Overlapping-gate architecture for silicon Hall bar MOSFET devices in the low electron density regime

We report the fabrication and study of Hall bar MOSFET devices in which an overlapping-gate architecture allows four-terminal measurements of low-density 2D electron systems, while maintaining a high density at the ohmic contacts. Comparison with devices made using a standard single gate show that measurements can be performed at much lower densities and higher channel resistances, despite a reduced peak mobility. We also observe a voltage threshold shift which we attribute to negative oxide charge, injected during electron-beam lithography processing.Comment: 4 pages, 4 figures, submitted for Applied Physics Letter

Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities

The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed in human pregnancies. A successful meiosis I (MI) division entails separation of homologous chromosome pairs and co-segregation of sister chromatids. For this to happen, sister kinetochores must form attachments to spindle kinetochore-fibres emanating from the same pole. In mouse and budding yeast, sister kinetochores remain closely associated with each other during MI, enabling them to act as a single unified structure. However, whether this arrangement also applies in human meiosis I oocytes was unclear. In this study, we perform high-resolution imaging of over 1900 kinetochores in human oocytes, to examine the geometry and architecture of the human meiotic kinetochore. We reveal that sister kinetochores in MI are not physically fused, and instead individual kinetochores within a pair are capable of forming independent attachments to spindle k-fibres. Notably, with increasing female age, the separation between kinetochores increases, suggesting a degradation of centromeric cohesion and/or changes in kinetochore architecture. Our data suggest that the differential arrangement of sister kinetochores and dual k-fibre attachments may explain the high proportion of unstable attachments that form in MI and thus indicate why human oocytes are prone to aneuploidy, particularly with increasing maternal age

Limpet feeding rate and the consistency of physiological response to temperature

Thermal reaction norms are fundamental relationships for geographic comparisons of organism response to temperature. They are shaped by an organism’s environmental history and provide insights into both the global patterns of thermal sensitivity and the physiological mechanisms underlying temperature response. In this study we conducted the first measure of the thermal reaction norm for feeding, comparing the radula rasping rate of two tropical and one polar limpet species. The consistency of thermal response was tested through comparisons with limpet duration tenacity. Feeding and duration tenacity of limpets are ecologically important muscular mechanisms that rely on very different aspects of muscle physiology, repeated concentric (shortening) and isometric (fixed length) contraction of muscles, respectively. In these limpets the thermal reaction norms of feeding limpets were best described by a single break point at a maximum temperature with linear declines at higher (Siphonaria atra) or lower temperatures (Nacella concinna and Cellana radiata) rather than a bell-shaped curve. The thermal reaction norms for duration tenacity were similar in the two tropical limpets. However, the rasping rate in Antarctic N. concinna increased linearly with temperature up to a maximum at 12.3 °C (maximal range 8.5–12.3 °C) when feeding stopped. In contrast, duration tenacity in N. concinna was maximal at 1.0 °C (−0.6 to 3.8 °C) and linearly decreased with increasing temperature. The thermal reaction norms of muscular activity were, therefore, inconsistent within and between species, indicating that different mechanisms likely underlie different aspects of species sensitivities to temperature

Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades. Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function. Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population

Non-overlapping Distributed Tracking System Utilizing Particle Filter

Tracking people across multiple cameras is a challenging research area in visual computing, especially when these cameras have non-overlapping field of views. The important task is to associate a current subject with other prior appearances of the same subject across time and space in a camera network. Several known techniques rely on Bayesian approaches to perform the matching task. However, these approaches do not scale well when the dimension of the problem increases; e.g. when the number of subject or possible path increases. The aim of this paper is to propose a unified tracking framework using particle filters to efficiently switch between visual tracking (field of view tracking) and track prediction (non-overlapping region tracking). The particle filter tracking system utilizes a map (known environment) to assist the tracking process when targets leave the field of view of any camera. We implemented and tested this tracking approach in an in-house multiple cameras system as well as using on-line data. Promising results were obtained which suggested the feasibility of such an approach

Aspirin inhibits the acute venodilator response to furosemide in patients with chronic heart failure

OBJECTIVES: We sought to determine the effect of aspirin on the venodilator effect of furosemide in patients with chronic heart failure (CHF) BACKGROUND: Furosemide has an acute venodilator effect preceding its diuretic action, which is blocked by nonsteroidal anti-inflammatory drugs. The ability of therapeutic doses of aspirin to block this effect of furosemide in patients with CHF has not been studied. For comparison, the venodilator response to nitroglycerin (NTG) was also studied. METHODS: Eleven patients with CHF were randomized to receive placebo, aspirin at 75 mg/day or aspirin at 300 mg/day for 14 days in a double-blind, crossover study. The effect of these pretreatments on the change in forearm venous capacitance (FVC) after 20 mg of intravenous furosemide was measured over 20 min by using venous occlusion plethysmography. In a second study, the effect of 400 μg of sublingual NTG on FVC was documented in 11 similar patients (nine participated in the first study). RESULTS: Mean arterial pressure, heart rate and forearm blood flow did not change in response to furosemide. After placebo pretreatment, furosemide caused an increase in FVC of 2.2% (95% confidence interval [CI] −0.9% to 5.2%; mean response over 20 min). By comparison, FVC fell by −1.1% (95% CI −4.2% to 1.9%) after pretreatment with aspirin at 75 mg/day, and by −3.7% (95% CI −6.8% to −0.7%) after aspirin at 300 mg/day (p = 0.020). In the second study, NTG increased FVC by 2.1% (95% CI −1.6% to 5.8%) (p = 0.95 vs. furosemide). CONCLUSIONS: In patients with CHF, venodilation occurs within minutes of the administration of intravenous dose of furosemide. Our observation that aspirin inhibits this effect further questions the use of aspirin in patients with CHF