Vertebrate TFPI-2 C-terminal peptides exert therapeutic applications against Gram-negative infections

Background: Tissue factor pathway inhibitor-2 (TFPI-2) is a serine protease inhibitor that exerts multiple physiological and patho-physiological activities involving the modulation of coagulation, angiogenesis, tumor invasion, and apoptosis. In previous studies we reported a novel role of human TFPI-2 in innate immunity by serving as a precursor for host defense peptides. Here we employed a number of TFPI-2 derived peptides from different vertebrate species and found that their antibacterial activity is evolutionary conserved although the amino acid sequence is not well conserved. We further studied the theraputic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model. Results: Hydrophobicity and net charge of many peptides play a important role in their host defence to invading bacterial pathogens. In vertebrates, the C-terminal portion of TFPI-2 consists of a highly conserved cluster of positively charged amino acids which may point to an antimicrobial activity. Thus a number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E. coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement. Under in vitro conditions the peptides displayed anti-coagulant activity by modulating the intrinsic pathway of coagulation and in vivo treatment with the mouse derived VKG24 peptide protects mice from an otherwise lethal LPS shock model. Conclusions: Our results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies

Civil Defence (Re)Emerged : A Multi-Level Perspective on Policy Developments in Post-Crimea Europe

This dissertation examines the (re)emergence of civil defence in Europe in the aftermath of Russia's annexation of Crimea in 2014. More specifically, it investigates the existing conceptions of civil defence and how these are shaped in a multi-level institutional context, focusing on the interplay between national, regional, and international levels. Through the lens of discursive institutionalism, the thesis emphasizes the dynamic relationship between ideas and institutions in shaping security policies, while revealing the limitations of ideational processes’ impact on policy implementation. Drawing on a novel set of data from interviews conducted between 2020 and 2023, and extensive document analysis, the dissertation maps the evolution of Sweden’s contemporary civil defence policy; the Nordic and Baltic states’ approaches to resilience; and the role of NATO and the European Union (EU) in the development of civil defence. Conceptually, it advances understandings of civil defence, resilience, and strategic autonomy within contemporary security paradigms. It pushes the concept of civil defence beyond exclusively nuclear associations; critically analyzes the conceptualization of resilience within the total defence principle; and emphasizes the role of strategic autonomy in strengthening dimensions of civil defence, particularly within the EU. Collectively, the four articles in this dissertation contribute with insights into complex and simultaneous security policy processes taking place in multiple institutional settings, offering a unique snapshot of a transformative era in European security. They emphasize the challenges of translating policy ideas into practice and assess the prospects for enhanced international cooperation, including by underscoring the potential for the EU to serve as a central platform for civil defence collaboration

Development of techniques for measuring the mobility of knee joints in children with Cerebral Palsy

Cerebral Palsy, commonly referred to as CP, is a neurological disorder that results in loss or impairment of motor function, which affects body movement, muscle control, muscle coordination and balance. In Sweden, about 200 children are diagnosed with Cerebral Palsy every year and the disorder can cause imbalances between the muscles. These imbalances can lead to contractures which is equiva- lent to permanent shortening of muscles and stiffness of joints. This can severely affect the mobility of the child and the quality of life. Today, the only way for physicians or physiotherapists to evaluate the movement of the joints, is during a patient’s short visits to the hospital. The purpose of this project was to develop a device that was able to measure the range of motion of the knee during a longer period of time, which could help customize the child’s rehabilitation. The initial approach was to implement two inertial measurement units (IMUs) and find the angle between the sensors. Different solutions on finding the angle was tested without being able to obtain stable data and the project members chose a new approach. Instead of IMUs, a potentiometer was used and stable data was obtained. A prototype was developed in an iterative and incremental product development process and data was collected during different types of physical exercise. The final prototype was wireless, able to collect data during ordinary life activities and had a battery life of over 30 hours. The data was analyzed and the results were accurate but showed that the prototype probably hindered some of the natural movement of the knee. The developed prototype is a step towards being able to measure the knee range of motion during a longer period of time, and could be a tool for physicians and other medical staff when evaluating and rehabilitating children with CP.Utveckling av mätteknik för mätning av rörligheten i knäleder hos barn med Cerebral pares Cerebral pares (CP) är en neurologisk störning som kan leda till förlust eller nedsättning av de motoriska funktioner som påverkar kroppens rörelser, muskelkontroll, koordination och balans. CP kan orsaka obalanser mellan musklerna som kan leda till kontrakturer. Kontrakturer innebär att musklerna förkortas permanent och styvheten i lederna ökar. Muskelförkortning och styva leder kan drastiskt påverka barnets rörlighet och därmed även livskvaliteten. I Sverige diagnostiseras cirka 200 barn varje år med CP och i dagsläget är det enda sättet för läkaren eller fysioterapeuten att utvärdera barnens rörelsefunktion under kortare besök på sjukhuset, 1-2 gånger per år. Därför var syftet med detta projekt att utveckla en prototyp som kunde mäta knäets ledrörlighet under en längre period

NPD Project Evaluation in the Manufacturing Industry

Title: NPD Project Evaluation in the Manufacturing Industry Seminar date: 26 May 2015 Course: FEKN90 Authors: Carl Ekbom and Alexander Wrange Supervisor: Ph.D. Christian Koch Key words: NPD projects, evaluation methods, evaluation criteria, portfolio management, manufacturing industry Purpose: The purpose of this thesis is to increase the understanding of how new project de-velopment (NPD) projects can be evaluated in terms of methods and processes. Furthermore, it aims at scrutinizing the impacts of actors and structures on the evaluation process. Moreo-ver, it aims at identifying what challenges and trade-offs companies face when choosing eval-uation methods and organising processes for NPD project evaluation. Method: Qualitative multiple-case study of three large manufacturing companies in Sweden, with embedded design and influence from action research. Theoretical perspectives: Theories in financial project evaluation, project evaluation criteria, agency theory, portfolio management Empirical foundation: Semi-structures, in-depth interviews with a total of ten managers with different functions at the three case companies. Conclusions: Financial methods are essential for NPD project evaluation, but complementary criteria that consider the complexity of NPD projects are necessary to include. Portfolio man-agement can be used as a process to combine financial methods and complementary criteria. The impact of actors limits objectivity, but they provide important knowledge and experience. The structures serve as a cross-functional framework to guarantee the involvement of actors from different functions in the evaluation process. Companies face several challenges in rela-tion to NPD project evaluation and have to choose between using a comprehensible or sophis-ticated evaluation method, a common method or different methods, and the same set of crite-ria for all projects or use different sets for different types of projects

A rare case of metastatic atypical meningioma that highlights the shortcomings of treatment options at present

We report a case of a locally invasive recurrent atypical meningioma in the temporal region with late onset of meningioma lung metastasis. The patient was diagnosed in early adolescence with an atypical meningioma believed to be radiotherapy induced following treatment of a benign pilocytic astrocytoma in the hypothalamus region at 6 years of age. Even though the patient underwent several surgical and radiotherapy treatments, the intracranial meningioma kept growing and was locally invasive. The patient received experimental treatment with bevacizumab, a vascular endothelial growth factor A (VEGF-A)-inhibitor, for 4 years from age 26. Treatment was withdrawn after proven tumor growth on routine control MRI. A DOTA-TOC PET-CT-scan was performed to evaluate the DOTA-TOC somatostatin receptor number for possible SSTR (somatostatin receptor targeted therapy). In the included scan plan multiple lung metastasis were detected and later verified. Genomic tumor sequencing was performed, but no targeted treatment options were found. Instead, the patient finally, as the last treatment option, underwent 4 series of SSTR-targeted therapy (Lutetium DOTA-TOC). Unfortunately, the intracranial tumor component significantly progressed during the final stages of the treatment and the patient died less than a year after treatment was withdrawn at age 32. This case story illustrates the shortcomings of atypical/anaplastic meningioma treatment strategies at present and highlights the possibility of extracranial metastasis.</p

Allosteric Modulators of Steroid Hormone Receptors : Structural Dynamics and Gene Regulation

Peer reviewedPublisher PD

Varför är Qatar inte en demokrati? En fallstudie med utgångspunkt i moderniseringsteorin

Qatar är ett ekonomiskt välmående land, med ett starkt auktoritärt politiskt system. Landet är därför ett avvikande fall ur moderniseringsteorin, som menar att ekonomiskt välmående leder till demokrati. Vi börjar med att förklara varför Qatar avviker från moderniseringsteorin, och fortsätter sedan med att pröva ett antal teorier och perspektiv, för att se om dessa bättre förklarar frånvaron av demokrati i landet. Följande teorier och ämnesområden diskuteras: politisk kultur och civilt samhälle, islams inverkan, sultanism, aktörsteoretiska perspektiv, rational choice, och slutligen oljans inverkan på Qatar. Två företeelser talar för demokratins frånvaro, islams starka närvaro i kulturen och politiken, samt landets ekonomiska beroende av oljeintäkter. Dessutom ger aktörsteorier och rational choice en lämplig teoretisk förklaring till frånvaron av demokrati i Qatar

Ecological impacts of non-native Pacific oysters (Crassostrea gigas) and management measures for protected areas in Europe

Pacific oysters are now one of the most ‘globalised’ marine invertebrates. They dominate bivalve aquaculture production in many regions and wild populations are increasingly becoming established, with potential to displace native species and modify habitats and ecosystems. While some fishing communities may benefit from wild populations, there is now a tension between the continued production of Pacific oysters and risk to biodiversity, which is of particular concern within protected sites. The issue of the Pacific oyster therefore locates at the intersection between two policy areas: one concerning the conservation of protected habitats, the other relating to livelihoods and the socio-economics of coastal aquaculture and fishing communities. To help provide an informed basis for management decisions, we first summarise evidence for ecological impacts of wild Pacific oysters in representative coastal habitats. At local scales, it is clear that establishment of Pacific oysters can significantly alter diversity, community structure and ecosystem processes, with effects varying among habitats and locations and with the density of oysters. Less evidence is available to evaluate regional-scale impacts. A range of management measures have been applied to mitigate negative impacts of wild Pacific oysters and we develop recommendations which are consistent with the scientific evidence and believe compatible with multiple interests. We conclude that all stakeholders must engage in regional decision making to help minimise negative environmental impacts, and promote sustainable industry development

Are silicone foul-release coatings a viable and environmentally sustainable alternative to biocidal antifouling coatings in the Baltic Sea region?

To combat unwanted fouling on immersed hulls, biocidal antifouling coatings are commonly applied to vessels trafficking the Baltic Sea. Here, the efficacy, environmental sustainability and market barriers of silicone foul-release coatings (FRCs) was assessed for this region to evaluate their viability as replacements for biocidal coatings. Coated panels were exposed statically over a 1 year period at three locations in the Baltic Sea region to assess the long-term performance of a biocide-free FRC and two copper coatings. The FRC was found to perform equally well or significantly better than the copper coatings. Even though most silicone FRCs on the market are biocide-free, a review of the literature regarding toxic effects and the identity and environmental fate of leachables shows that they may not be completely environmentally benign, simply for the lack of biocides. Nonetheless, FRCs are substantially less toxic compared to biocidal antifouling coatings and their use should be promoted

Näkökulmia kestävän kehityksen työelämätarpeisiin

Vuonna 2022 julkaistujen ammattikorkeakoulujen yhteisten osaamisten mukaan kaikkien amk-tutkinnoista valmistuvien edellytetään tuntevan kestävän kehityksen periaatteet, edistävän niiden toteutumista sekä toimivan vastuullisesti ammattilaisena ja yhteiskunnan jäsenenä. Tässä artikkelikokoelmassa valotetaan, millaista kestävyysosaamista eri aloilla tarvitaan vuonna 2024 ja millaisia näkemyksiä työelämän edustajilla on korkeakouluista valmistuneiden osaamisesta. Julkaisu on laadittu osana Arene ry:n Kestävä koulutus -ryhmän työtä