Publications

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

Several common fetal genetic variants have been associated with birth weight, but little is known about how maternal genetic variation influences fetal growth through the intra-uterine environment. To identify maternal genetic variants associated with birth weight, we performed a meta-analysis of 11 genome-wide association studies (GWAS; n = 19,626 women of European descent). We selected 18 single nucleotide polymorphisms (SNPs) for replication analysis in up to 13 further studies (n = 18,319 women of European descent). One SNP reached genome-wide significance (rs10830963, P = 2.0 x 10-11) in a combined analysis of discovery and replication results. Rs10830963 is intronic in MTNR1B and is known from previous GWAS to be associated with fasting glucose levels, type 2 diabetes and gestational diabetes. Each copy of rs10830963-G (the allele associated with higher fasting glucose) corresponded to a 31g [95%CI: 22, 41g] higher offspring birth weight. The association between maternal rs10830963 and birth weight was unaltered by adjustment for any potentially confounding effects of fetal genotype in 8716 maternal-fetal pairs. Although no other SNPs reached genome-wide significance, there was an excess of low P-values among SNPs known to be associated with fasting glucose levels. Our study demonstrates that maternal genetic variation at MTNR1B influences offspring birth weight and supports a broader role of genetic variation affecting maternal glucose levels in fetal growth. Our study also highlights that the effect sizes of associations between other maternal genetic variants and birth weight are unlikely to exceed 20g per allele, and therefore much larger sample sizes will be required to detect them.

Abstract Despite the growth of research in universities on point‐of‐care (POC) diagnostics for global health, most devices never leave the laboratory. The processes that move diagnostic technology from the laboratory to the field—the processes intended to evaluate operation and performance under realistic conditions—are more complicated than they might seem. Two case studies illustrate this process: the development of a paper‐based device to measure liver function, and the development of a device to identify sickle cell disease based on aqueous multiphase systems (AMPS) and differences in the densities of normal and sickled cells. Details of developing these devices provide strategies for forming partnerships, prototyping devices, designing studies, and evaluating POC diagnostics. Technical and procedural lessons drawn from these experiences may be useful to those designing diagnostic tests for developing countries, and more generally, technologies for use in resource‐limited environments.

The adsorption of n-alkanethiols onto polycrystalline thin films of palladium containing a strong (111) texture produces well-organized, self-assembled monolayers. The organization of the alkane chains in the monolayer and the nature of the bonding between the palladium and the thiol were studied by contact angle measurements, optical ellipsometry, reflection absorption infrared spectroscopy (RAIRS), and X-ray photoelectron spectroscopy (XPS). The XPS data reveals that a compound palladium-sulfide interphase is present at the surface of the palladium film. The RAIR spectra, ellipsometry data, and wetting properties show that the palladium-sulfide phase is terminated with an organized, methyl-terminated monolayer of alkanethiolates. The local molecular environment of the alkane chains transitions from a conformationally disordered, liquidlike state to a mostly all-trans, crystalline-like structure with increasing chain length (n = 8-26). The intensities and dichroism of the methylene and methyl stretching modes support a model for the average orientation of an ensemble of all-trans-conformer chains with a tilt angle of approximately 14-18 degrees with respect to the surface normal and a twist angle of the CCC plane relative to the tilt plane of approximately 45 degrees. The SAMs are stable in air, although the sulfur present at the surface oxidizes in air over a period of 2-5 days at room temperature. The differences in chain organization between SAMs formed by microcontact printing and by solution deposition are also examined by RAIRS and XPS.

Seamless and minimally invasive integration of 3D electronic circuitry within host materials could enable the development of materials systems that are self-monitoring and allow for communication with external environments. Here, we report a general strategy for preparing ordered 3D interconnected and addressable macroporous nanoelectronic networks from ordered 2D nanowire nanoelectronic precursors, which are fabricated by conventional lithography. The 3D networks have porosities larger than 99%, contain approximately hundreds of addressable nanowire devices, and have feature sizes from the 10-μm scale (for electrical and structural interconnections) to the 10-nm scale (for device elements). The macroporous nanoelectronic networks were merged with organic gels and polymers to form hybrid materials in which the basic physical and chemical properties of the host were not substantially altered, and electrical measurements further showed a >90% yield of active devices in the hybrid materials. The positions of the nanowire devices were located within 3D hybrid materials with ∼14-nm resolution through simultaneous nanowire device photocurrent/confocal microscopy imaging measurements. In addition, we explored functional properties of these hybrid materials, including (i) mapping time-dependent pH changes throughout a nanowire network/agarose gel sample during external solution pH changes, and (ii) characterizing the strain field in a hybrid nanoelectronic elastomer structures subject to uniaxial and bending forces. The seamless incorporation of active nanoelectronic networks within 3D materials reveals a powerful approach to smart materials in which the capabilities of multifunctional nanoelectronics allow for active monitoring and control of host systems.

We studied the low-energy states of spin-1/2 quantum dots defined in InAs/InP nanowires and coupled to aluminium superconducting leads. By varying the superconducting gap, \Delta, with a magnetic field, B, we investigated the transition from strong coupling, \Delta << T_{K}, to weak coupling, \Delta >> T_{K}, where T_{K} is the Kondo temperature. Below the critical field, we observe a persisting zero-bias Kondo resonance that vanishes only for low B or higher temperatures, leaving the room to more robust sub-gap structures at bias voltages between \Delta and 2\Delta. For strong and approximately symmetric tunnel couplings, a Josephson supercurrent is observed in addition to the Kondo peak. We ascribe the coexistence of a Kondo resonance and a superconducting gap to a significant density of intra-gap quasiparticle states, and the finite-bias sub-gap structures to tunneling through Shiba states. Our results, supported by numerical calculations, own relevance also in relation to tunnel-spectroscopy experiments aiming at the observation of Majorana fermions in hybrid nanostructures.

Immunglobulin-G-Template: Cluster von Gold-Nanopartikeln (siehe Bild) wachsen um Template aus selbstorganisierten IgGs, die durch synthetische zweibindige Antigene verbunden sind. Kohlenhydrate, die Bestandteile der IgGs sind, wirken dabei als Keimstellen für die stromlose Goldabscheidung. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z53161_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.