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The transcription factor STAT3 is a potential target for the treatment of castration-resistant prostate cancer. Galiellalactone (1), a direct inhibitor of STAT3, prevents the transcription of STAT3 regulated genes. In this study we characterized 6 (GPA512, Johansson, M.; Sterner, O. Patent WO 2015/132396 A1, 2015), a prodrug of 1. In vitro studies showed that 6 is rapidly converted to 1 in plasma
AbstractBackgroundAdrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship betw
Objective: Apart from improved health outcomes, treatment convenience per se may have a value to individuals. This is sometimes referred to as process utility and can be estimated in terms of willingness-to-pay (WTP) or quality-adjusted life-years (QALYs). Previous research has produced multiple studies on QALY gains and WTP estimates of insulin-related attributes. There are, however, significant
Purpose: Outcome after lumbar disc herniation (LDH) surgery in middle-aged patient is usually reported to fulfill the criteria for successful outcome. It is also known that women in these years have an inferior outcome compared to men. This study evaluates whether the same gender differences exist in elderly. Method: In the national Swedish register for spine surgery (SweSpine) we identified 1668
Waiting times in cancer care is a patient safety risk that needs increased attention. Mechanisms and effects need to be clarified, waiting time statistics should be openly presented and evidence-based strategies should be implemented. Cancer patient pathways are implemented in Sweden during 2015–2018 and are expected to reduce waiting times for some patient groups, but cannot be expected to presen
We examined undergraduate participants' (N = 98) self-related cognitive response to positive information about the self and how this response is related to global self-esteem and trait anxiety. Positive information about the self was defined as information that attributes positive qualities to the self or positive experiences for the self. The responses were measured by an open-ended questionnaire
Inferential Role Semantics is often criticized for being incompatible with the platitude that words of different speakers can mean the same thing. While many assume that this platitude can be accommodated by understanding sameness of meaning in terms of similarity of meaning, no worked out proposal has ever been produced for Inferential Role Semantics. I rectify this important omission by giving a
The concept of symbolic sequences play important role in study of complex systems. In the work we are interested in ultrametric structure of the set of cyclic sequences naturally arising in theory of dynamical systems. Aimed at construction of analytic and numerical methods for investigation of clusters we introduce operator language on the space of symbolic sequences and propose an approach based
Most eukaryotic organisms, except some animal clades, have mitochondrial alternative electron transport enzymes that allow respiration to bypass the energy coupling in oxidative phosphorylation. The energy bypass enzymes in plants include the external type II NAD(P)H dehydrogenases (DHs) of the NDB family, which are characterized by an EF-hand domain for Ca2+ binding. Here we investigate these pla
N-methyl-N-nitrosourea (MNU) has been reported to induce photoreceptor-specific degeneration with minimal inner retinal impact in small animals in vivo. Pending its use within a retinal transplantation paradigm, we here explore the effects of MNU on outer and inner retinal neurons and glia in an in vitro large animal model of retinal degeneration. The previously described degenerative culture expl
Voltage-activated potassium channels (Kv channels) in the microvillar photoreceptors of arthropods are responsible for repolarization and regulation of photoreceptor signaling bandwidth. On the basis of analyzing Kv channels in dipteran flies, it was suggested that diurnal, rapidly flying insects predominantly express sustained K+ conductances, whereas crepuscular and nocturnally active animals ex
That birds migrate in the reverse direction of the expected is a phenomenon of regular occurrence which has been observed at many sites. Here we use three different methods; tracking radar, radiotelemetry and ringing, to characterize the flights of these reverse migrants and investigate possible causes of reverse migration of nocturnally migrating passerines during autumn migration at Falsterbo pe
Serotonin (5-HT) is a biogenic monoamine that functions both as a neurotransmitter and a circulating hormone. Recently, the metabolic effects of 5-HT have gained interest and peripheral 5-HT has been proposed to influence lipid metabolism in various ways. Here, we investigated the metabolic effects of 5-HT in isolated, primary rat adipose cells. Incubation with 5-HT suppressed β-adrenergically sti
The report offers an analysis of the R&I system in Sweden for 2015, including relevant policies and funding, taking into account the priorities of the European Research Area and the Innovation Union. The report was prepared according to a set of guidelines for collecting and analysing a range of materials, including policy documents, statistics, evaluation reports, websites, etc. The quantitat
The radiocarbon concentration of different atherosclerotic plaque fragments obtained from 20 patients in Portugal, operated in 2000-2001, has been measured in order to define the year of plaque formation. A difference of 1.8-15 yr was observed, with the mean and median both 9 yr, between the bomb-pulse date estimated with the CALIBomb software and the operation date. Stable isotope (delta C-13 and
