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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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  • Villa, Luisa L., et al. (author)
  • Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18
  • 2006
  • In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:27-28, s. 5571-5583
  • 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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  • Woldmar, N., et al. (author)
  • Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases
  • 2023
  • In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Background: Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. Materials and methods: Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259. Results: Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases. Conclusions: This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.
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  • Abelsson, J, et al. (author)
  • The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries.
  • 2012
  • In: Bone Marrow Transplantation. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 47:3, s. 380-386
  • Journal article (peer-reviewed)abstract
    • Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.
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  • Baron, F, et al. (author)
  • Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
  • 2012
  • In: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 26:12, s. 2462-2468
  • Journal article (peer-reviewed)abstract
    • This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) 0.7, P = 0.02) translating into a trend for better overall survival (OS; HR 1.3; P = 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR 0.4, P andlt; 0.0.001) owing to high risk of nonrelapse mortality (NRM; HR 5.2, P andlt; 0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR 0.72; P = 0.07) translating into a better OS (HR 1.8; P andlt; 0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR 0.65; P = 0.02) but also with higher NRM (HR 3.5; P andlt; 0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P andlt; 0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR 0.65; P = 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. Leukemia (2012) 26, 2462-2468; doi: 10.1038/leu.2012.135
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  • Fischer, Andreas C., et al. (author)
  • Layer-by-layer 3D printing of Si micro- and nanostructures by Si deposition, ion implantation and selective Si etching
  • 2012
  • In: 12th IEEE Conference on Nanotechnology (IEEE-NANO), 2012. - : IEEE conference proceedings. - 9781467321983 ; , s. 1-4
  • Conference paper (peer-reviewed)abstract
    • In this paper we report a method for layer-by-layer printing of three-dimensional (3D) silicon (Si) micro- and nanostructures. This fabrication method is based on a sequence of alternating steps of chemical vapor deposition of Si and local implantation of gallium (Ga+) ions by focused ion beam (FIB) writing. The defined 3D structures are formed in a final step by selectively wet etching the non-implanted Si in potassium hydroxide (KOH). We demonstrate the viability of the method by fabricating 2 and 3-layer 3D Si structures, including suspended beams and patterned lines with dimensions on the nm-scale.
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  • Grahn, J. V., et al. (author)
  • A low-complexity 62-GHz f(T) SiGe heterojunction bipolar transistor process using differential epitaxy and in situ phosphorus-doped poly-Si emitter at very low thermal budget
  • 2000
  • In: Solid-State Electronics. - 0038-1101 .- 1879-2405. ; 44:3, s. 549-554
  • Journal article (peer-reviewed)abstract
    • A low-complexity SiGe heterojunction bipolar transistor process based on differential epitaxy and in situ phosphorus doped polysilicon emitter technology is described. Silane-based chemical vapor deposition at reduced pressure was used for low-temperature SiGe epitaxy. Following SiGe epitaxy, the process temperature budget was kept very low with 900 degrees C for 10 s as the highest temperature step. A very high current gain of almost 2000 and cut off frequency of 62 GHz were achieved for a uniform 12% Ge profile. The breakdown voltage BVCEO and forward Early voltage were equal to 2.9 and 6.5 V, respectively.
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  • Grudet, Cécile, et al. (author)
  • Vitamin D and inflammation in major depressive disorder
  • 2020
  • In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327. ; 267, s. 33-41
  • Journal article (peer-reviewed)abstract
    • Background: Increased inflammation is reported in Major Depressive Disorder (MDD), which may be more pronounced in suicidal subjects. Vitamin D deficiency may drive this pro-inflammatory state due to vitamin D's anti-inflammatory effects. Methods: We quantified plasma 25-hydroxyvitamin D (25(OH)D) and inflammatory markers interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and other inflammatory indices, neutrophil-to-lymphocyte ratio (NLR) and white blood cell count (WBC) in 48 un-medicated MDD subjects (n = 17 with mild-to-moderate suicidal ideation [SI]) and 54 controls. IL-6 and TNF-α were combined into a composite inflammation score. Results: There were no significant differences in 25(OH)D levels between MDD and controls (p = 0.24) or between MDD with and without SI (p = 0.61). However, 25(OH)D was negatively correlated with all measured inflammatory markers; these correlations were stronger in MDD subjects, and particularly in those with SI. MDD status significantly moderated the relationships between 25(OH)D and NLR (p = 0.03), and 25(OH)D and WBC (p < 0.05), and SI significantly moderated the relationship between 25(OH)D and NLR (p = 0.03). Limitations: The study was cross-sectional, thereby limiting causal inference, and had a small sample size. Only seventeen of the MDD subjects had SI. Conclusion: While 25(OH)D levels did not significantly differ in MDD vs. controls, or in MDD with or without SI, lower 25(OH)D was associated with indices of immune activation in MDD, especially in cases with SI. Although our findings do not address causality, they are consistent with findings that relatively low 25(OH)D levels in MDD are associated with a pro-inflammatory state.
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  • Jantti, H, et al. (author)
  • Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice
  • 2022
  • In: Cells. - : MDPI AG. - 2073-4409. ; 11:24
  • Journal article (peer-reviewed)abstract
    • The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing of amyloid precursor protein (APP) towards the generation of highly amyloidogenic Aβ42 peptide. We have previously shown that the PSEN1 ΔE9 mutation in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases Aβ42 production and impairs cellular responses. Here, we injected PSEN1 ΔE9 mutant astrosphere-derived glial progenitors into newborn mice and investigated mouse behavior at the ages of 8, 12, and 16 months. While we did not find significant behavioral changes in younger mice, spatial learning and memory were paradoxically improved in 16-month-old PSEN1 ΔE9 glia-transplanted male mice as compared to age-matched isogenic control-transplanted animals. Memory improvement was associated with lower levels of soluble, but not insoluble, human Aβ42 in the mouse brain. We also found a decreased engraftment of PSEN1 ΔE9 mutant cells in the cingulate cortex and significant transcriptional changes in both human and mouse genes in the hippocampus, including the extracellular matrix-related genes. Overall, the presence of PSEN1 ΔE9 mutant glia exerted a more beneficial effect on aged mouse brain than the isogenic control human cells likely as a combination of several factors.
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  • Malm, T M, et al. (author)
  • Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice
  • 2005
  • In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 18:1, s. 134-142
  • Journal article (peer-reviewed)abstract
    • The role of microglia recruited from bone marrow (BM) into the CNS during the progression of Alzheimer's disease (AD) is poorly understood. To investigate whether beta-amyloid (Abeta) associated microglia are derived from blood monocytes, we transplanted BM cells from enhanced green fluorescent protein expressing mice into young or old transgenic AD mice and determined the engraftment of BM-derived cells into the brain and their relative distribution near Abeta deposits. When young transgenic mice were transplanted before the onset of AD-like pathology and the brains analyzed 6.5 months later, the number of engrafted cells was significantly higher than in age-matched wild type mice. Moreover, the number of BM-derived cells associated with Abeta was significantly higher than in old transgenic mice transplanted after the establishment of AD-like pathology. Local inflammation caused by intrahippocampal lipopolysaccharide injection significantly increased the engraftment of BM-derived cells in old AD mice and decreased the hippocampal Abeta burden. These results suggest that infiltration of BM-derived monocytic cells into the brain contributes to the development of microglial reaction in AD.
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  • Uhlén, Mathias, et al. (author)
  • The human secretome
  • 2019
  • In: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
  • Journal article (peer-reviewed)abstract
    • The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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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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  • Banuazizi, Seyed Amir Hossein, et al. (author)
  • Order of magnitude improvement of nano-contact spin torque nano-oscillator performance
  • 2017
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 9:5, s. 1896-1900
  • Journal article (peer-reviewed)abstract
    • Spin torque nano-oscillators (STNO) represent a unique class of nano-scale microwave signal generators and offer a combination of intriguing properties, such as nano sized footprint, ultrafast modulation rates, and highly tunable microwave frequencies from 100 MHz to close to 100 GHz. However, their low output power and relatively high threshold current still limit their applicability and must be improved. In this study, we investigate the influence of the bottom Cu electrode thickness (t(Cu)) in nano-contact STNOs based on Co/Cu/NiFe GMR stacks and with nano-contact diameters ranging from 60 to 500 nm. Increasing t(Cu) from 10 to 70 nm results in a 40% reduction of the threshold current, an order of magnitude higher microwave output power, and close to two orders of magnitude better power conversion efficiency. Numerical simulations of the current distribution suggest that these dramatic improvements originate from a strongly reduced lateral current spread in the magneto-dynamically active region.
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  • Bayrak Pehlivan, Ilknur, et al. (author)
  • The climatic response of thermally integrated photovoltaic-electrolysis water splitting using Si and CIGS combined with acidic and alkaline electrolysis
  • 2020
  • In: Sustainable Energy & Fuels. - : ROYAL SOC CHEMISTRY. - 2398-4902. ; 4:12, s. 6011-6022
  • Journal article (peer-reviewed)abstract
    • The Horizon 2020 project PECSYS aims to build a large area demonstrator for hydrogen production from solar energy via integrated photovoltaic (PV) and electrolysis systems of different types. In this study, Si- and CIGS-based photovoltaics are developed together with three different electrolyzer systems for use in the corresponding integrated devices. The systems are experimentally evaluated and a general model is developed to investigate the hydrogen yield under real climatic conditions for various thin film and silicon PV technologies and electrolyser combinations. PV characteristics using a Si heterojunction (SHJ), thin film CuInxGa1-xSe2, crystalline Si with passivated emitter rear totally diffused and thin film Si are used together with temperature dependent catalyst load curves from both acidic and alkaline approaches. Electrolysis data were collected from (i) a Pt-IrO2-based acidic electrolysis system, and (ii) NiMoW-NiO-based and (iii) Pt-Ni foam-based alkaline electrolysis systems. The calculations were performed for mid-European climate data from Julich, Germany, which will be the installation site. The best systems show an electricity-to-hydrogen conversion efficiency of 74% and over 12% solar-to-hydrogen (STH) efficiencies using both acidic and alkaline approaches and are validated with a smaller lab scale prototype. The results show that the lower power delivered by all the PV technologies under low irradiation is balanced by the lower demand for overpotentials for all the electrolysis approaches at these currents, with more or less retained STH efficiency over the full year if the catalyst area is the same as the PV area for the alkaline approach. The total yield of hydrogen, however, follows the irradiance, where a yearly hydrogen production of over 35 kg can be achieved for a 10 m(2) integrated PV-electrolysis system for several of the PV and electrolyser combinations that also allow a significant (100-fold) reduction in necessary electrolyser area for the acidic approach. Measuring the catalyst systems under intermittent and ramping conditions with different temperatures, a 5% lowering of the yearly hydrogen yield is extracted for some of the catalyst systems while the Pt-Ni foam-based alkaline system showed unaffected or even slightly increased yearly yield under the same conditions.
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  • 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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  • 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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43.
  • Edström, Anneli M L, et al. (author)
  • The major bactericidal activity of human seminal plasma is zinc-dependent and derived from fragmentation of the semenogelins.
  • 2008
  • In: Journal of immunology. - 1550-6606. ; 181:5, s. 3413-3421
  • Journal article (peer-reviewed)abstract
    • One of the major roles of seminal plasma is to provide antimicrobial protection for the spermatozoa in the female reproductive tract. We found that the bactericidal activity of seminal plasma was highest after resolution of the seminal clot and that this antibacterial activity subsequently became greatly diminished. The antibacterial activity was derived from peptides generated by fragmentation of the semenogelins while the semenogelin holoproteins displayed no antibacterial activity. After ejaculation the semenogelin-derived peptides were fragmented to smaller and smaller fragments over time and thereby lost antibacterial activity. This paralleled the loss of antibacterial activity of whole seminal plasma both in vitro and after sexual intercourse. Moreover, the antibacterial activity of the semenogelin-derived peptides generated in seminal plasma was strictly zinc-dependent both at neutral and low pH. These data provide novel roles for the resolution of seminal clots and for the high zinc concentration in human seminal plasma.
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49.
  • Klöckner, M., et al. (author)
  • Insights into automation of construction process using parallel-kinematic manipulators
  • 2022
  • In: Proceedings of the 39th International Symposium on Automation and Robotics in Construction, ISARC 2022. - 9789526952420 ; , s. 25-32
  • Conference paper (peer-reviewed)abstract
    • This paper discusses challenges, experiences and lessons learned so far while transforming a masonry build system based mostly on manual labour into a robot automated build system. Our motivation for selection of this masonry process is to try out how robot automation could impact the architects in their design work by providing a tool to directly manipulate wall expression down to individual brick level. Such manipulation is often much too costly for manual labour today. Moreover, masonry is a challenging application to automate. Understanding the manual processes involved and transforming them into automation equivalents faces several challenges; among them handling and distribution of the different materials involved, selection of tooling, sensing for handling of variation and digital tooling for the programming of the process. A novel parallel-kinematic manipulator (PKM) with computerized numerical control (CNC) is used as target for experiments, because the performance properties in stiffness, workspace and accuracy will allow us to extend work into further construction processes involving heavy and dirty manual labour.
  •  
50.
  • Malm-Erjefält, M., et al. (author)
  • Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation
  • 2005
  • In: Clin Exp Allergy. ; 35:10
  • Journal article (peer-reviewed)abstract
    • Summary Background In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. Objective To determine the degranulation status of circulating eosinophils in common allergic diseases. Methods Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. Results Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). Conclusion In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.
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