A Chemical Proteomic Probe for Detecting Dehydrogenases: \u3cem\u3eCatechol Rhodanine\u3c/em\u3e

The inherent complexity of the proteome often demands that it be studied as manageable subsets, termed subproteomes. A subproteome can be defined in a number of ways, although a pragmatic approach is to define it based on common features in an active site that lead to binding of a common small molecule ligand (ex. a cofactor or a cross-reactive drug lead). The subproteome, so defined, can be purified using that common ligand tethered to a resin, with affinity chromatography. Affinity purification of a subproteome is described in the next chapter. That subproteome can then be analyzed using a common ligand probe, such as a fluorescent common ligand that can be used to stain members of the subproteome in a native gel. Here, we describe such a fluorescent probe, based on a catechol rhodanine acetic acid (CRAA) ligand that binds to dehydrogenases. The CRAA ligand is fluorescent and binds to dehydrogenases at pH \u3e 7, and hence can be used effectively to stain dehydrogenases in native gels to identify what subset of proteins in a mixture are dehydrogenases. Furthermore, if one is designing inhibitors to target one or more of these dehydrogenases, the CRAA staining can be performed in a competitive assay format, with or without inhibitor, to assess the selectivity of the inhibitor for the targeted dehydrogenase. Finally, the CRAA probe is a privileged scaffold for dehydrogenases, and hence can easily be modified to increase affinity for a given dehydrogenase

High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers.

Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis

Snap-through behaviour of a bistable structure based on viscoelastically generated prestress

A novel form of shape-changing bistable structure has been successfully developed through the use of viscoelastically generated prestress. Bistability is achieved through pairs of deflecting viscoelastically prestressed polymeric matrix composite (VPPMC) strips, which are orientated to give opposing cylindrical configurations within a thin, flexible resin-impregnated fibreglass sheet. This arrangement enables the structure to ‘snap through’ between one of two states by external stimulation. Deflection from the VPPMC strips occurs through compressive stresses generated from the non-uniform spatial distribution of nylon 6,6 fibres undergoing viscoelastic recovery. In this study, snap-through behaviour of the bistable structure is investigated both experimentally and through finite element (FE) analysis. By using experimental results to calibrate FE parameter values, the modelling has facilitated investigation into the development of bistability and the influence of modulus ratio (fibreglass sheet: VPPMC strip) on the snap-through characteristics. Experimental results and FE simulation show good agreement with regard to snap-through behaviour of the bistable structure and from this, the bistability mechanisms are discussed

Anti-chiral edge states in an exciton polariton strip

We present a scheme to obtain anti-chiral edge states in an exciton-polariton honeycomb lattice with strip geometry, where the modes corresponding to both edges propagate in the same direction. Under resonant pumping the effect of a polariton condensate with nonzero velocity in one linear polarization is predicted to tilt the dispersion of polaritons in the other, which results in an energy shift between two Dirac cones and the otherwise flat edge states become tilted. Our simulations show that due to the spatial separation from the bulk modes the edge modes are robust against disorder.Comment: 6 pages, 5 figure

Early-stage star forming cloud cores in GLIMPSE Extended Green Objects (EGOs) as traced by organic species

In order to investigate the physical and chemical properties of massive star forming cores in early stages, we analyse the excitation and abundance of four organic species, CH3OH, CH3OCH3, HCOOCH3 and CH3CH2CN, toward 29 Extended Green Object (EGO) cloud cores that were observed by our previous single dish spectral line survey. The EGO cloud cores are found to have similar methanol J_3-J_2 rotation temperatures of ~44 K, a typical linear size of ~0.036 pc, and a typical beam averaged methanol abundance of several 10^(-9) (the beam corrected value could reach several 10^(-7)). The abundances of the latter three species, normalized by that of methanol, are found to be correlated also across a large variety of clouds such as EGO cloud cores, hot corinos, massive hot cores and Galactic Center clouds. The chemical properties of the EGO cloud cores lie between that of hot cores and hot corinos. However, the abundances and abundance ratios of the four species can not be satisfactorily explained by recent chemical models either among the EGO cloud cores or among the various types of cloud cores from literature

Minimum Wage and Compliance in a Model of Search On-the-Job

minimum wages, compliance, job search, wage growth