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LEAD Technologies Inc. is a privately held software company headquartered in Charlotte, North Carolina, USA. LEAD develops, markets and supports a line of imaging toolkits called LEADTOOLS. Wikipedia.

White J.P.M.,Imperial College London | Urban L.,Lead Technologies | Nagy I.,Imperial College London
Current Pharmaceutical Biotechnology | Year: 2011

The transient receptor potential vanilloid type 1 ion channel (TRPV1) was identified as a receptor responsible for mediating the intense burning sensation following exposure to heat greater than ~43 °C, or to capsaicin, the pungent ingredient of hot chilli peppers. More importantly, however, it has been shown that TRPV1 plays a pivotal role in the development of the burning pain sensation associated with inflammation in peripheral tissues. More recently, there has been a virtual avalanche of sightings of TRPV1 on the anatomical landscape, coupled with association of TRPV1 with a wide range of non-pain-related physiological and pathological conditions. Here, we consider the continuously expanding set of functions in both health and disease which TRPV1 is understood to subserve at present. The widespread expression of TRPV1 in the human suggests that, in addition to the development of burning pain associated with acute exposure to heat or capsaicin, and with inflammation, TRPV1 may also be involved in an array of vitally important functions, such as those of the urinary tract, the respiratory and auditory systems. Moreover, TRPV1 may also be involved in the maintenance of body and cell homeostasis, metabolism, regulation of hair growth, and development of cancer. Thus, controlling TRPV1 function may possess the potential of providing exciting opportunities for therapeutic interventions. At the same time, however, the widespread distribution of these ion channels introduces a tremendous complication in developing a drug to serve in one disease context which may have profound implications for normal TRPV1 functioning in other non-pathological contexts. © 2011 Bentham Science Publishers Ltd. Source

Aneiros E.,Pfizer | Aneiros E.,Lead Technologies | Cao L.,Pfizer | Papakosta M.,Pfizer | And 3 more authors.
EMBO Journal | Year: 2011

The capsaicin receptor TRPV1, a member of the transient receptor potential family of non-selective cation channels is a polymodal nociceptor. Noxious thermal stimuli, protons, and the alkaloid irritant capsaicin open the channel. The mechanisms of heat and capsaicin activation have been linked to voltage-dependent gating in TRPV1. However, until now it was unclear whether proton activation or potentiation or both are linked to a similar voltage-dependent mechanism and which molecular determinants underlie the proton gating. Using the whole-cell patch-clamp technique, we show that protons activate and potentiate TRPV1 by shifting the voltage dependence of the activation curves towards more physiological membrane potentials. We further identified a key residue within the pore region of TRPV1, F660, to be critical for voltage-dependent proton activation and potentiation. We conclude that proton activation and potentiation of TRPV1 are both voltage dependent and that amino acid 660 is essential for proton-mediated gating of TRPV1. © 2011 European Molecular Biology Organization | All Rights Reserved. Source

MacKinnon M.T.,Rolls-Royce | Shaw J.D.,Rolls-Royce | Quiones M.,Lead Technologies
Journal of Engineering for Gas Turbines and Power | Year: 2012

As part of the United States Navy green energy initiative, engineers at Rolls-Royce and NAVSEA conducted a combustion assessment for a blend of 50 algae-derived HRD76 biofuel and 50 conventional F76 military diesel. The assessment consisted of combustion rig testing with Rolls-Royce Model 501-K34 gas turbine combustion system hardware. Identical tests were performed with the biofuel blend and a baseline fuel consisting of 100 F76 military diesel. The test results quantified the impact of the alternative fuel blend on ignition, lean blow-out, combustor exit temperature profile, combustion system hardware temperatures, primary zone flame radiance, carbon deposition, and emissions. This paper discusses the methods and results of the combustion rig tests. © 2012 American Society of Mechanical Engineers. Source

Hilal T.,Schering | Puetter V.,Lead Technologies | Otto C.,Bayer AG | Parczyk K.,Schering | Bader B.,Schering
Journal of Biomolecular Screening | Year: 2010

The human estrogen receptors (hER) are members of the nuclear hormone receptor (NHR) superfamily and represent important drug targets for the pharmaceutical industry. Initially, ligand binding assays were used to identify novel ligands using receptors purified from native tissues. With the advent of molecular cloning techniques, cell-based transactivation assays have been the gold standard for many years of drug discovery. With the elucidation of the structural mechanisms underlying the activation of NHRs, cell-free assays with purified receptors have become important tools to directly assess different binding sites (e.g., the hormone binding site or the cofactor binding site). The available cell-free assays have so far facilitated the study of one binding site at a time. With the introduction of Terbium (Tb 3+)-based time-resolved fluorescence energy transfer (TR-FRET), it has become possible to measure 2 different interactions within 1 test tube in parallel. The authors have applied this technology to develop a dual readout system for the simultaneous monitoring of steroid hormone site binding and cofactor peptide recruitment. They took advantage of a commercially available fluorescent tracer as an indicator for classical steroid site binding and designed a novel peptide derived from the peroxisome proliferator-activated receptor gamma coactivator-la (PGCIa) as an indicator for functional agonistic behavior of a test compound. The established assay is able to differentiate between agonists, antagonists, partial agonists, and compounds binding to the cofactor recruitment site. The IC 50 values obtained for a number of reference compounds in the multiplexed assay are in concordance with published data. The simple 1 -step mix-and-measure protocol gives excellent quality and robustness and can be miniaturized to 5-μL volume. © 2010 Society for Biomolecular Sciences. Source

Automotive engineering processes are dynamic, iterative and driven by changes. Reasons for changes on development artifacts are manifold, but the result is a new evolution step which may influence all, some, or just a single development artifact. Consequently, research on impact analysis put forth approaches to assess the adverse effects of changes. However, understanding and implementing functional changes and its consequences in the safety domain is often aggravated by dependencies between different types of development artifacts, scattered in various (tool) formats. Safety properties may change depending on the type of a modification. Thereby, connected analyses like fault trees, Failure Modes and Effects Analysis (FMEA), and safety concepts cannot be reused easily if the artifacts on which they are based on are affected by changes. In this paper we suggest a new difference analysis approach which allows a (semi-)automated comparison of safety work products based on models. As a model we understand any formalized data structure with well-defined (abstract) syntax and semantics defined by a metamodel [1]. Moreover, we propose a Safety Change Impact Rules Language (SCIRL) targeted at heterogeneous safety artifacts in a model-based safety framework. SCIRL can access artifacts, which are described by metamodels. Moreover, the language is compliant to the Object Constraint Language (OCL) for queries and constraints [2]. The advantage of SCIRL is to synchronize models in a semi-automated manner or refer to artifacts in the safety lifecycle impacted by a change request. © Copyright 2016 SAE International. Source

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