A5069957192- Tuberculosis Research and Epidemiology
- Photonic and Optical Devices
- Bacterial Infections and Vaccines
- Photorefractive and Nonlinear Optics
- Electrostatics and Colloid Interactions
- Nanopore and Nanochannel Transport Studies
- Infectious Diseases and Tuberculosis
- Advanced Optical Imaging Technologies
- IgG4-Related and Inflammatory Diseases
- Semiconductor Lasers and Optical Devices
- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Pancreatic function and diabetes
- Advanced Fiber Optic Sensors
- Lysosomal Storage Disorders Research
- Diabetes Treatment and Management
- Liquid Crystal Research Advancements
- Studies on Chitinases and Chitosanases
- Microfluidic and Capillary Electrophoresis Applications
- Polymer Science and Applications
- DNA and Nucleic Acid Chemistry
- Optical and Acousto-Optic Technologies
- Optical Imaging and Spectroscopy Techniques
- Cell Image Analysis Techniques
- Spectroscopy and Quantum Chemical Studies
University of Cambridge
2020-2023
MRC Laboratory of Molecular Biology
2020-2023
Faculty of Public Health
2023
Leiden University Medical Center
2023
Dana-Farber Cancer Institute
2023
Medical Research Council
2021
University of Washington
2005-2007
Agilent Technologies (United States)
2000-2002
Hewlett-Packard (United States)
2002
Polaroid (United States)
1987-1990
Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence drug resistance. Drug discovery efforts would be facilitated facile screening tools that incorporate complexities human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects tuberculosis pathogenesis and treatment. Here, we develop a model for rapid in vivo using fluorescence-based methods serial quantitative assessment efficacy toxicity. We provide...
Tuberculosis treatment requires months-long combination chemotherapy with multiple drugs, shorter treatments leading to relapses. A major impediment shortening is that
Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation 5-10% the cases. intolerance may reflect localized high concentrations metformin gut. We hypothesized that reduced transport via plasma membrane monoamine transporter (PMAT) and organic cation 1 (OCT1) could increase risk severe gastrointestinal effects.The study included 286 metformin-intolerant 1,128 metformin-tolerant individuals from IMI DIRECT...
Bedaquiline is the cornerstone of a new regimen for treatment drug-resistant tuberculosis. However, its clinical use threatened by emergence bedaquiline-resistant strains Mycobacterium targets mycobacterial ATP synthase but predominant route to bedaquiline resistance via upregulation MmpS5L5 efflux pump due mutations that inactivate transcriptional repressor Rv0678. Here, we show reduces susceptibility as well new, more potent derivative TBAJ-876 and other antimicrobial substrates, including...
Significance Despite appropriate antibiotic treatment, tuberculous meningitis carries a high mortality ascribed to overexuberant inflammation. Genetic variations in the enzyme, LTA4H, alter inflammation, with individuals carrying inflammation-associated LTA4H variant benefitting from antiinflammatory steroids administered alongside antibiotics. A prior study found poor correlation between genotype and cerebrospinal fluid levels of cytokines, key mediators The used “frequentist” statistical...
Biallelic mutations in the glucocerebrosidase (
Electron micrographs of volume phase holograms recorded in DMP-128 reveal microstructure that is responsible for holographic activity. Solid and porous layers alternate with a spacing commensurate the fringe pattern. The difference material density between solid regions accounts refractive index modulation therefore activity holograms. pores are interconnected can be filled many low moderate viscosity liquids. Diffraction efficiency, bandwidth, wavelength maximum efficiency profoundly...
The authors present a novel, compact single mode fiber cross-connect switch which diverts light from one waveguide to crossing in silica planar lightwave circuit (PLC) using total internal reflection (TIR) off the interface between and thermally-generated bubble.
Abstract Coulomb's law for the electrostatic interactions between ions is modified when discontinuities in dielectric constant (relative permittivity) occur. In a DNA solution such discontinuity occurs at interface molecular helix and surrounding water. We take interaction potentials from previous report [ Macromolecules (1986) 19 , 1186–1194] use them with Monte Carlo method to find distribution of univalent bivalent counterions around absence coions (i.e., no added salt). comparing ion...
Tuberculous meningitis has high mortality, linked to excessive inflammation. However, adjunctive anti-inflammatory corticosteroids reduce mortality by only 30%, suggesting that inflammatory pathophysiology causes a subset of deaths. In Vietnam, the survival benefit was most pronounced in patients with C/T promoter variant leukotriene A 4 hydrolase ( LTA4H ) gene encoding an enzyme regulates eicosanoids. TT increased expression had survival, consistent benefiting individuals...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrostatic interactions between ions and DNA estimated with an electrolyte tankMark Troll, Daniel Roitman, Joan Conrad, Bruno H. ZimmCite this: Macromolecules 1986, 19, 4, 1186–1194Publication Date (Print):April 1, 1986Publication History Published online1 May 2002Published inissue 1 April 1986https://pubs.acs.org/doi/10.1021/ma00158a041https://doi.org/10.1021/ma00158a041research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of Polymer Solutions. 3. An Instrument for Stress Relaxations on Dilute Solutions Large MoleculesMark Troll, Ken A. Dill, and Bruno H. ZimmCite this: Macromolecules 1980, 13, 2, 436–438Publication Date (Print):March 1, 1980Publication History Published online1 May 2002Published inissue 1 March 1980https://pubs.acs.org/doi/10.1021/ma60074a043https://doi.org/10.1021/ma60074a043research-articleACS PublicationsRequest reuse permissionsArticle...
Scanning electron micrographs of volume phase, reflection holograms recorded in DMP-128 reveal microstructure that is responsible for holographic efficiency. Solid and porous payers alternate with a spacing commensurate the fringe pattern. The difference material density between solid regions accounts refractive index modulation therefore activity holograms. pores hologram are interconnected filled many low moderate viscosity liquids upon immersion. Important optical properties profoundly...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDielectric saturation effects in cylindrical polyelectrolytesMark Troll and Bruno H. ZimmCite this: J. Phys. Chem. 1983, 87, 17, 3197–3201Publication Date (Print):August 1, 1983Publication History Published online1 May 2002Published inissue 1 August 1983https://pubs.acs.org/doi/10.1021/j100240a008https://doi.org/10.1021/j100240a008research-articleACS PublicationsRequest reuse permissionsArticle Views52Altmetric-Citations9LEARN ABOUT THESE...
Optical and microstructural properties of reflection holograms recorded in DMP-128 are reported. The optical determined from transmission spectra the by ignoring relatively small effects light scattering absorption. Microstructure is revealed electron microscopic examination hologram sections prepared either diamond grit abrasion or freeze fracture. Fringe planes clearly seen with both sectioning procedures. spacing between adjacent strongly affected processing conditions. Standard produces...
Initial results of a comprehensive design software that optimizes parameters for fluorescence analysis user-defined fluorophore are presented. SLAP (spectral LED aggregation program) automatically selects configurations LEDs that, in system, maximize the emission signal (useful output) as function excitation (interference), optics, photodetection modality, and sample characteristics. draw on an extensive database blue, blue-green, green purple characterized across range nominal overdrive...
Optical cross-connect switches based on bubble-actuated total internal reflection have been demonstrated with low values of insertion loss, polarization dependent and crosstalk. Recent results vibration sensitivity switching time reduction are presented.
Abstract Tuberculous meningitis (TBM) remains the most devastating form of tuberculosis (TB) with high mortality despite effective antimicrobial treatment. As has been linked to excessive inflammation, anti-inflammatory glucocorticoids are now routinely used as adjunctive treatment therapy. However, they reduce by only ~ 30%, raising possibility that a subset TBM deaths caused inflammatory pathophysiology. Studies in Vietnam found survival benefit was limited individuals common promoter...
Abstract An all optical cross-connect for communications networks is presented here. Optical switching accomplished in a planar silica lightwave circuit where the array matrix defined by system of intersecting waveguides. Small microchannels are fabricated at waveguide intersection and filled with an index matched liquid. Microbubbles thermally manipulated to allow light be either transmitted or reflected total internal reflection. The physics associated bubble behavior requirements reliable...
ABSTRACT Adjunctive treatment with anti-inflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates a C/T variant Leukotriene A4 Hydrolase (LTA4H ), which regulates expression of the pro-inflammatory mediator leukotriene B4 (LTB4). TT homozygotes, increased LTB4, have highest when treated and lowest without. While T allele is present only minority world’s population, confer modest benefit worldwide. Using Bayesian...
Abstract Biallelic mutations in the glucocerebrosidase ( GBA1 ) gene cause Gaucher disease, characterized by lysosomal accumulation of glucosylceramide and glucosylsphingosine macrophages. This other diseases occur with high frequency Ashkenazi Jews. It has been proposed that underlying confer a selective advantage, particular conferring protection against tuberculosis. Here, using zebrafish disease model, we find mutation N370S, predominant among Jews, increases resistance to tuberculosis...
ABSTRACT The type VII secretion system ESX-1 mediates virulence in Mycobacterium tuberculosis and marinum . We find that M. , the synthetic organoselenium compound ebselen inhibits of ESAT-6, a major substrate. vitro activity AAA+ ATPase EccA1, which potentiates substrate function. Ebselen modifies cysteine its N-terminal tetratricopeptide repeat domain is required for EccA1’s activity. Surprisingly, mutational analyses show this not or ebselen’s activity, showing independently inhibiting...