One-dimensional modelling of pulse wave propagation in human airway bifurcations in space-time variables

Airflow in the respiratory system is complicated as it goes through various regions with different geometries and mechanical properties. Three-dimensional (3-D) simulations are typically limited to local areas of the system because of their high computational cost. On the other hand, the one-dimensional (1-D) equations of flow in compliant tubes offer a good compromise between accuracy and computational cost when a global assessment of airflow in the system is required. The aim of the current study is to apply the 1-D formulation in space and time variables to study the propagation of a pulse wave in human airways; first in a simple system composed of just one bifurcation, trachea-main bronchi, according to the symmetrical Weibel model. Then extending the system to include a further generation, the bronchi branches. Pulse waveforms carry information about the functionality and morphology of the respiratory system and the 1-D modelling, in terms of space and time variables, represents an innovative approach for respiratory response interpretation. 1-D modelling in space-time variables has been extensively applied to simulate blood pressure and flow in the cardiovascular system. This work represents the first attempt to apply this formulation to study pulse waveforms in the human bronchial tree

The use of time-resolved fluorescence imaging in the study of protein kinase C localisation in cells

Background: Two-photon-excitation fluorescence lifetime imaging (2P-FLIM) was used to investigate the association of protein kinase C alpha (PKCα) with caveolin in CHO cells. PKCα is found widely in the cytoplasm and nucleus in most cells. Upon activation, as a result of increased intracellular Ca2+ and production of DAG, through G-protein coupled-phospholipase C signalling, PKC translocates to a variety of regions in the cell where it phosphorylates and interacts with many signalling pathways. Due to its wide distribution, discerning a particular interaction from others within the cell is extremely difficult. Results: Fluorescence energy transfer (FRET), between GFP-PKCα and DsRed-caveolin, was used to investigate the interaction between caveolin and PKC, an aspect of signalling that is poorly understood. Using 2P-FLIM measurements, the lifetime of GFP was found to decrease (quench) in certain regions of the cell from ~2.2 ns to ~1.5 ns when the GFP and DsRed were sufficiently close for FRET to occur. This only occurred when intracellular Ca2+ increased or in the presence of phorbol ester, and was an indication of PKC and caveolin co-localisation under these conditions. In the case of phorbol ester stimulated PKC translocation, as commonly used to model PKC activation, three PKC areas could be delineated. These included PKCα that was not associated with caveolin in the nucleus and cytoplasm, PKCα associated with caveolin in the cytoplasm/perinuclear regions and probably in endosomes, and PKC in the peripheral regions of the cell, possibly indirectly interacting with caveolin. Conclusion: Based on the extent of lifetime quenching observed, the results are consistent with a direct interaction between PKCα and caveolin in the endosomes, and possibly an indirect interaction in the peripheral regions of the cell. The results show that 2P-FLIM-FRET imaging offers an approach that can provide information not only confirming the occurrence of specific protein-protein interactions but where they occur within the cell

Changes of SERCA activity have only modest effects on sarcoplasmic reticulum Ca2+ content in rat ventricular myocytes

ABSTRACT: Changes of the activity of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) affect the amplitude of the systolic Ca(2+) transient and thence cardiac contractility. This is thought to be due to alterations of SR Ca(2+) content. Recent work on mice in which the expression of SERCA is decreased found that a large reduction of SERCA expression resulted in a proportionately much smaller decrease of SR Ca(2+) content. The aim of the current work was to investigate the quantitative nature of the dependence of both the amplitude of the systolic Ca(2+) transient and SR Ca(2+) content on SERCA activity during acute partial inhibition of SERCA. Experiments were performed on rat ventricular myocytes. Brief application of thapsigargin (1 μm) resulted in a decrease of SERCA activity as measured from the rate of decay of the systolic Ca(2+) transient. This was accompanied by a decrease in the amplitude of the systolic Ca(2+) transient which was linearly related to that of SERCA activity. However, the fractional decrease in the SR Ca(2+) content was much less than that of SERCA activity. On average SR Ca(2+) content was proportional to SERCA activity raised to the 0.38 ± 0.07 power. This shallow dependence of SR content on SERCA activity arises because Ca(2+) release is a steep function of SR Ca(2+) content. In contrast SR Ca(2+) content was increased 4.59 ± 0.40 (n = 8)-fold by decreasing ryanodine receptor opening with tetracaine (1 mm). Therefore a modest decrease of SR Ca(2+) content results in a proportionately larger fall of Ca(2+) release from the SR which can balance a larger initiating decrease of SERCA. In conclusion, the shallow dependence of SR Ca(2+) content on SERCA activity is expected for a system in which small changes of SR Ca(2+) content produce larger effects on the amplitude of the systolic Ca(2+) transient

Genomic comparison of two O111:H^- enterohemorrhagic Escherichia coli isolates from a historic hemolytic-uremic syndrome outbreak in Australia

© 2016, American Society for Microbiology. Enterohemorrhagic Escherichia coli (EHEC) is an important cause of diarrhea and hemolytic-uremic syndrome (HUS) worldwide. Australia's worst outbreak of HUS occurred in Adelaide in 1995 and was one of the first major HUS outbreaks attributed to a non-O157 Shiga-toxigenic E. coli (STEC) strain. Molecular analyses conducted at the time suggested that the outbreak was caused by an O111:H- clone, with strains from later in the outbreak harboring an extra copy of the genes encoding the potent Shiga toxin 2 (Stx2). Two decades later, we have used next-generation sequencing to compare two isolates from early and late in this important outbreak. We analyzed genetic content, single-nucleotide polymorphisms (SNPs), and prophage insertion sites; for the latter, we demonstrate how paired-end sequence data can be leveraged to identify such insertion sites. The two strains are genetically identical except for six SNP differences and the presence of not one but two additional Stx2-converting prophages in the later isolate. Isolates from later in the outbreak were associated with higher levels of morbidity, suggesting that the presence of the additional Stx2-converting prophages is significant in terms of the virulence of this clone

Casimir forces on a silicon micromechanical chip

Quantum fluctuations give rise to van der Waals and Casimir forces that dominate the interaction between electrically neutral objects at sub-micron separations. Under the trend of miniaturization, such quantum electrodynamical effects are expected to play an important role in micro- and nano-mechanical devices. Nevertheless, utilization of Casimir forces on the chip level remains a major challenge because all experiments so far require an external object to be manually positioned close to the mechanical element. Here, by integrating a force-sensing micromechanical beam and an electrostatic actuator on a single chip, we demonstrate the Casimir effect between two micromachined silicon components on the same substrate. A high degree of parallelism between the two near-planar interacting surfaces can be achieved because they are defined in a single lithographic step. Apart from providing a compact platform for Casimir force measurements, this scheme also opens the possibility of tailoring the Casimir force using lithographically defined components of non-conventional shapes

New distance measures for classifying X-ray astronomy data into stellar classes

The classification of the X-ray sources into classes (such as extragalactic sources, background stars, ...) is an essential task in astronomy. Typically, one of the classes corresponds to extragalactic radiation, whose photon emission behaviour is well characterized by a homogeneous Poisson process. We propose to use normalized versions of the Wasserstein and Zolotarev distances to quantify the deviation of the distribution of photon interarrival times from the exponential class. Our main motivation is the analysis of a massive dataset from X-ray astronomy obtained by the Chandra Orion Ultradeep Project (COUP). This project yielded a large catalog of 1616 X-ray cosmic sources in the Orion Nebula region, with their series of photon arrival times and associated energies. We consider the plug-in estimators of these metrics, determine their asymptotic distributions, and illustrate their finite-sample performance with a Monte Carlo study. We estimate these metrics for each COUP source from three different classes. We conclude that our proposal provides a striking amount of information on the nature of the photon emitting sources. Further, these variables have the ability to identify X-ray sources wrongly catalogued before. As an appealing conclusion, we show that some sources, previously classified as extragalactic emissions, have a much higher probability of being young stars in Orion Nebula.Comment: 29 page

Quantum key distribution over multicore fiber

We present the first quantum key distribution (QKD) experiment over multicore fiber. With space division multiplexing, we demonstrate that weak QKD signals can coexist with classical data signals launched at full power in a 53 km 7-core fiber, while showing negligible degradation in performance. Based on a characterization of intercore crosstalk, we perform additional simulations highlighting that classical data bandwidths beyond 1Tb/s can be supported with high speed QKD on the same fiber.S.J.K. acknowledges support from the EPSRC CDT in Photonic Systems Development

Deployment of spatial attention towards locations in memory representations: an EEG study

Recalling information from visual short-term memory (VSTM) involves the same neural mechanisms as attending to an actually perceived scene. In particular, retrieval from VSTM has been associated with orienting of visual attention towards a location within a spatially-organized memory representation. However, an open question concerns whether spatial attention is also recruited during VSTM retrieval even when performing the task does not require access to spatial coordinates of items in the memorized scene. The present study combined a visual search task with a modified, delayed central probe protocol, together with EEG analysis, to answer this question. We found a temporal contralateral negativity (TCN) elicited by a centrally presented go-signal which was spatially uninformative and featurally unrelated to the search target and informed participants only about a response key that they had to press to indicate a prepared target-present vs. -absent decision. This lateralization during VSTM retrieval (TCN) provides strong evidence of a shift of attention towards the target location in the memory representation, which occurred despite the fact that the present task required no spatial (or featural) information from the search to be encoded, maintained, and retrieved to produce the correct response and that the go-signal did not itself specify any information relating to the location and defining feature of the target

Seed systems smallholder farmers use

Seed can be an important entry point for promoting productivity, nutrition and resilience among smallholder farmers. While investments have primarily focused on strengthening the formal sector, this article documents the degree to which the informal sector remains the core for seed acquisition, especially in Africa. Conclusions drawn from a uniquely comprehensive data set, 9660 observations across six countries and covering 40 crops, show that farmers access 90.2 % of their seed from informal systems with 50.9 % of that deriving from local markets. Further, 55 % of seed is paid for by cash, indicating that smallholders are already making important investments in this arena. Targeted interventions are proposed for rendering formal and informal seed sector more smallholder-responsive and for scaling up positive impacts

A single sub-km Kuiper Belt object from a stellar Occultation in archival data

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects (KBOs). Small, sub-km sized, KBOs elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied KBO abundances are inconsistent with each other and far exceed theoretical expectations. Here, we report an analysis of archival data that reveals an occultation by a body with a 500 m radius at a distance of 45 AU. The probability of this event to occur due to random statistical fluctuations within our data set is about 2%. Our survey yields a surface density of KBOs with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The fact that we detected only one event, firmly shows a deficit of sub-km sized KBOs compared to a population extrapolated from objects with r>50 km. This implies that sub-km sized KBOs are undergoing collisional erosion, just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until 1800 hours London time on 16 December. 19 pages; 7 figure