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Bexarotene, a retinoid X receptor (RXR) agonist, is being tested as a potential disease modifying treatment for neurodegenerative conditions. To limit the peripheral exposure of bexarotene and release it only in the affected areas of the brain, we designed a prodrug strategy based on the enzyme NAD(P)H/quinone oxidoreductase (NQO1) that is elevated in neurodegenerative diseases. A series of indole
Background. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal, noncurable, but treatable diseases that strongly affect the patients. Objective. To describe patients' experience of information relating to PAH or CTEPH. Methods. A qualitative method using content analysis was applied. Seventeen patients (thirteen women and four men) aged 28-73
BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently
Apart from acting synergistically or additively, threats to species may be associated or disassociated. Here we link global data on threatened Chordata species, mainly birds, mammals, and amphibians, with a probabilistic methodology to test whether the impact from invasive alien species co-occurs purely randomly, associated, or disassociated with impact from nine other major threats to biodiversit
Drawing on the literature on active objects and combining it with an ethnographic study of engineering work, this paper offers an alternative and complementary understanding of the problem of control in knowledge-intensive work. This problem concerns largely the question of how creative processes of knowing are enabled on behalf of the organization. The dominant response to this question revolves
This systematic review was designed to provide more precise effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development. Asystematic literature search was performed to include cohort studies published in peer-reviewed journals w
The adsorption induced conformational changes of human carbonic anhydrase I (HCAi) and pseudo wild type human carbonic anhydrase II truncated at the 17th residue at the N-terminus (trHCAii) were studied in presence of nanoparticles of different sizes and polarities. Isothermal titration calorimetry (ITC) studies showed that the binding to apolar surfaces is affected by the nanoparticle size in com
Portable biosensor systems would benefit from reduced dependency on external power supplies as well as from further miniaturization and increased detection rate. Systems built around self-propelled biological molecular motors and cytoskeletal filaments hold significant promise in these regards as they are built from nanoscale components that enable nanoseparation independent of fluidic pumping. Pr
Nanoparticles interfere with protein amyloid formation. Catalysis of the process may occur due to increased local protein concentration and nucleation on the nanoparticle surface, whereas tight binding or a large particle/protein surface area may lead to inhibition of protein aggregation. Here we show a clear correlation between the intrinsic protein stability and the nanoparticle effect on the ag
This paper deals with testing an innovative Jordan River Basin boardgame implemented in various contexts. A short description of hydropolitics in the Jordan River Basin and an overview of the positions of the riparians is given. Secondly, the impact of regional hydropolitics at community level in two case studies and the development of the Jordan River Basin game will be discussed. The paper will
The solar proxy Be-10, measured in natural archives, has previously been assumed to lag solar activity by 1-2 yr. This reflects its residence time in the stratosphere where its main source lies. This study, based on a 30-yr global model simulation of the atmospheric transport of Be-10, shows that the stratospheric fraction of production varies significantly with the phase of solar activity. This l
Previously, a healthy Nordic diet (ND) has been shown to have beneficial health effects close to those of Mediterranean diets.
We consider the problem of approximating functions by sums of few exponentials functions, either on an interval or on the positive half-axis. We study both continuous and discrete cases, i.e. when the function is replaced by a number of equidistant samples. Recently, an algorithm has been constructed by Beylkin and Monzón for the discrete case. We provide a theoretical framework for understanding
The IKZF1 gene at 7p12.2 codes for IKAROS (also termed IKZF1), an essential transcription factor in haematopoiesis involved primarily in lymphoid differentiation. Its importance is underlined by the fact that deregulation of IKAROS results in leukaemia in both mice and men. During recent years, constitutional as well as acquired genetic changes of IKZF1 have been associated with human disease. For
Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to fam
Fungus gardens of the basidiomycete Leucocoprinus gongylophorus sustain large colonies of leaf-cutting ants by degrading the plant material collected by the ants. Recent studies have shown that enzyme activity in these gardens is primarily targeted toward starch, proteins and the pectin matrix associated with cell walls, rather than toward structural cell wall components such as cellulose and hemi
BACKGROUND: A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomark
Lynch syndrome and familial colorectal cancer type X, FCCTX, represent the two predominant colorectal cancer syndromes. Whereas Lynch syndrome is clinically and genetically well defined, the genetic cause of FCCTX is unknown and genomic differences between Lynch syndrome and FCCTX tumours are largely unknown. We applied array-based comparative genomic hybridisation to 23 colorectal cancers from FC
