| 1. |
- Abrahamsson, Olle, et al.
(författare)
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Opinion Dynamics with Random Actions and a Stubborn Agent
- 2019
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Ingår i: CONFERENCE RECORD OF THE 2019 FIFTY-THIRD ASILOMAR CONFERENCE ON SIGNALS, SYSTEMS & COMPUTERS. - : IEEE. - 9781728143002 ; , s. 1486-1490
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Konferensbidrag (refereegranskat)abstract
- We study opinion dynamics in a social network with stubborn agents who influence their neighbors but who themselves always stick to their initial opinion. We consider first the well-known DeGroot model. While it is known in the literature that this model can lead to consensus even in the presence of a stubborn agent, we show that the same result holds under weaker assumptions than has been previously reported. We then consider a recent extension of the DeGroot model in which the opinion of each agent is a random Bernoulli distributed variable, and by leveraging on the first result we establish that this model also leads to consensus, in the sense of convergence in probability, in the presence of a stubborn agent. Moreover, all agents opinions converge to that of the stubborn agent.
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| 2. |
- Alveteg, Mattias, et al.
(författare)
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Vad räknas som belägg för studenters måluppfyllelse?
- 2018
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Ingår i: 10:e Pedagogiska Inspirationskonferensen 2018. - 2003-3761 .- 2003-377X. ; 10
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Konferensbidrag (refereegranskat)abstract
- Universitetskanslerämbetet (UKÄ) ställer numera krav på svenska lärosäten att vi ska utvärdera oss själva. Vi på LTH bör då gemensamt försöka hitta sätt att uppfylla UKÄs krav som även ger de verktyg vi själva behöver för att förbättra våra utbildningars kvalitét.Hur tar vi reda på våra utbildningars styrkor och svagheter och vad vi kan göra för att förbättra dem ytterligare? Ett sätt är att undersöka hur väl studenterna uppfyller examensmålen. Vad som ska räknas som belägg för studenters måluppfyllelse är dock svårt, av flera olika skäl. Vår rekommendation blir att triangulera olika typer av belägg samt att tydligt involvera institutionerna i arbetet.
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| 3. |
- Andersson, Anna-Maria, 1990-
(författare)
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Mycobacterium tuberculosis and HIV coinfection : Effects on innate immunity and strategies to boost the immune response
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) still remains a big threat today, being the leading cause of death by a single infectious agent. The TB epidemic is fueled by HIV along with the increasing drug-resistance which prolongs the already long treatment duration and decreases the success rate for curing TB. In most cases an infection results in latency but HIV patients have a 20-30 times higher risk of developing active TB. There are around 36.9 million people living with HIV globally, with the highest burden in Africa. Although there are effective treatments against the disease, there is no cure for AIDS and the availability of the lifelong treatment is limited in low-income countries were the burden is highest. HIV infection causes an immunodeficiency characterized by the progressive loss of CD4 T cells which increases the risk of opportunistic infections, and infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB. Mtb spreads through aerosols from one person with active tuberculosis to a healthy person. Upon inhalation the bacteria are phagocytosed by alveolar macrophages that secrete cytokines and chemokines to recruit more cells, such as dendritic cells, macrophages and lymphocytes, leading to the formation of a granuloma. During a single TB infection the bacteria are usually contained within the granuloma, but HIV can disrupt the stable granuloma, causing a rupture and dissemination of Mtb. This inflammatory site is also beneficial to HIV since it promotes replication of the virus within infected cells. HIV and Mtb are two successful intracellular pathogens able to avoid immune defense mechanisms both of the innate and adaptive immunity in order to persist and replicate. Their virulence factors can manipulate or inhibit cell signaling, phagosome maturation, autophagy, ROS production, apoptosis and antigen presentation, to promote survival. Boosting of immune defenses with host-directed therapies (HDT) has been proposed as a treatment strategy against TB, either alone or adjunctive to the current regimen.In this thesis, ways to boost the innate immune responses in Mtb and HIV coinfected macrophages were investigated, along with studies of the effect of HIV on Mtb antigen presentation in coinfected dendritic cells. The initial hypothesis was that autophagy induction through inhibition of mammalian target of rapamycin (mTOR) could suppress Mtb growth in HIV coinfected macrophages. However, during a low grade infection, autophagy induction increased Mtb replication due to a decreased autophagic flux and acidification of Mtb phagosomes. A general autophagic flux was induced, although not localized to the Mtb phagosomes, thus not inducing a xenophagy (autophagy of intracellular pathogens). Other ways of inducing autophagy or boosting the response in coinfected macrophages might be more beneficial and therefore the effect of efferocytosis was investigated. Uptake of apoptotic neutrophils by coinfected macrophages did not induce autophagy but enhanced the control of Mtb by other means. Upon efferocytosis, the macrophages acquired active myeloperoxidase (MPO) from the neutrophils that suppressed Mtb growth. The coinfected macrophages also produced more ROS after efferocytosis. The inhibition of Mtb growth could thus be mediated by MPO and the increased ROS production either directly or indirectly.The possibility to boost the innate immunity could prove to be important during an HIV coinfection, when the adaptive immunity is deficient. In addition to the well-known decline in CD4 T cells during the course of HIV progression, we found that HIV infection of dendritic cells inhibited antigen presentation by suppressing the expression of HLA-DR and co-stimulatory molecules on coinfected dendritic cells. Furthermore, HIV reduced secretion of pro-inflammatory cytokines and suppressed antigen processing through inhibition of autophagy. This impaired antigen presentation in coinfected dendritic cells resulted in a decreased activation and response of Mtb-specific CD4 T cells.In conclusion, this thesis shows how HIV can manipulate antigen presentation in Mtb coinfected dendritic cells and subsequently inhibit the adaptive immune response. It also contributes to insights on how efferocytosis of apoptotic neutrophils can boost the innate immune responses during coinfection. Lastly, autophagy induction through mTOR inhibition does not enhance protection against TB. Induction of autophagy should therefore be handled with care, particularly during HIV coinfection.
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| 4. |
- Angelika Ihle, Michaela, et al.
(författare)
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HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat.
- 2016
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Ingår i: The journal of pathology. Clinical research. - : Wiley. - 2056-4538. ; 2:2, s. 59-71
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Tidskriftsartikel (refereegranskat)abstract
- Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b has been shown to be a potential biomarker for sensitivity to HDACi therapy in cutaneous T-cell lymphoma and hepatocellular carcinoma. We aimed to evaluate HR23b as a candidate biomarker for HDACi response in sarcomas and gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed comprehensively by western blot in sarcoma and GIST cell lines covering all major clinically relevant subtypes. MTT assay and ApoTox-Glo(TM) Triplex assay were performed after treatment with vorinostat, belinostat, mocetinostat and entinostat. HR23b protein expression was measured under HDACi treatment. Furthermore, HR23b expression levels were immunohistochemically determined in a large set of 523 clinical samples from sarcoma and GIST patients. Western blot analyses showed that sarcomas differ significantly in their expression of HR23b protein. All HDACi were able to regulate proliferation and apoptosis in vitro. Sensitivity to vorinostat correlated significantly with HR23b protein expression. Immunohistochemical prevalence screening in clinical samples of relevant adult-type tumours revealed that 12.5% of sarcomas (among them malignant peripheral nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic effects in sarcomas depending on the expression level of HR23b. These findings suggest that HR23b represents a candidate biomarker for HDACi sensitivity in certain sarcoma types and in GIST.
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| 5. |
- Bojmar, Linda
(författare)
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Metastatic Mechanisms in Malignant Tumors
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ultimate cause of cancer related deaths is metastasis. This thesis is about three of the main human cancers; breast, colorectal and pancreatic cancer, that together account for more than 25% of the cancer-related deaths worldwide. The focus of the thesis is the spread of cancer, metastasis, and the aim was to investigate mechanisms that can be of importance for this process. We analyzed patient samples to validate the role of epithelialto-mesenchymal transition in vivo and found regulations of many related factors. However, these changes tend to fluctuate along the metastatic process, something which makes targeting complicated. We, moreover, focused on the influence of the tumor microenvironment for metastatic spread. In pancreatic cancer, the stroma constitutes the main part of many tumors. We analyzed the crosstalk between tumor and stromal cell and focused on the mediating inflammatory factor interleukin-1 (IL-1) and regulation of microRNAs. The results showed that the most commonly mutated factor in pancreatic cancer, KRAS, associates with the expression of IL-1 and subsequent activation of stromal cells. Blocking KRAS signaling together with IL-1 blockage give a more pronounced effect on in vitro proliferation and migration of cancer cells and suggests the use of a combination therapy. The cancer-associated activation of the stroma was found to be related to changes in microRNA expression. microRNA was analyzed separately in epithelial cells and stromal cells after microdissection of matched samples of primary and secondary tumors of breast and colorectal cancers. miR-214 and miR-199a were upregulated in stroma associated with progressive tumors and in pancreatic cancer stroma we could show that their expression alters the activation of stromal cells and thereby the growth and migratory ability of associated pancreatic tumor cells. In breast and colorectal cancers we found several common microRNAs to be up- or downregulated in line with progression. We could show that one of these candidates, miR-18a, had a prognostic value in metastatic breast cancer. To further develop these studies we analyzed this microRNA in circulating microvesicles, i.e. exosomes, and investigated their role in the preparation of a pre-metastatic niche. MicroRNAs are stable biomarkers in the circulation, especially protected in exosomes, which can moreover specifically deliver their message to recipient cells. These studies facilitate the understanding of metastatic behavior and suggest new targets to stop cancer metastasis.
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| 6. |
- Bojmar, Linda, et al.
(författare)
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miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.
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| 7. |
- Carrasco, David, et al.
(författare)
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Characterization of olfactory sensory neurons in the red clover seed weevil, Protapion trifolii (Coleoptera : Brentidae) and comparison to the closely related species P. fulvipes
- 2019
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Ingår i: Journal of Insect Physiology. - : Elsevier BV. - 0022-1910 .- 1879-1611. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- Protapion trifolii and P. fulvipes (Coleoptera: Brentidae) are major pests in European clover seed production. Previous studies have reported a high host plant fidelity of these weevils for red and white clover species, respectively, driven by host plant olfactory cues. Given the specific host preferences observed in these weevils, we aimed to elucidate to which extent such selectivity is reflected in their peripheral olfactory systems. Using an electrophysiological approach, we performed the first functional characterisation of olfactory sensory neurons (OSNs) in P. trifolii to a panel of volatile compounds emitted by red clover plants, and compared the results with the reported OSN types of P. fulvipes. Nineteen OSN classes were characterized in P. trifolii, with the majority of these neurons responding strongly to common volatiles released by the host plant. Based on response profiles, eight of these OSN classes have clear matches to OSN classes in P. fulvipes. The OSN colocalisation patterns and antennal frequency of these classes are similar in the two species. Additionally, the responses of these OSNs are generally highly conserved in the two species, with clear response shifts only revealed for two of the OSN classes. These response shifts in combination with additional response dissimilarities for compounds that vary in abundance between red and white clover plants may underlie the species-specific host preferences. Further behavioural and field experiments should focus on these differentially detected compounds to elucidate their potential role in host selection and use in semiochemical-based control of these pests.
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| 8. |
- DAWODY, JAZAER, 1959, et al.
(författare)
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An integrated system for energy-efficient exhaust aftertreatment for heavy-duty vehicles
- 2015
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Ingår i: Renewable Energy in the Service of Mankind. - Cham : Springer International Publishing. - 9783319177779 - 9783319177762 ; 1, s. 133-143
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- © Springer International Publishing Switzerland 2015. This chapter presents a unique system approach applied in a joint academic- industrial research programme, E4 Mistra, to attain the goals of high energy efficiency and low emissions in an exhaust aftertreatment system for heavy-duty vehicles. The high energy efficiency is achieved by heat recuperation, onboard hydrogen production for NOx reduction, and by finding new solutions for making the aftertreatment system active at low exhaust temperatures. To reach low particulate emissions, a mechanical filter using a sintered metal powder is developed and coated with catalytic material to improve the soot oxidation efficiency. Low NOx emissions are achieved by an efficient NOx reduction catalyst. The integrated E4 Mistra system comprises four technological advances: thermoelectric (TE) materials for heat recuperation, catalytic reduction of NOx over innovative catalyst substrates using either the onboard diesel or biodiesel, H2 from a high-efficiency fuel reformer, and particulate filtration over a porous metal filter. The TE materials are used in a TE generator (TEG) which converts thermal energy into electricity. The TEG is used to recuperate heat from the exhaust-gas recirculation (EGR) circuit of heavy-duty trucks and is expected to generate ~1 kW electric power from 20 kW heat in the exhaust gas. The TEG is integrated in a plate heat exchanger (HEX) designed particularly for this application. Apart from the knowledge and experiences in TEG and heat exchange technologies, a thorough fluid dynamics and TE analysis are performed in this project to understand the governing processes and optimize the system accordingly. The components of the E4 Mistra system are explained in the chapter in addition to test results, which show the system's capacity for H2 production, NOx conversion, particulate matter filtration and soot oxidation, and finally electric power generation via heat recuperation from the exhaust gas using the developed TEG-HEX system.
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| 9. |
- Ekman, Simon, et al.
(författare)
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A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma : A phase I clinical trial
- 2016
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:2, s. 140-148
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors.MATERIAL AND METHODS: This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing.RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.
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| 10. |
- Glad, Camilla A M, 1981, et al.
(författare)
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The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population.
- 2015
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 172:2, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the hypothesis that the growth hormone (GH) receptor (GHR) d3/fl polymorphism influences anthropometry and body composition in the general population. Design and Setting: The Swedish Obese Subjects (SOS) reference study is a cross-sectional population-based study, randomly selected from a population registry. A sub-group of the population-based Malmö Diet and Cancer Study (MDC-CC) was used as a replication cohort. Methods: The SOS reference study comprises 1135 subjects (46.2% men), with an average age of 49.5 yrs. The MDC-CC includes 5451 successfully genotyped subjects (41.5% men), with an average age of 57.5 yrs. GHR d3/fl genotypes were determined using tagSNP rs6873545. Linear regression analyses were used to test for genotype - phenotype associations. Results: In the SOS reference study, subjects homozygous for the d3-GHR weighed approximately four kilos more (p=0.011), had larger waist-to-hip ratio (WHR, p=0.036), waist circumference (p=0.016) and more fat free mass estimated from total body potassium (TBK, p=0.026) than grouped fl/d3 and fl/fl subjects (d3-recessive genetic model). The association with WHR was replicated in the MDC-CC (p=0.002), but not those with other anthropometric traits. Conclusions: In this population-based study the GHR d3/fl polymorphism was found to be of functional relevance and associated with central adiposity, such that subjects homozygous for the d3-GHR showed an increased abdominal obesity.
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