Fabrication and Electric Field Dependent Transport Measurements of Mesoscopic Graphite Devices

We have developed a unique micromechanical method to extract extremely thin graphite samples. Graphite crystallites with thicknesses ranging from 10 - 100 nm and lateral size $\sim$ 2 $\mu$m are extracted from bulk. Mesoscopic graphite devices are fabricated from these samples for electric field dependent conductance measurements. Strong conductance modulation as a function of gate voltage is observed in the thinner crystallite devices. The temperature dependent resistivity measurements show more boundary scattering contribution in the thinner graphite samples.Comment: 3 pages, 3 figures included, submitted to Appl. Phys. Let

Operation of Graphene Transistors at GHz Frequencies

Top-gated graphene transistors operating at high frequencies (GHz) have been fabricated and their characteristics analyzed. The measured intrinsic current gain shows an ideal 1/f frequency dependence, indicating an FET-like behavior for graphene transistors. The cutoff frequency fT is found to be proportional to the dc transconductance gm of the device. The peak fT increases with a reduced gate length, and fT as high as 26 GHz is measured for a graphene transistor with a gate length of 150 nm. The work represents a significant step towards the realization of graphene-based electronics for high-frequency applications

Modulation of Thermoelectric Power of Individual Carbon Nanotubes

Thermoelectric power (TEP) of individual single walled carbon nanotubes (SWNTs) has been measured at mesoscopic scales using a microfabricated heater and thermometers. Gate electric field dependent TEP-modulation has been observed. The measured TEP of SWNTs is well correlated to the electrical conductance across the SWNT according to the Mott formula. At low temperatures, strong modulations of TEP were observed in the single electron conduction limit. In addition, semiconducting SWNTs exhibit large values of TEP due to the Schottky barriers at SWNT-metal junctions.Comment: to be published in Phys. Rev. Let

Electric Field Modulation of Galvanomagnetic Properties of Mesoscopic Graphite

Electric field effect devices based on mesoscopic graphite are fabricated for galvanomagnetic measurements. Strong modulation of magneto-resistance and Hall resistance as a function of gate voltage is observed as sample thickness approaches the screening length. Electric field dependent Landau level formation is detected from Shubnikov de Haas oscillations in magneto-resistance. The effective mass of electron and hole carriers has been measured from the temperature dependant behavior of these oscillations.Comment: 4 pages, 4 figures included, submitted to Phys. Rev. Let

Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.

The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance. To this end, we conducted a phase II trial of enzalutamide treatment (160 mg/d) in 36 men with metastatic CRPC. Thirty-four patients were evaluable for the primary end point of a prostate-specific antigen (PSA)50 response (PSA decline ≥50% at 12 wk vs. baseline). Nine patients were classified as nonresponders (PSA decline <50%), and 25 patients were classified as responders (PSA decline ≥50%). Failure to achieve a PSA50 was associated with shorter progression-free survival, time on treatment, and overall survival, demonstrating PSA50's utility. Targeted DNA-sequencing was performed on 26 of 36 biopsies, and RNA-sequencing was performed on 25 of 36 biopsies that contained sufficient material. Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis (GSEA) to identify pathways whose activity state correlated with de novo resistance. TP53 gene alterations were more common in nonresponders, although this did not reach statistical significance (P = 0.055). AR gene alterations and AR expression were similar between groups. Importantly, however, transcriptional measurements demonstrated that specific gene sets-including those linked to low AR transcriptional activity and a stemness program-were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance

Multiple complementary studies clarify which co-occurring congener presents the greatest hybridization threat to a rare Texas endemic wildflower (Hibiscus dasycalyx: Malvaceae)

The Neches River Rose Mallow (Hibiscus dasycalyx) is a rare wildflower endemic to Texas that is federally protected in the U.S.A. While previous work suggests that H. dasycalyx may be hybridizing with its widespread congeners, the Halberd-leaved Rose Mallow (H. laevis) and the Woolly Rose Mallow (H. moscheutos), this has not been studied in detail. We evaluated the relative threats to H. dasycalyx posed by hybridization with H. laevis and H. moscheutos by 1) examining their relatedness to one another via modern phylogenomic methods, 2) examining their ecological (dis)similarities to one another using ecological niche modeling, and 3) looking for genomic evidence of hybrid-ization among them. Our results suggest that H. dasycalyx is very closely related and ecologically similar to H. laevis, and that H. laevis is interbreeding with H. dasycalyx in the wild. Conversely, H. moscheutos appears to be more distantly related to H. dasycalyx and more ecologi-cally dissimilar, and the two are most likely not hybridizing. For these reasons, we believe that H. laevis poses a greater threat to H. dasycalyxthan H. moscheutos. We offer some hypotheses as to why H. dasycalyx and H. laevis are coming into secondary contact where hybridization can occur

The associations of parity and maternal age with small-for-gestational-age, preterm, and neonatal and infant mortality: a meta-analysis

Abstract Background Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC). Methods Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed. Results Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years. Conclusions Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period. Funding Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant R01 DC00117National Institutes of Health Grant R01 DC02032National Institutes of Health/National Institute of Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research Grant N61339-96-K-0002U.S. Navy - Office of Naval Research Grant N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-97-1-0635U.S. Navy - Office of Naval Research Grant N00014-97-1-0655U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202National Institutes of Health Grant RO1 NS33778Massachusetts General Hospital, Center for Innovative Minimally Invasive Therapy Research Fellowship Gran

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele