A5063888435- Phonetics and Phonology Research
- Voice and Speech Disorders
- Language Development and Disorders
- Cleft Lip and Palate Research
- Hepatitis B Virus Studies
- Ion channel regulation and function
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Speech Recognition and Synthesis
- Nicotinic Acetylcholine Receptors Study
- Hearing Loss and Rehabilitation
- Software Reliability and Analysis Research
- Distributed systems and fault tolerance
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Chemical Synthesis and Analysis
- Family and Disability Support Research
- Genomic variations and chromosomal abnormalities
- Click Chemistry and Applications
- Neuroscience and Neuropharmacology Research
- Evolutionary Game Theory and Cooperation
- Linguistic Variation and Morphology
- Dysphagia Assessment and Management
- RNA and protein synthesis mechanisms
- Interpreting and Communication in Healthcare
University College Cork
2014-2024
Boston Children's Hospital
2013-2024
Concord Repatriation General Hospital
2009-2024
The University of Sydney
2009-2024
MIT Lincoln Laboratory
2021-2024
Case Western Reserve University
2024
Albert Einstein College of Medicine
2024
Tun Hussein Onn University of Malaysia
2023
University of Hong Kong
2002-2023
Harvard University
1987-2023
Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function membrane voltage comes from movement positively charged amino acids, arginine or lysine, across field. We used mutations with natural unnatural electrophysiological recordings, x-ray crystallography to identify charge transfer center in that facilitates this movement. This consists rigid cyclic "cap" two negatively acids interact positive charge. Specific...
Toxins from scorpion venom interact with potassium channels. Resin-attached, mutant K + channels Streptomyces lividans were used to screen Leiurus quinquestriatus hebraeus , and the toxins that interacted channel rapidly identified by mass spectrometry. One of toxins, agitoxin2, was further studied mutagenesis radioligand binding. The results show a prokaryotic has same pore structure as eukaryotic This structural conservation, through application techniques presented here, offers new...
Pore-blocking toxins inhibit voltage-dependent K+ channels (Kv channels) by plugging the ion-conduction pathway. We have solved crystal structure of paddle chimera, a Kv channel in complex with charybdotoxin (CTX), pore-blocking toxin. The toxin binds to extracellular pore entryway without producing discernable alteration selectivity filter and is oriented project its Lys27 into pore. most binding site (S1) devoid electron-density when wild-type CTX bound, but density present some extent...
I understand by a factor of evolution any source progressive change in the constants—mean values, variabilities, correlations—which suffice to define an organ or character, interrelations group organs characters, at stage form life. To demonstrate existence such we require show more than plausibility its effectiveness, need that numerical measure changes organic constants shall be obtained from actual statistical data. These data must sufficient extent render determinations large as compared...
Voltage-dependent ion channels gate open in response to changes cell membrane voltage. This form of gating permits the propagation action potentials. We present two structures voltage-dependent K + channel KvAP, complex with monoclonal Fv fragments (3.9 Å) and without antibody (8 Å). also studied KvAP disulfide cross-bridges lipid membranes. Analyzing these data context crystal structure Kv1.2 EPR on we reach following conclusions: ( i ) is similar a very modest difference orientation its...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPurification and Characterization of Three Inhibitors Voltage-Dependent K+ Channels from Leiurus Quinquestriatus var. Hebraeus VenomMaria L. Garcia, Margarita Garcia-Calvo, Patricia Hidalgo, Alice Lee, Roderick MacKinnonCite this: Biochemistry 1994, 33, 22, 6834–6839Publication Date (Print):June 7, 1994Publication History Published online1 May 2002Published inissue 7 June 1994https://doi.org/10.1021/bi00188a012RIGHTS & PERMISSIONSArticle...
Purpose.: To evaluate the pharmacokinetics of ciliary neurotrophic factor (CNTF) delivered over a period up to 2 years by an intraocular encapsulated cell technology (ECT) implant in patients with retinitis pigmentosa (RP) and geographic atrophy (GA). Methods.: Patients from phase 1 RP (CNTF1); GA (CNTF2); late early stage (CNTF3, CNTF4) studies received ECT-CNTF implant, designated as “NT-501,” one eye. Per protocol, all implants (n = 10) were removed at 6 months CNTF1 study patients....
Pazopanib, an oral multikinase angiogenesis inhibitor, prolongs progression-free survival in adults with soft tissue sarcoma (STS). A phase I pharmacokinetic and pharmacodynamic study of two formulations pazopanib was performed children STS or other refractory solid tumors.Pazopanib (tablet formulation) administered once daily 28-day cycles at four dose levels (275 to 600 mg/m(2)) using the rolling-six design. Dose determination for a powder suspension initiated 50% maximum-tolerated (MTD)...
(1.) A certain number of characters in living forms are capable easy observation, and thus themselves suitable for but they do not admit an exact quantitative measurement, or only this with very great labour. The object the present paper is to illustrate a method by which correlation such may he effectively dealt considerable cases. conditions requisite following:— (i.) should order, although it be impossible give numerical value character any individual. Thus at brown, bay, roan horse, put...
(1.) The present paper endeavours to deal with a problem upon which I have long been occupied, adopting the widest basis compatible time and means at my disposal. In first place, often impressed small reduction in variability can be produced by selection. offspring of single parent while diverging character, possibly very widely from average character race, will still that only slightly reduced, say most 10 per cent, below racial variability. Even if we select ancestry for an indefinite...
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 schizophrenia, and 59 autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, had 20 60 detectable single-nucleotide mutations, but ~6% harbored hundreds mutations. Hypermutability was associated age damaging in genes implicated cancers and, some brains, reflected vivo clonal expansions. Somatic duplications, likely arising during development, were found ~5% normal...
A SECOND STUDY OF THE VARIATION AND CORRE LATION HUMAN SKULL, WITH SPECIAL REFERENCE TO NAQADA CRANIA. Get access CICELY D. FAWCETT, B.Sc., B.Sc. University CollegeLondon Search for other works by this author on: Oxford Academic Google Scholar ALICE LEE, D.Sc. Biometrika, Volume 1, Issue 4, August 1902, Pages 408–467, https://doi.org/10.1093/biomet/1.4.408 Published: 01 1902
The discovery of a series novel, potent, and highly selective inhibitors the DNA damage control kinase chk2 is disclosed. Here we report first SAR study around this kinase. High-throughput screening purified human led to identification novel 2-arylbenzimidazole Optimization was facilitated using homology models docking inhibitors, leading potent 2h (IC50 15 nM). Compound an ATP-competitive inhibitor that dose dependently protects CD4+ CD8+ T-cells from apoptosis due ionizing radiation. This...
Increasing resistance to currently available influenza antivirals highlights the need develop alternate approaches for prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against A and B viruses. Here, we use mouse model evaluate efficacy highly pathogenic avian H5N1 virus. When used treat mice daily beginning 1 day before infection with...