A5086523668- VLSI and Analog Circuit Testing
- Integrated Circuits and Semiconductor Failure Analysis
- Migraine and Headache Studies
- Neuropeptides and Animal Physiology
- Spectroscopy Techniques in Biomedical and Chemical Research
- Cancer-related Molecular Pathways
- Advancements in Semiconductor Devices and Circuit Design
- Engineering and Test Systems
- Molecular Biology Techniques and Applications
- Parallel Computing and Optimization Techniques
- Embedded Systems Design Techniques
- HIV Research and Treatment
- AI in cancer detection
- Trigeminal Neuralgia and Treatments
- Spectroscopy and Chemometric Analyses
- Interconnection Networks and Systems
- Low-power high-performance VLSI design
- Chemical Synthesis and Analysis
- Retinoids in leukemia and cellular processes
- Cardiac electrophysiology and arrhythmias
- Spectroscopy and Laser Applications
- Genetic factors in colorectal cancer
- Nicotinic Acetylcholine Receptors Study
- Cold Atom Physics and Bose-Einstein Condensates
- Fault Detection and Control Systems
United States Military Academy
2010-2024
Renishaw (United Kingdom)
2010-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
1998-2024
University of St Andrews
2023
Ricardo (United Kingdom)
2019-2022
National Institute of Standards and Technology
2022
MUJHU Research Collaboration
2021
Allergan (United States)
2020
Renishaw (Ireland)
2015-2019
University of Oxford
1993-2018
Abstract Purpose: The BRAF gene encodes a serine/threonine kinase and plays an important role in the mitogen-activated protein signaling pathway. mutations sporadic colorectal cancer with microsatellite instability (MSI) are more frequently detected than those stable cancer. In this study, we sought to compare frequencies of MSI hereditary nonpolyposis (HNPCC). Experimental Design: We analyzed 26 cell lines, 80 cancers, 20 tumors from HNPCC patients by DNA sequencing sequence-specific PCR....
The IEEE Mixed-Signal Technical Activity Committee is developing a common set of benchmark circuits for use in researching and evaluating analog fault modeling, test generation, design-for-test, built-in self-test methodologies. first release are based on MITEL Semiconductor's 1.5 /spl mu/m 1.2 CMOS technologies they will allow engineers researchers working mixed-signal testing to compare results as done the digital domain. This paper presents typical described by netlists HSPICE format....
Abstract. This paper introduces new insights into the hydrochemical functioning of lowland river systems using field-based spectrophotometric and electrode technologies. The streamwater concentrations nitrogen species phosphorus fractions were measured at hourly intervals on a continuous basis two contrasting sites tributaries River Thames – one draining rural catchment, Enborne, more urban system, Cut. measurements complement those from an existing network multi-parameter water quality...
Calcitonin gene-related peptide (CGRP) is a potent neuropeptide whose agonist interaction with the CGRP receptor (CGRP-R) in periphery promotes vasodilation, neurogenic inflammation and trigeminovascular sensory activation. This process implicated cause of migraine headaches, CGRP-R antagonists clinical development have proven effective treating migraine-related pain humans. expressed on blood vessel smooth muscle trigeminal neurons fibers as well central nervous system. However, it not...
A growing body of evidence has implicated the calcitonin gene–related peptide (CGRP) receptors in migraine pathophysiology. With approval monoclonal antibodies targeting CGRP or receptor, inhibition CGRP-mediated signaling emerged as a promising approach for preventive treatments adults. Recently, small-molecule anti-CGRP have shown efficacy treating migraine. The current studies aimed to characterize pharmacologic properties ubrogepant, an orally bioavailable receptor antagonist acute...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic studies on the peroxidase activity of selenosubtilisinIan M. Bell, Megan L. Fisher, Zhen Ping Wu, and Donald HilvertCite this: Biochemistry 1993, 32, 14, 3754–3762Publication Date (Print):April 13, 1993Publication History Published online1 May 2002Published inissue 13 April 1993https://pubs.acs.org/doi/10.1021/bi00065a030https://doi.org/10.1021/bi00065a030research-articleACS PublicationsRequest reuse permissionsArticle...
Calcitonin gene-related peptide (CGRP) has long been hypothesized to play a key role in migraine pathophysiology, and the advent of small-molecule antagonists clearly demonstrated clinical link between blocking CGRP receptor efficacy. 2-[(8R)-8-(3,5-Difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide (MK-3207) represents third antagonist display efficacy trials. Here, we report pharmacological...
Abstract Background The molecular genetic classification of gliomas, particularly the identification isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes unique vibrations a sample to accurately characterize its composition. No processing required allowing rapid analysis tissue. aim this study was evaluate ability rapidly identify common subtypes diffuse glioma in neurosurgical setting using fresh biopsy In addition,...
OBJECTIVE Raman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It nondestructive and no sample preparation required. The aim of this study was evaluate the ability glioma normal brain when using fresh biopsy samples and, in case glioblastomas, compare performance predict presence or absence tumor with 5-aminolevulinic acid (5-ALA)–induced fluorescence. METHODS A principal component analysis (PCA)–fed linear discriminant (LDA) machine...
Background The trigeminal sensory neuropeptide calcitonin gene–related peptide (CGRP) is identified as an essential element in migraine pathogenesis. Methods In vitro and vivo studies evaluated pharmacologic properties of the CGRP receptor antagonist atogepant. Radioligand binding using 125 I-CGRP cyclic adenosine monophosphate (cAMP) accumulation assays were conducted human embryonic kidney 293 cells to assess affinity, functional potency selectivity. Atogepant was assessed rat...
The Nef protein of simian immunodeficiency virus (SIV) is dispensable for replication in established T- cell lines but essential high level the adult host, though mechanism by which contributes to this has remained unclear. We demonstrate here that SIV binds ζ chain T-cell receptor (TCR). proteins interact with TCR a yeast two-hybrid system also reduce surface expression levels αβ, CD3 and CD4. These findings are first demonstration can bind directly component TCR-CD3 complex modulate its expression.
We compared the frequency of CpG island methylation phenotype (CIMP), inactivation APC, p53 and DCC genes K-ras BRAF mutations in 39 mucinous carcinomas (MC) 34 non-mucinous (NMC) colorectum with different microsatellite instability (MSI) status. The higher incidence MSI (36% vs. 18%) was observed MC NMC. APC occurred more frequently NMC (APC, 88%, p<0.001; K-ras, 58%, p=0.01) than 24%; 28%) regardless mutation at a (18%, (0%). However, respect to DCC, status did matter both MC, frequent MSS...
A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear FTIs such as compound 1, macrocycles 49 combined improved pharmacokinetic properties a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due attenuated clearance. It observed that vivo clearance correlated the flexibility molecules this concept proved useful design...
Abstract Regional DNA hypermethylation and global hypomethylation are 2 epigenetic alterations associated with colorectal cancers. However, their correlation microsatellite instability (MSI) chromosomal (CIN) in cancer, relationship chromatin conformation histone modification not clear. In this study, we analyzed regional methylation 16 cell lines 64 primary We found that MSI CIN alternative events most tumors. Furthermore, also cases. observed a strong between hypomethylation. further...
Incorporation of polar functionality into a series highly potent calcitonin gene-related peptide (CGRP) receptor antagonists was explored in an effort to improve pharmacokinetics. This strategy identified piperazinone analogues that possessed improved solubility at acidic pH and increased oral bioavailability monkeys. Further optimization led the discovery clinical candidate...
The serine-arginine-specific protein kinase SRPK1 is a common binding partner of the E1^E4 diverse human papillomavirus types. We show here for first time that interaction between HPV1 and leads to potent inhibition phosphorylation host serine-arginine (SR) proteins have critical roles in mRNA metabolism, including pre-mRNA processing, export, translation. Furthermore, we phosphorylates serine residues SR/RS dipeptides hinge region E2 vitro assays inhibits this phosphorylation. After...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPeroxide dependence of the semisynthetic enzyme selenosubtilisinIan M. Bell and Donald HilvertCite this: Biochemistry 1993, 32, 50, 13969–13973Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://doi.org/10.1021/bi00213a029RIGHTS & PERMISSIONSArticle Views159Altmetric-Citations64LEARN ABOUT THESE METRICSArticle Views are COUNTER-compliant sum full text article downloads...
I. Bell, E. R. H. Jones and M. C. Whiting, J. Chem. Soc., 1958, 1313 DOI: 10.1039/JR9580001313
The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification led the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human receptor) vivo (intravenous AD50 0.71 mg/kg rat), bioavailability (90% rat, 96% dog), aqueous solubility (>8.5...