Characterising a Novel Therapeutic Target for Psoriasis, TYK2, Using Functional Genomics.

Psoriasis (Ps) is a debilitating immune-mediated chronic skin condition. It affects about 1-3% of the world population, with an 8-11% prevalence in Northern European populations. Tyrosine kinase 2 (TYK2) is a newly identified target for Ps.

Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world's population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with Genome-Wide Association (GWAS) studies showing that many psoriasis risk genes lie along the IL-23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs.

TYK2 as a novel therapeutic target in psoriasis.

Introduction: Psoriasis is a chronic inflammatory skin disease affecting approximately 60 million people worldwide. Genome-wide association studies (GWAS) have allowed identification of novel therapeutic targets in psoriasis including tyrosine kinase 2 (TYK2) where an exonic variant within the gene increases the risk of developing psoriasis.

Areas Covered: This review discusses the role of TYK2 in psoriasis pathogenesis, how that relates to genetic variants and recently published ground-breaking clinical trials of novel TYK2 inhibitors.

Quantification of a Facility Radiological Security Risk Index With a Graphical User Interface Tool.

Healthcare facilities around the world routinely use radioactive sources to diagnose and treat illness. To effectively manage the security of radioactive sources, these facilities need to understand the risk, which is comprised of threat, vulnerability, and consequences. The threat component of risk requires knowledge of potential adversaries and understanding their capabilities and intentions.

Adaptation of an ELISA assay for detection of IgG responses against therapeutic monoclonal antibodies in a mouse immunization model.

Biotherapeutic monoclonal antibodies (mAb) play important roles in clinical medicine but their potential to elicit immune responses in patients remains a major issue. In a study designed to investigate the effect of aggregation on immunogenic responses, mice were immunized with two monoclonal antibodies (mAb1 and mAb2). Serum levels of total IgG, IgG, and IgG were measured by ELISA.

Development of a Potential Facility Risk Index for Radiological Security.

Given the threat of radiological and nuclear terrorism, it is imperative to understand and evaluate the security risk of radioactive sources. In this context, risk assessment is a function of threat, vulnerability, and consequences. Currently, no broad risk index exists for radiological facilities, such as healthcare centers and universities.

Eosinophilic Airway Inflammation in Patients with Stable Biomass Smoke- versus Tobacco Smoke-Associated Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease with predominant involvement of neutrophils, macrophages and CD8+ lymphocytes. Eosinophilic airway inflammations are reported in stable state and during acute exacerbations of tobacco smoke-associated COPD (TS-COPD). Women exposed to biomass fuel smoke are known to have eosinophils in sputum.

Impact of a Heat Shock Protein Impurity on the Immunogenicity of Biotherapeutic Monoclonal Antibodies.

Purpose: Anti-drug antibodies can impair the efficacy of therapeutic proteins and, in some circumstances, induce adverse health effects. Immunogenicity can be promoted by aggregation; here we examined the ability of recombinant mouse heat shock protein 70 (rmHSP70) - a common host cell impurity - to modulate the immune responses to aggregates of two therapeutic mAbs in mice.

Methods: Heat and shaking stress methods were used to generate aggregates in the sub-micron size range from two human mAbs, and immunogenicity assessed by intraperitoneal exposure in BALB/c mice.

Nuclear and Radiological Source Security Culture Assessment of Radioactive Material Users at a University.

Securing radioactive sources has become increasingly important given the rising threat of radiological terrorism. While radiation safety has long been established in most applicable industries, the importance of nuclear and radiological source security has lagged behind in nonnuclear material specific industries, such as academic institutions and medical facilities. To evaluate the attitudes and behaviors regarding nuclear security culture, an assessment of nuclear and radiological material practices was developed and conducted on 73 radioactive material users at a university.

(47)Ca production for (47)Ca/(47)Sc generator system using electron linacs.

In this work we have studied the feasibility of photonuclear production of (47)Ca from (48)Ca for (47)Ca/(47)Sc generators. Photon flux distribution for electron beams of different energies incident on a tungsten converter was calculated using the MCNPX radiation transport code. The (47)Ca production rate dependence on electron beam energy was found and (47)Ca/(47)Sc yields were estimated for a 40MeV electron beam.

Novel prostate acid phosphatase-based peptide vaccination strategy induces antigen-specific T-cell responses and limits tumour growth in mice.

Treatment options for patients with advanced prostate cancer remain limited and rarely curative. Prostatic acid phosphatase (PAP) is a prostate-specific protein overexpressed in 95% of prostate tumours. An FDA-approved vaccine for the treatment of advanced prostate disease, PROVENGE® (sipuleucel-T), has been shown to prolong survival, however the precise sequence of the PAP protein responsible for the outcome is unknown.