4,437 research outputs found

    Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome

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    Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA) in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. We found that expression of human COQ9 rescues the growth of the temperature-sensitive yeast mutant, coq9-ts19, on a non-fermentable carbon source and increases the content of Q6, by enhancing Q biosynthesis from 4-hydroxybenzoic acid (4HB). To study the mechanism for the rescue by human COQ9, we determined the steady-state levels of yeast Coq polypeptides in the mitochondria of the temperature-sensitive yeast coq9 mutant expressing human COQ9. We show that the expression of human COQ9 significantly increased steady-state levels of yeast Coq4, Coq6, Coq7, and Coq9 at permissive temperature. Human COQ9 polypeptide levels persisted at non-permissive temperature. A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model

    Fundamental Aspects of the ISM Fractality

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    The ubiquitous clumpy state of the ISM raises a fundamental and open problem of physics, which is the correct statistical treatment of systems dominated by long range interactions. A simple solvable hierarchical model is presented which explains why systems dominated by gravity prefer to adopt a fractal dimension around 2 or less, like the cold ISM and large scale structures. This has direct relation with the general transparency, or blackness, of the Universe.Comment: 6 pages, LaTeX2e, crckapb macro, no figure, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

    Cavitation in high-capacity tensiometers:effect of water reservoir surface roughness

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    High-capacity tensiometers (HCTs) are sensors made to measure negative pore water pressure (suction) directly. In this paper, a new approach is proposed to expand the range and duration of suction measurements for a newly designed HCT. A new technique is employed to reduce significantly the roughness of the diaphragm’s surface on the water reservoir side in order to minimise the possibility of gas nuclei development and the subsequent early cavitation at the water–diaphragm interface. The procedures employed for the design, fabrication, saturation and calibration of the new tensiometers are explained in detail. Furthermore, the performance of the developed HCTs is examined based on a series of experiments carried out on a number of unsaturated clay specimens. An improvement in maximum sustainable suction in the range of 120–150% of their nominal capacity was obtained from different surface treatment methods. Moreover, the results show an improvement of up to 177% for the long-term stability of measurements, compared to the developed ordinary HCTs with untreated diaphragms

    Probing diffusion of water and metabolites to assess white matter microstructure in Duchenne muscular dystrophy

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    \ua9 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.Duchenne muscular dystrophy (DMD) is a progressive X-linked neuromuscular disorder caused by the absence of functional dystrophin protein. In addition to muscle, dystrophin is expressed in the brain in both neurons and glial cells. Previous studies have shown altered white matter microstructure in patients with DMD using diffusion tensor imaging (DTI). However, DTI measures the diffusion properties of water, a ubiquitous molecule, making it difficult to unravel the underlying pathology. Diffusion-weighted spectroscopy (DWS) is a complementary technique which measures diffusion properties of cell-specific intracellular metabolites. Here we performed both DWS and DTI measurements to disentangle intra- and extracellular contributions to white matter changes in patients with DMD. Scans were conducted in patients with DMD (15.5 \ub1 4.6 y/o) and age- and sex-matched healthy controls (16.3 \ub1 3.3 y/o). DWS measurements were obtained in a volume of interest (VOI) positioned in the left parietal white matter. Apparent diffusion coefficients (ADCs) were calculated for total N-acetylaspartate (tNAA), choline compounds (tCho), and total creatine (tCr). The tNAA/tCr and tCho/tCr ratios were calculated from the non-diffusion-weighted spectrum. Mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and fractional anisotropy of water within the VOI were extracted from DTI measurements. DWS and DTI data from patients with DMD (respectively n = 20 and n = 18) and n = 10 healthy controls were included. No differences in metabolite ADC or in concentration ratios were found between patients with DMD and controls. In contrast, water diffusion (MD, t = −2.727, p = 0.011; RD, t = −2.720, p = 0.011; AD, t = −2.715, p = 0.012) within the VOI was significantly higher in patients compared with healthy controls. Taken together, our study illustrates the potential of combining DTI and DWS to gain a better understanding of microstructural changes and their association with disease mechanisms in a clinical setting

    Prediction and Topological Models in Neuroscience

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    In the last two decades, philosophy of neuroscience has predominantly focused on explanation. Indeed, it has been argued that mechanistic models are the standards of explanatory success in neuroscience over, among other things, topological models. However, explanatory power is only one virtue of a scientific model. Another is its predictive power. Unfortunately, the notion of prediction has received comparatively little attention in the philosophy of neuroscience, in part because predictions seem disconnected from interventions. In contrast, we argue that topological predictions can and do guide interventions in science, both inside and outside of neuroscience. Topological models allow researchers to predict many phenomena, including diseases, treatment outcomes, aging, and cognition, among others. Moreover, we argue that these predictions also offer strategies for useful interventions. Topology-based predictions play this role regardless of whether they do or can receive a mechanistic interpretation. We conclude by making a case for philosophers to focus on prediction in neuroscience in addition to explanation alone

    Large-scale air mass characteristics observed over the remote tropical Pacific Ocean during March-April 1999: Results from PEM-Tropics B field experiment

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    Eighteen long-range flights over the Pacific Ocean between 38° S to 20° N and 166° E to 90° W were made by the NASA DC-8 aircraft during the NASA Pacific Exploratory Mission (PEM) Tropics B conducted from March 6 to April 18, 1999. Two lidar systems were flown on the DC-8 to remotely measure vertical profiles of ozone (O3), water vapor (H2O), aerosols, and clouds from near the surface to the upper troposphere along their flight track. In situ measurements of a wide range of gases and aerosols were made on the DC-8 for comprehensive characterization of the air and for correlation with the lidar remote measurements. The transition from northeasterly flow of Northern Hemispheric (NH) air on the northern side of the Intertropical Convergence Zone (ITCZ) to generally easterly flow of Southern Hemispheric (SH) air south of the ITCZ was accompanied by a significant decrease in O3, carbon monoxide, hydrocarbons, and aerosols and an increase in H2O. Trajectory analyses indicate that air north of the ITCZ came from Asia and/or the United States, while the air south of the ITCZ had a long residence time over the Pacific, perhaps originating over South America several weeks earlier. Air south of the South Pacific Convergence Zone (SPCZ) came rapidly from the west originating over Australia or Africa. This air had enhanced O3 and aerosols and an associated decrease in H2O. Average latitudinal and longitudinal distributions of O3 and H2O were constructed from the remote and in situ O3 and H2O data, and these distributions are compared with results from PEM-Tropics A conducted in August-October 1996. During PEM-Tropics B, low O3 air was found in the SH across the entire Pacific Basin at low latitudes. This was in strong contrast to the photochemically enhanced O3 levels found across the central and eastern Pacific low latitudes during PEM-Tropics A. Nine air mass types were identified for PEM-Tropics B based on their O3, aerosols, clouds, and potential vorticity characteristics. The data from each flight were binned by altitude according to air mass type, and these results showed the relative observational frequency of the different air masses as a function of altitude in seven regions over the Pacific. The average chemical composition of the major air mass types was determined from in situ measurements in the NH and SH, and these results provided insight into the origin, lifetime, and chemistry of the air in these regions. Copyright 2001 by the American Geophysical Union

    Detection of Anomalous Traffic Patterns and Insight Analysis from Bus Trajectory Data

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    © 2019, Springer Nature Switzerland AG. Detection of anomalous patterns from traffic data is closely related to analysis of traffic accidents, fault detection, flow management, and new infrastructure planning. Existing methods on traffic anomaly detection are modelled on taxi trajectory data and have shortcoming that the data may lose much information about actual road traffic situation, as taxi drivers can select optimal route for themselves to avoid traffic anomalies. We employ bus trajectory data as it reflects real traffic conditions on the road to detect city-wide anomalous traffic patterns and to provide broader range of insights into these anomalies. Taking these considerations, we first propose a feature visualization method by mapping extracted 3-dimensional hidden features to red-green-blue (RGB) color space with a deep sparse autoencoder (DSAE). A color trajectory (CT) is produced by encoding a trajectory with RGB colors. Then, a novel algorithm is devised to detect spatio-temporal outliers with spatial and temporal properties extracted from the CT. We also integrate the CT with the geographic information system (GIS) map to obtain insights for understanding the traffic anomaly locations, and more importantly the road influence affected by the corresponding anomalies. Our proposed method was tested on three real-world bus trajectory data sets to demonstrate the excellent performance of high detection rates and low false alarm rates
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