Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical testing. However, 17-AAG is difficult to formulate and displays weak activity ag...

We report here a relationship between intramolecular epitope spreading and the clinical onset of the endemic form of pemphigus foliaceus in a Brazilian community with a high prevalence and incidence of the disease. Also known as Fogo Selvagem (FS), this disease is characterized by severe skin blistering and pathogenic anti-desmoglein-1 (Dsg1) autoantibodies. These autoantibodies bind the Dsg1 e...

Clustered protocadherins (Pcdhs) mediate numerous neural patterning functions, including neuronal self-recognition and non-self-discrimination to direct self-avoidance among vertebrate neurons. Individual neurons stochastically express a subset of Pcdh isoforms, which assemble to form a stochastic repertoire of cis-dimers. We describe the structure of a PcdhγB7 cis-homodimer, which includes the...

The paper reports the results of a collapse test performed on a 6 m span timber-concrete composite beam with glued re-bar connection. The beam was first ramp loaded to failure, then some push-out tests were performed on specimens cut from the end of the beam in order to fully characterise the connection. During the tests all relevant quantities such as deflections, slips and strains were monito...

A ceramic–ceramic actuator composed of two piezoelectric ceramic layers with opposite poling directions was developed. One layer of the actuator had a high coercive electric field (PZT (Pb(Zr,Ti)O3)-I; Ec5 1.1 kV/mm), while the other had a relatively low coercive electric field (PZT-II; Ec5 0.6 kV/mm). The actuator was fabricated by cofiring a green compact composed of the PZT-I powder on top o...

Emergence of drug resistant strains to currently available antibiotics has resulted in the quest for novel antimicrobial agents. Antimicrobial peptides (AMPs) are receiving attention as alternatives to antibiotics. In this study, we used phage-display random peptide library to identify peptides binding to the cell surface of E. coli. The peptide with sequence RLLFRKIRRLKR (EC5) bound to the cel...

Dowel-type connections are commonly used in timber engineering for a large range of structural applications. The current generation of design rules is largely based on empiricism and testing and lacks in many parts a stringent mechanical foundation. This often blocks an optimized use of the connections, which is essential for the design of economically efficient structures. Moreover, it severel...

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease characterized by autoantibodies (auto-ab) against the desmosomal adhesion molecules desmoglein3 (Dsg3) and Dsg1. Binding of Dsg specific auto-ab to target structures induces an interruption integrity which ultimately results in clinical manifestation flaccid blisters erosions PV patients. Underlying mechanisms inducing blister fo...

A comprehensive understanding of the distribution and water movement substrate in root areas is crucial to design management drip irrigation systems, which a significant step maximizing crop use efficiency by hydrodynamics soilless substrates. In this study, an improved HYDRUS-2D model dynamic growth was used simulate under condition uptake process root, then, compared with observed data. Subst...