A strategy that combines virtual screening and structureguided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer

The influence of dispersion and interaction of Graphene Oxide (GO) in semi-crystalline Polyhydroxy butyrate (PHB) and glassy amorphous Poly(tBP-oda) is explored by Positron Annihilation Lifetime Spectroscopy (PALS). The ortho-Positronium lifetimes which represent the main free volume hole size of both polymers are mainly affected by the large differences in internal stresses built up by the shrink

This paper explores the spatial and temporal land-cover variability within the main cultural landscape units in Denmark during the last 3,000 years. Quantitative estimates of the cover of trees, grasses, Cerealia and Calluna around nine Danish lakes were obtained using the recently developed Landscape Reconstruction Algorithm (LRA) (Sugita 2007a, b). The performance of the approach was evaluated b

The paddyfield warbler, Acrocephalus agricola, has extended its breeding range from Central Asia to the western Black Sea coast. The Balkan population offers a unique chance to test the effect of breeding range expansion on the genetically programmed migratory direction. We studied 21 paddyfield warblers at Durankulak Lake, NE Bulgaria, by recording their autumn migratory orientation in circular o

Pharmacological and revascularization strategies following myocardial infarction (MI) have changed substantially during the last two decades. We investigated the temporal trends in heart failure (HF) incidence and mortality during the first 90days following first-time MI between 1997 and 2010 in Denmark.

Landscape genetics offers a powerful approach to understanding species’ dispersal patterns. However, a central obstacle is to account for ecological processes operating at multiple spatial scales, while keeping research outcomes applicable to conservation management. We address this challenge by applying a novel multilevel regression approach to model landscape drivers of genetic structure at both

Androgen deprivation therapy (ADT) is frequently used for the treatment of advanced prostate cancer. ADT is associated with numerous side effects related to its mode of action, namely the suppression of testosterone to castrate levels. Recently, several large retrospective studies have also reported an increased risk of diabetes and cardiovascular disease in men receiving ADT, although these risks

We used isotension-ensemble Monte Carlo simulations to study the properties of brush layers of bottle-brush polymers under lateral compression. The polymers were represented by a freely jointed hard-bead model with one side chain grafted to each bead of the main chain, and we considered variations in side-chain length and bead size. Brush properties, including brush height and surface pressure, we

Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in pa

Non-invasive diode laser spectroscopy was, for the first time, used to assess gas content in the intestines and the lungs of a new-born, 4 kg, baby. Two gases, water vapor and oxygen, were studied with two low-power tunable diode lasers, illuminating the surface skin tissue and detecting the diffusely emerging light a few centimeters away. The light, having penetrated into the tissue, had experien

With fast growing power consumption and device miniaturization, micro/minichannels are superior to macrochannels or conventional channels for high heat-flux dissipation due to their large surface area to volume ratios and high heat transfer coefficients. However, the associated large pressure drop penalty and flow boiling instability of micro/minichannels hinder their advancement in many practical

Our simple dynamic-simulation model shows that the global supply of Rare Earth Elements is limited for meeting the future demands of new technologies. Unless improved recycling policies are adapted strategic elements may become scarce in the next half-century as a result of a “peak Rare Earths Elements” phenomenon. The model results also show that the market alone cannot solve the resource-ineffic

Characteristic mode analysis provides unparalleled insights into designing high performance multiple-input multiple-output (MIMO) terminal antennas at frequencies where the antenna elements are constrained to be electrically small. Conventionally, an electrically small single-antenna utilizes the fundamental characteristic mode of the terminal chassis to obtain sufficient bandwidth while maintaini

How are people facing a virtual agent affected by the vividness and graphical fidelity of the agent and its environment? A choice blindness (CB) experiment - measuring detection rate of hidden manipulations - was conducted presenting a high versus low immersion virtual environment. The hypothesis was that the lower quality virtual environment (low immersion) would increase the detection rate for t

A portable and time-integrating field sampler based on the supported liquid membrane (SLM) extraction technique was constructed. Using two programmable syringe pumps and one programmable valve, the sampler could carry out automatic unattended extraction for up to seven extracts, combining the steps of sampling, trace enrichment and clean-up. The sampler was applied to the extraction of four s-tria

Salt-inducible kinase (SIK) 3 is a virtually unstudied, ubiquitously expressed serine/threonine kinase, belonging to the AMP-activated protein kinase (AMPK)-related family of kinases, all of which are regulated by LKB1 phosphorylation of a threonine residue in their activation (T)-loops. Findings in adrenal cells have revealed a role for cAMP in the regulation of SIK1, and recent findings suggest

Background/Aims: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: The following three-phase procedure was used: (1) elaboration of a

Cellobiose dehydrogenase (CDH) is capable of direct electron transfer (DET) on various carbon and thiol-modified gold electrodes. As a result, these systems have been utilized as biocatalyst in biosensors and biofuel cell anodes. Class I CDHs, from basidiomycetous fungi, are highly specific to cellulose or lactose, and DET is only observed at pH values below 5.5. To extend the applicability of CDH

Crack tip conditions in SUS 304 austenitic stainless steel are studied using a constitutive model in which the martensitic phase transformation is an integral part. The phase transformation occurring in the crack tip region gives rise to fracture toughening of the material whereby the resistance against crack initiation, as well as the macroscopic material response are strongly altered by the pres

We present the first dynamical implementation of the combined GW and dynamical mean-field scheme ("GW + DMFT") for first-principles calculations of the electronic properties of correlated materials. The application to the ternary transition metal oxide SrVO3 demonstrates that this scheme inherits the virtues of its two parent theories: a good description of the local low-energy correlation physics