- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- DNA and Nucleic Acid Chemistry
- Substance Abuse Treatment and Outcomes
- Protein Structure and Dynamics
- Advanced biosensing and bioanalysis techniques
- Chronic Myeloid Leukemia Treatments
- Biochemical and Molecular Research
- Homelessness and Social Issues
- Crystallization and Solubility Studies
- Quinazolinone synthesis and applications
- Retinal and Macular Surgery
- Alcoholism and Thiamine Deficiency
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Virology and Viral Diseases
- Protein purification and stability
- Protein Kinase Regulation and GTPase Signaling
- Click Chemistry and Applications
- Synthesis and biological activity
- RNA modifications and cancer
- Eosinophilic Disorders and Syndromes
- Synthesis and Characterization of Heterocyclic Compounds
- Cannabis and Cannabinoid Research
Ionis Pharmaceuticals (United States)
2014-2023
NHS Greater Glasgow and Clyde
2019
Massachusetts Institute of Technology
1973-2018
Penn State Milton S. Hershey Medical Center
1977-2018
Pennsylvania State University
1977-2018
Australian College of Applied Psychology
2013
Glasgow Royal Infirmary
2012
Glasgow Life
2012
University of California, Irvine
2000-2011
University of Alabama in Huntsville
2010
Abstract The copper(I)‐catalyzed cycloaddition reaction between azides and alkynes has been employed to make metal‐adhesive materials. Copper brass surfaces supply the necessary catalytic Cu ions, thus polymerization process occurs selectively on these metals in absence of added catalysts. Alternatively, copper compounds can be monomer mixtures then introduced reducing metal such as zinc initiate polymerization. resulting materials were found possess comparable or superior adhesive strength...
Endometrial growth and repair after menstruation are associated with profound angiogenesis. Abnormalities in these processes result excessive or unpredictable bleeding patterns common many women. It is therefore important to understand which factors regulate normal endometrial Vascular endothelial factor (VEGF) an cell-specific mitogen that plays role pathological In this study we show expression of VEGF regulated by hypoxia human endometrium. Culture vitro for 24 h under hypoxic conditions...
Today the determination of successful crystallization conditions for a particular macromolecule remains highly empirical process. Sparse-matrix and grid-screening procedures are rapid economical means to determine preliminary conditions. During optimization variable set (pH, precipitant type concentration) utilized in these is screened an attempt appropriate nucleation growth single crystals suitable X-ray diffraction analysis. Unfortunately, many cases this strategy will not produce We have...
ABSTRACT Isolated human immunodeficiency virus (HIV) and HIV-infected lymphocytes in culture have been imaged for the first time by atomic force microscopy (AFM). Purified particles spread on glass substrates are roughly spherical, reasonably uniform, though pleomorphic appearance, diameters of about 120 nm. Similar also seen infected cell surfaces, but morphologies sizes considerably more varied, possibly a reflection budding process. The surfaces HIV exhibit “tufts” protein, presumably...
Twenty-one soluble proteins, five tRNAs, and three protein-nucleic acid complexes were studied in a systematic manner with regard to their crystallization behavior from polyethylene glycol ammonium sulfate solutions the presence of 0 1.5% beta-octyl glucoside. Our observations suggest that this neutral detergent does influence very positive way growth characteristics macromolecules included experiment. In general, more reproducible rapid was noted an increased number large individual...
Quasi-elastic light scattering (QELS) was used to investigate quantitatively the mechanisms of nucleation, postnucleation growth, and dissolution in ensembles both crystalline amorphous aggregates satellite tobacco mosaic virus (STMV), ferritin, apoferritin pumpkin seed globulin. At low supersaturation conditions, as described previously for small molecule crystallization, metastable region obtained. Under these conditions aggregation took place, but crystallization did not proceed critical...
Though the molecular weight of EF-Tu from E. coli has been reported to be 42,000 (7) and 47,000 (8), discrepancy is due a difference in techniques for determination rather than properties or amino acid cornposition.To avoid confusion with other literature reports, relative mass tryptic fragments discusser!herein will based on value 44,000 daltons undigested EF-Tu.
An alternative approach to promoting the crystallization of proteins is enhance intermolecular contacts between macromolecules or eliminate interactions with solvent that might inhibit crystallization. Site-specific mutations have been employed, as truncations by genetic proteolytic means. There are, however, significant problems. Because structure target macromolecule unknown, there may be no good basis for design mutants truncations. In addition, requires protein produced recombinant DNA...
Vaccinia virus was treated in a controlled manner with various combinations of nonionic detergents, reducing agents, and proteolytic enzymes, successive products the reactions were visualized using atomic force microscopy (AFM). Following removal outer lipid/protein membrane, layer 20 to 40 nm thickness encountered that composed fibrous elements which, under conditions, rapidly decomposed into individual monomers on substrate. Beneath this core its prominent lateral bodies, which could be...
Paracrystalline inclusions known as Hirano bodies characteristically appear in the hippocampal region of brains humans exhibiting senile and presenile dementias well several other neurodegenerative diseases. We present evidence that currently accepted model for those structures based on alternating filament sheets is not correct, but are stacked membrane-bound ribosomal particles derived from partially degraded rough endoplasmic reticulum or Nissl substance. Using fluorescence staining with...
Age-related macular degeneration (AMD) is one of the leading causes loss vision in industrialized world. Attenuating VEGF signal eye to treat AMD has been validated clinically. A large body evidence suggests that inhibitors targeting VEGFr pathway may be effective for treatment AMD. Recent studies using Src/YES knockout mice suggest along with VEGF, Src and YES play a crucial role vascular leak might useful treating edema associated Therefore, we have developed several potent benzotriazine...
Antisense oligonucleotides (ASOs) conjugated to triantennary N-acetyl galactosamine (GalNAc) ligands represent an emerging approach antisense therapy. Our current generation of GalNAc-ASO conjugates link the GalNAc 5′-terminus ASO. The conjugation reaction can be accomplished using solution-phase or solid-phase techniques. Here we show a direct comparison and strategy. approach, amine-pentafluorophenyl (PFP) ester coupling, is higher yielding gives material slightly purity, but requires...
Chronic myelogenous leukemia (CML) is a hematological stem cell disorder caused by increased and unregulated growth of myeloid cells in the bone marrow, accumulation excessive white blood cells. Abelson tyrosine kinase (ABL) non-receptor involved proliferation usually under tight control. However, 95% CML patients have ABL gene from chromosome 9 fused with breakpoint cluster (BCR) 22, resulting short known as Philadelphia chromosome. This responsible for production BCR-ABL, constitutively...
Background: Guidelines exist for the management of alcohol withdrawal syndrome (AWS) but few have been assessed as to their suitability general hospitals. The Glasgow Assessment and Management guideline has specifically developed use in this context.
Procedures are described for the crystallization of proteins, nucleic acids and viruses in a silica-gel matrix using otherwise standard reagents conditions. Methods given based on both vapor diffusion sitting drop liquid-liquid diffusion. Using variety macromolecules our results suggest that gel suppresses nucleation, reduces rate growth, generally leads to larger, higher-quality crystals enhanced stability. Presumably these effects arise from decreased mobility their flux at crystal surface...
The designation of starting materials (SMs) for pharmaceuticals has been a topic great interest and debate since the first ICH quality guidance was published. increase in number variety commercialized oligonucleotides (antisense oligonucleotides—ASOs, small interfering RNAs—siRNAs, etc.) recent years reignited dialogue on this because unique complexity monomeric nucleotides other contributory used to manufacture oligonucleotides. SM working group European Pharma Oligonucleotide Consortium...