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991.
Ulf Persson Fredrik Montgomery ?ke Carlsson Bj?rn Lindgren Lennart Ahnfelt 《BMJ (Clinical research ed.)》1988,296(6615):99-102
Selection of a cost effective method of prophylaxis against infection for patients undergoing total joint replacement was shown to depend on the number of arthroplasties performed each year at individual hospitals. When 100 arthroplasties were performed each year the prophylactic use of systemic antibiotics minimised the total costs of the department—that is, the combined costs of prophylaxis and reoperation for deep sepsis. Some departments also used local antibiotic prophylaxis in the form of polymethylmethacrylate cement impregnated with gentamicin or a combination of systemic and local prophylaxis at almost as low a total cost and with comparable effect.Selection of a method of prophylaxis should not be determined solely on the basis of reducing costs. When a value was assigned to the effects of loss of health an economic optimum was established that allowed selection of a more costly method of prophylaxis together with further reductions in the incidence of infection and the need for reoperation. 相似文献
992.
Riccardo Di Guida Jasper Engel J. William Allwood Ralf J. M. Weber Martin R. Jones Ulf Sommer Mark R. Viant Warwick B. Dunn 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):93
Introduction
The generic metabolomics data processing workflow is constructed with a serial set of processes including peak picking, quality assurance, normalisation, missing value imputation, transformation and scaling. The combination of these processes should present the experimental data in an appropriate structure so to identify the biological changes in a valid and robust manner.Objectives
Currently, different researchers apply different data processing methods and no assessment of the permutations applied to UHPLC-MS datasets has been published. Here we wish to define the most appropriate data processing workflow.Methods
We assess the influence of normalisation, missing value imputation, transformation and scaling methods on univariate and multivariate analysis of UHPLC-MS datasets acquired for different mammalian samples.Results
Our studies have shown that once data are filtered, missing values are not correlated with m/z, retention time or response. Following an exhaustive evaluation, we recommend PQN normalisation with no missing value imputation and no transformation or scaling for univariate analysis. For PCA we recommend applying PQN normalisation with Random Forest missing value imputation, glog transformation and no scaling method. For PLS-DA we recommend PQN normalisation, KNN as the missing value imputation method, generalised logarithm transformation and no scaling. These recommendations are based on searching for the biologically important metabolite features independent of their measured abundance.Conclusion
The appropriate choice of normalisation, missing value imputation, transformation and scaling methods differs depending on the data analysis method and the choice of method is essential to maximise the biological derivations from UHPLC-MS datasets.993.
Natural killer (NK) cells belong to the innate immune system and protect against cancers and a variety of viruses including retroviruses by killing transformed or infected cells. They express activating and inhibitory receptors on their cell surface and often become activated after recognizing virus-infected cells. They have diverse antiviral effector functions like the release of cytotoxic granules, cytokine production and antibody dependent cellular cytotoxicity. The importance of NK cell activity in retroviral infections became evident due to the discovery of several viral strategies to escape recognition and elimination by NK cells. Mutational sequence polymorphisms as well as modulation of surface receptors and their ligands are mechanisms of the human immunodeficiency virus-1 to evade NK cell-mediated immune pressure. In Friend retrovirus infected mice the virus can manipulate molecular or cellular immune factors that in turn suppress the NK cell response. In this model NK cells lack cytokines for optimal activation and can be functionally suppressed by regulatory T cells. However, these inhibitory pathways can be overcome therapeutically to achieve full activation of NK cell responses and ultimately control dissemination of retroviral infection. One effective approach is to modulate the crosstalk between NK cells and dendritic cells, which produce NK cell-stimulating cytokines like type I interferons (IFN), IL-12, IL-15, and IL-18 upon retrovirus sensing or infection. Therapeutic administration of IFNα directly increases NK cell killing of retrovirus-infected cells. In addition, IL-2/anti-IL-2 complexes that direct IL-2 to NK cells have been shown to significantly improve control of retroviral infection by NK cells in vivo. In this review, we describe novel approaches to improve NK cell effector functions in retroviral infections. Immunotherapies that target NK cells of patients suffering from viral infections might be a promising treatment option for the future. 相似文献
994.
Mike Fischer Baerbel Spies-Weisshart Karin Schrenk Bernd Gruhn Susan Wittig Anita Glaser Andreas Hochhaus Sebastian Scholl Ulf Schnetzke 《PloS one》2016,11(3)
Background
Patients with acute myeloid leukemia (AML) who undergo induction chemotherapy are at high risk for invasive fungal disease (IFD). Dectin-1, a C-type lectin family member represents one of the most important pattern recognition receptors of the innate immune system and single nucleotide polymorphisms (SNPs) in the Dectin-1 gene have been associated with an increased risk of infectious complications. We sought to investigate the impact of three different Dectin-1 SNPs and one TLR2 SNP on developing IFD in 186 adult patients with newly diagnosed AML following anthracycline-based induction chemotherapy.Patients and methods
Genotyping of Dectin-1 SNPs (rs16910526, rs3901533 and rs7309123) and TLR2 SNP (rs5743708) was performed by TaqMan method and pyrosequencing. IFD was defined according to the EORTC/MSG consensus guidelines. Multiple logistic regression analyses were applied to evaluate the association between the polymorphisms and the occurrence of pulmonary infections. Dectin-1 expression studies with SNP genotyped human monocytes were performed to elucidate susceptibility to IFD following chemotherapy.Results
We could demonstrate that patients carrying the Dectin-1 SNP rs7309123 G/G (n = 47) or G/G and C/G (n = 133) genotype revealed a significant higher risk for developing both pneumonia in general (adjusted odds ratio (OR): 2.5; p = 0.014 and OR: 3.0, p = 0.004) and pulmonary IFD (OR: 2.6; p = 0.012 and OR: 2.4, p = 0.041, respectively). Patients carrying the TLR2 SNP rs5743708 (R753Q, GA/AA genotype, n = 12) also revealed a significantly higher susceptibility to pneumonia including IFD. Furthermore, Dectin-1 mRNA expression in human monocytes was lower following chemotherapy.Conclusion
To our best knowledge, this study represents the first analysis demonstrating that harbouring polymorphisms of Dectin-1 (rs7309123) or TLR2 (rs5743708) represents an independent risk factor of developing IFD in patients with AML undergoing induction chemotherapy. 相似文献995.
This survey was conducted in two protected areas in Nigeria to genetically identify individual lions and to determine the genetic variation within and between the populations. We used faecal sample DNA, a non-invasive alternative to the risky and laborious task of taking samples directly from the animals, often preceded by catching and immobilization. Data collection in Yankari Game Reserve (YGR) spanned through a period of five years (2008 –2012), whereas data in Kainji Lake National Park (KLNP) was gathered for a period of three years (2009, 2010 and 2012). We identified a minimum of eight individuals (2 males, 3 females, 3 unknown) from YGR and a minimum of ten individuals (7 males, 3 females) from KLNP. The two populations were found to be genetically distinct as shown by the relatively high fixation index (FST = 0.17) with each population exhibiting signs of inbreeding (YGR FIS = 0.49, KLNP FIS = 0.38). The genetic differentiation between the Yankari and Kainji lions is assumed to result from large spatial geographic distance and physical barriers reducing gene flow between these two remaining wild lion populations in Nigeria. To mitigate the probable inbreeding depression in the lion populations within Nigeria it might be important to transfer lions between parks or reserves or to reintroduce lions from the zoos back to the wild. 相似文献
996.
Sebastian L. Riedel Jingnan Lu Ulf Stahl Christopher J. Brigham 《Applied microbiology and biotechnology》2014,98(4):1469-1483
Lipid and fatty acid metabolism has been well studied in model microbial organisms like Escherichia coli and Bacillus subtilis. The major precursor of fatty acid biosynthesis is also the major product of fatty acid degradation (β-oxidation), acetyl-CoA, which is a key metabolite for all organisms. Controlling carbon flux to fatty acid biosynthesis and from β-oxidation allows for the biosynthesis of natural products of biotechnological importance. Ralstonia eutropha can utilize acetyl-CoA from fatty acid metabolism to produce intracellular polyhydroxyalkanoate (PHA). R. eutropha can also be engineered to utilize fatty acid metabolism intermediates to produce different PHA precursors. Metabolism of lipids and fatty acids can be rerouted to convert carbon into other value-added compounds like biofuels. This review discusses the lipid and fatty acid metabolic pathways in R. eutropha and how they can be used to construct reagents for the biosynthesis of products of industrial importance. Specifically, how the use of lipids or fatty acids as the sole carbon source in R. eutropha cultures adds value to these biotechnological products will be discussed here. 相似文献
997.
Florian Müller-Dahlhaus Caroline Lücke Ming-Kuei Lu Noritoshi Arai Anna Fuhl Eva Herrmann Ulf Ziemann 《PloS one》2015,10(6)
Paired associative stimulation (PASLTP) of the human primary motor cortex (M1) can induce LTP-like plasticity by increasing corticospinal excitability beyond the stimulation period. Previous studies showed that two consecutive PASLTP protocols interact by homeostatic metaplasticity, but animal experiments provided evidence that LTP can be augmented by repeated stimulation protocols spaced by ~30min. Here we tested in twelve healthy selected PASLTP responders the possibility that LTP-like plasticity can be augmented in the human M1 by systematically varying the interval between two consecutive PASLTP protocols. The first PASLTP protocol (PAS1) induced strong LTP-like plasticity lasting for 30-60min. The effect of a second identical PASLTP protocol (PAS2) critically depended on the time between PAS1 and PAS2. At 10min, PAS2 prolonged the PAS1-induced LTP-like plasticity. At 30min, PAS2 augmented the LTP-like plasticity induced by PAS1, by increasing both magnitude and duration. At 60min and 180min, PAS2 had no effect on corticospinal excitability. The cumulative LTP-like plasticity after PAS1 and PAS2 at 30min exceeded significantly the effect of PAS1 alone, and the cumulative PAS1 and PAS2 effects at 60min and 180min. In summary, consecutive PASLTP protocols interact in human M1 in a time-dependent manner. If spaced by 30min, two consecutive PASLTP sessions can augment LTP-like plasticity in human M1. Findings may inspire further research on optimized therapeutic applications of non-invasive brain stimulation in neurological and psychiatric diseases. 相似文献
998.
Per Almqvist Carin Larsson-Backström Lisbet Nilsson Ulf Haglund 《Regulatory peptides》1984,9(3):165-171
Human beta-endorphin was injected into the cerebrospinal fluid in rabbits by means of a needle inserted into the lateral ventricle of the brain. Control rabbits received an equal amount of saline. beta-Endorphin induced a significant pulmonary platelet trapping compared to control. beta-Endorphin had no effect on arterial blood pressure, heart rate, platelet aggregability ex vivo or fibrinolytic activity (fibrinolytic plates). The plasma activity of antithrombin III, kallikrein-like activity and kallikrein inhibitor determined by means of chromogenic substrates was not influenced by beta-endorphin. 相似文献
999.
Sabin Llona-Minguez Maria Häggblad Ulf Martens Adam Throup Olga Loseva Ann-Sofie Jemth Bo Lundgren Martin Scobie Thomas Helleday 《Bioorganic & medicinal chemistry letters》2017,27(16):3897-3904
A high-throughput screening campaign using a commercial compound library (ChemBridge DiverSET) revealed diverse chemotypes as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). Triazole, triazolopyrimidine, triazinoindole, quinoline hydrazone and arylpiperazine hits were clustered, confirmed by IC50 determinations, and their preliminary structure-activity-relationships (SAR) and ligand efficiency scores are discussed in this letter. 相似文献
1000.