| 1. |
- Malm, Gunilla, et al.
(author)
-
Maternal serum vitamin D level in early pregnancy and risk for preeclampsia : A casecontrol study in Southern Sweden
- 2023
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:2 February
-
Journal article (peer-reviewed)abstract
- Background Preeclampsia is considered a major cause of maternal and fetal morbidity and mortality. The aim of the present case-control study in Sweden was to assess the hypothesized association between low serum vitamin D concentrations in early pregnancy and the risk of developing preeclampsia since vitamin D may play a role in early placental development. Methods The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Serum samples were obtained from a biobank of samples collected in early pregnancy including almost all pregnancies in Southern Sweden. Concentrations of 25-hydroxyvitamin D3 (vitamin D) were analyzed using liquid chromatography-tandemmass- spectrometry (LC/MS/MS). The cases were divided into two categories: i) infants were born before gestational week 34 (early onset) and/or born small-for-gestational age (SGA)(n = 51), ii) and others defined as late onset (n = 245). Vitamin D concentrations were analyzed both as a continuous and a categorized variable. Results When all preeclampsia cases were included in the analyses no consistent patterns were observed. However, the median serum concentrations of vitamin D were significantly lower among the cases who were early onset and/or were born SGA (median 39.2 nmol/L, range 1.2-93.6) as compared to the controls (49.0 nmol/L, 0.1-219; p = 0.01). In addition, high concentrations were statistically significantly associated with a decreased risk of preeclampsia (>66.9 vs ≤30.1 nmol/L; crude OR 0.39, 95% CI 0.16-0.96). When potential confounders were included in the models the associations were even more pronounced. Conclusions Our results support the hypothesis that vitamin D deficiency is a risk factor for preeclampsia, but only in preeclampsia cases who were early-onset and/or were born SGA. Preeclampsia is not a homogenous condition and more studies are needed before vitamin D supplementation during pregnancy can be recommended.
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| 2. |
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| 3. |
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| 4. |
- Bernstone, Christian, et al.
(author)
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Verifiering av struktur och fuktmekaniska beräkningsverktyg : Tillämpning på reaktorinneslutningars betongkonstruktioner, Vercors Fas 1
- 2017
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Reports (other academic/artistic)abstract
- Électricité de France har utanför Paris byggt en 1/3 skalmodell av en reaktorinneslutning motsvarande en fransk fullskalereaktor modell P4. Anläggningen möjliggör studier av hur åldringsprocesser påverkar förspända reaktorinneslutningar. Syftet är att efter de 7 år som ett övergripande forskningsprojektet vid på anläggningen pågår, uppnå påverkan motsvarande den åldring som en fullskalereaktor har utsatts för efter 6o års drift.Konstruktionen har försetts med ett omfattande instrumenteringsprogram som gör det möjligt att följa konstruktionens beteende i tidigt skede och över tid. Ett av anläggningens forskningsprojekt omfattar en benchmark av olika beräkningsverktygs möjlighet att kunna förutse konstruktionens beteende i tidigt skede och under själva åldrandet, dess täthet till följd av åldrandet och beteende under svåra haveriförhållanden. Denna benchmark har genomförts via en öppen inbjudning till intresserade experter att delta. I projektet, benämnt VeRCoRs , bidrar deltagande organisationer med egna modelleringsarbeten utifrån de tre olika teman. Arbetet med det första temat startade 2015 (tidigt skede), därefter följer den åldrade konstruktionen (2017) och svåra haverisituationer (2021). Denna rapport redovisar det arbete som har gjorts för det första temat (Tema 1) inom ramen för ett Energiforskuppdrag.Modelleringsarbetet har till största delen genomförts av LTH i nära samarbete med KTH och Vattenfall. Simuleringar har gjorts för den unga betongens beteende under den ett år långa byggfasen, med hänsyn tagen till betongens hydratation (temperaturberäkningar/värmeutveckling), uttorkning (självuttorkning och fukttransport) och deformationer (temperatur-, fukt-, kryp-, och spänningsrelaterade deformationer). Resultatet har jämförts mot data från anläggningens instrumentering. Dessutom så har en genomgång gjorts av resultaten från övriga deltagares arbeten i Tema 1.Sammanfattningsvis så visar resultaten på de fördelar som finns med att genom avancerade beräkningar verifiera designparametrar och prognostisering av reaktorinneslutningars funktion, men också på utmaningar. Med hjälp av FEmodellering så kan det tidiga skedet efter färdigställd konstruktion beskrivas både vad gäller temperatur- och deformationer med rimlig tillförlitlighet. Det finns dock potential till förbättringar. Även om betongens temperatur kan predikteras noggrant så kan det skilja kraftigt i uppskattningen av inducerade påkänningar. En viktig orsak till dessa skillnader beror på osäkerheter i bestämning av krypning och krympning i betongen tidiga skede.
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| 5. |
- Berta, Judit, et al.
(author)
-
Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
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| 6. |
- Betancourt, Lazaro Hiram, et al.
(author)
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Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
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| 7. |
- Betancourt, Lazaro Hiram, et al.
(author)
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The hidden story of heterogeneous B-raf V600E mutation quantitative protein expression in metastatic melanoma—association with clinical outcome and tumor phenotypes
- 2019
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 11:12
-
Journal article (peer-reviewed)abstract
- In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.
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| 8. |
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| 9. |
- Betancourt, Lazaro Hiram, et al.
(author)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
-
Journal article (peer-reviewed)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 10. |
- Brynielsson, Joel, et al.
(author)
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Using Temporal Analytics for Early Discovery of Upcoming Threats
- 2011
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In: Proceedings of the National Symposium on Technology and Methodology for Security and Crisis Management 2011 (TAMSEC 2011). ; , s. 16-
-
Conference paper (peer-reviewed)abstract
- An ocean of data is available on the web. From this ocean of data, information can in theory be extracted and used by analysts for detecting emergent trends. However, to do this manually is a daunting and nearly impossible task. We describe an implemented semi-automatic system in which data is automatically collected from selected sources, and to which linguistic analysis is applied to extract, e.g., entities and events. The extracted information is automatically transformed into OSINT reports which are clustered and visualized. The user can interact with the system in order to obtain a better awareness of historic as well as emergent trends.
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| 11. |
- Carlsson, Christian J., et al.
(author)
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An evaluation of the interference of hydroxycobalamin with chemistry and co-oximetry tests on nine commonly used instruments
- 2011
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71:5, s. 378-386
-
Journal article (peer-reviewed)abstract
- The administration of hydroxocobalamin (OHCob), alone or with sodium thiosulfate, is a standard therapy for cyanide poisoning. OHCob is a red chromophore, and its interference with co-oximetric and colorimetric laboratory measurements has been evaluated in a few conflicting reports. The interference of OHCob was investigated in samples spiked with 10 different concentrations of OHCob (0-1500 mg/L). The concentration of 73 different analytes was measured using nine different analysers (ABL 800 Flex, Advia 1800, Advia Centaur Xp, Architect ci8200, Immulite 2500, Konelab 30i, Modular Analytics SWA, Synchron LX 20 and Vitros 5.1). All instruments yielded some results that were affected by OHCob at concentrations equivalent to a single therapeutic dose. Of the 73 different analytes, 64% showed interference on at least one instrument. Of all 187 tests performed, 47% were biased with more than 10%. Interference was generally limited to photometric assays, whereas immunological and ion-selective electrode measurements were unaffected. OHCob present in the blood after treatment for cyanide poisoning interfered with many laboratory assays in an unpredictable way, making some results invalid. Some affected tests are important in the treatment of cyanide poisoning. The interference is not solely due to wavelength, but also to chemical interaction. Without delaying the administration of OHCob, blood should, preferably, be drawn in advance, or, at least, the laboratory should be informed about the OHCob treatment. If the laboratory receives OHCob-containing samples, methods and instruments should be selected to minimize bias, and the manufacturer of the OHCob should recommend relevant precautions to customers in the package insert.
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| 12. |
- Gil, Jeovanis, et al.
(author)
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Clinical protein science in translational medicine targeting malignant melanoma
- 2019
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In: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 35:4, s. 293-332
-
Journal article (peer-reviewed)abstract
- Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment. Malignant melanoma is a highly aggressive skin cancer and metastases rapidly extend to the regional lymph nodes (stage 3) and to distal organs (stage 4). Targeted oncotherapy is one of the standard treatment for progressive stage 4 melanoma, and BRAF inhibitors (e.g. vemurafenib, dabrafenib) combined with MEK inhibitor (e.g. trametinib) can effectively counter BRAFV600E-mutated melanomas. Compared to conventional chemotherapy, targeted BRAFV600E inhibition achieves a significantly higher response rate. After a period of cancer control, however, most responsive patients develop resistance to the therapy and lethal progression. The many underlying factors potentially causing resistance to BRAF inhibitors have been extensively studied. Nevertheless, the remaining unsolved clinical questions necessitate alternative research approaches to address the molecular mechanisms underlying metastatic and treatment-resistant melanoma. In broader terms, proteomics can address clinical questions far beyond the reach of genomics, by measuring, i.e. the relative abundance of protein products, post-translational modifications (PTMs), protein localisation, turnover, protein interactions and protein function. More specifically, proteomic analysis of body fluids and tissues in a given medical and clinical setting can aid in the identification of cancer biomarkers and novel therapeutic targets. Achieving this goal requires the development of a robust and reproducible clinical proteomic platform that encompasses automated biobanking of patient samples, tissue sectioning and histological examination, efficient protein extraction, enzymatic digestion, mass spectrometry–based quantitative protein analysis by label-free or labelling technologies and/or enrichment of peptides with specific PTMs. By combining data from, e.g. phosphoproteomics and acetylomics, the protein expression profiles of different melanoma stages can provide a solid framework for understanding the biology and progression of the disease. When complemented by proteogenomics, customised protein sequence databases generated from patient-specific genomic and transcriptomic data aid in interpreting clinical proteomic biomarker data to provide a deeper and more comprehensive molecular characterisation of cellular functions underlying disease progression. In parallel to a streamlined, patient-centric, clinical proteomic pipeline, mass spectrometry–based imaging can aid in interrogating the spatial distribution of drugs and drug metabolites within tissues at single-cell resolution. These developments are an important advancement in studying drug action and efficacy in vivo and will aid in the development of more effective and safer strategies for the treatment of melanoma. A collaborative effort of gargantuan proportions between academia and healthcare professionals has led to the initiation, establishment and development of a cutting-edge cancer research centre with a specialisation in melanoma and lung cancer. The primary research focus of the European Cancer Moonshot Lund Center is to understand the impact that drugs have on cancer at an individualised and personalised level. Simultaneously, the centre increases awareness of the relentless battle against cancer and attracts global interest in the exceptional research performed at the centre.
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| 13. |
-
IMPROVER D2.2 Report of criteria for evaluating resilience
- 2016
-
Reports (other academic/artistic)abstract
- In the recent years, the focus has moved from critical infrastructure protection to that of resilience. But how do we know whether a critical infrastructure is resilient or not, how can it be evaluated, measured and enhanced? Drawing on, combining and developing the ideas of the existing literature and practices, the current report develops a holistic, easy-to-use and computable methodology to evaluate critical infrastructure resilience, called Critical Infrastructure Resilience Index (CIRI). The methodology is applicable to all types of critical infrastructure, including a possibility to tailor it to the specific needs of different sectors, facilities and hazard scenarios. The proposed methodology is especially suitable for organizational and technological resilience evaluation, but permits including also elements of societal resilience indicators to the evaluations. The methodology is based on four levels of hierarchically organized indicators. Level 1 consists of the phases well known from the so-called crisis management cycle. Under these phases, we find sets of Level 2 rather generic indicators. Thus under level 1 ‘Prevention’, for instance, we may find a Level 2 indicator such as ‘Resilient design’, further divided into Level 3 more detailed indicators such as ‘Physical robustness’, ‘Cyber robustness’, ‘Redundancy’, ‘Modularity’, and ‘Independency’. The task is to study these indicators on Level 4 in the context of concrete critical infrastructure facilities and hazard scenarios, that is, applying Level 3 indicators into concrete circumstances. The methodology then permits to transfer quantitative, semi-quantitative and qualitative evaluations of individual sector-specific resilience indicators into uniform metrics, based on process maturity levels. This in turn makes it possible to give a specific critical infrastructure, or its part, a resilience value on the scale 0-5. While the real resilience value becomes clear only when one engages in the analysis of several indicators, the methodology can be used also as a step-by-step measurement and development tool for resilience, without necessary immediately engaging in time-consuming total resilience analysis. The user of this methodology is supposed to be the operator of critical infrastructure, or part of it, in the spirit of self-auditing. In case it would be implemented in a wider scale, in cooperation between the operators and authorities, it would give the authorities a holistic picture about the respective society’s critical infrastructure resilience. In this report, we draw a concise picture of the methodology and illustrate how this methodology could be applied to a specific infrastructure and hazard scenario.
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| 14. |
- Jakobsson, Anders, et al.
(author)
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Vetenskapskommunikation och skolutveckling som en del av den tredje uppgiften
- 2019
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In: En historiker korsar sitt spår. - : Malmö universitet. - 9789178770335 - 9789178770458 ; , s. 221-237
-
Book chapter (other academic/artistic)abstract
- I detta kapitel fokuserar vi hur universitetens samverkan med det omgivande samhället kan bidra med ny forskning och samtidigt verka för spridning av nya forskningsresultat. I forskarskolan Communicate science in school (CSiS) deltar tio lärare i en forskarutbildning där deltagarna efter avslutad utbildning erhåller en licentiatexamen i naturvetenskapernas didaktik. Ett viktigt syfte med forskarskolan är att fortlöpande samla förvaltningschefer, rektorer och forskarstuderande för att diskutera och förstärka skolutveckling i förskolan, grundskolan och gymnasieskolan på vetenskaplig grund. Det innebär att initiera samtal om hur de berörda lärarnas kunskaper ska komma kommunernas skolutveckling till godo efter avlagd examen. Gemensamt för samtliga forskarstuderande har varit att problematisera skolämnenas innehåll i relation till modern forskning i naturvetenskap och teknik men också att ta del av internationell utbildningsvetenskaplig forskning i relation till undervisningsformer och organisering av själva undervisningen.
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| 15. |
- Johansson, Fredrik, et al.
(author)
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Detecting Emergent Conflicts through Web Mining and Visualization
- 2011
-
In: Proceedings of the IEEE European Intelligence and Security Informatics Conference 2011 (EISIC 2011). ; , s. 346-353
-
Conference paper (peer-reviewed)abstract
- An ocean of data is available on the web. From this ocean of data, information can in theory be extracted and used by analysts for detecting emergent trends (trend spotting). However, to do this manually is a daunting and nearly impossible task. We describe a semi-automatic system in which data is automatically collected from selected sources, and to which linguistic analysis is applied to extract, e.g., entities and events. After combining the extracted information with human intelligence reports, the results are visualized to the user of the system who can interact with it in order to obtain a better awareness of historic as well as emergent trends. A prototype of the proposed system has been implemented and some initial results are presented in the paper.
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| 16. |
- Kim, Yonghyo, et al.
(author)
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Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes
- 2020
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
-
Research review (peer-reviewed)abstract
- Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatments have focused on the success of targeted therapies in the MAPK pathway that are based on BRAF (BRAF V600E) and MEK. The majority of patients with tumors that have higher expression of BRAF V600E show poorer prognosis than patients with a lower level of the mutated protein. Based on the molecular basis of melanoma, these findings are supported by distinct tumor phenotypes determined from differences in tumor heterogeneity and protein expression profiles. With these aspects in mind, continued challenges are to: (1) deconvolute the complexity and heterogeneity of MM; (2) identify the signaling pathways involved; and (3) determine protein expression to develop targeted therapies. Here, we provide an overview of the results from protein expression in MM and the link to disease presentation in a variety of tumor phenotypes and how these will overcome the challenges of clinical problems and suggest new promising approaches in metastatic melanoma and cancer therapy.
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| 17. |
- Leosdottir, Margrét, et al.
(author)
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Age and gender differences in the association between Nt-proBNP and glucometabolic disturbances.
- 2011
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In: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 45, s. 294-300
-
Journal article (peer-reviewed)abstract
- Abstract Objectives. Glucometabolic disturbances are associated with myocardial dysfunction. Brain natriuretic peptides (BNP) are used for detecting myocardial dysfunction in clinical practice. However, studies on elderly subjects and gender-specific analyses are sparse. Design. We examined cross-sectional associations between Nt-proBNP and 1) fasting plasma glucose (FPG), and 2) categories of glucometabolic disturbances, in middle-aged and older subjects (1266 men, 526 women), applying multivariate linear regression analysis. Results. FPG was positively correlated with Nt-proBNP among middle-aged men (p = 0.04) and negatively albeit non-significantly (p = 0.1) among middle-aged women. Weaker non-significant correlations were seen among older subjects. Middle-aged men with new-onset and prevalent diabetes had higher Nt-proBNP than the reference group (FPG ≤5.0 mmol/L): 9.53 (p = 0.002) and 8.23 (p = 0.02) vs. 5.71 pmol/L. No differences in Nt-proBNP between categories of glucometabolic disturbance were observed among older men or women. Conclusions. The results indicate an age- and gender difference in the ability of Nt-proBNP to identify myocardial dysfunction in relation to glucometabolic disturbances. Therefore, Nt-proBNP should be used with caution as a general surrogate marker for myocardial dysfunction in this setting.
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| 18. |
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| 19. |
- Malm, Ellen, et al.
(author)
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Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Early Pregnancy and Small for Gestational Age in Southern Sweden
- 2023
-
In: Toxics. - 2305-6304. ; 11:9
-
Journal article (peer-reviewed)abstract
- Small for gestational age (SGA) is considered an adverse birth outcome. Per- and polyfluoralkyl substances (PFAS) have become increasingly investigated as contributing environmental factors, thus far with inconclusive results. The current study aimed to investigate the hypothesized association between increased maternal PFAS levels in early pregnancy and an increased risk for SGA birth. This population-based study used data from a sample of children born in Scania, Southern Sweden, between 1995 and 2009. Two groups were compared: cases born with SGA (n = 298) and non-SGA controls (n = 580). The cases consisted of two subgroups: one included women whose children’s growth in late pregnancy was in the lowest quartile, and another included women from the remaining growth quartiles. Corresponding maternal serum samples were collected from a biobank and analyzed for concentrations of four types of PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) using liquid chromatography–tandem mass spectrometry (LC/MS/MS). The results were combined with information from birth registers and analyzed using Mann–Whitney U-tests and logistic regression—unadjusted as well as adjusted for potential confounders. In conclusion, elevated maternal concentrations of PFAS were not associated with an increased risk of SGA birth. However, significant ORs were observed in a subgroup analysis restricted to women of Nordic origin (unadjusted OR 3.2 and adjusted OR 2.4) for PFHxS.
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| 20. |
- Malm, Erik, et al.
(author)
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Reference shape effects on Fourier transform holography
- 2022
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In: Optics Express. - 1094-4087. ; 30:21, s. 38424-38438
-
Journal article (peer-reviewed)abstract
- Soft-x-ray holography which utilizes an optics mask fabricated in direct contact with the sample, is a widely applied x-ray microscopy method, in particular, for investigating magnetic samples. The optics mask splits the x-ray beam into a reference wave and a wave to illuminate the sample. The reconstruction quality in such a Fourier-transform holography experiment depends primarily on the characteristics of the reference wave, typically emerging from a small, high-aspect-ratio pinhole in the mask. In this paper, we study two commonly used reference geometries and investigate how their 3D structure affects the reconstruction within an x-ray Fourier holography experiment. Insight into these effects is obtained by imaging the exit waves from reference pinholes via high-resolution coherent diffraction imaging combined with three-dimensional multislice simulations of the x-ray propagation through the reference pinhole. The results were used to simulate Fourier-transform holography experiments to determine the spatial resolution and precise location of the reconstruction plane for different reference geometries. Based on our findings, we discuss the properties of the reference pinholes with view on application in soft-x-ray holography experiments.
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| 21. |
- Malm, Helene, et al.
(author)
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CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice.
- 2002
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In: Transplantation. - 1534-6080. ; 73:2, s. 293-297
-
Journal article (peer-reviewed)abstract
- BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model.
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| 22. |
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| 23. |
- Malm, Richard, 1980-, et al.
(author)
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Assessing the structural safety of cracked concrete dams subjectedto harsh environment
- 2019
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In: Sustainable and Safe Dams Around the World. - Canada. - 9780367334222 ; , s. 383-397
-
Conference paper (peer-reviewed)abstract
- As the dams are aging and the design requirements continuously increase, complexanalyses may be required that consider aspects previously excluded in the original design.Due to the harsh environment in cold regions with significant seasonal temperature variations,many con- crete dams have cracked. The development of cracks may result in internal failuremodes, where parts of the dam may fail. These internal failure modes are thereby primarily governedby the material failure of reinforcement and concrete. When assessing cracked hydraulicstructures, how- ever, many design guidelines are based on global safety factors for stability failuremodes, i.e. overturning and sliding, while the partial coefficient methods are used for thestructural design related to material failures. By using a developed design methodology basedon finite element analysis, all these failure modes but also combinations of different failuremodes can be consid- ered. In this paper, the design methodology is presented and implementedto assess the structural safety of a cracked concrete spillway section. The result provides supportfor dam owners on how to manage pillars of concrete dams subjected to extensive cracking.
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| 24. |
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| 25. |
- Priskorn, Lærke, et al.
(author)
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RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity
- 2021
-
In: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 9:6, s. 1828-1842
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Journal article (peer-reviewed)abstract
- Background: Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?. Material and Methods: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.
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| 26. |
- Sanchez, Aniel, et al.
(author)
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Novel functional proteins coded by the human genome discovered in metastases of melanoma patients
- 2020
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In: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 36:3, s. 261-272
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Journal article (peer-reviewed)abstract
- In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research over the last 10 years, and the introduction of novel therapies such as targeted therapies and immunomodulators, the rather dark horizon of the median survival has dramatically changed from under 1 year to several years. With the advent of proteomics, deep-mining studies can reach low-abundant expression levels. The complexity of the proteome, however, still surpasses the dynamic range capabilities of current analytical techniques. Consequently, many predicted protein products with potential biological functions have not yet been verified in experimental proteomic data. This category of ‘missing proteins’ (MP) is comprised of all proteins that have been predicted but are currently unverified. As part of the initiative launched in 2016 in the USA, the European Cancer Moonshot Center has performed numerous deep proteomics analyses on samples from MM patients. In this study, nine MPs were clearly identified by mass spectrometry in MM metastases. Some MPs significantly correlated with proteins that possess identical PFAM structural domains; and other MPs were significantly associated with cancer-related proteins. This is the first study to our knowledge, where unknown and novel proteins have been annotated in metastatic melanoma tumour tissue.
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| 27. |
- Sugihara, Yutaka, et al.
(author)
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Endogenous expression mapping of malignant melanoma by mass spectrometry imaging
- 2018
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 7, s. 1-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Currently, only a limited number of molecular biomarkers for malignant melanoma exist. This is the case for both diagnosing the disease, staging, and efficiently measuring the response to therapy by tracing the progression of disease development and drug impact. There is a great need to identify novel landmarks of disease progression and alterations.METHODS: Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) has been developed within our group to study drug localisation within micro-environmental tissue compartments. Here, we expand further on this technology development and introduce for the first time melanoma tumour tissues to map metabolite localisation utilising high resolution mass spectrometry. MALDI-MSI can measure and localise the distribution pattern of a number of small molecule metabolites within tissue compartments of tumours isolated from melanoma patients. Data on direct measurements of metabolite identities attained at the local sites in tissue compartments has not been readily available as a measure of a clinical index for most cancer diseases. The current development on the mapping of endogenous molecular expression melanoma tumours by mass spectrometry imaging focuses on the establishment of a cancer tissue preparation process whereby a matrix crystal formation is homogenously built on the tissue surface, providing uniform molecular mapping. We apply this micro-preparation technology to disease presentation by mapping the molecular signatures from patient tumour sections.RESULTS: We have automated the process with a micro-technological dispensing platform. This provides the basis for thin film generation of the cancer patient tissues prior to imaging screening. Compartmentalisation of the tumour regions are displayed within the image analysis interfaced with histopathological grading and characterisation.CONCLUSIONS: This enables site localisation within the tumour with image mapping to disease target areas such as melanoma cells, macrophages, and lymphocytes.
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| 28. |
- Villa, Luisa L., et al.
(author)
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Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18
- 2006
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:27-28, s. 5571-5583
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Journal article (peer-reviewed)abstract
- Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naive and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were similar to 12- to 26-fold higher than those observed in baseline-naive women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported. (c) 2006 Elsevier Ltd. All rights reserved.
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| 29. |
- Welinder, Charlotte, et al.
(author)
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A protein deep sequencing evaluation of metastatic melanoma tissues.
- 2015
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Journal article (peer-reviewed)abstract
- Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank) were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation). Fractionation produced higher numbers of protein identifications (4284). Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.
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| 30. |
- Welinder, Charlotte, et al.
(author)
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Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Journal article (peer-reviewed)abstract
- Background Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. Patients and methods Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease.Results In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival. Conclusion In this feasibility study, promising results show the feasibility of relating proteomics to histopathology and clinical outcome, and insight thus can be gained into the molecular processes driving the disease. The combined analysis of histological features including the sample cellular composition with protein expression of each metastasis enabled the identification of novel, differentially expressed proteins. Further studies are necessary to determine whether these putative biomarkers can be utilized in diagnostics and prognostic prediction of metastatic melanoma.
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| 31. |
- Åhs, Magnus, et al.
(author)
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Modelling creep in a pre-stressed mock-up reactor containment : The VeRCoRs 2018 benchmark case
- 2018
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Conference paper (other academic/artistic)abstract
- In this study, a multiphysics model is presented that predicts creep in three months old concrete cylinders subjected to drying. The model includes concrete hydration, and a moisture transport model with relative humidity as the driving potential. These parameters are important to include in order to simulate creep. The model was implemented in the finite element software COMSOL Multiphysics. The calculated axial deformation of the cylinder was compared with measurements performed on an experimental set-up. The model was found to be able to predict the axial deformations with reasonable accuracy. This study is a part of the VeRCoRs 2018 benchmark provided by the Electricité de France, EDF.
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| 32. |
- Åhs, Magnus, et al.
(author)
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Modelling creep in concrete cylinders subjected to different relative humidity levels–the VeRCoRs 2018 benchmark
- 2018
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Conference paper (other academic/artistic)abstract
- In this study, a multiphysics model is presented that predicts creep in three months old concrete cylinders subjected to drying. The model includes concrete hydration, and a moisture transport model with relative humidity as the driving potential. These parameters are important to include in order to simulate creep. The model was implemented in the finite element software COMSOL Multiphysics. The calculated axial deformation of the cylinder was compared with measurements performed on an experimental set-up. The model was found to be able to predict the axial deformations with reasonable accuracy. This study is a part of the VeRCoRs 2018 benchmark provided by the Electricité de France, EDF.
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| 33. |
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| 34. |
- Östling, Mikael, et al.
(author)
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Novel integration concepts for sige-based rf-MOSFETs
- 2005
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In: Proc. Electrochem. Soc.. ; , s. 270-284
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Conference paper (peer-reviewed)abstract
- An overview of critical integration issues for future generation rf-MOSFETs is presented. The process requirements and implementation of selective epitaxy for the source and drain regions is given. In-situ doping of highly boron doped recessed SiGe S/D is demonstrated. Channel region engineering is discussed and 50 nm strained SiGe pMOSFETs are demonstrated. Implementation of high-κ gate dielectrics is presented and device performance is demonstrated for surface channel MOSFETs with a gate stack based on ALD-formed HfO2/Al 2O3. Low frequency noise properties for those devices are analyzed. Contact metallization issues are critical for ultra scaled devices and here the implementation of NiSi on SiGe(C) regions as well as on ultra thin body SOI MOSFETs are presented. Finally, a spacer pattering technology using optical lithography to fabricate sub-50 nm high-frequency MOSFETs is demonstrated.
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