The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway

Amino acids signal to the mTOR complex I (mTORC1) growth pathway through the Rag GTPases. Multiple distinct complexes regulate the Rags, including GATOR1, a GTPase activating protein (GAP), and GATOR2, a positive regulator of unknown molecular function. Arginine stimulation of cells activates mTORC1, but how it is sensed is not well understood. Recently, SLC38A9 was identified as a putative lysosomal arginine sensor required for arginine to activate mTORC1 but how arginine deprivation represses mTORC1 is unknown. Here, we show that CASTOR1, a previously uncharacterized protein, interacts with GATOR2 and is required for arginine deprivation to inhibit mTORC1. CASTOR1 homodimerizes and can also heterodimerize with the related protein, CASTOR2. Arginine disrupts the CASTOR1-GATOR2 complex by binding to CASTOR1 with a dissociation constant of ∼30 μM, and its arginine-binding capacity is required for arginine to activate mTORC1 in cells. Collectively, these results establish CASTOR1 as an arginine sensor for the mTORC1 pathway.United States. National Institutes of Health (R01CA103866)United States. National Institutes of Health (AI47389)United States. Department of Energy (W81XWH-07-0448)United States. National Institutes of Health (F31 CA180271)United States. National Institutes of Health (F31 CA189437

TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243]

Agitated or violent patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians and clinical practice all differ. Systematic reviews show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments. Worldwide, current treatment is not based on evidence from randomised trials. In Brazil, the combination haloperidol-promethazine is frequently used, but no studies involving this mix exist. TREC-Rio (Tranquilização Rápida-Ensaio Clínico [Translation: Rapid Tranquillisation-Clinical Trial]) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro, Brazil. TREC-Rio is a randomised, controlled, pragmatic and open study. Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed. TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible. Because the design of this trial does not substantially complicate clinical management, and in several aspects simplifies it, the study can be large, and treatments used in everyday practice can be evaluated

Astrometric Methods and Instrumentation to Identify and Characterize Extrasolar Planets: A Review

I present a review of astrometric techniques and instrumentation utilized to search for, detect, and characterize extra-solar planets. First, I briefly summarize the properties of the present-day sample of extrasolar planets, in connection with predictions from theoretical models of planet formation and evolution. Next, the generic approach to planet detection with astrometry is described, with significant discussion of a variety of technical, statistical, and astrophysical issues to be faced by future ground-based as well as space-borne efforts in order to achieve the required degree of measurement precision. After a brief summary of past and present efforts to detect planets via milli-arcsecond astrometry, I then discuss the planet-finding capabilities of future astrometric observatories aiming at micro-arcsecond precision. Lastly, I outline a number experiments that can be conducted by means of high-precision astrometry during the next decade, to illustrate its potential for important contributions to planetary science, in comparison with other indirect and direct methods for the detection and characterization of planetary systems.Comment: 61 pages, 8 figures, PASP, accepted (October 2005 issue

Predictive use of the Maximum Entropy Production principle for Past and Present Climates

In this paper, we show how the MEP hypothesis may be used to build simple climate models without representing explicitly the energy transport by the atmosphere. The purpose is twofold. First, we assess the performance of the MEP hypothesis by comparing a simple model with minimal input data to a complex, state-of-the-art General Circulation Model. Next, we show how to improve the realism of MEP climate models by including climate feedbacks, focusing on the case of the water-vapour feedback. We also discuss the dependence of the entropy production rate and predicted surface temperature on the resolution of the model

Submillimetric GPS distance measurement over short baselines: case study in inner consistency

Distance determination in the open air with submillimetric accuracy is a challenging task usually carried out with the use of submillimetric distancemeters and costly observation campaigns. The present paper represents a first step in the research of the potential use of GPS for submillimetric distance determination for distances up to a few hundred metres consisting in the evaluation of GPS distance determination reproducibility. As will be concluded, reliable submillimetric precision is attainable after some hours of observation if the same equipment in both baseline ends is used, even considering that there still remain some long-term systematic effects of a few tenths of a millimetre. The need for precise absolute antenna calibration values is also shown to be critical for submillimetric distance reproducibility.This research is funded by the Spanish Ministry of Science and Innovation (AYA2011-23232). The authors are grateful to the editor and the anonymous reviewers for their valuable suggestions, corrections and comments that helped improve the original manuscript.Baselga Moreno, S.; García-Asenjo Villamayor, L.; Garrigues Talens, P. (2013). Submillimetric GPS distance measurement over short baselines: case study in inner consistency. Measurement Science and Technology. 24(7):750011-750018. https://doi.org/10.1088/0957-0233/24/7/075001S750011750018247Amiri-Simkooei, A. R., & Tiberius, C. C. J. M. (2006). Assessing receiver noise using GPS short baseline time series. GPS Solutions, 11(1), 21-35. doi:10.1007/s10291-006-0026-8Bruyninx, C., Altamimi, Z., Boucher, C., Brockmann, E., Caporali, A., Gurtner, W., … Weber, G. (2009). The European Reference Frame: Maintenance and Products. International Association of Geodesy Symposia, 131-136. doi:10.1007/978-3-642-00860-3_20Doloca, N. R., Meiners-Hagen, K., Wedde, M., Pollinger, F., & Abou-Zeid, A. (2010). Absolute distance measurement system using a femtosecond laser as a modulator. Measurement Science and Technology, 21(11), 115302. doi:10.1088/0957-0233/21/11/115302Dow, J. M., Neilan, R. E., & Rizos, C. (2009). The International GNSS Service in a changing landscape of Global Navigation Satellite Systems. Journal of Geodesy, 83(3-4), 191-198. doi:10.1007/s00190-008-0300-3Firuzabadì, D., & King, R. W. (2011). GPS precision as a function of session duration and reference frame using multi-point software. GPS Solutions, 16(2), 191-196. doi:10.1007/s10291-011-0218-8Hyun, S., Kim, Y.-J., Kim, Y., Jin, J., & Kim, S.-W. (2009). Absolute length measurement with the frequency comb of a femtosecond laser. Measurement Science and Technology, 20(9), 095302. doi:10.1088/0957-0233/20/9/095302Koivula, H., Häkli, P., Jokela, J., Buga, A., & Putrimas, R. (2011). GPS Metrology: Bringing Traceable Scale to a Local Crustal Deformation GPS Network. International Association of Geodesy Symposia, 105-112. doi:10.1007/978-3-642-20338-1_13Ray, J., Altamimi, Z., Collilieux, X., & van Dam, T. (2007). Anomalous harmonics in the spectra of GPS position estimates. GPS Solutions, 12(1), 55-64. doi:10.1007/s10291-007-0067-7Schuhler, N., Salvadé, Y., Lévêque, S., Dändliker, R., & Holzwarth, R. (2006). Frequency-comb-referenced two-wavelength source for absolute distance measurement. Optics Letters, 31(21), 3101. doi:10.1364/ol.31.003101Snay, R. A., & Soler, T. (2008). Continuously Operating Reference Station (CORS): History, Applications, and Future Enhancements. Journal of Surveying Engineering, 134(4), 95-104. doi:10.1061/(asce)0733-9453(2008)134:4(95

Testing of aspheric surfaces with computer generated holograms

Aspherical surfaces are becoming more important and can even be mass producted. There is a need for flexible test methods of high accuracy. The paper describes the combination of a computer generated holograms with a partially compensating lens as a powerful tool. An example for testing a steep aspheric surface will be given

Clouds, aerosols, and precipitation in the marine boundary layer: an ARM Mobile Facility Deployment

The Clouds, Aerosol, and Precipitation in the Marine Boundary Layer (CAP-MBL) deployment at Graciosa Island in the Azores generated a 21-month (April 2009–December 2010) comprehensive dataset documenting clouds, aerosols, and precipitation using the Atmospheric Radiation Measurement Program (ARM) Mobile Facility (AMF). The scientific aim of the deployment is to gain improved understanding of the interactions of clouds, aerosols, and precipitation in the marine boundary layer. Graciosa Island straddles the boundary between the subtropics and midlatitudes in the northeast Atlantic Ocean and consequently experiences a great diversity of meteorological and cloudiness conditions. Low clouds are the dominant cloud type, with stratocumulus and cumulus occurring regularly. Approximately half of all clouds contained precipitation detectable as radar echoes below the cloud base. Radar and satellite observations show that clouds with tops from 1 to 11 km contribute more or less equally to surface-measured precipitation at Graciosa. A wide range of aerosol conditions was sampled during the deployment consistent with the diversity of sources as indicated by back-trajectory analysis. Preliminary findings suggest important two-way interactions between aerosols and clouds at Graciosa, with aerosols affecting light precipitation and cloud radiative properties while being controlled in part by precipitation scavenging. The data from Graciosa are being compared with short-range forecasts made with a variety of models. A pilot analysis with two climate and two weather forecast models shows that they reproduce the observed time-varying vertical structure of lower-tropospheric cloud fairly well but the cloud-nucleating aerosol concentrations less well. The Graciosa site has been chosen to be a permanent fixed ARM site that became operational in October 2013

The PreVOCA experiment: modeling the lower troposphere in the Southeast Pacific

The Preliminary VOCALS Model Assessment (PreVOCA) aims to assess contemporary atmospheric modeling of the subtropical South East Pacific, with a particular focus on the clouds and the marine boundary layer (MBL). Models results from fourteen modeling centers were collected including operational forecast models, regional models, and global climate models for the month of October 2006. Forecast models and global climate models produced daily forecasts, while most regional models were run continuously during the study period, initialized and forced at the boundaries with global model analyses. Results are compared in the region from 40° S to the equator and from 110° W to 70° W, corresponding to the Pacific coast of South America. Mean-monthly model surface winds agree well with QuikSCAT observed winds and models agree fairly well on mean weak large-scale subsidence in the region next to the coast. However they have greatly differing geographic patterns of mean cloud fraction with only a few models agreeing well with MODIS observations. Most models also underestimate the MBL depth by several hundred meters in the eastern part of the study region. The diurnal cycle of liquid water path is underestimated by most models at the 85° W 20° S stratus buoy site compared with satellite, consistent with previous modeling studies. The low cloud fraction is also underestimated during all parts of the diurnal cycle compared to surface-based climatologies. Most models qualitatively capture the MBL deepening around 15 October 2006 at the stratus buoy, associated with colder air at 700 hPa

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis