Single-Molecule Junction Conductance through Diaminoacenes

The study of electron transport through single molecules is essential to the development of molecular electronics. Indeed, trends in electronic conductance through organic nanowires have emerged with the increasing reliability of electron transport measurements at the single-molecule level. Experimental and theoretical work has shown that tunneling distance, HOMO-LUMO gap and molecular conformation influence electron transport in both saturated and pi-conjugated nanowires. However, there is relatively little experimental data on electron transport through fused aromatic rings. Here we show using diaminoacenes that conductivity depends not only on the number of fused aromatic rings in the molecule, which defines the molecular HOMO-LUMO gap, but also on the position of the amino groups on the rings. Specifically, we find that conductance is highest with minimal disruption of aromaticity in fused aromatic nanowires.Comment: 2 pages, 3 figure

Mechanistic studies using antihydrophobic agents

Abstract: The hydrophobic effect-that decreases the solubilities of organic compounds in water and leads to aggregation of such species in water solution+an be diminished by various additives that we have termed antihydrophobic agents. When relatively small amounts are used, this may be the principal effect of such additives on solubilities and reaction rates. If so, quantitative studies can reveal the amount of hydrophobic surface that becomes isolated from the water solvent in a transition state; this is a direct guide to transition state structure. This paper describes the evidence for this new approach to elucidating transition state structures for some reactions in water, and the relevance of this information to the situation in other solvents. Introduction. Molecules with apolar surfaces tend to aggregate in water solution because of the hydrophobic effect. This-the tendency of non-polar surfaces to avoid contact with water-is often ascribed to the strong self-association of water, but a quantitative study reveals that the major factor is the superior solvation of hydrocarbons by other hydrocarbons, rather than by water (1). Regardless of its cause, the hydrophobic effect can be invoked as a major determinant of the solubility of many organic compounds in water. Thus agents that increase the hydrophobic effect cause a decreased solubility of hydrocarbons in water, while agents that we have termed antihydrophobic cause an increase on hydrocarbon solubility. Such antihydrophobic agents are also denaturants of proteins and nucleic acids, whose three-dimensional structures are in large part the result of hydrophobic interactions between amino acid sidechains or nucleotide bases

Highly Conducting pi-Conjugated Molecular Junctions Covalently Bonded to Gold Electrodes

We measure electronic conductance through single conjugated molecules bonded to Au metal electrodes with direct Au-C covalent bonds using the scanning tunneling microscope based break-junction technique. We start with molecules terminated with trimethyltin end groups that cleave off in situ resulting in formation of a direct covalent sigma bond between the carbon backbone and the gold metal electrodes. The molecular carbon backbone used in this study consist of a conjugated pi-system that has one terminal methylene group on each end, which bonds to the electrodes, achieving large electronic coupling of the electrodes to the pi-system. The junctions formed with the prototypical example of 1,4-dimethylenebenzene show a conductance approaching one conductance quantum (G0 = 2e2/h). Junctions formed with methylene terminated oligophenyls with two to four phenyl units show a hundred-fold increase in conductance compared with junctions formed with amine-linked oligophenyls. The conduction mechanism for these longer oligophenyls is tunneling as they exhibit an exponential dependence of conductance with oligomer length. In addition, density functional theory based calculations for the Au-xylylene-Au junction show near-resonant transmission with a cross-over to tunneling for the longer oligomers.Comment: Accepted to the Journal of the American Chemical Society as a Communication

A universal TagModule collection for parallel genetic analysis of microorganisms

Systems-level analyses of non-model microorganisms are limited by the existence of numerous uncharacterized genes and a corresponding over-reliance on automated computational annotations. One solution to this challenge is to disrupt gene function using DNA tag technology, which has been highly successful in parallelizing reverse genetics in Saccharomyces cerevisiae and has led to discoveries in gene function, genetic interactions and drug mechanism of action. To extend the yeast DNA tag methodology to a wide variety of microorganisms and applications, we have created a universal, sequence-verified TagModule collection. A hallmark of the 4280 TagModules is that they are cloned into a Gateway entry vector, thus facilitating rapid transfer to any compatible genetic system. Here, we describe the application of the TagModules to rapidly generate tagged mutants by transposon mutagenesis in the metal-reducing bacterium Shewanella oneidensis MR-1 and the pathogenic yeast Candida albicans. Our results demonstrate the optimal hybridization properties of the TagModule collection, the flexibility in applying the strategy to diverse microorganisms and the biological insights that can be gained from fitness profiling tagged mutant collections. The publicly available TagModule collection is a platform-independent resource for the functional genomics of a wide range of microbial systems in the post-genome era

California Men's Health Study (CMHS): a multiethnic cohort in a managed care setting

BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002 – 2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men's Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men's health

Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort

OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995–1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30–35 years, or at ages 18–22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11–2.22), P(trend) = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer

DataSHIELD: taking the analysis to the data, not the data to the analysis

Research in modern biomedicine and social science requires sample sizes so large that they can often only be achieved through a pooled co-analysis of data from several studies. But the pooling of information from individuals in a central database that may be queried by researchers raises important ethico-legal questions and can be controversial. In the UK this has been highlighted by recent debate and controversy relating to the UK's proposed 'care.data' initiative, and these issues reflect important societal and professional concerns about privacy, confidentiality and intellectual property. DataSHIELD provides a novel technological solution that can circumvent some of the most basic challenges in facilitating the access of researchers and other healthcare professionals to individual-level data. Commands are sent from a central analysis computer (AC) to several data computers (DCs) storing the data to be co-analysed. The data sets are analysed simultaneously but in parallel. The separate parallelized analyses are linked by non-disclosive summary statistics and commands transmitted back and forth between the DCs and the AC. This paper describes the technical implementation of DataSHIELD using a modified R statistical environment linked to an Opal database deployed behind the computer firewall of each DC. Analysis is controlled through a standard R environment at the AC. Based on this Opal/R implementation, DataSHIELD is currently used by the Healthy Obese Project and the Environmental Core Project (BioSHaRE-EU) for the federated analysis of 10 data sets across eight European countries, and this illustrates the opportunities and challenges presented by the DataSHIELD approach. DataSHIELD facilitates important research in settings where: (i) a co-analysis of individual-level data from several studies is scientifically necessary but governance restrictions prohibit the release or sharing of some of the required data, and/or render data access unacceptably slow; (ii) a research group (e.g. in a developing nation) is particularly vulnerable to loss of intellectual property-the researchers want to fully share the information held in their data with national and international collaborators, but do not wish to hand over the physical data themselves; and (iii) a data set is to be included in an individual-level co-analysis but the physical size of the data precludes direct transfer to a new site for analysis