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Microdosing is a new concept in drug development that-if implemented in the pharmaceutical industry-would mean that new drugs can be tested earlier in humans than done today. The human microdosing concept-or 'Phase 0'-may offer improved candidate selection, reduced failure rates in the drug development line and a reduction in the use of laboratory animals in early drug development, factors which w

Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeuti

In this retrospective epidemiologic study, we present pneumococcal carriage data from 109 Swedish day care centers over a period of 10 years. Aspects of season, age, personnel and group size were studied. We found a significant seasonal variation in pneumococcal carriage. Group size was a significant risk factor for pneumococcal carriage. Pneumococcal carriage was 4.5 % in personnel.

Ductile shear zones associated with emplacement of high-pressure nappes are key features to resolve exhumation mechanisms. The Eastern Segment of the Sveconorwegian orogen hosts an eclogite-bearing fold nappe, whose basal shear zone shows structures associated with emplacement of the eclogite-bearing nappe and decompression under high to intermediate pressure granulite and upper amphibolite fades

Risk-taking can be either adaptive or maladaptive depending on the context, but maladaptive risk-taking sometimes has serious consequences. Understanding how self-control and other aspects of personality are related to risk-taking is important, as self-control can be improved through training. We examined how the regulative temperamental trait Activation control interacts with the reactive traits

Recent advances in experimental plant biology have led to an increased potential to investigate plant development at a systems level. The emerging research field of Computational Morphodynamics has the aim to lead this development by combining dynamic spatial experimental data with computational models of molecular networks, growth, and mechanics in a multicellular context. The increased number of

We present the calculation of the self-energy of the isolated hydrogen atom within the GW approximation starting from the noninteracting Green's function constructed from the exact wave functions of the hydrogen atom. The error in the electron removal energy of the 1s state is found to be about 0.02 eV, which is much smaller than what one would expect. This small error is explained by the cancella

A unique anti-inflammatory property of IgG, independent of antigen specificity, is described. IgG with modification of the heavy-chain glycan on asparagine 297 by the streptococcal enzyme endo-beta-N-acetylglucosaminidase (EndoS) induced a dominant suppression of immune complex (IC)-mediated inflammation, such as arthritis, through destabilization of local ICs by fragment crystallizable-fragment c

Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clea

We present a synthesis of the results of a multiproxy, multisite, palaeoecological study of Holocene environmental change in Kamchatka, Far East Russia, details of which are presented elsewhere in the volume. We summarise the results of the analyses of pollen, diatom, chironomid, and testate amoebae assemblages, together with stable isotopes of oxygen and carbon, and sediment characteristics from

Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer

Oxidative stress has been suggested to contribute to the development of non-alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which could accelerates oxidative stress under over

The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary

Energy security is one of the main drivers of energy policies. Understanding energy security implications of long-term scenarios is crucial for informed policy making, especially with respect to transformations of energy systems required to stabilize climate change. This paper evaluates energy security under several global energy scenarios, modeled in the REMIND and WITCH integrated assessment mod

More than 4 orders of magnitude of cavity-linewidth narrowing in a rare-earth-ion-doped crystal cavity, emanating from strong intracavity dispersion caused by off-resonant interaction with dopant ions, is demonstrated. The dispersion profiles are engineered using optical pumping techniques creating significant semipermanent but reprogrammable changes of the rare-earth absorption profiles. Several