Browsing by Subject "STRATEGY"

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  • Pekkanen, Jami Joonas Olavi; Lappi, Otto; Rinkkala, Paavo; Tuhkanen, Niko Samuel; Frantsi, Roosa; Summala, Kari Heikki Ilmari (2018)
    We present a computational model of intermittent visual sampling and locomotor control in a simple yet representative task of a car driver following another vehicle. The model has a number of features that take it beyond the current state of the art in modelling natural tasks, and driving in particular. First, unlike most control theoretical models in vision science and engineering—where control is directly based on observable (optical) variables—actions are based on a temporally enduring internal representation. Second, unlike the more sophisticated engineering driver models based on internal representations, our model explicitly aims to be psychologically plausible, in particular in modelling perceptual processes and their limitations. Third, unlike most psychological models, it is implemented as an actual simulation model capable of full task performance (visual sampling and longitudinal control). The model is developed and validated using a dataset from a simplified car-following experiment (N = 40, in both three-dimensional virtual reality and a real instrumented vehicle). The results replicate our previously reported connection between time headway and visual attention. The model reproduces this connection and predicts that it emerges from control of action uncertainty. Implications for traffic psychological models and future developments for psychologically plausible yet computationally rigorous models of full natural task performance are discussed.
  • Holmgren, Noel Michael Andre; Norrstrom, Niclas; Aps, Robert; Kuikka, Sakari (2014)
  • Wallin, Antti; Leino, Helena; Jokinen, Ari; Laine, Markus; Tuomisaari, Johanna; Backlund, Pia (2018)
    Urban strategies, representing stories of possible futures, often intervene in already established local communities and therefore call for a considerate urban intervention. This article utilises the ideas of Henri Lefebvre's socially produced space and of literature on stories involved in planning. Our empirical example tells a story of urban densification aspirations for an inner-city neighbourhood in Tampere, Finland. By combining the interviews of local people and planners with policy documents, we argue that planners' stories pay too little attention to the place and to local stories. Planners' abstract visions of the future and local stories building on lived experiences both draw meanings from the same place but have very different intentions. In our case, the consultation of the project started out wrong because the planners neglected a neighbourhood thick in symbolic meanings and the local stories' power in resistance. By understanding the place as polyphonic in its foundation, planners could learn about the symbolic elements and reasons for people's place attachment, and thus end up re-writing the place together. Urban interventions such as urban densification should connect to the place as part of its polyphonic historical continuum and acknowledge the residents' place attachments.
  • Richardson, Dominique; Itkonen, Jaakko; Nievas, Julia; Urtti, Arto; Casteleijn, Marco G. (2018)
    The use of living cells for the synthesis of pharmaceutical proteins, though state-of-the-art, is hindered by its lengthy process comprising of many steps that may affect the protein’s stability and activity. We aimed to integrate protein expression, purification, and bioconjugation in small volumes coupled with cell free protein synthesis for the target protein, ciliary neurotrophic factor. Split-intein mediated capture by use of capture peptides onto a solid surface was efficient at 89–93%. Proof-of-principle of light triggered release was compared to affinity chromatography (His6 fusion tag coupled with Ni-NTA). The latter was more efficient, but more time consuming. Light triggered release was clearly demonstrated. Moreover, we transferred biotin from the capture peptide to the target protein without further purification steps. Finally, the target protein was released in a buffer-volume and composition of our choice, omitting the need for protein concentration or changing the buffer. Split-intein mediated capture, protein trans splicing followed by light triggered release, and bioconjugation for proteins synthesized in cell free systems might be performed in an integrated workflow resulting in the fast production of the target protein.
  • Penketh, J. A.; Nolan, J. P.; Skrifvars, M. B.; Rylander, C.; Frenell; Tirkkonen, J.; Reynolds, E. C.; Parr, M. J. A.; Aneman, A. (2020)
    Aim: To determine the type of airway devices used during in-hospital cardiac arrest (IHCA) resuscitation attempts. Methods: International multicentre retrospective observational study of in-patients aged over 18 years who received chest compressions for cardiac arrest from April 2016 to September 2018. Patients were identified from resuscitation registries and rapid response system databases. Data were collected through review of resuscitation records and hospital notes. Airway devices used during cardiac arrest were recorded as basic (adjuncts or bag-mask), or advanced, including supraglottic airway devices, tracheal tubes or tracheostomies. Descriptive statistics and multivariable regression modelling were used for data analysis. Results: The final analysis included 598 patients. No airway management occurred in 36 (6%), basic airway device use occurred at any time in 562 (94%), basic airway device use without an advanced airway device in 182 (30%), tracheal intubation in 301 (50%), supraglottic airway in 102 (17%), and tracheostomy in 1 (0.2%). There was significant variation in airway device use between centres. The intubation rate ranged between 21% and 90% while supraglottic airway use varied between 1% and 45%. The choice of tracheal intubation vs. supraglottic airway as the second advanced airway device was not associated with immediate survival from the resuscitation attempt (odds ratio 0.81; 95% confidence interval 0.35-1.8). Conclusion: There is wide variation in airway device use during resuscitation after IHCA. Only half of patients are intubated before return of spontaneous circulation and many are managed without an advanced airway. Further investigation is needed to determine optimal airway device management strategies during resuscitation following IHCA.
  • Kostopoulos, Ioannis; Elzinga, Janneke; Ottman, Noora; Klievink, Jay T.; Blijenberg, Bernadet; Aalvink, Steven; Boeren, Sjef; Mank, Marko; Knol, Jan; de Vos, Willem M.; Belzer, Clara (2020)
    Akkermansia muciniphila is a well-studied anaerobic bacterium specialized in mucus degradation and associated with human health. Because of the structural resemblance of mucus glycans and free human milk oligosaccharides (HMOs), we studied the ability of A. muciniphila to utilize human milk oligosaccharides. We found that A. muciniphila was able to grow on human milk and degrade HMOs. Analyses of the proteome of A. muciniphila indicated that key-glycan degrading enzymes were expressed when the bacterium was grown on human milk. Our results display the functionality of the key-glycan degrading enzymes (alpha -l-fucosidases, beta -galactosidases, exo-alpha -sialidases and beta -acetylhexosaminidases) to degrade the HMO-structures 2 ' -FL, LNT, lactose, and LNT2. The hydrolysation of the host-derived glycan structures allows A. muciniphila to promote syntrophy with other beneficial bacteria, contributing in that way to a microbial ecological network in the gut. Thus, the capacity of A. muciniphila to utilize human milk will enable its survival in the early life intestine and colonization of the mucosal layer in early life, warranting later life mucosal and metabolic health.
  • Bousquet, Jean; Haahtela, Tari; Blain, Hubert; Czarlewski, Wienczyslawa; Zuberbier, Torsten; Bedbrook, Anna; Cruz, Alvaro A.; Fonseca, Joao A.; Klimek, Ludger; Kuna, Piotr; Samolinski, Boleslaw; Valiulis, Arunas; Lemaire, Antoine; Anto, Josep M. (2022)
    Vaccination is a highly effective preventive measure against COVID-19. However, complementary treatments are needed to better control the disease. Fermented vegetables and spices, agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and TRPA1/V1 channels (Transient Receptor Potential Ankyrin 1 and Vanillin 1), may help in the control of COVID-19. Some preliminary clinical trials suggest that curcumin (spice) can prevent some of the COVID-19 symptoms. Before any conclusion can be drawn and these treatments recommended for COVID-19, the data warrant confirmation. In particular, the benefits of the foods need to be assessed in more patients, through research studies and large trials employing a double-blind, placebo-controlled design.
  • Osswald, Simon; Zippel, Christoph; Hassan, Zahid; Nieger, Martin; Braese, Stefan (2022)
    A new versatile method for the C-P bond formation of (hetero)aryl halides with trimethyl phosphite via a UV-induced photo-Arbuzov reaction, accessing diverse phosphonate-grafted arenes, heteroarenes and co-facially stacked cyclophanes under mild reaction conditions without the need for catalyst, additives, or base is developed. The UV-induced photo-Arbuzov protocol has a wide synthetic scope with large functional group compatibility exemplified by over 30 derivatives. Besides mono-phosphonates, di- and tri-phosphonates are accessible in good to excellent yields. Mild and transition metal-free reaction conditions consolidate this method's potential for synthesizing pharmaceutically relevant compounds and precursors of supramolecular nanostructured materials.
  • Hietanen, Joel; Sihvonen, Antti (2021)
    There is a rich tradition of inquiry in consumer research into how collective consumption manifests in various forms and contexts. While this literature has shown how group cohesion prescribes ethical and moral positions, our study explores how ethicality can arise from consumers and their relations in a more emergent fashion. To do so, we present a Levinasian perspective on consumer ethics through a focus on Restaurant Day, a global food carnival that is organized by consumers themselves. Our ethnographic findings highlight a non-individualistic way of approaching ethical subjectivity that translates into acts of catering to the needs of other people and the subversion of extant legislation by foregrounding personal responsibility. These findings show that while consumer gatherings provide participants a license to temporarily subvert existing roles, they also allow the possibility of ethical autonomy when the mundane rules of city life are renegotiated. These sensibilities also create ‘ethical surplus’, which is an affective excess of togetherness. In the Levinasian register, Restaurant Day thus acts as an inarticulable ‘remainder’—a trace of the possibility of being able to live otherwise alongside one another in city contexts.
  • Lynch, Robert; Lummaa, Virpi; Briga, Michael; Chapman, Simon; Loehr, John (2020)
    Understanding how conditions experienced during development affect reproductive timing is of considerable cross-disciplinary interest. Life-history theory predicts that organisms will accelerate reproduction when future survival is unsure. In humans, this can be triggered by early exposure to mortality. Previous studies, however, have been inconclusive due to several confounds that are also likely to affect reproduction. Here we take advantage of a natural experiment in which a population is temporarily divided by war to analyze how exposure to mortality affects reproduction. Using records of Finnish women in World War II, we find that young girls serving in a paramilitary organization wait less time to reproduce, have shorter inter-birth intervals, and have more children than their non-serving peers or sisters. These results support the hypothesis that exposure to elevated mortality rates during development can result in accelerated reproductive schedules and adds to our understanding of how participation in warfare affects women.
  • Saeed, Khalid; Ojamies, Poojitha; Pellinen, Teijo; Eldfors, Samuli; Turkki, Riku; Lundin, Johan; Järvinen, Petrus; Nisén, Harry; Taari, Kimmo; af Hällström, Taija Maria; Rannikko, Antti; Mirtti, Tuomas; Kallioniemi, Olli-Pekka; Östling, Päivi (2019)
    Renal cell cancer (RCC) has become a prototype example of the extensive intratumor heterogeneity and clonal evolution of human cancers. However, there is little direct evidence on how the genetic heterogeneity impacts on drug response profiles of the cancer cells. Our goal was to determine how genomic clonal evolution impacts drug responses. Finding from our study could help to define the challenge that clonal evolution poses on cancer therapy. We established multiple patient-derived cells (PDCs) from different tumor regions of four RCC patients, verified their clonal relationship to each other and to the uncultured tumor tissue by genome sequencing. Furthermore, comprehensive drug-sensitivity testing with 460 oncological drugs was performed on all PDC clones. The PDCs retained many cancer-specific copy number alterations and mutations in driver genes such as VHL, PBRM1, PIK3C2A, KMD5C and TSC2 genes. The drug testing highlighted vulnerability in the PDCs toward approved RCC drugs, such as the mTOR-inhibitor temsirolimus, but also novel sensitivities were uncovered. The individual PDC clones from different tumor regions in a patient showed distinct drug-response profiles, suggesting that genomic heterogeneity contributes to the variability in drug responses. Studies of multiple PDCs from a patient with cancer are informative for elucidating cancer heterogeneity and for the determination on how the genomic evolution is manifested in cancer drug responsiveness. This approach could facilitate tailoring of drugs and drug combinations to individual patients.
  • Woiwode, Ulrich; Ferri, Martina; Maier, Norbert M.; Lindner, Wolfgang; Lämmerhofer, Michael (2018)
    Abstract A cardinal requirement for effective 2D-HPLC separations is sufficient complementarity in the retention profiles of first and second dimension separations. It is shown that retention and enantioselectivity of chiral selectors derived from cinchona alkaloids can be conveniently modulated by structural variation of the carbamate residue of the quinine/quinidine carbamate ligand of such chiral stationary phases (CSP). A variety of aliphatic and aromatic residues have been tested in comparison to non-carbamoylated quinine CSP. Various measures of orthogonality have been utilized to derive the CSP that is most complementary to the tert-butylcarbamoylated quinine CSP (tBuCQN CSP), which is commercially available as Chiralpak QN-AX column. It turned out that O-9-(2,6-diisopropylphenylcarbamoyl)-modified quinine is most promising in this respect. Its implementation as a complementary CSP for the separation of amino acids derivatized with Sanger’s reagent (2,4-dinitrophenylated amino acids) in the first dimension combined with a tBuCQN CSP in the second dimension revealed successful enantiomer separations in a comprehensive chiral×chiral 2D-HPLC setup. However, the degree of complementarity could be greatly enhanced when simultaneously the absolute configurations were exchanged from quinine to quinidine in the chiral selector of the first dimension separation resulting in opposite elution orders of the enantiomers in the two dimensions. The advantage of such a chiral×chiral over achiral×chiral 2D-HPLC setup, amongst others, is the perfect compatibility of the mobile phase because in both dimensions the identical eluent can be used.
  • Nowakowska, Maria; Selby, Katja; Przykopanski, Adina; Krüger, Maren; Krez, Nadja; Dorner, Brigitte G.; Dorner, Martin B.; Jin, Rongsheng; Minton, Nigel P.; Rummel, Andreas; Lindström, Miia (2022)
    Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes.
  • Colis, Laureen; Ernst, Glen; Sanders, Sara; Liu, Hester; Sirajuddin, Paul; Peltonen, Karita; DePasquale, Michael; Barrow, James C.; Laiho, Marikki (2014)
    RNA polymerase I (Pol I) is a dedicated polymerase that transcribes the 45S ribosomal (r) RNA precursor. The 45S rRNA precursor is subsequently processed into the mature 5.8S, 18S, and 28S rRNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. On the basis of the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides have been evaluated as inhibitors of Pol I and activators of the destruction of RPA194, the Poll large catalytic subunit protein. Structure-activity relationships in assays of nucleolar stress and cell viability demonstrate key pharmacophores and their physicochemical properties required for potent activation of Pol I stress and cytotoxidty. This work identifies a set of bioactive compounds that potently cause RPA194 degradation that function in a tightly constrained chemical space. This work has yielded novel derivatives that contribute to the development of Pol I inhibitory cancer therapeutic strategies.
  • Yin, Shenglai; Xu, Yanjie; Batbayar, Nyambyar; Takekawa, John Y.; Si, Yali; Prosser, Diann J.; Newman, Scott H.; Prins, Herbert H. T.; de Boer, Willem F. (2021)
    Long-distance migrations influence the dynamics of host pathogen interactions and understanding the role of migratory waterfowl in the spread of the highly pathogenic avian influenza viruses (HPAIV) is important. While wild geese have been associated with outbreak events, disease ecology of closely related species has not been studied to the same extent. The swan goose (Anser cygnoides) and the bar-headed goose (Anser indicus) are congeneric species with distinctly different HPAIV infection records; the former with few and the latter with numerous records. We compared movements of these species, as well as the more distantly related whooper swan (Cygnus cygnus) through their annual migratory cycle to better understand exposure to HPAIV events and how this compares within and between congeneric and non congeneric species. In spite of their record of fewer infections, swan geese were more likely to come in contact with disease outbreaks than bar-headed geese. We propose two possible explanations: i) frequent prolonged contact with domestic ducks increases innate immunity in swan geese, and/or ii) the stress of high -elevation migration reduces immunity of bar-headed geese. Continued efforts to improve our understanding of species-level pathogen response is critical to assessing disease transmission risk.
  • Bousquet, Jean; Le Moing, Vincent; Blain, Hubert; Czarlewski, Wienczyslawa; Zuberbier, Torsten; Torre, Raphael de la; Lozano, Nieves Pizarro; Reynes, Jacques; Bedbrook, Anna; Cristol, Jean-Paul; Cruz, Alvaro A.; Fiocchi, Alessandro; Haahtela, Tari; Iaccarino, Guido; Klimek, Ludger; Kuna, Piotr; Melén, Erik; Mullol, Joaquim; Samolinski, Boleslaw; Valiulis, Arunas; Anto, Josep M. (2021)
    COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 mmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.
  • Partanen, Lauri (2020)
    This paper represents the second contribution from an action research study on a bachelor-level quantum chemistry and spectroscopy course. In the proposed instructional model, active learning principles are extended outside lectures to form a student-centred course structure. The new model resulted in superior learning outcomes compared to a class where active learning elements were limited to course lectures, as demonstrated by previous research. In this article, I try to understand this improvement through an analysis of student motivation and experiences in the framework of self-determination theory. Based on my analysis of student feedback data and interviews, tasks that facilitated direct interaction with peers or course staff were seen as key factors in enhancing learning and motivation. In addition, the presence of various interconnected course components that supported students at different stages of the learning process was experienced as central to learning. Together, these two publications demonstrate that the incorporation of active learning principles outside lectures can substantially improve both learning and motivation.
  • Urinboyev, Rustam; Eraliev, Sherzod (2022)
    Despite the extensive literature on the nexus between civil society and democratization in non-democratic regimes, most existing scholarship focuses on politically oriented and claim-making civil society organizations. While these accounts provide useful insights, they appear to rely on Western-centric understandings of civil society. Undoubtedly, little space exists in non-democratic regimes within which civil society organizations may engage in overt political activism due to governmental restrictions. Notwithstanding these restrictions, there are politically less threatening social arenas, where it is possible to identify informally organized civil society initiatives with the potential to redefine and influence long-term state–society relations. This article argues that what we might think of as civil society initiatives in non-democratic regimes cannot be satisfactorily understood through the lens of Western-centric understandings of civil society. Instead, we should focus on informal civil society initiatives. These processes will be illustrated through the case study of mahalla institutions in Uzbekistan.
  • Weiss, Gerhard; Hansen, Eric; Ludvig, Alice; Nybakk, Erlend; Toppinen, Anne (2021)
    Innovation in the forest sector is a growing research interest and within this field, there is a growing attention for institutional, policy and societal dimensions and particular when it comes to the question of how to support innovativeness in the sector. This Special Issue therefore focuses on governance aspects, relating to and bridging business and political-institutional-societal levels. This includes social/societal factors, goals and implications that have recently been studied under the label of social innovation. Furthermore, the emergence of bioeconomy as a paradigm and policy goal has become a driver for a variety of innovation processes on company and institutional levels. Our article provides a tentative definition of & ldquo;innovation governance & rdquo; and attempts a stateof-art review of innovation governance research in the forest sector. For structuring the research field, we propose to distinguish between organizational/managerial, policy or innovation studies. For the forestry sector, specifically, we suggest to distinguish between studies focusing on (i) innovative governance of forest management and forest goods and services; on (ii) the governance of innovation processes as such, or (iii) on specific (transformational) approaches that may be derived from combined goals such as innovation governance for sustainability, regional development, or a bioeconomy. Studies in the forest sector are picking up new trends from innovation research that increasingly include the role of societal changes and various stakeholders such as civil society organizations and users. They also include public-private partnership models or participatory governance. We finally should not only look in how far research approaches from outside are applied in the sector but we believe that the sector could contribute much more to our general scientific knowledge on ways for a societal transformation to sustainability.
  • Arpalahti, Leena; Laitinen, Alli; Hagström, Jaana; Mustonen, Harri; Kokkola, Arto; Böckelman, Camilla; Haglund, Caj; Holmberg, Carina I. (2018)
    Gastric cancer is the second most common cause of cancer-related mortality worldwide. Accurate prediction of disease progression is difficult, and new biomarkers for clinical use are essential. Recently, we reported that the proteasome-associated deubiquitinating enzyme UCHL5/Uch37 is a new prognostic marker in both rectal cancer and pancreatic ductal adenocarcinoma. Here, we have assessed by immunohistochemistry UCHL5 tumor expression in gastric cancer. The study cohort comprised 650 patients, who underwent surgery in Helsinki University Hospital, Finland, between 1983 and 2009. We investigated the association of cytoplasmic UCHL5 tumor expression to assess clinicopathological parameters and patient survival. Positive cytoplasmic UCHL5 tumor immunoexpression is linked to increased survival of patients with small (