Richard D. Miller

ORCID: 0000-0002-6147-4774
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About
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Research Areas
  • Legionella and Acanthamoeba research
  • Reproductive tract infections research
  • Intellectual Property and Patents
  • Innovation Policy and R&D
  • Healthcare Policy and Management
  • Global Health Care Issues
  • Innovative Microfluidic and Catalytic Techniques Innovation
  • Bacterial biofilms and quorum sensing
  • Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Seismic Waves and Analysis
  • Urinary Tract Infections Management
  • Seismic Imaging and Inversion Techniques
  • Vibrio bacteria research studies
  • Cyclopropane Reaction Mechanisms
  • Heme Oxygenase-1 and Carbon Monoxide
  • Water Treatment and Disinfection
  • Chemical Synthesis and Analysis
  • Asymmetric Synthesis and Catalysis
  • Neonatal Health and Biochemistry
  • Gut microbiota and health
  • Pneumocystis jirovecii pneumonia detection and treatment
  • Synthetic Organic Chemistry Methods
  • Immune Response and Inflammation
  • Firm Innovation and Growth
  • Protein purification and stability

United States Patent and Trademark Office
2014-2020

Eli Lilly (United States)
1996-2019

Universidade de Ribeirão Preto
2016

Universidade de São Paulo
2016

Lithuanian University of Health Sciences
2016

Ben-Gurion University of the Negev
2016

University of Gothenburg
2016

Medical University of Vienna
2016

Kansas Geological Survey
1996-2015

United States Geological Survey
1996-2015

Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm more flexible continuous processing. Here we report the development of multistep continuous-flow CGMP (current good practices) process that produced 24 kilograms prexasertib monolactate monohydrate suitable for use human clinical trials. Eight unit operations were conducted produce target at roughly 3 per day using small reactors, extractors,...

10.1126/science.aan0745 article EN Science 2017-06-16

Using electron microscopy we documented some of the intracellular events that occur in Naegleria fowleri suspended Page amoeba saline after ingestion Legionella pneumophila. Photomicrographs showed vacuoles containing bacteria process binary fission was accompanied by alignment mitochondria and ribosome-like structures along vacuole membrane. Although these are remarkably similar to seen replication within human monocytes, could not demonstrate an increase number CFU or dark-field...

10.1128/iai.50.2.449-452.1985 article EN Infection and Immunity 1985-11-01

A chemically defined medium containing 21 amino acids and inorganic salts was developed which supported the growth of four isolates Legionnaires disease bacterium (Legionella pneumophila). Growth in liquid at 37 degrees C with shaking approximated generation time kinetics observed for complex media. After a 3-h lag, culture grew exponentially 6 h reached maximum optical density 230 Klett units (170 corrected pigment). soluble brown pigment first as entered late exponential to early...

10.1128/jcm.10.1.50-55.1979 article EN Journal of Clinical Microbiology 1979-07-01

ABSTRACT We have previously shown that different isolates of Chlamydia pneumoniae display heterogeneity in the vitro stimulation chemokines and adhesion molecules from infected human endothelial cells. In present study, we examined ability C. to promote transendothelial migration neutrophils monocytes. Human umbilical vein cells (HUVEC) were with low (<15)-passage A-03, PS-32, BR-393 high (>40)-passage BAL-16, TW-183, T-2634, levels neutrophil monocyte determined following 24 h...

10.1128/iai.67.3.1323-1330.1999 article EN Infection and Immunity 1999-03-01

The amino acids L-arginine, L-isoleucine, L-leucine, L-methionine, L-serine, L-threonine, and L-valine were essential for the growth of Legionella pneumophila in a chemically defined medium. A partial requirement L-cysteine (or L-cystine) was also observed. minimal medium containing only eight required supported this bacterium if supplemented with L-glutamic acid. This latter compound acid capable stimulating eight-amino

10.1128/jcm.13.5.865-869.1981 article EN Journal of Clinical Microbiology 1981-05-01

The utilization of amino acids and other compounds as carbon energy sources by Legionella pneumophila was examined. Based on the stimulation oxygen consumption in washed-cell suspensions, glutamate, serine, threonine, tyrosine were only which utilized sources. Other stimulators uptake lactate, pyruvate, acetate, fumarate, succinate. Citrate a good stimulator when bacteria grown presence substrate. Radiolabeling studies showed that [14C]glutamate rapidly metabolized, with label distributed...

10.1128/jb.154.3.1104-1109.1983 article EN Journal of Bacteriology 1983-06-01

Lactoferrin, an iron-binding protein found in mucosal secretions and specific granules of polymorphonuclear leukocytes, has been shown to be bactericidal for a variety organisms. In this study, the effect lactoferrin on Legionella pneumophila was investigated. Purified human apolactoferrin Knoxville 1 strain (serogroup 1), with 4-log decrease viability within 2 h at 37 degrees C. Killing dependent iron-free state since iron-saturated had no activity. Guinea pig passage did not affect its...

10.1128/iai.51.2.373-377.1986 article EN Infection and Immunity 1986-02-01

Fatty acids of various chain lengths (C(1) to C(24)) were examined for their effects on growth, oxygen consumption, and in vitro reduced nicotinamide adenine dinucleotide oxidase activity Neisseria gonorrhoeae CS-7. The growth inhibition caused by saturated fatty increased with increasing length a maximum palmitic acid (C(16)). Stearic (C(18)) longer showed little growth. However, unsaturated C(16) C(20) inhibitory. Similar was observed Bacillus subtilis deep rough mutant Salmonella...

10.1128/iai.17.2.303-312.1977 article EN Infection and Immunity 1977-08-01

Culture filtrates of Legionella pneumophila were cytotoxic for Chinese hamster ovary cells. The cytotoxin was found to be methanol soluble, heat stable, and stable from pH 5 through 8.

10.1128/iai.29.1.271-274.1980 article EN Infection and Immunity 1980-07-01

The development of reactions in a continuous fashion plug flow tube reactors (PFR) offers unique advantages to the drug and scale-up process can also enable chemistry that would be difficult perform via batch processing. Herein, we report two different approaches key 1H-4-substituted imidazole intermediate (5). In first generation approach, rapid optimization challenging cyclization reaction was demonstrated PFR under GMP conditions afford 29 kg protected product 2. This material further...

10.1021/op200351g article EN Organic Process Research & Development 2012-04-19

A rapid screening procedure was used to test the effect of 42 dyes on growth 30 bacteria solid media. The results indicated that many readily available might have potential application for selective isolation specific bacterial groups as well value in differentiating between closely related taxa. Separation Enterobacter from Escherichia, Salmonella Shigella , and Staphylococcus Micrococcus by selected also evaluated.

10.1128/am.25.5.793-799.1973 article EN Applied Microbiology 1973-05-01

The development and scale-up of a synthetic route to tasisulam sodium (5-bromo-thiophene-2-sulfonic acid 2,4-dichlorobenzoylamide salt, hereafter referred as tasisulam) utilizing continuous Schotten–Baumann reaction conditions is disclosed. A new for the cytotoxic API amenable processing was envisioned that would minimize potential worker exposure by reducing number unit operations allow commercial-scale production in laboratory fume hoods with inexpensive glassware. developed contained...

10.1021/op200344a article EN Organic Process Research & Development 2012-04-12

Development of a small volume continuous process that used combination batch and flow unit operations to manufacture the molecule oncolytic candidate merestinib is described. Continuous processing was enabled following identification development suitable chemical transformations operations. Aspects nascent control strategy were evaluated in context 20 kg laboratory demonstration campaign, executed walk-in fume hoods at throughput 5–10 active pharmaceutical ingredient per day. The comprised...

10.1021/acs.oprd.8b00441 article EN Organic Process Research & Development 2019-03-12

Interferon-γ (IFN-γ) induces tryptophan catabolism in HEp-2 cells, possibly via stimulation of host cell indoleamine-2,3-dioxygenase activity, a dose-dependent (12.5–1600 U/mL) fashion after 24 h, resulting 99% conversion to its metabolites at 1600 U/mL. Replication Chlamydia pneumoniae isolates A-03 and BAL-16 was inhibited cells following treatment with 50 100 U/mL IFN-γ, respectively; however, addition excess l-tryptophan (200 µg/mL) monolayers infected C. resulted unrestricted growth...

10.1086/515287 article EN The Journal of Infectious Diseases 1998-05-01

ABSTRACT Chlamydia pneumoniae is a respiratory pathogen that has been associated with chronic inflammatory diseases such as asthma and atherosclerosis. Recent isolation of C. from human carotid coronary atheromas provides additional support for role this organism in atherogenesis. We characterized the strain A-03 by sequence analysis major outer membrane protein gene ( omp1 ). In addition, vitro activities three strains (BAL-16, TW-183, T-2634) were examined infected umbilical vein...

10.1128/iai.66.4.1370-1376.1998 article EN Infection and Immunity 1998-04-01

ABSTRACT Recent data have shown that the respiratory pathogen Chlamydia pneumoniae expresses an altered gene transcription profile during gamma interferon (IFN-γ)-induced persistent infection in vitro. In present study, we examined, by proteomics, expression of C. proteins labeled intracellularly with [ 35 S]methionine/cysteine under normal conditions or IFN-γ-mediated persistence. The identity differentially expressed was determined matching spots to those identified elementary bodies...

10.1128/iai.70.6.2976-2981.2002 article EN Infection and Immunity 2002-06-01

Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study demonstrated the effects of gamma interferon (IFN-gamma)-mediated indoleamine 2,3-dioxygenase activity on C. persistence in HEp-2 cells, inclusion morphology, and ultrastructure. replication showed dose-dependent decrease when treated increasing concentrations IFN-gamma phenotypic switch resulting typical inclusions an increase smaller, less-dense atypical inclusions....

10.1128/iai.69.12.7927-7932.2001 article EN Infection and Immunity 2001-12-01

Abstract The role of nitric oxide (NO) radicals in killing the intracellular bacterial pathogen Legionella pneumophila (Lp) was examined infected macrophages. Murine (RAW 264.7) and human (HL-60) cell monolayers were treated with 100 U/mlγ-interferon (IFN) cocultured Lp presence absence NGMMA, a specific inhibitor NO production. Viable IFN-treated RAW 264.7 cells decreased from 3.8 to 0.7 ± 0.12 log CFU/ml after 24 h incubation, whereas IFN + NGMMA-treated cells, viable persisted at 2.2 0.2...

10.1002/jlb.52.6.625 article EN Journal of Leukocyte Biology 1992-12-01

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectronic control of the stereoselectivities electrocyclic reactions cyclobutenes against incredible steric oddsK. N. Houk, David C. Spellmeyer, Charles W. Jefford, G. Rimbault, Ying Wang, and R. D. MillerCite this: J. Org. Chem. 1988, 53, 9, 2125–2127Publication Date (Print):April 1, 1988Publication History Published online1 May 2002Published inissue 1 April...

10.1021/jo00244a058 article EN The Journal of Organic Chemistry 1988-04-01

A fully automated fill/empty reactor system for liquid–liquid biphasic Suzuki couplings is described. The was capable of charging reactant and catalyst solutions to a heated vessel, heating reagent by flow heat exchanger on the way into reactor, allowing reaction occur, monitoring completion, discharge product solution, initiation another cycle in repeating fashion. unique noncontact colorimetric method used monitor completion. exhibits many characteristics continuous such as (1) high...

10.1021/acs.oprd.6b00030 article EN Organic Process Research & Development 2016-03-29

Abstract This article describes the “USPTO Patent Examination Research Dataset” ( PatEx ) and explores possible selection issues representativeness of nearly 9.2 million US patent application records it contains. We find that data are sparse for years before 1981, serious affect on applications filed prior to 2001 due nonpublication in United States. Following implementation a policy change November 2000, both coverage improve substantially. uncover specific areas prone selectivity issues,...

10.1111/jems.12263 article EN Journal of Economics & Management Strategy 2018-07-31
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