Warfare: Influencers, Networks, and Narratives
QAnon refers to a set of far-right, conspiratorial ideologies that have risen
in popularity in the U.S. since their initial promotion in 2017 on the 4chan
internet message board. A central narrative element of QAnon is that a powerful
group of elite, liberal members of the Democratic Party engage in morally
reprehensible practices, but that former U.S. President Donald J. Trump was
prosecuting them. Five studies investigated the influence and network
connectivity of accounts promoting QAnon on Twitter from August, 2020 through
January, 2021. Selection of Twitter accounts emphasized on-line influencers and
"persons of interest" known or suspected of participation in QAnon propaganda
promotion activities. Evidence of large-scale coordination among accounts
promoting QAnon was observed, demonstrating rigorous, quantitative evidence of
"astroturfing" in QAnon propaganda promotion on Twitter, as opposed to strictly
"grassroots" activities of citizens acting independently. Further, evidence was
obtained supporting that networks of extreme far-right adherents engaged in
organized QAnon propaganda promotion, as revealed by network overlap among
accounts promoting far-right extremist (e.g., anti-Semitic) content and
insurrectionist themes; New Age, occult, and "esoteric" themes; and internet
puzzle games like Cicada 3301 and other "alternate reality games." Based on
well-grounded theories and findings from the social sciences, it is argued that
QAnon propaganda on Twitter in the months circa the 2020 U.S. Presidential
election likely reflected joint participation of multiple actors, including
nation-states like Russia, in innovative misuse of social media toward
undermining democratic processes by promoting "magical" thinking, ostracism of
Democrats and liberals, and salience of White extinction narratives common
among otherwise ideologically diverse groups on the extreme far-right.Comment: 60 pages, 14 figure
Novel strategies for the modulation and investigation of memories in the hippocampus
Disruptions of the memory systems in the brain are linked to the manifestation of many neuropsychiatric diseases such as Alzheimer’s disease, depression, and post-traumatic stress disorder. The limited efficacy of current treatments necessities the development of more effective therapies. Neuromodulation has proven effective in a variety of neurological diseases and could be an attractive solution for memory disorders. However, the application of neuromodulation requires a more detailed understanding of the network dynamics associated with memory formation and recall. In this work, we applied a combination of optical and computational tools in the development of a novel strategy for the modulation of memories, and have expanded its application for interrogation of the hippocampal circuitry underlying memory processing in mice.
First, we developed a closed-loop optogenetic stimulation platform to activate neurons implicated in memory processing (engram neurons) with a high temporal resolution. We applied this platform to modulate the activity of engram neurons and assess memory processing with respect to synchronous network activity. The results of our investigation support the proposal that encoding new information and recalling stored memories occur during distinct epochs of hippocampal network-wide oscillations.
Having established the high efficacy of the modulation of engram neurons’ activity in a closed-loop fashion, we sought to combine it with two-photon imaging to enable high spatial resolution interrogation of hippocampal circuitry. We developed a behavioral apparatus for head-fixed engram modulation and the assessment of memory recall in immobile animals. Moreover, through the optimization of dual color two-photon imaging, we improved the ability to monitor activity of neurons in the subfields of the hippocampus with cellular specificity. The platform created here will be applied to investigate the effects of engram reactivation on downstream projections targets with high spatial and cell subtype specificity.
Following these lines of investigations will enhance our understanding of memory modulation and could lead to novel neuromodulation treatments for neurological disorders associated with memory malfunctioning
Roadmap Towards Communitywide Intercalibration and Standardization of Ocean Nucleic Acids ‘Omics Measurements
In January 2020, the US Ocean Carbon & Biogeochemistry (OCB) Project Office funded the Ocean Nucleic Acids 'omics Intercalibration and Standardization workshop held at the University of North Carolina in Chapel Hill. Thirty-two participants from across the US, along with guests from Canada and France, met to develop a framework for standardization and intercalibration (S&I) of ocean nucleic acid ‘omics (na’omics) approaches (i.e., amplicon sequencing, metagenomics and metatranscriptomics). During the three-day workshop, participants discussed numerous topics, including: a) sample biomass collection and nucleic acid preservation for downstream analysis, b) extraction protocols for nucleic acids, c) addition of standard reference material to nucleic acid isolation protocols, d) isolation methods unique to RNA, e) sequence library construction, and f ) integration of bioinformatic considerations. This report provides a summary of these and other topics covered during the workshop and a series of recommendations for future S&I activities for na’omics approaches.The Ocean Nucleic Acids ‘Omics Intercalibration and Standardization Workshop was supported by grants from the Ocean Carbon & Biogeochemistry Program (OCB) – funding provided by the National Science Foundation (NSF) and the National Aeronautics and Space Administration (NASA) – and the Simons Foundation. This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)
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