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Tasquinimod Is an Allosteric Modulator of HDAC4 Survival Signaling within the Compromised Cancer Microenvironment

Tasquinimod is an orally active antiangiogenic drug that is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer. However, the target of this drug has remained unclear. In this study, we applied diverse strategies to identify the histone deacetylase HDAC4 as a target for the antiangiogenic activity of tasquinimod. Our comprehensive analysis revealed allo

Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal Insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation.

Context:Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective:The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of

Ultrafast Dynamics of Hole Injection and Recombination in Organometal Halide Perovskite Using Nickel Oxide as p-Type Contact Electrode.

There is a mounting effort to use nickel oxide (NiO) as p-type selective electrode for organometal halide perovskite-based solar cells. Recently, an overall power conversion efficiency using this hole acceptor has reached 18%. However, ultrafast spectroscopic investigations on the mechanism of charge injection as well as recombination dynamics have yet to be studied and understood. Using time-reso

Project Turnstone: Freedom of Movement and Passenger Experiences with Safety and Border Control in the Baltic Sea Area

Projekt Turnstone är ett samverkansprojekt delvis finansierat av Europeiska kommissionen. Projektet är ett initiativ av Stockholmspolisens gränsbevakningsenhet. Syftet med Projekt Turnstone är att minska gränsöverskridande brottslighet, förbättra dagligt samarbete mellan gräns, polis och kustbevakare i Östersjöregionen och förbättra säkerheten för passagerare i Östersjöregionen utan att göra avkalProject Turnstone is a collaborative project funded in part by the European Commission. The project is an initiative by the Stockholm Police. The purpose of the project is to improve day-to-day cooperation between border officers in the Baltic Sea region, decrease trans-boundary criminality, and increase security for passengers in the Baltic Sea area without compromising freedom of movement. Withi

Directed evolution of chemotaxis inhibitory protein of Staphylococcus aureus generates biologically functional variants with reduced interaction with human antibodies

Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is a protein that binds and blocks the C5a receptor (C5aR) and formylated peptide receptor, thereby inhibiting the immune cell recruitment associated with inflammation. If CHIPS was less reactive with existing human antibodies, it would be a promising anti-inflammatory drug candidate. Therefore, we applied directed evolution and comput

Physical activity in persons with late effects of polio

Physical activity is beneficial for the health of persons with disabilities but the levels of such activity are lower than for persons without disability. In addition the level of physical activity decreases with increasing age. For persons aging with a disability it may be a challenge to engage in physical activity, partly because of the disability and partly because of contextual barriers. One g

TLR4 dependent heparan sulphate-induced pancreatic inflammatory response is IRF3-mediated

Background: Degraded extracellular matrix can stimulate the innate immune system via the Toll-Like Receptor-4 (TLR4). In the pancreas, syndecan-anchored heparan sulphate (HS) on the ductal epithelium can be cleaved off its protein cores by the proteases (trypsin and elastase) and potentially activate TLR4 signalling. Methods: To investigate this signalling event, a low sulphated HS (500 mu g/ml) w

CASE STUDIES OF DESERTIFICATION MONITORING. -A DISCUSSION OF EU INITIATIVES

The word “desertification” was introduced in 1949 by the French scientist Aubreville in his report “Climats, forêts et désertification de l´Afrique tropicale”. The concept, however, was discussed earlier by European and American scientists in terms of increased sand movements, desiccation, desert and Sahara encroachment and man made deserts. Desertification, at the beginning of last century, mea

Modernitet och myt : avförtrollning och återförtrollning i Knut Hamsuns Sult, Mysterier och Pan

Knut Hamsun (1859-1952) is generally regarded as one of the first proponents of modern literature in Scandinavia. The present thesis discusses the author’s breakthrough phase which took place around the year 1890. This was an era when societal modernity became established in the Scandinavian countries, and new and revolutionary ideas and norms appeared concerning society, science, and art. Hamsun

Immunoassay for the discrimination of free prostate-specific antigen (fPSA) forms with internal cleavages at Lys(145) or Lys(146) from fPSA without internal cleavages at Lys(145) or Lys(146)

Total levels of circulating prostate-specific antigen (tPSA) are strongly associated with prostate cancer (PCa) risk and outcome but benign prostate disease is the most frequent cause of a moderately elevated PSA level. Free PSA (fPSA) forms are independently associated with PCa risk and contribute modest diagnostic enhancements above and beyond tPSA alone. We developed an immunoassay for fPSA sub

Characterisation of Arteriovenous Fistula’s sound recordings using principal component analysis

In this study, a signal analysis framework based on the Karhunen-Loève expansion and k-means clustering algorithm is proposed for the characterisation of arteriovenous (AV) fistula’s sound recordings. The Karhunen-Loève (KL) coefficients corresponding to the directions of maximum variance were used as classification features, which were clustered applying k-means algorithm. The results showed that

Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

TLR agonists are attractive candidate adjuvants for therapeutic cancer vaccines as they can induce a balanced humoral and T cell-mediated immune response. With a dense network of dendritic cells (DCs) and draining lymphatics, the skin provides an ideal portal for vaccine delivery. Beside direct DC activation, TLR agonists may also induce DC activation through triggering the release of inflammatory

Objective monitoring of nasal airway inflammation in rhinitis

Allergic rhinitis is an inflammatory nasal disorder in which a range of different cells participates. A variety of approaches has been used to monitor nasal inflammation objectively to investigate disease processes and to evaluate the effect of therapeutic intervention. These approaches include nasal lavage, nasal cytology, and nasal biopsy, together with the more recently established measurement

Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood

The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in

Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors

Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resist

A dose-dependent role for EBF1 in repressing non-B-cell-specific genes

In the absence of early B-cell factor 1 (EBF1), B-cell development is arrested at an uncommitted progenitor stage that exhibits increased lineage potentials. Previously, we investigated the roles of EBF1 and its DNA-binding partner Runx1 by evaluating B lymphopoiesis in single (EBF1(het) and Runx1(het)) and compound haploinsufficent (Ebf1(+/-) Runx1(+/-), ERhet) mice. Here, we demonstrate that dec

Antibodies to influenza virus A/H1N1 hemagglutinin in type 1 diabetes children diagnosed before, during and after the Swedish A(H1N1)pdm09 vaccination campaign 2009-2010.

We determined A/H1N1-HA antibodies in relation to HLA-DQ genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7-18 years old type 1 diabetes patients diagnosed April 2009 - December 2010. Antibodies to (35) S-methionine-labeled A/H1N1 hemagglutinin were determined in a radiobinding assay in patients diagnosed before (n=325), during (n=355) and after (n=461) the October 2009

Collagen VI Is Upregulated in COPD and Serves Both as an Adhesive Target and a Bactericidal Barrier for Moraxella catarrhalis.

Moraxella catarrhalis is a Gram-negative human mucosal commensal and pathogen. It is a common cause of exacerbation in chronic obstructive pulmonary disease (COPD). During the process of infection, host colonization correlates with recognition of host molecular patterns. Importantly, in COPD patients with compromised epithelial integrity the underlying extracellular matrix is exposed and provides