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Search Results: 1 - 10 of 325285 matches for " S. Klaver "
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Surveillance as an Option for the Treatment of Small Renal Masses
S. Klaver,S. Joniau,H. Van Poppel
Advances in Urology , 2008, DOI: 10.1155/2008/705958
Abstract: Objectives. To review the natural history and biological potential of small renal masses in order to evaluate surveillance as a treatment option. Methods. Literature search of Medline and additional references from non-Medline-indexed publications concerning surveillance of small renal masses. Results. The natural history and biological potential of small renal masses can still not be unambiguously predicted at present. There seems to be no clear correlation between tumour size and presence of benign histology. The majority of small renal masses grow and the majority are cancer, but one cannot safely assume that a lack of growth on serial CT scans is the confirmation of absence of malignancy. Needle core biopsies could be used to help in decision making. They show a high accuracy for histopathological tumour type but are less accurate in evaluating Fuhrman grade. Conclusions. At present, surveillance of small renal masses should only be considered in elderly and/or infirm patients with competing health risks, in those with a limited life expectancy, and in those for whom minimal invasive treatment or surgery is not an option. In all other patients, active surveillance should only be considered in the context of a study protocol. Long-term, prospective studies are needed to provide a more accurate assessment of the natural history and metastastic potential of small renal masses.
Measuring Semileptonic Asymmetries in LHCb
Suzanne Klaver,for the LHCb Collaboration
Physics , 2015,
Abstract: The $C\!P$-violating flavour-specific asymmetry in neutral $b$ mesons provides a method for testing the Standard Model. The measurements from the D0 experiment yield values of this asymmetry that disagree with the Standard Model at a level of 3.6 $\sigma$. This contribution discusses the latest LHCb measurements in this sector both from $B^0$ mesons ($a_{\mathrm{sl}}^d$) and $B^0_s$ mesons ($a_{\mathrm{sl}}^s$). Using their 2011 dataset, corresponding to an integrated luminosity of 1.0 $\mathrm{fb}^{-1}$ obtained in 2011, LHCb measured a value of $a_{\mathrm{sl}}^s = (-0.06 \pm 0.50_{\text{stat}} \pm 0.36_{\text{syst}}) \%$. Combining the 2011 and 2012 datasets, with an integrated luminosity of 3 $\mathrm{fb}^{-1}$, LHCb measured $a_{\mathrm{sl}}^d = (-0.02 \pm 0.19_{\text{stat}} \pm 0.30_{\text{syst}}) \%$. These are the most precise measurements of the parameters $a_{\mathrm{sl}}^s$ and $a_{\mathrm{sl}}^d$ to date. Plans for an updated result for $a_{\mathrm{sl}}^s$ using the full 3 $\mathrm{fb}^{-1}$ dataset are discussed. This will include new methods to determine detection asymmetries which are the dominating systematic uncertainty of the 2011 measurement.
Magnetic Nanoparticles as Mediators of Ligand-Free Activation of EGFR Signaling
Atul A. Bharde, Raghavendra Palankar, Cornelia Fritsch, Arjen Klaver, Johannes S. Kanger, Thomas M. Jovin, Donna J. Arndt-Jovin
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068879
Abstract: Background Magnetic nanoparticles (NPs) are of particular interest in biomedical research, and have been exploited for molecular separation, gene/drug delivery, magnetic resonance imaging, and hyperthermic cancer therapy. In the case of cultured cells, magnetic manipulation of NPs provides the means for studying processes induced by mechanotransduction or by local clustering of targeted macromolecules, e.g. cell surface receptors. The latter are normally activated by binding of their natural ligands mediating key signaling pathways such as those associated with the epidermal growth factor (EGFR). However, it has been reported that EGFR may be dimerized and activated even in the absence of ligands. The present study assessed whether receptor clustering induced by physical means alone suffices for activating EGFR in quiescent cells. Methodology/Principal Findings The EGFR on A431 cells was specifically targeted by superparamagnetic iron oxide NPs (SPIONs) carrying either a ligand-blocking monoclonal anti-EGFR antibody or a streptavidin molecule for targeting a chimeric EGFR incorporating a biotinylated amino-terminal acyl carrier peptide moiety. Application of a magnetic field led to SPION magnetization and clustering, resulting in activation of the EGFR, a process manifested by auto and transphosphorylation and downstream signaling. The magnetically-induced early signaling events were similar to those inherent to the ligand dependent EGFR pathways. Magnetization studies indicated that the NPs exerted magnetic dipolar forces in the sub-piconewton range with clustering dependent on Brownian motion of the receptor-SPION complex and magnetic field strength. Conclusions/Significance We demonstrate that EGFR on the cell surface that have their ligand binding-pocket blocked by an antibody are still capable of transphosphorylation and initiation of signaling cascades if they are clustered by SPIONs either attached locally or targeted to another site of the receptor ectodomain. The results suggest that activation of growth factor receptors may be triggered by ligand-independent molecular crowding resulting from overexpression and/or sequestration in membrane microdomains.
Presenilins and the γ-secretase: still a complex problem
David H Small, David W Klaver, Lisa Foa
Molecular Brain , 2010, DOI: 10.1186/1756-6606-3-7
Abstract: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Typically 5-10% of the population over the age of 65 have dementia, and of these cases, a large percentage have AD [1]. AD is characterised by the presence of proteinaceous deposits in the brain [2]. The extracellular amyloid deposits, which are found in the neuropil (amyloid plaques) and in association with small-medium size cerebral blood vessels (cerebral amyloid angiopathy), are composed of a 4 kDa polypeptide known as the amyloid-β protein (Aβ) which is derived by proteolytic cleavage from a much larger amyloid-β precursor protein (APP) [3]. Aβ displays a spontaneous ability to aggregate into oligomers and larger fibrillar structures, and it is generally thought that the accumulation of oligomeric Aβ is chiefly responsible for the neurodegeneration that occurs in AD [4].For the generation of Aβ, APP is first cleaved on the N-terminal side of the Aβ sequence by the β-site APP cleaving enzyme-1 (BACE1), a transmembrane aspartyl protease [3]. The resulting 99-amino acid residue C-terminal fragment (C99) is then cleaved by the γ-secretase to yield Aβ and a C-terminal APP intracellular domain (AICD) fragment (Fig. 1). The function of the AICD fragment is unclear, although it is thought to have a role in intracellular signalling. For example, AICD may be involved in the regulation of gene transcription, synaptic plasticity and cytoskeletal dynamics [5].The major form of Aβ possesses 40 amino-acid residues (Aβ1-40). However, other minor species are also produced which vary in the C-terminal sequence. Production of a longer 42-residue species (Aβ1-42) is thought to be intimately associated with AD pathogenesis [6]. Aβ1-42 aggregates more readily than Aβ1-40, and increased production of Aβ1-42 may seed aggregation of Aβ1-40 or other Aβ species [4].Approximately 5% of all AD cases are autosomal dominant [7]. Soon after the complete APP sequence was cloned in 1987 [8], it became clear that at le
Defect and solute properties in dilute Fe-Cr-Ni austenitic alloys from first principles
T. P. C. Klaver,D. J. Hepburn,G. J. Ackland
Physics , 2011, DOI: 10.1103/PhysRevB.85.174111
Abstract: We present results of an extensive set of first-principles density functional theory calculations of point defect formation, binding and clustering energies in austenitic Fe with dilute concentrations of Cr and Ni solutes.
First Principles Calculations of Defects in Unstable Crystals: Austenitic Iron
G. J. Ackland,T. P. C. Klaver,D. J. Hepburn
Physics , 2011,
Abstract: First principles calculations have given a new insight into the energies of point defects in many different materials, information which cannot be readily obtained from experiment. Most such calculation are done at zero Kelvin, with the assumption that finite temperature effects on defect energies and barriers are small. In some materials, however, the stable crystal structre of interest is mechanically unstable at 0K. In such cases, alternate approaches are needed. Here we present results of first principles calculations of austenitic iron using the VASP code. We determine an appropriate reference state for collinear magnetism to be the antiferromagnetic double-layer (AFM-d) which is both stable and lower in energy than other possible models for the low temperature limit of paramagnetic fcc iron. We then consider the energetics of dissolving typical alloying impurities (Ni, Cr) in the materials, and their interaction with point defects typical of the irradiated environment. We show that using standard methods there is a very strong dependence of calculated defect formation energies on the reference state chosen. Furthermore, there is a correlation between local free volume magnetism and energetics. The effect of substitutional Ni and Cr on defect properties is weak, rarely more than tenths of eV, so it is unlikely that small amounts of Ni and Cr will have a significant effect on the radiation damage in austenitic iron at high temperatures.
Analysis of Rare Variants in the C3 Gene in Patients with Age-Related Macular Degeneration
Maheswara R. Duvvari, Codrut C. Paun, Gabri?lle H. S. Buitendijk, Nicole T. M. Saksens, Elena B. Volokhina, Tina Ristau, Frederieke E. Schoenmaker-Koller, Johannes P. H. van de Ven, Joannes M. M. Groenewoud, Lambertus P. W. J. van den Heuvel, Albert Hofman, Sascha Fauser, André G. Uitterlinden, Caroline C. W. Klaver, Carel B. Hoyng, Eiko K. de Jong, Anneke I. den Hollander
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094165
Abstract: Age-related macular degeneration (AMD) is a progressive retinal disorder affecting over 33 million people worldwide. Genome-wide association studies (GWASs) for AMD identified common variants at 19 loci accounting for 15–65% of the heritability and it has been hypothesized that the missing heritability may be attributed to rare variants with large effect sizes. Common variants in the complement component 3 (C3) gene have been associated with AMD and recently a rare C3 variant (Lys155Gln) was identified which exerts a large effect on AMD susceptibility independent of the common variants. To explore whether additional rare variants in the C3 gene are associated with AMD, we sequenced all coding exons in 84 unrelated AMD cases. Subsequently, we genotyped all identified variants in 1474 AMD cases and 2258 controls. Additionally, because of the known genetic overlap between AMD and atypical hemolytic uremic syndrome (aHUS), we genotyped two recurrent aHUS-associated C3 mutations in the entire cohort. Overall, we identified three rare variants (Lys65Gln (P = 0.04), Arg735Trp (OR = 17.4, 95% CI = 2.2–136; P = 0.0003), and Ser1619Arg (OR = 5.2, 95% CI = 1.0–25; P = 0.05) at the C3 locus that are associated with AMD in our EUGENDA cohort. However, the Arg735Trp and Ser1619Arg variants were not found to be associated with AMD in the Rotterdam Study. The Lys65Gln variant was only identified in patients from Nijmegen, the Netherlands, and thus may represent a region-specific AMD risk variant.
Obesity and the Microvasculature: A Systematic Review and Meta-Analysis
Adrien Boillot, Sophia Zoungas, Paul Mitchell, Ronald Klein, Barbara Klein, Mohammad Kamran Ikram, Caroline Klaver, Jie Jin Wang, Bamini Gopinath, E. Shyong Tai, Aljoscha Steffen Neubauer, Serge Hercberg, Laima Brazionis, Seang-Mei Saw, Tien-Yin Wong, Sébastien Czernichow, META-EYE Study Group
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0052708
Abstract: Background Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber. Methods and Findings Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m2 increase in BMI was associated with a difference of 0.07 μm [95% CI: ?0.08; ?0.06] in arteriolar caliber and 0.22 μm [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children. Conclusions Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists.
A Vectorial Capacity Product to Monitor Changing Malaria Transmission Potential in Epidemic Regions of Africa
Pietro Ceccato,Christelle Vancutsem,Robert Klaver,James Rowland,Stephen J. Connor
Journal of Tropical Medicine , 2012, DOI: 10.1155/2012/595948
Abstract: Rainfall and temperature are two of the major factors triggering malaria epidemics in warm semi-arid (desert-fringe) and high altitude (highland-fringe) epidemic risk areas. The ability of the mosquitoes to transmit Plasmodium spp. is dependent upon a series of biological features generally referred to as vectorial capacity. In this study, the vectorial capacity model (VCAP) was expanded to include the influence of rainfall and temperature variables on malaria transmission potential. Data from two remote sensing products were used to monitor rainfall and temperature and were integrated into the VCAP model. The expanded model was tested in Eritrea and Madagascar to check the viability of the approach. The analysis of VCAP in relation to rainfall, temperature and malaria incidence data in these regions shows that the expanded VCAP correctly tracks the risk of malaria both in regions where rainfall is the limiting factor and in regions where temperature is the limiting factor. The VCAP maps are currently offered as an experimental resource for testing within Malaria Early Warning applications in epidemic prone regions of sub-Saharan Africa. User feedback is currently being collected in preparation for further evaluation and refinement of the VCAP model. 1. Introduction Malaria is a major public health threat to the African continent and its control is critical to achieving the Millennium Development Goals in this region [1]. Although considerable progress has been made to reduce the malaria burden in sub-Saharan Africa by introducing control measures such as the provision of insecticide-treated mosquito nets, indoor residual spraying, and easier access to effective antimalarial drugs [2], malaria epidemics continue to occur. Periodic epidemics of malaria are a major public health problem for many sub-Saharan African countries. Populations in epidemic-prone areas have a poorly developed immunity to malaria and the disease remains life threatening to all age groups [3]. The impact of epidemics could be minimized through prediction, improved prevention through timely vector control, and deployment of appropriate control measures. The implementation of a Malaria Early Warning System enables regional health ministries to focus on epidemiological surveillance and be better prepared to take necessary actions. Rainfall and temperature anomalies are two of the major environmental factors triggering epidemics in warm semi-arid and altitude areas. Increases in epidemics often occur in these regions after excessive rains or increases in temperature [4, 5]. The ability
Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands
Lars Michels,Kerstin Bucher,Rafael Lüchinger,Peter Klaver,Ernst Martin,Daniel Jeanmonod,Daniel Brandeis
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010298
Abstract: EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.
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