1,670 research outputs found
Improvement of NADPH bioavailability in Escherichia coli through the use of phosphofructokinase deficient strains
NADPH-dependent reactions play important roles
in production of industrially valuable compounds. In this
study, we used phosphofructokinase (PFK)-deficient strains
to direct fructose-6-phosphate to be oxidized through the
pentose phosphate pathway (PPP) to increase NADPH generation.
pfkA or pfkB single deletion and double-deletion strains
were tested for their ability to produce lycopene. Since lycopene
biosynthesis requires many NADPH, levels of lycopene
were compared in a set of isogenic strains, with the pfkA single
deletion strain showing the highest lycopene yield. Using
another NADPH-requiring process, a one-step reduction reaction
of 2-chloroacrylate to 2-chloropropionic acid by 2-
haloacrylate reductase, the pfkA pfkB double-deletion strain
showed the highest yield of 2-chloropropionic acid product.
The combined effect of glucose-6-phosphate dehydrogenase
overexpression or lactate dehydrogenase deletion with PFK
deficiency on NADPH bioavailability was also studied. The
results indicated that the flux distribution of fructose-6-
phosphate between glycolysis and the pentose phosphate
pathway determines the amount of NAPDH available for
reductive biosynthesis
A rapid, flexible method for incorporating controlled antibiotic release into porous polymethylmethacrylate space maintainers for craniofacial reconstruction
Severe injuries in the craniofacial complex, resulting from trauma or pathology, present several challenges to functional and aesthetic reconstruction. The anatomy and position of the craniofacial region make it vulnerable to injury and subsequent local infection due to external bacteria as well as those from neighbouring structures like the sinuses, nasal passages, and mouth. Porous polymethylmethacrylate (PMMA) “space maintainers” have proven useful in staged craniofacial reconstruction by promoting healing of overlying soft tissue prior to reconstruction of craniofacial bones. We describe herein a method by which the porosity of a prefabricated porous PMMA space maintainer, generated by porogen leaching, can be loaded with a thermogelling copolymer-based drug delivery system. Porogen leaching, space maintainer prewetting, and thermogel loading all significantly affected the loading of a model antibiotic, colistin. Weeks-long release of antibiotic at clinically relevant levels was achieved with several formulations. In vitro assays confirmed that the released colistin maintained its antibiotic activity against several bacterial targets. Our results suggest that this method is a valuable tool in the development of novel therapeutic approaches for the treatment of severe complex, infected craniofacial injuries
Mo\u3csup\u3eV\u3c/sup\u3e Electron Paramagnetic Resonance of Sulfite Oxidase Revisited: The Low-pH Chloride Signal
Valuable information on the active sites of molybdenum enzymes has been provided by MoV electron paramagnetic resonance (EPR) spectroscopy. In recent years, multiple resonance techniques have been extensively used to examine details of the active-site structure, but basic continuous-wave (CW) EPR has not been re-evaluated in several decades. Here, we present a re-examination of the CW EPR spectroscopy of the sulfite oxidase low-pH chloride species and provide evidence for direct coordination of molybdenum by chloride
Genetic and metabolic engineering
Recent advances in molecular biology techniques, analytical methods and
mathematical tools have led to a growing interest in using metabolic
engineering to redirect metabolic fluxes for industrial and medical
purposes. Metabolic engineering is referred to as the directed
improvement of cellular properties through the modification of specific
biochemical reactions or the introduction of new ones, with the use of
recombinant DNA technology (Stephanopoulos, 1999). This
multidisciplinary field draws principles from chemical engineering,
biochemistry, molecular and cell biology, and computational sciences.
The aim of this article is to give an overview of the various
strategies and tools available for metabolic engineers and to review
some of the recent work that has been conducted in our laboratories in
the metabolic engineering area
Use of Erythropoietin in Cancer Patients: Assessment of Oncologists’ Practice Patterns in the United States and Other Countries
PURPOSE: To assess physician use of erythropoietin in cancer patients before publication of the American Society of Clinical Oncology/American Society of Hematology guidelines. METHODS: Questionnaires about erythropoietin use in practice and 12 hypothetical clinical scenarios involving patients with cancer were mailed to 2000 oncologists/hematologists in the United States and 19 other countries. Response rates were 30% in the United States and 25% internationally. Data on erythropoietin use for ovarian cancer were obtained from one clinical trial. Multivariate regression models assessed predictors of erythropoietin prescription. RESULTS: Most physicians selected a hemoglobin level ≤10 g/dL as an upper threshold for erythropoietin use (36% to 51% of U.S. physicians and 21% to 32% of foreign physicians). Frequent erythropoietin use (defined as use in at least 10% of cancer patients) was higher in the United States than elsewhere (adjusted odds ratio [OR]=5.8; 95% confidence interval [CI]: 2.5 to 13.4). Among U.S. physicians, those who said they used erythropoietin frequently were more likely to be in fee-for-service than managed care settings (OR=2.2; 95% CI: 1.3 to 3.7). Those who reported never using erythropoietin practiced in countries that had lower annual per capita health care expenditures, lower proportions of privately funded health care, and a national health service (P \u3c0.05 for all comparisons). Of 235 ovarian cancer patients who received topotecan, 38% (45/118) of U.S. patients and 2% (2/117) of European patients who developed grade 1 anemia (hemoglobin level between 10 and 12 g/dL) were treated with erythropoietin (P\u3c0.01). CONCLUSION: Financial considerations and a hemoglobin level \u3c10 g/dL appear to influence erythropoietin use in the United States, whereas financial considerations alone determine erythropoietin use abroad
Effects of Antibiotic Physicochemical Properties on Their Release Kinetics from Biodegradable Polymer Microparticles
Purpose: This study investigated the effects of the physicochemical properties of antibiotics on the morphology, loading efficiency, size, release kinetics, and antibiotic efficacy of loaded poly(DL-lactic-co-glycolic acid) (PLGA) microparticles (MPs) at different loading percentages. Methods: Cefazolin, ciprofloxacin, clindamycin, colistin, doxycycline, and vancomycin were loaded at 10 and 20 wt% into PLGA MPs using a water-in-oil-in water double emulsion fabrication protocol. Microparticle morphology, size, loading efficiency, release kinetics, and antibiotic efficacy were assessed. Results: The results from this study demonstrate that the chemical nature of loaded antibiotics, especially charge and molecular weight, influence the incorporation into and release of antibiotics from PLGA MPs. Drugs with molecular weights less than 600 Da displayed biphasic release while those with molecular weights greater than 1,000 Da displayed triphasic release kinetics. Large molecular weight drugs also had a longer delay before release than smaller molecular weight drugs. The negatively charged antibiotic cefazolin had lower loading efficiency than positively charged antibiotics. Microparticle size appeared to be mainly controlled by fabrication parameters, and partition and solubility coefficients did not appear to have an obvious effect on loading efficiency or release. Released antibiotics maintained their efficacy against susceptible strains over the duration of release. Duration of release varied between 17 and 49 days based on the type of antibiotic loaded. Conclusions: The data from this study indicate that the chemical nature of antibiotics affects properties of antibiotic-loaded PLGA MPs and allows for general prediction of loading and release kinetics
Exploring the NRO Opportunity for a Hubble-sized Wide-field Near-IR Space Telescope -- NEW WFIRST
We discuss scientific, technical and programmatic issues related to the use
of an NRO 2.4m telescope for the WFIRST initiative of the 2010 Decadal Survey.
We show that this implementation of WFIRST, which we call "NEW WFIRST," would
achieve the goals of the NWNH Decadal Survey for the WFIRST core programs of
Dark Energy and Microlensing Planet Finding, with the crucial benefit of deeper
and/or wider near-IR surveys for GO science and a potentially Hubble-like Guest
Observer program. NEW WFIRST could also include a coronagraphic imager for
direct detection of dust disks and planets around neighboring stars, a
high-priority science and technology precursor for future ambitious programs to
image Earth-like planets around neighboring stars.Comment: 76 pages, 26 figures -- associated with the Princeton "New Telescope
Meeting
Grouping practices in the primary school: what influences change?
During the 1990s, there was considerable emphasis on promoting particular kinds of pupil grouping as a means of raising educational standards. This survey of 2000 primary schools explored the extent to which schools had changed their grouping practices in responses to this, the nature of the changes made and the reasons for those changes. Forty eight percent of responding schools reported that they had made no change. Twenty two percent reported changes because of the literacy hour, 2% because of the numeracy hour, 7% because of a combination of these and 21% for other reasons. Important influences on decisions about the types of grouping adopted were related to pupil learning and differentiation, teaching, the implementation of the national literacy strategy, practical issues and school self-evaluation
Challenges and Lessons Learned in Applying Sensitivity Analysis to Building Stock Energy Models
Uncertainty Analysis (UA) and Sensitivity Analysis (SA) offer essential tools to determine the limits of inference of a model and explore the factors which have the most effect on the model outputs. However, despite a well-established body of work applying UA and SA to models of individual buildings, a review of the literature relating to energy models for larger groups of buildings undertaken by Fennell et al. (2019) highlighted very limited application at larger scales. This contribution describes the efforts undertaken by a group of research teams in the context of IEA-EBC Annex 70 working with a diverse set of Building Stock Models (BSMs) to apply global sensitivity analysis methods and compare their results. Since BSMs are a class of model defined by their output and coverage rather than their structure and inputs, they represent a diverse set of modelling approaches. Key challenges for the application of SA are identified and explored, including the influence of model form, input data types and model outputs. This study combines results from 7 different modelling teams, each using different models across a range of urban areas to explore these challenges and begin the process of developing standardised workflows for SA of BSMs
HST NIR Snapshot Survey of 3CR Radio Source Counterparts II: An Atlas and Inventory of the Host Galaxies, Mergers and Companions
We present the second part of an H-band (1.6 microns) atlas of z<0.3 3CR
radio galaxies, using the Hubble Space Telescope Near Infrared Camera and
Multi-Object Spectrometer (HST NICMOS2). We present new imaging for 21 recently
acquired sources, and host galaxy modeling for the full sample of 101
(including 11 archival) -- an 87% completion rate. Two different modeling
techniques are applied, following those adopted by the galaxy morphology and
the quasar host galaxy communities. Results are compared, and found to be in
excellent agreement, although the former breaks down in the case of strongly
nucleated sources. Companion sources are tabulated, and the presence of
mergers, tidal features, dust disks and jets are catalogued. The tables form a
catalogue for those interested in the structural and morphological dust-free
host galaxy properties of the 3CR sample, and for comparison with morphological
studies of quiescent galaxies and quasar host galaxies. Host galaxy masses are
estimated, and found to typically lie at around 2*10^11 solar masses. In
general, the population is found to be consistent with the local population of
quiescent elliptical galaxies, but with a longer tail to low Sersic index,
mainly consisting of low-redshift (z<0.1) and low-radio-power (FR I) sources. A
few unusually disky FR II host galaxies are picked out for further discussion.
Nearby external sources are identified in the majority of our images, many of
which we argue are likely to be companion galaxies or merger remnants. The
reduced NICMOS data are now publicly available from our website
(http://archive.stsci.edu/prepds/3cr/)Comment: ApJS, 177, 148: Final version; includes revised figures 1, 15b, and
section 7.5 (and other minor changes from editing process. 65 pages, inc. 17
figure
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