Synthesis, Kinetic Evaluation and Utilization of a Biotinylated Dipeptide Proline Diphenyl Phosphonate for the Disclosure of Dipeptidyl Peptidase IV-like Serine Proteases

In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.

Computing Zeros of Analytic Functions in the Complex Plane without using Derivatives

A new approach to evaluating all multiple complex roots of analytical function f(z) confined to the specified rectangular domain of complex plane has been developed and implemented in Fortran code. Generally f (z), despite being holomorphic function, does not have a closed analytical form thereby inhibiting explicit evaluation of its derivatives. The latter constraint poses a major challenge to implementation of the robust numerical algorithm. This work is at the instrumental level and provides an enabling tool for solving a broad class of eigenvalue problems and polynomial approximations.

Analyzing the degree of conflict among belief functions.

The study of alternative combination rules in DS theory when evidence is in conflict has emerged again recently as an interesting topic, especially in data/information fusion applications. These studies have mainly focused on investigating which alternative would be appropriate for which conflicting situation, under the assumption that a conflict is identified. The issue of detection (or identification) of conflict among evidence has been ignored. In this paper, we formally define when two basic belief assignments are in conflict. This definition deploys quantitative measures of both the mass of the combined belief assigned to the emptyset before normalization and the distance between betting commitments of beliefs.We argue that only when both measures are high, it is safe to say the evidence is in conflict. This definition can be served as a prerequisite for selecting appropriate combination rules.

Gas-liquid two phase flow through a vertical 90deg elbow bend

Pressure drop data are reported for two phase air-water flow through a vertical to horizontal 90° elbow bend set in 0.026 m i.d. pipe. The pressure drop in the vertical inlet tangent showed some significant differences to that found for straight vertical pipe. This was caused by the elbow bend partially choking the inflow resulting in a build-up of pressure and liquid in the vertical inlet riser and differences in the structure of the flow regimes when compared to the straight vertical pipe. The horizontal outlet tangent by contrast gave data in general agreement with literature even to exhibiting a drag reduction region at low liquid rates and gas velocities between 1 and 2 m s -1. The elbow bend pressure drop was best correlated in terms of le/d determined using the actual pressure loss in the inlet vertical riser. The data showed a general increase with fluid rates that tapered off at high fluid rates and exhibited a negative pressure region at low rates. The latter was attributed to the flow being smoothly accommodated by the bend when it passed from slug flow in the riser to smooth stratified flow in the outlet tangent. A general correlation was presented for the elbow bend pressure drop in terms of total Reynolds numbers. A modified Lockhart-Martinelli model gave prediction of the data.

Proteomic Analysis of Recurrent Joint Inflammation in Juvenile Idiopathic Arthritis

The synovial fluid proteome in juvenile idiopathic arthritis was investigated to isolate joint-specific biomarkers that are expressed in patients displaying recurrent joint inflammation. To identify the synovial specific proteome, matched synovial fluid and plasma samples were subjected to protein separation by 2-dimension electrophoresis (2DE). Forty-three protein spots, overexpressed in the joint, were identified. Synovial fluids from children with single-event knee joint inflammation were then compared with a group with recurrent knee disease. Nine synovial specific proteins were significantly differentially expressed in the recurrent group. Proteolytic fragments of collagen X, fibrin beta-chain, and T-cell receptor alpha-region have been identified among this protein cluster. Putative biomarkers, overexpressed in the joint and differentially expressed in children with recurrent joint inflammation, have been identified. These proteins may play a significant role determining the pathological state within the chronically inflamed joint and influence disease progression in JIA. This is the first study of the synovial proteome in children.

Opacity in the upper atmospheres of active stars - II. AD Leonis

We present FUV and UV spectroscopic observations of AD Leonis, with the aim of investigating opacity effects in the transition regions of late-type stars. The C III lines in FUSE spectra show significant opacity during both the quiescent and flaring states of AD Leonis, with up to 30% of the expected flux being lost during the latter. Other FUSE emission lines tested for opacity include those of O VI, while C IV, Si IV and N V transitions observed with STIS are also investigated. These lines only reveal modest amounts of opacity with losses during flaring of up to 20%. Optical depths have been calculated for homogeneous and inhomogeneous geometries, giving path lengths of approximate to 20 - 60 km and approximate to 10 - 30 km, respectively, under quiescent conditions. However path lengths derived during flaring are approximate to 2 - 3 times larger. These values are in excellent agreement with both estimates of the small-scale structure observed in the solar transition region, and path lengths derived previously for several other active late-type stars.

An economical route to one-way quantum computation

We assess the effects of a realistic intrinsic model for imperfections in cluster states by introducing noisy cluster states and characterizing their role in the one-way computational model. A suitable strategy to counter-affect these non-idealities is represented by the use of small clusters, stripped of any redundancy, which leads to the search for compact schemes for one-way quantum computation. In light of this, we quantitatively address the behavior of a simple four-qubit cluster which simulates a controlled-NOT under the influences of our model for decoherence. Our scheme can be particularly useful in an all-optical setup and the strategy we address can be directly applied in those, experimental situations where small cluster states can be constucted.