Publications

Self-assembly of a ferrocenyl thiol and a quinone thiol onto Au microelectrodes forms the basis for a new microsensor concept: a two-terminal, voltammetric microsensor with reference and sensor functions on the same electrode. The detection is based on measurement of the potential difference of current peaks for oxidation and reduction of the reference (ferrocene) and indicator (quinone) in aqueous electrolyte in a two-terminal, linear sweep voltammogram in which a counterelectrode of relatively large surface area is used. The quinone has a half-wave potential, E((1/2)), that is pH-sensitive and can be used as a pH indicator; the ferrocene center has an E(1/2) that is a pH-insensitive reference. The key advantages are that such sensors require no separate reference electrode and function as long as current peaks can be located for reference and indicator molecules.

Waveguiding is observed in a liquid core/liquid cladding waveguide containing a suspension of dielectric particles in the core. The threshold for guiding is determined by the numerical aperture of the effective refractive index.

'Percutaneous Absorption' published in 'Encyclopedia of Nanotechnology'

Abstract Objective To examine the association of consumption of dairy foods with risk of total and cause specific mortality in women and men. Design Three prospective cohort studies with repeated measures of diet and lifestyle factors. Setting Nurses’ Health Study, Nurses’ Health Study II, and the Health Professionals Follow-up Study, in the United States. Participants 168 153 women and 49 602 men without cardiovascular disease or cancer at baseline. Main outcome measure Death confirmed by state vital records, the national death index, or reported by families and the postal system. During up to 32 years of follow-up, 51 438 deaths were documented, including 12 143 cardiovascular deaths and 15 120 cancer deaths. Multivariable analysis further adjusted for family history of cardiovascular disease and cancer, physical activity, overall dietary pattern (alternate healthy eating index 2010), total energy intake, smoking status, alcohol consumption, menopausal status (women only), and postmenopausal hormone use (women only). Results Compared to the lowest category of total dairy consumption (average 0.8 servings/day), the multivariate pooled hazard ratio for total mortality was 0.98 (95% confidence interval 0.96 to 1.01) for the second category of dairy consumption (average 1.5 servings/day), 1.00 (0.97 to 1.03) for the third (average 2.0 servings/day), 1.02 (0.99 to 1.05) for the fourth (average 2.8 servings/day), and 1.07 (1.04 to 1.10) for highest category (average 4.2 servings/day; P for trend <0.001). For the highest compared to the lowest category of total dairy consumption, the hazard ratio was 1.02 (0.95 to 1.08) for cardiovascular mortality and 1.05 (0.99 to 1.11) for cancer mortality. For subtypes of dairy products, whole milk intake was significantly associated with higher risks of total mortality (hazard ratio per 0.5 additional serving/day 1.11, 1.09 to 1.14), cardiovascular mortality (1.09, 1.03 to 1.15), and cancer mortality (1.11, 1.06 to 1.17). In food substitution analyses, consumption of nuts, legumes, or whole grains instead of dairy foods was associated with a lower mortality, whereas consumption of red and processed meat instead of dairy foods was associated with higher mortality. Conclusion These data from large cohorts do not support an inverse association between high amount of total dairy consumption and risk of mortality. The health effects of dairy could depend on the comparison foods used to replace dairy. Slightly higher cancer mortality was non-significantly associated with dairy consumption, but warrants further investigation.

<ns3:p><ns3:bold>Background</ns3:bold>: Globally, respiratory infections contribute to significant morbidity and mortality. However, genetic determinants of respiratory infections are understudied and remain poorly understood.</ns3:p><ns3:p> <ns3:bold>Methods</ns3:bold>: We conducted a genome-wide association study in 19,459 hospitalised respiratory infection cases and 101,438 controls from UK Biobank. We followed-up well-imputed top signals from the UK Biobank discovery analysis in 50,912 respiratory infection cases and 150,442 controls from 11 cohorts. We aggregated effect estimates across studies using inverse variance-weighted meta-analyses. Additionally, we investigated the function of the top signals in order to gain understanding of the underlying biological mechanisms.</ns3:p><ns3:p> <ns3:bold>Results</ns3:bold>: In the discovery analysis, we report 56 signals at <ns3:italic>P</ns3:italic>&lt;5<ns3:italic>×</ns3:italic>10<ns3:sup>-6</ns3:sup>, one of which was genome-wide significant (<ns3:italic>P</ns3:italic>&lt;5<ns3:italic>×</ns3:italic>10<ns3:sup>-8</ns3:sup>). The genome-wide significant signal was in an intron of <ns3:italic>PBX3</ns3:italic>, a gene that encodes pre-B-cell leukaemia transcription factor 3, a homeodomain-containing transcription factor. Further, the genome-wide significant signal was found to colocalise with gene-specific expression quantitative trait loci (eQTLs) affecting expression of <ns3:italic>PBX3</ns3:italic> in lung tissue, where the respiratory infection risk alleles were associated with decreased <ns3:italic>PBX3</ns3:italic> expression in lung tissue, highlighting a possible biological mechanism. Of the 56 signals, 40 were well-imputed in UK Biobank and were investigated in the 11 follow-up cohorts. None of the 40 signals replicated, with effect estimates attenuated.</ns3:p><ns3:p> <ns3:bold>Conclusions</ns3:bold>: Our discovery analysis implicated <ns3:italic>PBX3</ns3:italic> as a candidate causal gene and suggests a possible role of transcription factor binding activity in respiratory infection susceptibility. However, the <ns3:italic>PBX3</ns3:italic> signal, and the other well-imputed signals, did not replicate when aggregating effect estimates across 11 independent cohorts. Significant phenotypic heterogeneity and differences in study ascertainment may have contributed to this lack of statistical replication. Overall, our study highlighted putative associations and possible biological mechanisms that may provide insight into respiratory infection susceptibility.</ns3:p>

'Physical Modification' published in 'Encyclopedia of Nanotechnology'

This paper describes the synthesis and characterization of patterned polymer multilayers on self-assembled monolayers (SAMs) and the use of these structures as etch resists for gold. The procedure used to build polymer multilayers consisted of five steps:  (i) A polar thiolHS(CH2)15COOHwas patterned on gold or silver films by microcontact printing (μCP) with a poly(dimethylsiloxane) (PDMS) stamp. (ii) The patterned surface was placed in a solution containing CH3(CH2)15SH to form a nonpolar, methyl-terminated SAM on the remaining bare metal surface. (iii) The regions of the SAM patterned with CO2H groups were activated for further chemical reaction by conversion into interchain anhydride groups. (iv) The activated substrate was allowed to react with poly(ethylene imine) (PEI, branched chain, Mw 750 000). (v) A second polymer layer was attached to the PEI layer by allowing the amine-terminated surface to react with poly(octadecene-alt-maleic anhydride) (POMA, Mw 30 000) or poly(styrene-alt-maleic anhydride)...

A thin film of crosslinked poly(acrylic acid) (PAA), patterned within microfluidic channels (see figure) and crosslinked with metal cations, serves as a platform for rapid “on-chip” growth of patterned metallic and semiconductor nanoparticles. The embedded particles serve as catalysts for electroless deposition of metal films.

<b>Rationale:</b> Recent prospective studies suggest diabetes as a risk factor for the development of obstructive sleep apnea (OSA). However, the extent to which diabetes-related traits, such as hyperglycemia and insulin resistance, are related to OSA risk remains uncertain. <b>Objectives:</b> To examine the risk of developing OSA according to baseline concentrations of fasting insulin and hemoglobin A1c (HbA1c). <b>Methods:</b> Participants from four prospective U.S. cohorts were included: NHS (Nurses' Health Study; 2002-2012), NHSII (Nurses' Health Study II; 1995-2013), HPFS (Health Professionals Follow-up Study; 1996-2012), and MESA (Multi-Ethnic Study of Atherosclerosis; 2000-2012). OSA was assessed by self-reported clinical diagnosis in NHS/NHSII/HPFS and at-home polysomnography in MESA (defined as Apnea-Hypopnea Index ⩾30). <b>Results:</b> Of 9,283 participants with fasting insulin data, 790 (8.5%) developed OSA over 10 to 18 years of follow-up. After adjusting for sociodemographic, lifestyle, and comorbidity factors, the odds ratio for incident OSA comparing the extreme quintiles of fasting insulin was 3.59 (95% confidence interval, 2.67-4.82; <i>P</i>-trend < 0.0001). Of 6,342 participants with HbA1c data, 715 (11.3%) developed OSA. The comparable odds ratio for HbA1c was 2.21 (95% confidence interval, 1.69-2.89; <i>P</i>-trend < 0.0001). Additional adjustment for body mass index and waist circumference attenuated the associations for fasting insulin (<i>P</i>-trend = 0.005) and HbA1c (<i>P</i>-trend = 0.03). In the fully adjusted model simultaneously including both biomarkers, only fasting insulin but not HbA1c was associated with OSA risk. <b>Conclusions:</b> Independent of obesity, insulin resistance may play a more important role than hyperglycemia in the pathogenesis of OSA. Given the limitation of using self-reported diagnosis to exclude baseline prevalent OSA cases, additional studies are needed to further establish the temporal relationship and assess whether improving insulin resistance may reduce OSA risk.

Background: C-reactive protein (CRP) is associated with risk of coronary heart disease (CHD). Whether CRP is causally associated with CHD or merely a marker of underlying atherosclerosis is uncerta...

This Account reviews nanoskiving−a new technique that combines thin-film deposition of metal on a topographically contoured substrate with sectioning using an ultramicrotome−as a method of fabricating nanostructures that could replace conventional top-down techniques in selected applications. Photolithography and scanning beam lithography, conventional top-down techniques to generate nanoscale structures and nanostructured materials, are useful, versatile, and highly developed, but they also have limitations: high capital and operating costs, limited availability of the facilities required to use them, an inability to fabricate structures on nonplanar surfaces, and restrictions on certain classes of materials. Nanoscience and nanotechnology would benefit from new, low-cost techniques to fabricate electrically and optically functional structures with dimensions of tens of nanometers, even if (or perhaps especially if) these techniques have a different range of application than does photolithography or scanning beam lithography. Nanoskiving provides a simple and convenient procedure to produce arrays of structures with cross-sectional dimensions in the 30-nm regime. The dimensions of the structures are determined by (i) the thickness of the deposited thin film (tens of nanometers), (ii) the topography (submicrometer, using soft lithography) of the surface onto which the thin film is deposited, and (iii) the thickness of the section cut by the microtome (≥30 nm by ultramicrotomy). The ability to control the dimensions of nanostructures, combined with the ability to manipulate and position them, enables the fabrication of nanostructures with geometries that are difficult to prepare by other methods. The nanostructures produced by nanoskiving are embedded in a thin epoxy matrix. These epoxy slabs, although fragile, have sufficient mechanical strength to be manipulated and positioned; this mechanical integrity allows the nanostructures to be stacked in layers, draped over curved surfaces, and suspended across gaps, while retaining the in-plane geometry of the nanostructures embedded in the epoxy. After removal of the polymer matrix by plasma oxidation, these structures generate suspended and draped nanostructures and nanostructures on curved surfaces. Two classes of applications, in optics and in electronics, demonstrate the utility of nanostructures fabricated by nanoskiving. This technique will be of primary interest to researchers who wish to generate simple nanostructures, singly or in arrays, more simply and quickly than can be accomplished in the clean-room. It is easily accessible to those not trained in top-down procedures for fabrication and those with limited or no access to the equipment and facilities needed for photolithography or scanning-beam fabrication. This Account discusses a new fabrication method (nanoskiving) that produces arrays of metal nanostructures. The defining process in nanoskiving is cutting slabs from a polymeric matrix containing embedded, more extended metal structures.

Nearly monodisperse iron nanoclusters have been used to define the diameters of carbon nanotubes grown by chemical vapor deposition (CVD). Iron nanoparticles with average diameters of 3, 9, and 13 nm were used to grow carbon nanotubes with average diameters of 3, 7, and 12 nm, respectively. Transmission electron microscopy studies of the nanotubes show that the as-grown nanotubes are single-walled carbon nanotubes (SWNTs) or thin multiwalled carbon nanotubes (MWNTs) with 2 or 3 layers. Investigations of the growth conditions also demonstrate that the supply of carbon reactant is critical for enabling the growth of large diameter nanotubes from large iron nanoclusters, and that the growth temperature is especially important for achieving high-quality large diameter nanotubes. The implications of these results and possible applications of the nanotubes are discussed.