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1.
  • Adam, A, et al. (author)
  • Abstracts from Hydrocephalus 2016.
  • 2017
  • In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
  • Journal article (peer-reviewed)
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  • Fedirko, V., et al. (author)
  • Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case-control study
  • 2014
  • In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 60:4, s. 1222-1230
  • Journal article (peer-reviewed)abstract
    • The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n=138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR=0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend=0.04; per 10 nmol/L increase: IRR=0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. © 2014 by the American Association for the Study of Liver Diseases.
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  • Buckland, G., et al. (author)
  • Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
  • 2014
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:10, s. 2504-2511
  • Journal article (peer-reviewed)abstract
    • There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. What's new? Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire-based associations between dietary factors and bladder cancer risk.
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6.
  • Malm, Carl Johan, et al. (author)
  • Preoperative platelet function predicts perioperative bleeding complications in ticagrelor-treated cardiac surgery patients: a prospective observational study
  • 2016
  • In: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 117:3, s. 309-315
  • Journal article (peer-reviewed)abstract
    • Background: Treatment with P2Y(12) receptor antagonists increases the risk for perioperative bleeding, but there is individual variation in the antiplatelet effect and time to offset of this effect. We investigated whether preoperative platelet function predicts the risk of bleeding complications in ticagrelor-treated cardiac surgery patients. Methods: Ninety patients with ticagrelor treatment within <5 days of surgery were included in a prospective observational study. Preoperative platelet aggregation was assessed with impedance aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating peptide (TRAP) as initiators. Severe bleeding complications were registered using a new universal definition of perioperative bleeding. The accuracy of aggregability tests for predicting severe bleeding was assessed using receiver operating characteristic (ROC) curves, which also identified optimal cut-off values with respect to sensitivity and specificity, based on Youden's index. Results: The median time from the last ticagrelor dose to surgery was 35 (range 4-108)h. The accuracy of platelet function tests to predict severe bleeding was highest for ADP [area under the ROC curve 0.73 (95% confidence interval 0.63-0.84, P<0.001); TRAP 0.61 (0.49-0.74); AA 0.53 (0.40-0.66)]. The optimal cut-off for ADP-induced aggregation was 22 U. In subjects with ADP-induced aggregation below the cut-off value, 24/38 (61%) developed severe bleeding compared with 8/52 (14%) when aggregation was at or above the cut-off value (P<0.001). The positive and negative predictive values for this cut-off value were 63 and 85%, respectively. Conclusions: Preoperative ADP-induced platelet aggregability predicts the risk for severe bleeding complications in ticagrelor-treated cardiac surgery patients.
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  • Cadenas, J., et al. (author)
  • Regulation of human oocyte maturation in vivo during the final maturation of follicles
  • 2023
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 38:4, s. 686-700
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION: Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo? SUMMARY ANSWER: The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. WHAT IS KNOWN ALREADY: Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-β family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. MAIN RESULTS AND THE ROLE OF CHANCE: All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12-17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12-17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus-oocyte complex during the follicle aspiration from 0 to 32 h. WIDER IMPLICATIONS OF THE FINDINGS: Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared.
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  • Nilsson, C. L., et al. (author)
  • Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
  • 2013
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 134-149
  • Journal article (peer-reviewed)abstract
    • A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC–MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
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  • Stiel, H., et al. (author)
  • 2D and 3D Nanoscale Imaging Using High Repetition Rate Laboratory-Based Soft X-Ray Sources
  • 2018
  • In: X-Ray Lasers 2016 - Proceedings of the 15th International Conference on X-Ray Lasers. - Cham : Springer International Publishing. - 9783319730240 ; 202, s. 265-272
  • Conference paper (peer-reviewed)abstract
    • In this contribution, we report about tomographic nanoscale imaging using a laser-produced plasma-based laboratory transmission X-ray microscope (LTXM) in the water window. The soft X-ray radiation of the LTXM is provided by a high average power laser-produced (1.3 kHz repetition rate, 0.5 ns pulse duration, 140 W average power) plasma source, a multilayer condenser mirror, an objective zone plate, and a back-illuminated CCD camera as a detector. In the second part of the contribution, we will present recent results on holography and coherent diffraction imaging using our high repetition rate X-ray laser. We will discuss advantages of these methods and its potential for nanoscale imaging.
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  • Sävblom, C, et al. (author)
  • Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA
  • 2009
  • In: International Journal of Andrology. - : Wiley-Blackwell. - 0105-6263 .- 1365-2605. ; 32:5, s. 479-485
  • Journal article (peer-reviewed)abstract
    • Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G-allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.
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  • Tsilidis, Konstantinos K., et al. (author)
  • Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
  • 2014
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:2, s. 372-381
  • Journal article (peer-reviewed)abstract
    • The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer. What's new? Emerging evidence suggests that men with type 2 diabetes are at lower risk to develop prostate cancer. Using data obtained within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors show that the prostate cancer risk was, indeed, reduced by 26% in men with type 2 diabetes but no association with cancer stage or grade was observed. In a subset of men for whom data on circulating hormones were available, levels of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in those with diabetes as compared to those without diabetes, giving clues to how having diabetes could affect prostate cancer development.
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  • von Korff Schmising, C., et al. (author)
  • Imaging Non-Local Magnetization Dynamics
  • 2016
  • In: Synchrotron Radiation News. - : Informa UK Limited. - 0894-0886 .- 1931-7344. ; 29:3, s. 26-31
  • Journal article (peer-reviewed)abstract
    • Many fundamental processes in magnetism take place on a nanometer length and sub-picosecond time scale. An important example of such phenomena in magnetism is ultrafast, spin-polarized transport of laser-excited hot electrons, which is now being recognized as playing a crucial role for novel spintronic devices and for optically induced magnetic switching. Recent experimental examples include the demonstration of all-optical helicity dependent control of spin-polarized currents at interfaces [1], the design of novel and efficient terahertz emitters [2], and nanoscale spin reversal in chemically heterogeneous GdFeCo driven by non-local transfer of angular momentum [3]. In particular, for advanced information technologies with bit densities already exceeding 1 terabit per square inch with bit cell dimensions of (15 × 38 nm2) [4], it is of fundamental importance to understand and eventually control the mechanisms responsible for optically induced spin dynamics on the nanoscale.
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  • Ye, L, et al. (author)
  • Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.
  • 2003
  • In: Journal of Medicinal Chemistry. ; 24;46:9, s. 1580-8
  • Journal article (peer-reviewed)abstract
    • Endogenous thyroid receptor hormones 3,5,3',5'-tetraiodo-l-thyronine (T(4), 1) and 3,5,3'-triiodo-l-thyronine (T(3), 2) exert a significant effects on growth, development, and homeostasis in mammals. They regulate important genes in intestinal, skeletal, and cardiac muscles, the liver, and the central nervous system, influence overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood and overall sense of well being. The literature suggests many or most effects of thyroid hormones on the heart, in particular on the heart rate and rhythm, are mediated through the TRalpha(1) isoform, while most actions of the hormones on the liver and other tissues are mediated more through the TRbeta(1) isoform of the receptor. Some effects of thyroid hormones may be therapeutically useful in nonthyroid disorders if adverse effects can be minimized or eliminated. These potentially useful features include weight reduction for the treatment of obesity, cholesterol lowering for treating hyperlipidemia, amelioration of depression, and stimulation of bone formation in osteoporosis. Prior attempts to utilize thyroid hormones pharmacologically to treat these disorders have been limited by manifestations of hyperthyroidism and, in particular, cardiovascular toxicity. Consequently, development of thyroid hormone receptor agonists that are selective for the beta-isoform could lead to safe therapies for these common disorders while avoiding cardiotoxicity. We describe here the synthesis and evaluation of a series of novel TR ligands, which are selective for TRbeta(1) over TRalpha(1). These ligands could potentially be useful for treatment of various disorders as outlined above. From a series of homologous R(1)-substituted carboxylic acid derivatives, increasing chain length was found to have a profound effect on affinity and selectivity in a radioreceptor binding assay for the human thyroid hormone receptors alpha(1) and beta(1) (TRalpha(1) and TRbeta(2)) as well as a reporter cell assay employing CHOK1-cells (Chinese hamster ovary cells) stably transfected with hTRalpha(1) or hTRbeta(1) and an alkaline phosphatase reporter-gene downstream thyroid response element (TRAFalpha(1) and TRAFbeta(1)). Affinity increases in the order formic, acetic, and propionic acid, while beta-selectivity is highest when the R(1) position is substituted with acetic acid. Within this series 3,5-dibromo-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (11a) and 3,5-dichloro-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (15) were found to reveal the most promising in vitro data based on isoform selectivity and were selected for further in vivo studies. The effect of 2, 11a, and 15 in a cholesterol-fed rat model was monitored including potencies for heart rate (ED(15)), cholesterol (ED(50)), and TSH (ED(50)). Potency for tachycardia was significantly reduced for the TRbeta selective compounds 11a and 15 compared with 2, while both 11a and 15 retained the cholesterol-lowering potency of 2. This left an approximately 10-fold therapeutic window between heart rate and cholesterol, which is consistent with the action of ligands that are approximately 10-fold more selective for TRbeta(1). We also report the X-ray crystallographic structures of the ligand binding domains of TRalpha and TRbeta in complex with 15. These structures reveal that the single amino acid difference in the ligand binding pocket (Ser277 in TRalpha or Asn331 in TRbeta) results in a slightly different hydrogen bonding pattern that may explain the increased beta-selectivity of 15.
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  • Almeida, Natália, et al. (author)
  • Mapping the melanoma plasma proteome (MPP) using single-shot proteomics interfaced with the WiMT database
  • 2021
  • In: Cancers. - : MDPI AG. - 2072-6694. ; 13:24
  • Journal article (peer-reviewed)abstract
    • Plasma analysis by mass spectrometry-based proteomics remains a challenge due to its large dynamic range of 10 orders in magnitude. We created a methodology for protein identification known as Wise MS Transfer (WiMT). Melanoma plasma samples from biobank archives were directly analyzed using simple sample preparation. WiMT is based on MS1 features between several MS runs together with custom protein databases for ID generation. This entails a multi-level dynamic protein database with different immunodepletion strategies by applying single-shot proteomics. The highest number of melanoma plasma proteins from undepleted and unfractionated plasma was reported, mapping >1200 proteins from >10,000 protein sequences with confirmed significance scoring. Of these, more than 660 proteins were annotated by WiMT from the resulting ~5800 protein sequences. We could verify 4000 proteins by MS1t analysis from HeLA extracts. The WiMT platform provided an output in which 12 previously well-known candidate markers were identified. We also identified low-abundant proteins with functions related to (i) cell signaling, (ii) immune system regulators, and (iii) proteins regulating folding, sorting, and degradation, as well as (iv) vesicular transport proteins. WiMT holds the potential for use in large-scale screening studies with simple sample preparation, and can lead to the discovery of novel proteins with key melanoma disease functions.
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  • Andersson, J. Y., et al. (author)
  • Quantum structure based infrared detector research and development within Acreo's centre of excellence IMAGIC
  • 2010
  • In: Infrared physics & technology. - : Elsevier BV. - 1350-4495 .- 1879-0275. ; 53:4, s. 227-230
  • Journal article (peer-reviewed)abstract
    • Acreo has a long tradition of working with quantum structure based infrared (IR) detectors and arrays. This includes QWIP (quantum well infrared photodetector), QDIP (quantum dot infrared photodetector), and InAs/GaInSb based photon detectors of different structure and composition. It also covers R&D on uncooled microbolometers. The integrated thermistor material of such detectors is advantageously based on quantum structures that are optimised for high temperature coefficient and low noise. Especially the SiGe material system is preferred due to the compatibility with silicon technology. The R&D work on IR detectors is a prominent part of Acreo's centre of excellence "IMAGIC" on imaging detectors and systems for non-visible wavelengths. IMAGIC is a collaboration between Acreo, several industry partners and universities like the Royal Institute of Technology (KTH) and Linkoping University. (C) 2010 Elsevier B.V. All rights reserved.
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  • Betancourt, Lazaro Hiram, et al. (author)
  • The human melanoma proteome atlas-Defining the molecular pathology
  • 2021
  • 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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26.
  • Billstrom, R., et al. (author)
  • Acute myeloid leukemia with inv(16)(p13q22) : Involvement of cervical lymph nodes and tonsils is common and may be a negative prognostic sign
  • 2002
  • In: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 71:1, s. 15-19
  • Journal article (peer-reviewed)abstract
    • Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant t(16,16)(p13,q22), is strongly associated with the FAB subtype M4Eo. A high incidence of CNS involvement was reported in the 1980s, but otherwise little is known about the pattern of extamedullary leukemia (EML) manifestations in this AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML cases with inv(16)/t(16,16) from southern Sweden. In general, these AMLs displayed the clinical features that have previously been described as characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo morphology, and a favorable prognosis. However, CNS leukemia was only seen in relapse in one patient diagnosed in 1980, whereas the most common EML manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical with or without gross tonsillar enlargement. A review of previously published, clinically informative cases corroborates that lymphadenopathy, with preference for the cervical region, is the most common EML at diagnosis in inv(16)-positive AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17% of the cases, mostly in the relapse setting, with a diminishing frequency over time, possibly due to protective effects of high-dose cytarabine. Other reported EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was in our series associated with a shorter duration of first remission, (P< 0.05), and may hence prove to be an important clinical parameter when deciding treatment strategies in AML with inv(16)/t(16,16). © 2002 Wiley-Liss, Inc.
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  • Billstrom, R, et al. (author)
  • Poor survival in t(8;21) (q22;q22)-associated acute myeloid leukaemia with leukocytosis
  • 1997
  • In: European Journal of Haematology. - 1600-0609. ; 59:1, s. 47-52
  • Journal article (peer-reviewed)abstract
    • Twenty-nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM) karyotype were retrospectively studied concerning clinical, morphological and cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during 18 yr. Auer rods were the most consistent t(8;21)-associated morphological finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the patients were > 60 yr old. Twenty-four patients had received induction chemotherapy; 22 of these (91%) entered a complete remission (CR). The median survival time in treated patients was 18 months. Leukocytosis at diagnosis (> or = 20 x 10(9)/1) was significantly (p = 0.01) associated with shorter survival time. All four children are still in first CR after 9-80 months. Seven cases (25%) developed granulocytic sarcomas, discovered either at diagnosis (n = 4) or at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of the cases, most often loss of a sex chromosome. The presence of such secondary aberrations did not correlate with any morphological or clinical characteristics, including survival. This first Scandinavian study of AML with t(8;21) corroborates the previous findings that these AMLs are characterized by distinct morphological features, a high frequency of CR and a striking tendency to develop extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a less favourable prognosis.
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  • Bjartell, Anders, et al. (author)
  • Distribution and tissue expression of semenogelin I and II in man as demonstrated by in situ hybridization and immunocytochemistry
  • 1996
  • In: Journal of Andrology. - 0196-3635. ; 17, s. 17-26
  • Journal article (peer-reviewed)abstract
    • Semenogelin I and II (Sgl, Sgll) are two separate gene products of chromosome 20 with extensive (80%) identity in primary structure. They are mainly responsible for immediate gel formation of freshly ejaculated semen. Degradation of Sgl and Sgll is due to the proteolytic action of prostate-specific antigen (PSA); it results within 5-15 minutes in liquefaction of semen and release of progressively motile spermatozoa. By means of cDNA cloning and Northern blots, Sgl and Sgll transcripts have previously been shown to be abundant in human seminal vesicles, but Sgll alone is suggested to be expressed at low levels in the epididymis. To characterize the expression and tissue distribution of Sgl and Sgll in greater detail, we produced monoclonal immunoglobulin Gs (lgGs for immunocytochemistry (lCC) and specific [35S]-, digoxigenin-, or alkaline phosphatase-labeled 30-mer antisense probes to Sgl and Sgll for in situ hybridization (lSH). Immunocytochemical staining for both Sgl and Sgll, and lSH detection of both Sgl and Sgll transcripts, were demonstrated in the cytoplasm of seminal vesicle epithelium. lSH showed Sgll alone to be expressed in the epithelium of the epididymal cauda. Neither lCC nor lSH yielded any evidence of Sgl or Sgll expression in caput or corpus epithelium or in any stromal cells of the epididymis. Consistent with our previous findings using polyclonal lgG, monoclonal anti-Sgll Sgll lgGs identified epitopes on the posterior head, midpiece, and tail of ejaculated spermatozoa. Spermatozoa in the epididymal cauda were also immunoreactive, but those in the caput or corpus region of the epididymis as well as those in the testis were negative. As shown by lCC, neither Sgl nor Sgll were expressed in the testis, the prostate, the female genital tract, or other normal human tissue specimens. Although the significance of Sg attachment to epididymal and ejaculated spermatozoa remains to be established, monoclonal anti-Sg lgG might prove useful in establishing the origin of seminal vesicle tissue components in prostate core biopsies or other biopsy specimens.
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29.
  • Bjorkholm, M., et al. (author)
  • Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms
  • 2011
  • In: Journal of Clinical Oncology. - : American Society of Clinical Oncology: JCO. - 0732-183X .- 1527-7755. ; 29:17, s. 2410-2415
  • Journal article (peer-reviewed)abstract
    • Purpose: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). Methods: On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. Results: Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P32), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P32 greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. Conclusion: The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P32 and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors. © 2011 by American Society of Clinical Oncology.
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30.
  • Björklund, Erik, et al. (author)
  • Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome.
  • 2021
  • In: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 4:8
  • Journal article (peer-reviewed)abstract
    • Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak.To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy.This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020.Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only.Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up.A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P=.34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P=.29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P=.011). Sensitivity analyses confirmed the results.In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.
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31.
  • Björklund, Erik, et al. (author)
  • Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting
  • 2023
  • In: HEART. - 1355-6037 .- 1468-201X.
  • Journal article (peer-reviewed)abstract
    • Objective To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction.Methods All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk.Results Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event.Conclusions The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.
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32.
  • Björklund, Erik, et al. (author)
  • Postoperative platelet function is associated with severe bleeding in ticagrelor-treated patients
  • 2019
  • In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9293 .- 1569-9285. ; 28:5, s. 709-715
  • Journal article (peer-reviewed)abstract
    • Objectives: Preoperative testing of platelet function predicts bleeding risk in cardiac surgery patients treated with dual antiplatelet therapy, but the value of postoperative platelet function testing, reflecting both preoperative antiplatelet therapy and perioperative changes in platelet function, has not been evaluated. Methods: Seventy-four patients with acute coronary syndrome treated with acetylsalicylic acid and ticagrelor within 5 days before cardiac surgery were included in a prospective observational study. Platelet aggregation induced by adenosine diphosphate, arachidonic acid and thrombin receptor-activating peptide was assessed with multiple electrode impedance aggregometry immediately before surgery and 2 h after weaning off cardiopulmonary bypass. Receiver operating characteristic curves were used to determine any association between platelet aggregation and severe bleeding according to the universal definition of perioperative bleeding in adult cardiac surgery. Results: Severe bleeding occurred in 25 of 74 patients (34%). Preoperative and postoperative adenosine diphosphate-induced platelet aggregations were associated with bleeding, with comparable areas under the receiver operating characteristic curve [0.77 (95% confidence interval 0.65-0.89) vs 0.75 (0.62-0.87)]. Postoperative arachidonic acid-and thrombin receptor-activating peptide-induced aggregation had markedly smaller areas under the curve. There were significant correlations between preoperative and postoperative platelet aggregation induced by adenosine diphosphate (r2 = 0.77, P < 0.001), arachidonic acid (r2 = 0.24, P < 0.001) and thrombin receptoractivating peptide (r2 = 0.21, P < 0.001) but with large interindividual variations. Conclusions: Poor postoperative platelet function was associated with severe bleeding, with accuracy comparable to that of preoperative platelet function. There was a correlation between preoperative and postoperative platelet function, but the predictability in an individual patient was limited. © 2018 The Author(s). Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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33.
  • Björklund, Erik, et al. (author)
  • Secondary prevention medications after coronary artery bypass grafting and long-term survival : a population-based longitudinal study from the SWEDEHEART registry.
  • 2019
  • In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:17, s. 1653-1661
  • Journal article (peer-reviewed)abstract
    • AIMS: To evaluate the long-term use of secondary prevention medications [statins, β-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality.METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for β-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between β-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54).CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of β-blockers may be questioned.
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35.
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36.
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37.
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38.
  • Crijns, Harry J., et al. (author)
  • Safe and effective conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009.
  • 2006
  • In: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 3:11, s. 1321-1331
  • Journal article (peer-reviewed)abstract
    • Background Acute drug conversion of persistent atrial fibrillation usually fails. Objectives The purpose of this study was to test the proarrhythmic potential, safety, and efficacy of the novel antiarrhythmic agent AZD7009 in patients with persistent atrial fibrillation (AF) or atrial flutter (mean duration 43 days) scheduled for direct current (DC) cardioversion. Methods Patients were randomized to AZD7009 (3-hour intravenous infusion; n = 86) or placebo (n = 36). AZD7009 was given in doses intended to produce target pseudo–steady-state plasma levels of 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, or 2.5 μmol/L after 30 minutes of infusion. DC cardioversion was performed if conversion to sinus rhythm (SR) did not occur within 2 hours of infusion. Results AZD7009 in a concentration-dependent manner increased the rate of conversion of AF to SR and shortened the time to conversion. At the three highest target concentrations of AZD7009, 45%, 64%, and 70% of AF patients converted after a mean time of 62, 55, and 26 minutes, respectively, whereas no placebo-treated patients converted. SR was maintained for 24 hours in 21 of 22 patients with drug-associated conversion. AZD7009 treatment was associated with QT-interval prolongation; the increase in QT corrected according to Fridericia typically ranged from 40 to 80 ms at targeted pseudo–steady-state plasma concentrations ≥0.75 μmol/L, but a number of outliers with QT corrected according to Fridericia >550 ms were seen in the higher concentration groups, particularly after conversion to SR and prolonged infusion. None of the patients exhibited torsades de pointes according to predefined criteria; however, one patient exhibited a nonsustained, polymorphic ventricular tachycardia of eight beats with torsades de pointes–like features after AZD7009 infusion (asymptomatic and discovered only upon retrospective Holter tape analysis). Clinical adverse events (primarily dizziness, bradycardia, hypotension, and nausea) were significantly more common in the highest target concentration AZD7009 group vs placebo (P <.001). Conclusion AZD7009 exhibited dose-dependent effects in converting AF to SR in AF patients and appeared to be associated with a low risk of proarrhythmia despite continued administration during a period of heightened vulnerability.
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39.
  • Eklund, B., et al. (author)
  • Toxic effects of decomposing red algae on littoral organisms
  • 2005
  • In: Estuarine, Coastal and Shelf Science. - 0272-7714 .- 1096-0015. ; 62:4, s. 621-626
  • Journal article (peer-reviewed)abstract
    • Large masses of filamentous red algae of the genera Polysiphonia, Rhodomela, and Ceramium are regularly washed up on beaches of the central Baltic Sea. As the algal masses start to decay, red coloured effluents leak into the water, and this tinge may be traced several hundred meters off shore. In this study, possible toxic effects of these effluents were tested on littoral organisms from different trophic levels. Effects on fertilisation, germination and juvenile survival of the brown seaweed Fucus vesiculosus were investigated, and mortality tests were performed on the crustaceans Artemia salina and Idotea baltica, as well as on larvae and adults of the fish Pomatoschistus microps. Fucus vesiculosus was the most sensitive species of the tested organisms to the red algal extract. The survival of F. vesiculosus recruits was reduced with 50% (LC50) when exposed to a concentration corresponding to 1.7 g l(-1) dw red algae. The lethal concentration for L baltica, A. salina and P. microps were approximately ten times higher. The toxicity to A. salina was reduced if the algal extract was left to decompose during two weeks but the decline in toxicity was not affected by different light or temperature conditions. This study indicates that the filamentous red algae in the central Baltic Sea may produce and release compounds with negative effects on the littoral ecosystem. The effects may be particularly serious for the key species F. vesiculosus, which reproduce in autumn when filamentous red algal blooms are most severe. (C) 2004 Elsevier Ltd. All rights reserved.
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43.
  • Ezzat, Kariem, et al. (author)
  • The viral protein corona directs viral pathogenesis and amyloid aggregation
  • 2019
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Journal article (peer-reviewed)abstract
    • Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid beta-peptide (A beta(42)), a major constituent of amyloid plaques in Alzheimer's disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.
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44.
  • Fermuller, C, et al. (author)
  • Uncertainty in visual processes predicts geometrical optical illusions
  • 2004
  • In: Vision Research. - : Elsevier BV. - 1878-5646 .- 0042-6989. ; 44:7, s. 727-749
  • Journal article (peer-reviewed)abstract
    • It is proposed in this paper that many geometrical optical illusions, as well as illusory patterns due to motion signals in line drawings. are due to the statistics of visual computations. The interpretation of image patterns is preceded by a step where image features such as lines, intersections of lines, or local image movement must be derived. However, there are many sources of noise or uncertainty in the formation and processing of images, and they cause problems in the estimation of these features; in particular, they cause bias. As a result, the locations of features are perceived erroneously and the appearance of the patterns is altered. The bias occurs with any visual processing of line features; under average conditions it is not large enough to be noticeable, but illusory patterns are Such that the bias is highly pronounced. Thus, the broader message of this paper is that there is a general uncertainty principle which governs the workings of vision systems, and optical illusions are an artifact of this principle.
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47.
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48.
  • Fioretos, Thoas, et al. (author)
  • Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia
  • 1993
  • In: Leukemia. - 1476-5551. ; 7:8, s. 1225-1231
  • Journal article (peer-reviewed)abstract
    • We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.
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49.
  • Fischer, Andreas C., 1982-, et al. (author)
  • 3D Free-Form Patterning of Silicon by Ion Implantation, Silicon Deposition, and Selective Silicon Etching
  • 2012
  • In: Advanced Functional Materials. - : Wiley-VCH Verlagsgesellschaft. - 1616-301X .- 1616-3028. ; 22:19, s. 4004-4008
  • Journal article (peer-reviewed)abstract
    • A method for additive layer-by-layer fabrication of arbitrarily shaped 3D silicon micro- and nanostructures is reported. The fabrication is based on alternating steps of chemical vapor deposition of silicon and local implantation of gallium ions by focused ion beam (FIB) writing. In a final step, the defined 3D structures are formed by etching the silicon in potassium hydroxide (KOH), in which the local ion implantation provides the etching selectivity. The method is demonstrated by fabricating 3D structures made of two and three silicon layers, including suspended beams that are 40 nm thick, 500 nm wide, and 4 μm long, and patterned lines that are 33 nm wide.
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