Developmental and Reproductive Effects of Iron Oxide Nanoparticles in Arabidopsis thaliana

Increasing use of iron oxide nanoparticles in medicine and environmental remediation has led to concerns regarding exposure of these nanoparticles to the public. However, limited studies are available to evaluate their effects on the environment, in particular on plants and food crops. Here, we investigated the effects of positive (PC) and negative (NC) charged iron oxide (Fe₂O₃) nanoparticles (IONPs) on the physiology and reproductive capacity of Arabidopsis thaliana at concentrations of 3 and 25 mg/L. The 3 mg/L treated plants did not show evident effects on seeding and root length. However, the 25 mg/L treatment resulted in reduced seedling (positive-20% and negative-3.6%) and root (positive-48% and negative-negligible) length. Interestingly, treatment with polyethylenimine (PEI; IONP-PC coating) also resulted in reduced root length (39%) but no change was observed with polyacrylic acid (PAA; IONP-NC coating) treatment alone. However, treatment with IONPs at 3 mg/L did lead to an almost 5% increase in aborted pollen, a 2%–6% reduction in pollen viability and up to an 11% reduction in seed yield depending on the number of treatments. Interestingly, the treated plants did not show any observable phenotypic changes in overall size or general plant structure, indicating that environmental nanoparticle contamination could go dangerously unnoticed.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Operating Penalties in Single-Fiber Operation 10-Gb/s, 1024-Way Split, 110-km Long-Reach Optical Access Networks

We report for the first time optical signal-to-noise penalties which lead to performance degradations in single-fiber long-reach optical access networks when compared to identical dual-fiber systems. A simplified architecture, with reduced optical amplifier count compared to previous work, for single-fiber operation of a symmetrical 10-Gb/s, 1024-way split, 110-km long-reach optical access network is presented and demonstrated. In addition, a possible solution to remove the optical signal-to-noise penalty is suggested     

Search for high-performance probe-fed stacked patches using optimization

High-performance circular probe-fed stacked patch antenna designs are explored through the use of numerical optimization. New trends are sought to aid understanding and to suggest novel solutions. We describe the optimization technique, present a new design trend relating efficiency and bandwidth to the choice of substrate dielectric, and propose and demonstrate a novel, optimized antenna achieving 33% bandwidth whilst maintaining greater than 80% surface wave efficiency.     

Magnet Safety Assessment for ITER

The ITER magnet system consists of structurally linked sets of toroidal (TF) and poloidal (PF) field coils, central solenoid (CS), and various support structures. The coils are superconducting, force flow Helium cooled with a Kapton-Glass-Epoxy multilayer insulation system. The stored magnetic energy is about 100GJ in the TF system and 20GJ in the PF-CS. Coils and structure are maintained at 4 K by enclosing them in a vacuum cryostat. The cryostat, comprising an outer envelope to the magnets, forms most of the second radioactivity confinement barrier. The inner primary barrier is formed by the vacuum vessel, its ports and their extensions. To keep the machine size within acceptable bounds, it is essential that the magnets are in close proximity to both of the nuclear confinement barriers. The objective of the magnet design is that, although local damage to one of the barriers may occur in very exceptional circumstances, large scale magnet structural or thermal failure leading to simultaneous breaching of both barriers is not credible. Magnet accidents fall into three categories: thermal (which includes arcing arising from insulation failure and local overheating due to discharge failure in the event of a superconductor quench), structural (which includes component mechanical failure arising from material inadequacies, design errors and exceptional force patterns arising from coil shorts or control failures), and fluid (Helium release due to cooling line failure). After a preliminary survey to select initial faults conceivable within the present design, these faults are systematically analyzed to provide an assessment of the damage potential. The results of this damage assessment together with an assessment of the reliability of the monitoring and protective systems, shows that the magnets can operate with the required safety condition.     

Treatment of hypertension in nondiabetic renal disease

To clarify whether long-term impaired glucose tolerance (IGT) is associated with dysfunction of peripheral and autonomic nerves, age-matched men with IGT and diabetes mellitus were followed prospectively for 12-15 years, when peripheral and autonomic nerve function was assessed. The patients comprised four subgroups: (1) 51 IGT subjects (duration of IGT at least 12-15 years); (2) 35 diabetic patients, with IGT 12-15 years ago, who later developed diabetes; (3) 34 diabetic patients, duration of diabetes at least 12-15 years; and (4) 62 age-matched non-diabetic control subjects. Mean age of the whole study population was 61 +/- 2 years (mean +/- SD), not different in the four groups. Peripheral nerve function tests included nerve conduction velocities, amplitudes, distal latencies, F-reflexes, and sensory perception thresholds for heat, cold, and vibration. Autonomic nerve function tests included the heart rate reaction during deep breathing (expiration to inspiration ratio) and to tilt (acceleration and brake indices). Despite 12-15 years of IGT, peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio (a sign of vagal nerve dysfunction) was significantly more common (15/51 versus 5/62; p < 0.01) in IGT than in control subjects. Diabetic patients (groups 2 and 3) showed lower conduction velocities (in general 2-4 m s-1 lower) than IGT and control subjects in all tested nerves. In conclusion, diabetes but not IGT, is associated with peripheral nerve dysfunction.     

Magnetic anisotropy of Co-Cr thin films as a function of substrate temperature during deposition

A sequence of Co78Cr22films, 500 nm in thickness, was prepared by deposition on glass in a modified Varian D.C. magnetron S-gun sputtering system. The substrate temperature during deposition, Ts, was fixed at various values with an upper limit of 300°C. Specimens were examined by VSM, TM, FMR and TEM. Msrises significantly with increasing Ts, peaking at 200°C at 370 emu/cm³. The effective volume-averaged anisotropy drops for Ts>110°C from +1.6 KOe to progressively negative values (-4.3 KOe at 300°C). From FMR we find indications of the presence, in addition to the transition and bulk layers, of a highly negative anisotropy constituent (sim-11.5KOe anisotropy field). This resonance appears at Tsvalues of 150°C and above. TEM plane and cross-section views taken on a Ts= 150°C specimen show islands composed of tilted columns within the bulk. For vertical recording, specimens prepared at Tsvalues between 50 and 100°C are recommended. On the other hand, for longitudinal recording applications, films prepared at Tsvalues above 250°C would seem to be appropriate.