Auxiliary Subunit GSG1L Acts to Suppress Calcium-Permeable AMPA Receptor Function

UNLABELLED: AMPA-type glutamate receptors are ligand-gated cation channels responsible for a majority of the fast excitatory synaptic transmission in the brain. Their behavior and calcium permeability depends critically on their subunit composition and the identity of associated auxiliary proteins. Calcium-permeable AMPA receptors (CP-AMPARs) contribute to various forms of synaptic plasticity, and their dysfunction underlies a number of serious neurological conditions. For CP-AMPARs, the prototypical transmembrane AMPAR regulatory protein stargazin, which acts as an auxiliary subunit, enhances receptor function by increasing single-channel conductance, slowing channel gating, increasing calcium permeability, and relieving the voltage-dependent block by endogenous intracellular polyamines. We find that, in contrast, GSG1L, a transmembrane auxiliary protein identified recently as being part of the AMPAR proteome, acts to reduce the weighted mean single-channel conductance and calcium permeability of recombinant CP-AMPARs, while increasing polyamine-dependent rectification. To examine the effects of GSG1L on native AMPARs, we manipulated its expression in cerebellar and hippocampal neurons. Transfection of GSG1L into mouse cultured cerebellar stellate cells that lack this protein increased the inward rectification of mEPSCs. Conversely, shRNA-mediated knockdown of endogenous GSG1L in rat cultured hippocampal pyramidal neurons led to an increase in mEPSC amplitude and in the underlying weighted mean single-channel conductance, revealing that GSG1L acts to suppress current flow through native CP-AMPARs. Thus, our data suggest that GSG1L extends the functional repertoire of AMPAR auxiliary subunits, which can act not only to enhance but also diminish current flow through their associated AMPARs. SIGNIFICANCE STATEMENT: Calcium-permeable AMPA receptors (CP-AMPARs) are an important group of receptors for the neurotransmitter glutamate. These receptors contribute to various forms of synaptic plasticity, and alterations in their expression or regulation are also seen in a number of serious neurological conditions, including stroke, motor neuron disease, and cocaine addiction. Several groups of auxiliary transmembrane proteins have been described that enhance the function and cell-surface expression of AMPARs. We now report that the recently identified auxiliary protein GSG1L decreases weighted mean channel conductance and calcium permeability of CP-AMPARs while increasing polyamine-dependent rectification by diminishing outward current. Our experiments reveal that GSG1L is an auxiliary subunit that can markedly suppress CP-AMPAR function, in both recombinant systems and central neurons

Fuel injection assembly for gas turbine engine combustor

A fuel injection assembly for a gas turbine engine combustor, including at least one fuel stem, a plurality of concentrically disposed tubes positioned within each fuel stem, wherein a cooling supply flow passage, a cooling return flow passage, and a tip fuel flow passage are defined thereby, and at least one fuel tip assembly connected to each fuel stem so as to be in flow communication with the flow passages, wherein an active cooling circuit for each fuel stem and fuel tip assembly is maintained by providing all active fuel through the cooling supply flow passage and the cooling return flow passage during each stage of combustor operation. The fuel flowing through the active cooling circuit is then collected so that a predetermined portion thereof is provided to the tip fuel flow passage for injection by the fuel tip assembly

Model Telediagnosis Serangan Jantung untuk Para Praktisi Kesehatan Menggunakan Mobile Phone

The lack of medical experts such as doctors at rural areas resulted in some problems such as the high cost of medical care and low service of doctors and medical resource provider. The conditions results in an idea to implement a communication system between rural medical practitioners and doctors in urban areas to perform remote diagnosis on patients (telediagnosis). The research involves several parties such as doctors, health centers, health practitioners (paramedics), patients, and hospitals and health institutions. The telediagnosis system development consists of the construction of a software application prototype as media input for patient data which will be sent to doctors at town, database systems design, integration of basic multimedia devices, medical diagnostic device integration, and application testing of telediagnosis performance using an android-based mobile application. Data integration patterns include patient data delivery patterns, checking a patient's diagnosis, saving and continuing to the physician or health care practitioner with real-timesystem. This study is conducted according to standard research stages: problem collection, problem analysis, research materials collection, research design, and research implementation. Telediagnosis system is used to facilitate remote diagnosis of patients at rural areas which is able to serve patients more quickly, and helps find out nearest location for patients to get medicines as well as recommendation of nearest hospital. This system helps decrease the workload of hospitals

Synergistic cross-scale coupling of turbulence in a tokamak plasma

For the first time, nonlinear gyrokinetic simulations spanning both the ion and electron spatio-temporal scales have been performed with realistic electron mass ratio ((m[subscript D] [over m [subscript e])[superscript 1 over 2] = 60.0), realistic geometry, and all experimental inputs, demonstrating the coexistence and synergy of ion (k[subscript θρs] ~O(1.0)) and electron-scale (k[subscript θρe] ~O(1.0)) turbulence in the core of a tokamak plasma. All multi-scale simulations utilized the GYRO code [J. Candy and R. E. Waltz, J. Comput. Phys. 186, 545 (2003)] to study the coupling of ion and electron-scale turbulence in the core (r/a = 0.6) of an Alcator C-Mod L-mode discharge shown previously to exhibit an under-prediction of the electron heat flux when using simulations only including ion-scale turbulence. Electron-scale turbulence is found to play a dominant role in setting the electron heat flux level and radially elongated (k[subscript r] ≪ k[subscript θ]) “streamers” are found to coexist with ion-scale eddies in experimental plasma conditions. Inclusion of electron-scale turbulence in these simulations is found to increase both ion and electron heat flux levels by enhancing the transport at the ion-scale while also driving electron heat flux at sub-ρ[subscript i] scales. The combined increases in the low and high-k driven electron heat flux may explain previously observed discrepancies between simulated and experimental electron heat fluxes and indicates a complex interaction of short and long wavelength turbulence.United States. Dept. of Energy. Office of Science (Contract DE-AC02-05CH11231)United States. Dept. of Energy (Contract DE-FC02-99ER54512-CMOD)United States. Dept. of Energy. Fusion Energy Postdoctoral Research Program (Oak Ridge Institute for Science and Education

Analisis Metode Pelaksanaan Plat Precast Dengan Plat Konvensional Ditinjau Dari Waktu Dan Biaya (Studi Kasus : Markas Komando Daerah Militer Manado)

Pemilihan metode pelaksanaan suatu proyek konstruksi sangat penting karena metode pelaksanaan yang tepat dapat memberikan hasil yang maksimal terutama jika ditinjau dari segi biaya maupun waktu. Salah satu USAha yang dilakukan oleh pengelola proyek adalah mengganti cara –cara konvensional menjadi lebih modern, yaitu dengan cara penerapan beton pracetak. Tujuan penelitian ini : (1) membandingkan metode pelaksanaan pembangunan antara penggunaan sistem beton konvensional. (2) Menganalisa biaya yang diperlukan pada kedua sistem tersebut dengan perhitungan Rab. (3) Menganalisa pengaruh waktu pelaksanaan antara sistem konvensional dan Precast terhadap biaya dengan Kurva S dari kedua sistem tersebut. Dari hal-hal tersebut akan diketahui sistem pengecoran mana yang efisien dari segi waktu, biaya, peralatan, maupun faktor pendukung, serta membandingkan antara precast fabrikasi dengan precast cast in situ. Beberapa aspek tentunya berbeda, baik untuk waktu, alat maupun proses yang akan dilakukan. Hasil penelitian memperlihatkan bahwa : dengan menggunakan metode precast membutuhkan waktu pelaksanaan selama 198 hari dengan Total biaya langsungnya adalah Rp 30,352,740,000,00, sedang untuk metode konvensional membutuhkan waktu pelaksanaan selama 226 hari dengan total biaya langsung Rp 30,230,145,000,00. Perbandingan biaya adalah Rp 122,595,000,00 sedang perbandingan waktu adalah 28 hari. Dapat disimpulkan bahwa pekerjaan menggunakan sistem precast membutuhkan biaya yang lebih besar dibandingkan sistem konvensional akan tetapi dengan waktu pengerjaan yang lebih singkat. Semakin besar volume pekerjaan dengan menggunakan sistem precast, semakin murah pula harganya dibandingkan dengan metode konvensional dan waktu pelaksanaannya juga lebih cepat, apalagi dengan menggunakan sistem Precast cast in situ

Multi-scale gyrokinetic simulations: Comparison with experiment and implications for predicting turbulence and transport

To better understand the role of cross-scale coupling in experimental conditions, a series of multi-scale gyrokinetic simulations were performed on Alcator C-Mod, L-mode plasmas. These simulations, performed using all experimental inputs and realistic ion to electron mass ratio ((mi/me)1∕2 = 60.0), simultaneously capture turbulence at the ion (kθρs∼(1.0)) and electron-scales (kθρe∼(1.0)). Direct comparison with experimental heat fluxes and electron profile stiffness indicates that Electron Temperature Gradient (ETG) streamers and strong cross-scale turbulence coupling likely exist in both of the experimental conditions studied. The coupling between ion and electron-scales exists in the form of energy cascades, modification of zonal flow dynamics, and the effective shearing of ETG turbulence by long wavelength, Ion Temperature Gradient (ITG) turbulence. The tightly coupled nature of ITG and ETG turbulence in these realistic plasma conditions is shown to have significant implications for the interpretation of experimental transport and fluctuations. Initial attempts are made to develop a “rule of thumb” based on linear physics, to help predict when cross-scale coupling plays an important role and to inform future modeling of experimental discharges. The details of the simulations, comparisons with experimental measurements, and implications for both modeling and experimental interpretation are discussed.United States. Department of Energy (DE-AC02-05CH11231)United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-SC0006957)United States. Department of Energy (DE-FG02-06ER54871

The under reporting of recruitment strategies in research with children with life threatening illnesses: A systematic review

BACKGROUND: Researchers report difficulties in conducting research with children and young people (CYP) with life-limiting conditions (LLC) or life-threatening illnesses (LTI) and their families. Recruitment is challenged by barriers including ethical, logistical and clinical considerations. AIM: To explore how children and young people (aged 0-25 years) with life-limiting conditions or life-threatening illnesses and their families were identified, invited and consented to research published in the last 5 years. DESIGN: Systematic review. DATA SOURCES: Medline, PsycINFO, Web of Science, Sciences Citation Index, SCOPUS were searched for original English language research published between 2009-2014, recruiting children and young people with life-limiting conditions or life-threatening illness and their families. RESULTS: Two-hundred and fifteen studies; 152 qualitative, 54 quantitative, 9 mixed methods were included. Limited recruitment information but a range of strategies and difficulties were provided. The proportion of eligible participants from those screened could not be calculated in 80% of studies. Recruitment rates could not be calculated in 77%. Thirty-one per cent of studies recruited less than 50% of eligible participants. Reasons given for non-invitation included missing clinical or contact data, or clinician judgements of participant unsuitability. Reasons for non-participation included lack of interest and participants’ perceptions of potential burdens. CONCLUSIONS: All stages of recruitment were under reported. Transparency in reporting of participant identification, invitation and consent is needed to enable researchers to understand research implications, bias risk and to whom results apply. Research is needed to explore why consenting participants decide to take part or not and their experiences of research recruitment

Drug therapy for delirium in terminally ill adult patients.

BACKGROUND: Delirium is a syndrome characterised by a disturbance of consciousness (often fluctuating), cognition and perception. In terminally ill patients it is one of the most common causes of admission to clinical care. Delirium may arise from any number of causes and treatment should be directed at addressing these causes rather than the symptom cluster. In cases where this is not possible, or treatment does not prove successful, the use of drug therapy to manage the symptoms may become necessary. This is an update of the review published on 'Drug therapy for delirium in terminally ill adult patients' in The Cochrane Library 2004, Issue 2 ( Jackson 2004). OBJECTIVES: To evaluate the effectiveness of drug therapies to treat delirium in adult patients in the terminal phase of a disease. SEARCH METHODS: We searched the following sources: CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to 2012), EMBASE (1980 to 2012), CINAHL (1982 to 2012) and PSYCINFO (1990 to 2012). SELECTION CRITERIA: Prospective trials with or without randomisation or blinding involving the use of drug therapies for the treatment of delirium in adult patients in the terminal phase of a disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality using standardised methods and extracted trial data. We collected outcomes related to efficacy and adverse effects. MAIN RESULTS: One trial met the criteria for inclusion. In the 2012 update search we retrieved 3066 citations but identified no new trials. The included trial evaluated 30 hospitalised AIDS patients receiving one of three agents: chlorpromazine, haloperidol and lorazepam. The trial under-reported key methodological features. It found overall that patients in the chlorpromazine group and those in the haloperidol group had fewer symptoms of delirium at follow-up (to below the diagnostic threshold using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and that both were equally effective (at two days mean difference (MD) 0.37; 95% confidence interval (CI) -4.58 to 5.32; between two and six days MD -0.21; 95% CI -5.35 to 4.93). Chlorpromazine and haloperidol were found to be no different in improving cognitive status in the short term (at 48 hours) but at subsequent follow-up cognitive status was reduced in those taking chlorpromazine. Improvements from baseline to day two for patients randomised to lorazepam were not apparent. All patients on lorazepam (n = 6) developed adverse effects, including oversedation and increased confusion, leading to trial drug discontinuation. AUTHORS' CONCLUSIONS: There remains insufficient evidence to draw conclusions about the role of drug therapy in the treatment of delirium in terminally ill patients. Thus, practitioners should continue to follow current clinical guidelines. Further research is essential

The evolution of Palaeolake Flixton and the environmental context of Star Carr:An oxygen and carbon isotopic record of environmental change for the early Holocene

This paper presents δ18O and δ13C values from three early Holocene lacustrine carbonate sequences from Palaeolake Flixton in northeastern England. The δ13C values are typical of carbonates precipitating in an open lake system with the exception of samples from the very uppermost parts of these sequences which have values more typical of palustrine or tufaceous carbonates and, therefore, indicate the progressive contraction and shrinkage of the lake system overtime. The δ18O values record an initial increase to an early peak at the onset of the Holocene but a subsequent decline in values of such a magnitude that by ca 8000 yrs B.P. the δ18O value of the precipitated carbonate is consistent with carbonates that precipitated at the end of the Loch Lomond Stadial. The early increase and peak in δ18O values is suggested to reflect the climatic amelioration at the onset of the Holocene, as temperatures progressively rose. The decline cannot be explained by any known temperature shifts, however, this “depletion trend” is seen in several other early Holocene lacustrine records from across the British Isles. This decline is suggested to reflect a shift in the seasonality of precipitation from a more seasonal precipitation regime typical of a “continental” climate, with strong seasonal contrasts in rainfall, to a more “maritime” climate which was characterised by consistent levels of rainfall occurring across the year. The relative timing of human activity at Star Carr suggests human occupation occurred after this isotopic decline under “maritime” rather than “continental” climates

A wireless RF CMOS mixed-signal interface for soil moisture measurements

This paper describes a wireless RF CMOS interface for soil moisture measurements. The interface basically comprises a Delta-Sigma (ΔΣ) modulator for acquiring an external sensor signal, and a RF section where data is transmitted to a local processing unit. The ΔΣ modulator is a single-bit, second-order modulator and it is implemented using switched-capacitors techniques in a fully-differential topology. With a sampling frequency of 423.75 kHz and an oversampling ratio (OSR) of 256, the modulator achieves a dynamic range of 98.7 dB (16.1 bit). The output of the modulator is applied to a counter, as a first-order decimation filter, and the result is stored. Prior to transmission, data is encoded as a pulse width modulated signal and assembled in a frame containing preamble and checksum control fields. This frame is then transmitted through a power amplifier operating at 433.92 MHz in class-E mode. To evaluate the ΔΣ modulator performance, the bitstream was acquired and transferred to a personal computer to perform digital filtering and decimation using MATLAB. The soil moisture sensor is based on dual-probe heat-pulse (DPHP) method and is implemented by using an integrated temperature sensor and a heater. After applying a heat-pulse for a fixed period of time, the temperature rise, that is a function of soil moisture, generates a differential voltage that is amplified and applied to the mixed-signal interface input. The described interface can also be used with other kinds of environmental sensors in a wireless sensors network. The CMOS mixed-signal interface has been implemented in a single-chip using a standard CMOS 0.7 μm process (AMI C07M-A, n-well, 2 metals and 1 poly)