Sphingosine-1-Phosphate Receptors Modulators Decrease Signs of Neuroinflammation and Prevent Parkinson's Disease Symptoms in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model.

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid mediator that acts as a natural ligand upon binding to five different receptors that are located in astrocytes, oligodendrocytes, microglial and neuronal cells. Recently, global activation of these receptors by FTY720 (fingolimod) has been suggested to provide neuroprotection in animal model of Parkinson's disease (PD). Among S1P receptors, the subtype 1 (S1P1R) has been linked to features of neuroprotection and, using the selective agonist SEW2871, the present investigation assessed potential benefits (and mechanisms) of this receptor subtype in an established animal model of PD.

Factorial Design Approach in Proportioning Prestressed Self-Compacting Concrete.

In order to model the effect of mixture parameters and material properties on the hardened properties of, prestressed self-compacting concrete (SCC), and also to investigate the extensions of the statistical models, a factorial design was employed to identify the relative significance of these primary parameters and their interactions in terms of the mechanical and visco-elastic properties of SCC. In addition to the 16 fractional factorial mixtures evaluated in the modeled region of -1 to +1, eight axial mixtures were prepared at extreme values of -2 and +2 with the other variables maintained at the central points. Four replicate central mixtures were also evaluated.

Pull-Out Strength and Bond Behavior of Prestressing Strands in Prestressed Self-Consolidating Concrete.

With the extensive use of self-consolidating concrete (SCC) worldwide, it is important to ensure that such concrete can secure uniform mechanical properties that are similar to those obtained with properly consolidated concrete of conventional fluidity. Ensuring proper stability of SCC is essential to enhance the uniformity of mechanical properties, including bond to embedded reinforcement, which is critical for structural engineers considering the specification of SCC for prestressed applications. In this investigation, Six wall elements measuring 1540 mm × 2150 mm × 200 mm were cast using five SCC mixtures and one reference high-performance concrete (HPC) of normal consistency to evaluate the uniformity of bond strength between prestressing strands and concrete as well as the distribution of compressive strength obtained from cores along wall elements.

Performance-Based Specifications of Workability Characteristics of Prestressed, Precast Self-Consolidating Concrete-A North American Prospective.

Adequate selection of material constituents and test methods are necessary for workability specifications and performance of hardened concrete. An experimental program was performed to evaluate the suitability of various test methods for workability assessment and to propose performance specifications of prestressed concrete. In total, 33 self-consolidating concrete (SCC) mixtures made with various mixture proportioning parameters, including maximum size and type of aggregate, type and content of binder, and w/cm were evaluated.

The amino-terminus of angiotensin II contacts several ectodomains of the angiotensin II receptor AT1.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and major targets for drug development. Herein, we sought to identify the regions of the human angiotensin II (AngII) type 1 (hAT(1)) receptor binding cleft that interact with all positions of the AngII using photoaffinity labeling. We conducted a complete iterative walk-through of the AngII sequence with either p-benzoyl-L-phenylalanine (Bpa) or p-[3-(trifluoromethyl)-3H-diazirin-3-yl]-L-phenylalanine (Tdf) to yield two series of eight photoreactive analogues.