An Engineered E. coli Strain for Direct in Vivo Fluorination

Selectively fluorinated compounds are found frequently in pharmaceutical and agrochemical products where currently 25–30 % of optimised compounds emerge from development containing at least one fluorine atom. There are many methods for the site-specific introduction of fluorine, but all are chemical and they often use environmentally challenging reagents. Biochemical processes for C−F bond formation are attractive, but they are extremely rare. In this work, the fluorinase enzyme, originally identified from the actinomycete bacterium Streptomyces cattleya, is engineered into Escherichia coli in such a manner that the organism is able to produce 5′-fluorodeoxyadenosine (5′-FDA) from S-adenosyl-l -methionine (SAM) and fluoride in live E. coli cells. Success required the introduction of a SAM transporter and deletion of the endogenous fluoride efflux capacity in order to generate an E. coli host that has the potential for future engineering of more elaborate fluorometabolites.     

Material,Immunological, and Practical Perspectives on Eye Drop Formulation

Eye drops are the most common and inexpensive approach to topical ocular drug delivery. Eye drops offer a noninvasive treatment strategy; however, this can be detrimental to therapeutic efficacy when compared to invasive methods such as surgeries, implants, and injections. Improvements to the efficacy of the topical delivery of drugs to ocular tissues are currently being explored and much of this work centers on adjusting the formulation of the eye drops and prolonging the bioavailability of the therapeutic agent. This is often in preference to improving other patient‐focused or clinical factors. In this progress report, conventional, commercially available polymer eye drops are explored and the ability for current and future innovations to maintain the existing benefits of eye drops to the patient is assessed. The final materials and form of the drops (liquid, gel, or other) and the immunological implications for the user are explored. There is currently no consensus for how to most effectively improve the ocular retention and drug delivery capabilities of eye drops, but key issues are highlighted in the context of current methods under development, and potential questions and considerations for future innovations are raised.     

A comprehensive modeling method for proton exchange membrane electrolyzer development

Hydrogen attracts significant interests as an effective energy carrier that can be derived from renewable sources. Hydrogen production using a proton-exchange membrane (PEM) electrolyzer can efficiently convert renewable power via water splitting in wide scales—from large, centralized generation to on-site production. Mathematical models with multiple scales and fidelities facilitate the continuing improvements of PEM electrolyzer development to improve performance, cost, and reliability. The model scopes and methods are presented in this paper, which also introduces a comprehensive PEM electrolysis modeling tool based on computational fluid dynamics (CFD) software, ANSYS/Fluent. The modeling tool incorporates electrochemical model of a PEM electrolysis cell to simulate the performance of coupled thermal-fluid, species transport, and electrochemical processes in a product-scale cell or stack by leveraging the powerful meshing generation and CFD solver of ANSYS/Fluent. The thermal-fluid modeling includes liquid water/gas two-phase flow and simulates a PEM electrolysis cell by using Fluent user-defined functions as add-on modules accounting for PEM-specific species transport and electrochemical processes. The modeling outcomes expediate PEM electrolyzer scaling up from basic material development and laboratory testing.     

A preliminary investigation into a genetic basis for cis-3-hexen-1-ol odour perception: A genome-wide association approach

Odour perception is controlled by environmental and genetic influences. Most people can discriminate over 10,000 different odours, but the molecular basis of this ability is poorly understood. Little is known about which odorant receptors (ORs) detect what odour compounds, and additional research is required to gain knowledge of why detection thresholds for some odorants vary 1000-fold, or more, across people. The primary purpose of this paper is to describe a research strategy for investigating the genetic basis of human odour perception. Background information on human olfaction, human genetics and the associated research approaches is presented. This is followed by a case study on cis-3-hexen-1-ol, a compound which contributes to the ‘green leaf’ odour (and flavour) in fruit, vegetables and wine. Odour detection threshold data for 48 participants were obtained using the rating R-index methodology. The ability to perceive cis-3-hexen-1-ol odour was tested for association with genetic variability on a genome-wide scale by microarray probe genotyping. A group of significant SNPs on chromosome 6 around the SNP rs9295791 was identified and these localise with a cluster of OR genes which could potentially be involved in perception of cis-3-hexen-1-ol. Further steps required to identify genes and alleles that encode the different ability to perceive cis-3-hexen-1-ol are outlined.     

Impact of Administered <Emphasis Type="Italic">Bifidobacterium</Emphasis> on Murine Host Fatty Acid Composition

Recently, we reported that administration of Bifidobacteria resulted in increased concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in murine adipose tissue [1]. The objective of this study was to assess the impact of co-administration of Bifidobacterium breve NCIMB 702258 and the substrate for EPA, α-linolenic acid, on host fatty acid composition. α-Linolenic acid-supplemented diets (1%, wt/wt) were fed to mice (n = 8), with or without B. breve NCIMB 702258 (daily dose of 10⁹ microorganisms) for 8 weeks. Two further groups received either supplement of B. breve alone or unsupplemented diet. Tissue fatty acid composition was assessed by gas liquid chromatography. Dietary supplementation of α-linolenic acid resulted in higher (P < 0.05) α-linolenic acid and EPA concentrations in liver and adipose tissue and lower (P < 0.05) arachidonic acid in liver, adipose tissue and brain compared with mice that did not receive α-linolenic acid. Supplementation with B. breve NCIMB 702258 in combination with α-linolenic acid resulted in elevated (P < 0.05) liver EPA concentrations compared with α-linolenic acid supplementation alone. Furthermore, the former group had higher (P < 0.05) DHA in brain compared with the latter group. These results suggest a role for interactions between fatty acids and commensals in the gastrointestinal tract. This interaction between administered microbes and fatty acids could result in a highly effective nutritional approach to the therapy of a variety of inflammatory and neurodegenerative conditions.     

Phenolic compounds and methylglyoxal in some New Zealand manuka and kanuka honeys

The principal phenolic compounds and methylglyoxal were analysed in New Zealand Leptospermum scoparium (manuka) and Kunzea ericoides (kanuka) honeys. These honeys shared six phenolic acids as primary components and differentiation was possible as relative proportions varied. Manuka honey contained an elevated concentration of a trimethoxybenzoic acid and methylglyoxal; and 2-methoxybenzoic acid and methylglyoxal concentrations were linearly correlated in fresh manuka honey. Kanuka honey contained an elevated concentration of methoxyphenyllactic acid. The concentration of the phenolic components increased with maturation in both honey types; and this profile development, along with a corresponding increase of methylglyoxal concentration, was linear in manuka honey. Nectar analysed from the plant species contained the same phenolic components as the honeys. These results demonstrated the phenolic profile could be used to differentiate the honey types, heat treatment of honey could be identified, and the presence of these components may contribute to the efficacy of these honeys in therapeutic uses.     

Liquefaction Resistance of Soils: Summary Report from the 1996 NCEER and 1998 NCEER∕NSF Workshops on Evaluation of Liquefaction Resistance of Soils

Following disastrous earthquakes in Alaska and in Niigata, Japan in 1964, Professors H. B. Seed and I. M. Idriss developed and published a methodology termed the “simplified procedure” for evaluating liquefaction resistance of soils. This procedure has become a standard of practice throughout North America and much of the world. The methodology which is largely empirical, has evolved over years, primarily through summary papers by H. B. Seed and his colleagues. No general review or update of the procedure has occurred, however, since 1985, the time of the last major paper by Professor Seed and a report from a National Research Council workshop on liquefaction of soils. In 1996 a workshop sponsored by the National Center for Earthquake Engineering Research (NCEER) was convened by Professors T. L. Youd and I. M. Idriss with 20 experts to review developments over the previous 10 years. The purpose was to gain consensus on updates and augmentations to the simplified procedure. The following topics were reviewed and recommendations developed: (1) criteria based on standard penetration tests; (2) criteria based on cone penetration tests; (3) criteria based on shear-wave velocity measurements; (4) use of the Becker penetration test for gravelly soil; (4) magnitude scaling factors; (5) correction factors for overburden pressures and sloping ground; and (6) input values for earthquake magnitude and peak acceleration. Probabilistic and seismic energy analyses were reviewed but no recommendations were formulated.     

Do patient‐reported measures of symptoms and health status predict mortality in hemodialysis? An assessment of POS‐S Renal and EQ‐5D

Introduction Experience with the use of patient‐reported outcome measures such as EQ‐5D and the symptom module of the Palliative care Outcome Scale—Renal Version (POS‐S Renal) as mortality prediction tools in hemodialysis is limited. Methods A prospective survival study of people receiving hemodialysis (N = 362). The EQ‐5D and the POS‐S Renal were used to assess symptom burden and self‐rated health (with a self‐rated component). Participants were followed from instrument completion to death or study end. Competing risks survival analysis was used to evaluate associations with time to death, with renal transplant as a competing risk. Findings 32% (N = 116) of participants died over a median (25th–75th centile) of 2.6 (1.41–3.38) years. Factors most notably associated with mortality adjusted hazard ratio (95%CI) included: lower EQ VAS score 2.7 (1.4, 5.2) P = 0.004 (lowest tertile), higher POS‐S Renal score 2.4 (1.3, 4.3) P = 0.004 (highest tertile), and lower EQ‐5D score 2.6 (1.3, 5.3) P = 0.01 (lowest tertile) as well as the presence of: “problems with mobility?” 2 (1.1, 3.3) P = 0.01, or “problems with usual activities?” 2.1 (1.4, 3.3), P < 0.001. After age adjustment area under the receiver operating curves (AUC) (95%CI) for mortality were: 0.71 (0.62, 0.79) for EQ VAS score, 0.71 (0.63, 0.80) for POS‐S Renal‐S Renal score, and 0.76 (0.68, 0.84) for EQ‐5D score. AUC 95%CI was highest for our fourth model at 0.79 (0.72, 0.86) comprised of individual elements from both instruments and established risk factors. Discussion EQ VAS scores and predictive models based on combinations of elements from the POS‐S Renal and EQ‐5D instruments may aid in mortality discrimination and possibly in the delivery of supportive care services.