Publications

ABSTRACT Myosin II (MII) activity is required for elongating mammalian sensory axons to change speed and direction in response to Nerve Growth Factor (NGF) and laminin-1 (LN). NGF signaling induces faster outgrowth on LN through regulation of actomyosin restraint of microtubule advance into the growth cone periphery. It remains unclear whether growth cone turning on LN works through the same mechanism and, if it does, how the mechanism produces directed advance. Using a novel method for substrate patterning, we tested how directed advance occurs on LN by creating a gap immediately in front of a growth cone advancing on a narrow LN path. The growth cone stopped until an actin-rich protrusion extended over the gap, adhered to LN, and became stabilized. Stepwise advance over the gap was triggered by microtubule +tip entry up to the adhesion site of the protrusion and was independent of traction force pulling. We found that the probability of microtubule entry is regulated at the level of the individual protrusion and is sensitive to the rate of microtubule polymerization and the rate of rearward actin flow as controlled by adhesion-cytoskeletal coupling and MII. We conclude that growth cone navigation is an iterative process of variation and selection. Growth cones extend leading edge actin-rich protrusions that adhere transiently (variation). Microtubule entry up to an adhesion site stabilizes a protrusion (selection) leading to engorgement, consolidation, protrusive activity distal to the adhesion site, and stepwise growth cone advance. The orientation of the protrusion determines the direction of advance.

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In this paper, we review recent results on hybrid silicon mode-locked lasers with a focus on low phase noise optical pulse generation. Taking a high level

X-ray reflection (both specular and off-specular) and grazing incidence diffraction (GID) have been used to study the structure of alkylsiloxane monolayers (n-C18H37SiO1.5) formed by self-assembly from solution on silicon wafers. GID studies of complete monolayers reveal a single ring of scattering associated with the monolayer. The Lorentzian line shape of this ring indicates that the film is characterized by liquidlike order, with a typical translational correlation length of about 45 Å. The thermal coefficient of expansion of the monolayer, as determined from the GID peak position, is approximately equal to the value for liquid n-alkanes. Upon either heating or cooling, the monolayer correlation lengths decrease, suggesting that the differential thermal-expansion coefficients of the film and substrate figure prominently in thermal changes of the molecular ordering. GID data for incomplete monolayers also reveal a single ring of scattering associated with the monolayer. While both the translational correlation lengths and integrated peak areas are significantly reduced relative to complete monolayers, the peak positions of the incomplete monolayers are comparable to those of complete monolayers. Given the lower average areal density of incomplete monolayers, this finding implies that incomplete monolayers are inhomogeneous.

Abstract Context Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association. Objective To evaluate the association between a metabolomic signature for psychological distress and diabetes risk. Methods We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses' Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 matched controls. Blood samples were collected between 1989 and 1990 and incident diabetes was diagnosed between 1992 and 2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes risk according to MDS. Results After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; P-trend <.0001). This association was moderately attenuated after additional adjustment for body mass index (comparable OR: 1.17; 95% CI: 1.02, 1.35; P-trend = .02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (P = .04). Conclusion MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk.

The fabrication of complex metallic microstructures in 3D by injecting liquid solder into microfluidic channels and allowing the solder to cool and solidify is demonstrated; after fabrication, the metallic structures can be flexed, bent, or twisted (see figure and cover). With this method it is possible to build flexible electronic circuits, complex embedded or freestanding 3D metal microstructures, 3D electronic components, and hybrid electronic–microfluidic devices.

The mechanisms of electron transport in metal-insulator-metal junctions are incompletely understood. A metal-insulator-metal junction consisting of a self-assembled monolayer (SAM) supported on a mercury drop in mechanical contact with a SAM on a planar metal electrode has been developed as a test-bed with which to study electron transport through organic films. This review provides a summary of results intended to characterize this junction including: i) the determination of the electrical breakdown field of organic monolayers, ii) the determination of the tunneling decay constant for aliphatic and aromatic organic oligomers, and iii) the examination of molecular rectifier.

Abstract It is becoming increasingly recognized that early‐life nutritional, metabolic and environmental factors can have a long‐term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early‐life experiences. The current research challenge is to determine the primary pathways contributing to ‘non‐ or epi‐genetic’ causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet‐induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early‐life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues.

Background— The present study was conducted to examine the relationship of physical activity with risk of cardiovascular disease (CVD) and mortality among men with type 2 diabetes. CVD risk and mortality are increased in type 2 diabetes. Few epidemiological studies have investigated the effect of physical activity on these outcomes among type 2 diabetics. Methods and Results— Of the 3058 men who reported a diagnosis of diabetes at age 30 years or older in the Health Professionals’ Follow-up Study (HPFS), we excluded 255 who reported a physical impairment. In the remaining 2803 men, physical activity was assessed every 2 years; 266 new cases of CVD and 355 deaths of all causes were identified during 14 years of follow-up. Relative risks of CVD and death were estimated from Cox proportional hazards analysis with adjustment for potential confounders. The multivariate relative risks of CVD incidence corresponding to quintiles of total physical activity were 1.0, 0.87, 0.64, 0.72, and 0.67 ( P trend =0.07). The corresponding multivariate relative risks for total mortality were 1.0, 0.80, 0.57, 0.58, and 0.58 ( P trend =0.005). Walking was associated with reduced risk of total mortality. Relative risks across quintiles of walking were 1.0, 0.97, 0.87, 0.97, and 0.57 ( P trend =0.002). Walking pace was inversely associated with CVD, fatal CVD, and total mortality independently of walking hours. Conclusions— Physical activity was associated with reduced risk of CVD, cardiovascular death, and total mortality in men with type 2 diabetes. Walking and walking pace were associated with reduced total mortality.

The controlled growth of nanowires (NWs) with dimensions comparable to the Fermi wavelengths of the charge carriers allows fundamental investigations of quantum confinement phenomena. Here, we present studies of proximity-induced superconductivity in undoped Ge/Si core/shell NW heterostructures contacted by superconducting leads. By using a top gate electrode to modulate the carrier density in the NW, the critical supercurrent can be tuned from zero to greater than 100 nA. Furthermore, discrete sub-bands form in the NW due to confinement in the radial direction, which results in stepwise increases in the critical current as a function of gate voltage. Transport measurements on these superconductor–NW–superconductor devices reveal high-order (n = 25) resonant multiple Andreev reflections, indicating that the NW channel is smooth and the charge transport is highly coherent. The ability to create and control coherent superconducting ordered states in semiconductor–superconductor hybrid nanostructures allows for new opportunities in the study of fundamental low-dimensional superconductivity.