A5090197209- Atmospheric and Environmental Gas Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Atmospheric Ozone and Climate
- Atmospheric chemistry and aerosols
- Protein purification and stability
- Methane Hydrates and Related Phenomena
- Geology and Paleoclimatology Research
- Glycosylation and Glycoproteins Research
- Hydrocarbon exploration and reservoir analysis
- T-cell and B-cell Immunology
- Viral Infectious Diseases and Gene Expression in Insects
- Isotope Analysis in Ecology
- Archaeology and ancient environmental studies
- Mass Spectrometry Techniques and Applications
- Nuclear Physics and Applications
- Advanced Biosensing Techniques and Applications
- Immune Cell Function and Interaction
- Marine and coastal ecosystems
- Radioactive contamination and transfer
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Ocean Acidification Effects and Responses
- Eosinophilic Esophagitis
- Ion-surface interactions and analysis
- CAR-T cell therapy research
AstraZeneca (United Kingdom)
2020-2023
AstraZeneca (Germany)
2021
AC Immune (Switzerland)
2018-2019
University of Minnesota
2018
Granta Design (United Kingdom)
2017
Aimmune Therapeutics (United Kingdom)
2013
Victoria University of Wellington
2012
National Institute of Water and Atmospheric Research
1997-2010
Australian Antarctic Division
2005
National Oceanic and Atmospheric Administration
2005
We report a 2000-year Antarctic ice-core record of stable carbon isotope measurements in atmospheric methane (delta13CH4). Large delta13CH4 variations indicate that the budget varied unexpectedly during late preindustrial Holocene (circa 0 to 1700 A.D.). During first thousand years (0 1000 A.D.), was at least 2 per mil enriched compared expected values, and following 700 years, an about depletion occurred. Our modeled source partitioning implies biomass burning emissions were high from A.D....
Abstract In response to infections and irritants, the respiratory epithelium releases alarmin interleukin (IL)-33 elicit a rapid immune response. However, little is known about regulation of IL-33 following its release. Here we report that biological activity at receptor ST2 rapidly terminated in extracellular environment by formation two disulphide bridges, resulting an extensive conformational change disrupts binding site. Both reduced (active) bonded (inactive) forms can be detected lung...
Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and promising target for treatment of disease. Here, we describe the identification tozorakimab (MEDI3506), potent, human anti-IL-33 monoclonal antibody, which inhibit reduced IL-33 (IL-33red) oxidized (IL-33ox) activities through distinct serum-stimulated 2 (ST2) receptor advanced glycation end products/epidermal growth factor (RAGE/EGFR complex) signalling...
Epithelial cells that line the human intestinal mucosa are initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category epithelial cell response to infection. Human colon shown undergo following infection with invasive enteric pathogens, such Salmonella or enteroinvasive Escherichia coli. In contrast rapid onset seen after mouse monocyte-macrophage lines, commitment lines is delayed for at least 6 h infection, requires entry and replication,...
Abstract The program death 1 (PD-1) receptor and its ligands, PD-1 ligand (PD-L)1 PD-L2, define a novel regulatory pathway with potential inhibitory effects on T, B, monocyte responses. In the present study, we show that human CD4+ T cells express PD-1, PD-L1, PD-L2 upon activation, Abs to can be agonists or antagonists of pathway. Under optimal conditions stimulation, ICOS but not CD28 costimulation prevented by engagement. IL-2 levels induced are critical in determining outcome Thus, low...
The reaction of the hydroxyl radical (HO) with stable carbon isotopes methane has been studied as a function temperature from 273 to 353 K. measured ratio rate coefficients for 12 CH 4 relative 13 ( k / ) was 1.0054 (±0.0009 at 95% confidence interval), independent within precision measurement, over range studied. present value is much improved that previous studies, and this result provides important constraints on current understanding cycling through atmosphere use isotope measurements.
Increased intestinal fluid secretion is a protective host response after enteric infection with invasive bacteria that initiated within hours infection, and mediated by prostaglandin H synthase (PGHS) products in animal models of infection. Intestinal epithelial cells are the first to become infected bacteria, which enter pass through these initiate mucosal, ultimately systemic, The present studies characterized role secretory bacteria. Infection cultured human cell lines but not noninvasive...
14 C measured in trace gases clean air helps to determine the sources of such gases, their long-range transport atmosphere, and exchange with other carbon cycle reservoirs. In order separate sources, exchange, it is necessary interpret measurements using models these processes. We present atmospheric CO 2 made New Zealand since 1954 at various Pacific Ocean sites for shorter periods. analyze latitudinal seasonal variation, latter being consistent a seasonally varying rate between...
The mixing ratio of formaldehyde (HCHO) has been determined for air samples collected at a moderately polluted continental site (Jülich, Federal Republic Germany) and coastal sites in Ireland New Zealand. In addition the HCHO North South Atlantic during cruise F/S Meteor from Hamburg 55°N to Montevideo 35°S October November 1980. clean tropical marine is order 0.2 parts per billion by volume, about 50% lower than predicted current photochemical models that include CH 4 oxidation as only...
Recent measurements of the apparent kinetic isotope effect (KIE) methane (CH 4 ) atmospheric sink in extratropical Southern Hemisphere (ETSH) have shown KIE to be larger magnitude than expected if were hydroxyl radical (OH • alone. We present results from simulations using U.K. Met Office's Unified Model (UM) evaluate whether atomic chlorine (Cl marine boundary layer (MBL) could give this effect. modify UM include sources 12 CH and 13 , soil stratospheric sinks, a tropospheric OH sink. Also...
Abstract Uncontrolled self-association is a major challenge in the exploitation of proteins as therapeutics. Here we describe development structural proteomics approach to identify amino acids responsible for aberrant monoclonal antibodies and design variant with reduced aggregation increased serum persistence vivo. We show that human antibody, MEDI1912, selected against nerve growth factor binds picomolar affinity, but undergoes reversible has poor pharmacokinetic profile both rat...
Relative to other extrinsic factors, the effects of hydrodynamic flow fields on protein stability and conformation remain poorly understood. Flow-induced remodeling and/or aggregation is observed both in Nature during large-scale industrial manufacture proteins. Despite its ubiquity, relationships between type magnitude flow, a protein's structure stability, resultant propensity are unclear. Here, we assess defined quantified field dominated by extensional BSA, β2-microglobulin (β2m),...
HIV-1 entry into cells is mediated by the envelope glycoprotein receptor-binding (gp120) and membrane fusion-promoting (gp41) subunits. The gp41 heptad repeat 1 (HR1) domain molecular target of fusion-inhibitor drug enfuvirtide (T20). HR1 sequence highly conserved therefore considered an attractive for vaccine development, but it unknown whether antibodies can access HR1. Herein, we use gp41-based peptides to select a human antibody, 5H/I1-BMV-D5 (D5), that binds inhibits assembly fusion...
Measurements of 13 C in atmospheric methane made at Baring Head, New Zealand (41°S), over the 4‐year period, 1989–1993, display a persistent but highly variable seasonal cycle. Values for δ peak summer about −46.9‰ and drop to around −47.5‰ late winter. Methane concentration shows similar cycle, with winter peaks minima. Similar features are observed Antarctic station, Scott Base, 78°S. While phase cycle is consistent kinetic isotope effect that preferentially leaves enriched atmosphere...
We present a record of variations in the O 2 /N ratio air at 41°S latitude from 1991–1994 based on mass spectrometric analysis flask samples Cape Grim, Tasmania, and Baring Head, New Zealand. Results for Grim period June 1991 to February 1992 are good agreement with previously published data Keeling Shertz [1992]. Plotted versus time, ratios show expected annual cycles. increases austral spring summer (caused mainly by net oceanic production) decreases fall winter ventilation seasonal main...
A large 1.29 x 10(11) antibody fragment library, based upon variable (V) genes isolated from human B-cells 160 donors has been constructed and its performance measured against a panel of 28 different clinically relevant antigens. Over 5000 target-specific antibodies were to the antigens with 3340 identified as modulating biological function (e.g. antagonism, agonism) target antigen. This represents an average approximately 120 functionally active per target. Analysis sample >800 unselected...
Key Points Rituximab causes a polarization of B cells, involving reorganization CD20, intercellular adhesion molecule 1, and moesin, orientation the microtubule organizing center. The cells induced by rituximab augments its therapeutic role in triggering ADCC effector NK cells.
Abstract Protein tyrosine kinases differ widely in their propensity to undergo rearrangements of the N-terminal Asp–Phe–Gly (DFG) motif activation loop, with some, including FGFR1 kinase, appearing refractory this so-called ‘DFG flip’. Recent inhibitor-bound structures have unexpectedly revealed for first time a ‘DFG-out’ state. Here we use conformationally selective inhibitors as chemical probes interrogation structural and dynamic features that appear govern DFG flip FGFR1. Our detailed...
Abstract The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous other integrins, stabilize specific conformational states, have high thermal stability could utility. Existing small molecule antibody inhibitors do not all these properties, hence new approaches needed. Here we describe a generalized method for computationally designing RGD-containing...
A novel method for the compound specific determination of δ 13 C in VOC is presented. It combines a cryogenic preconcentration procedure with gas chromatographic separation, on‐line combustion and isotope ratio mass spectrometry. The allows values at sub ppb levels precision 0.5‰. suitable routine operation. accuracy same quality as reproducibility measurements. first ever measurements selected clean air are presented compared data from samples contaminated air. variability atmospheric much...