Neurologic Abnormalities in Workers of a 1-Bromopropane Factory

We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34–49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system

Theory of coupled ion-electron transfer kinetics

The microscopic theory of chemical reactions is based on transition state theory, where atoms or ions transfer classically over an energy barrier, as electrons maintain their ground state. Electron transfer is fundamentally different and occurs by tunneling in response to solvent fluctuations. Here, we develop the theory of coupled ion-electron transfer, in which ions and solvent molecules fluctuate cooperatively to facilitate electron transfer. We derive a general formula of the reaction rate that depends on the overpotential, solvent properties, the electronic structure of the electron donor/acceptor, and the excess chemical potential of ions in the transition state. For Faradaic reactions, the theory predicts curved Tafel plots with a concentration-dependent reaction-limited current. For moderate overpotentials, our formula reduces to the Butler-Volmer equation and explains its relevance, not only in the well-known limit of large electron-transfer (solvent reorganization) energy, but also in the opposite limit of large ion-transfer energy. The rate formula is applied to Li-ion batteries, where reduction of the electrode host material couples with ion insertion. In the case of lithium iron phosphate, the theory accurately predicts the concentration dependence of the exchange current measured by {\it in operando} X-Ray microscopy without any adjustable parameters. These results pave the way for interfacial engineering to enhance ion intercalation rates, not only for batteries, but also for ionic separations and neuromorphic computing

Stability of Mina v2 for Robot-Assisted Balance and Locomotion

The assessment of the risk of falling during robot-assisted locomotion is critical for gait control and operator safety, but has not yet been addressed through a systematic and quantitative approach. In this study, the balance stability of Mina v2, a recently developed powered lower-limb robotic exoskeleton, is evaluated using an algorithmic framework based on center of mass (COM)- and joint-space dynamics. The equivalent mechanical model of the combined human-exoskeleton system in the sagittal plane is established and used for balance stability analysis. The properties of the Linear Linkage Actuator, which is custom-designed for Mina v2, are analyzed to obtain mathematical models of torque-velocity limits, and are implemented as constraint functions in the optimization formulation. For given feet configurations of the robotic exoskeleton during flat ground walking, the algorithm evaluates the maximum allowable COM velocity perturbations along the fore-aft directions at each COM position of the system. The resulting velocity extrema form the contact-specific balance stability boundaries (BSBs) of the combined system in the COM state space, which represent the thresholds between balanced and unbalanced states for given contact configurations. The BSBs are obtained for the operation of Mina v2 without crutches, thus quantifying Mina v2's capability of maintaining balance through the support of the leg(s). Stability boundaries in single and double leg supports are used to analyze the robot's stability performance during flat ground walking experiments, and provide design and control implications for future development of crutch-less robotic exoskeletons

A microsatellite marker for yellow rust resistance in wheat

Bulk segregant analysis (BSA) was used to identify molecular markers associated with yellow rust disease resistance in wheat (Triticum aestivum L.). DNAs isolated from the selected yellow rust tolerant and susceptible F-2 individuals derived from a cross between yellow rust resistant and susceptible wheat genotypes were used to established a "tolerant" and a "susceptible" DNA pool. The BSA was then performed on these DNA pools using 230 markers that were previously mapped onto the individual wheat chromosomes. One of the SSR markers (Xgwm382) located on chromosome group 2 (A, B, D genomes) was present in the resistant parent and the resistant bulk but not in the susceptible parent and the susceptible bulk, suggesting that this marker is linked to a yellow rust resistance gene. The presence of Xgwm382 was also tested in 108 additional wheat genotypes differing in yellow rust resistance. This analysis showed that 81% of the wheat genotypes known to be yellow rust resistant had the Xgwm382 marker, further suggesting that the presence of this marker correlates with yellow rust resistance in diverse wheat germplasm. Therefore, Xgwm382 could be useful for marker assisted selection of yellow rust resistances genotypes in wheat breeding programs

Copy number and gene expression differences between African American and Caucasian American prostate cancer

<p>Abstract</p> <p>Background</p> <p>The goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach.</p> <p>Methods</p> <p>AA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K).</p> <p>Results</p> <p>BAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fisher's exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response.</p> <p>Conclusions</p> <p>Our data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response.</p

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel

Microarchitecture and Nanomechanical Properties of Trabecular Bone After Strontium Administration in Osteoporotic Goats

Strontium (Sr) ralenate is a new agent used for the prevention and treatment of osteoporosis. As a bone-seeking element, 98% of Sr is deposited in the bone and teeth after oral ingestion. However, the effect of Sr treatment on bone microarchitecture and bone nanomechanical properties remains unclear. In this study, 18 osteoporotic goats were divided into four groups according to the treatment regimen: control, calcium alone (Ca), calcium and Sr at 24 mg/kg (Ca + 24Sr), and calcium and Sr at 40 mg/kg (Ca + 40Sr). The effects of Sr administration on bone microarchitecture and nanomechanical properties of trabecular bones were analyzed with micro-CT and nanoindentation test, respectively. Serum Sr levels increased six- and tenfold in the Ca + 24Sr and Ca + 40Sr groups, respectively. Similarly, Sr in the bone increased four- and sixfold in these two groups. Sr administration significantly increased trabecular bone volume fraction, trabecular thickness, and double-labeled new bone area. Sr administration, however, did not significantly change the nanomechanical properties of trabecular bone (elastic modulus and hardness). The data suggested that Sr administration increased trabecular bone volume and improved the microarchitecture while maintaining the intrinsic tissue properties in the osteoporotic goat model

Global wetland contribution to 2000-2012 atmospheric methane growth rate dynamics

Increasing atmospheric methane (CH4) concentrations have contributed to approximately 20% of anthropogenic climate change. Despite the importance of CH4 as a greenhouse gas, its atmospheric growth rate and dynamics over the past two decades, which include a stabilization period (1999–2006), followed by renewed growth starting in 2007, remain poorly understood. We provide an updated estimate of CH4 emissions from wetlands, the largest natural global CH4 source, for 2000–2012 using an ensemble of biogeochemical models constrained with remote sensing surface inundation and inventory-based wetland area data. Between 2000–2012, boreal wetland CH4 emissions increased by 1.2 Tg yr−1 (−0.2–3.5 Tg yr−1), tropical emissions decreased by 0.9 Tg yr−1 (−3.2−1.1 Tg yr−1), yet globally, emissions remained unchanged at 184 ± 22 Tg yr−1. Changing air temperature was responsible for increasing high-latitude emissions whereas declines in low-latitude wetland area decreased tropical emissions; both dynamics are consistent with features of predicted centennial-scale climate change impacts on wetland CH4 emissions. Despite uncertainties in wetland area mapping, our study shows that global wetland CH4 emissions have not contributed significantly to the period of renewed atmospheric CH4 growth, and is consistent with findings from studies that indicate some combination of increasing fossil fuel and agriculture-related CH4 emissions, and a decrease in the atmospheric oxidative sink