Reconstructing WIMP properties through an interplay of signal measurements in direct detection, Fermi-LAT, and CTA searches for dark matter

NASA Astrophysics Data System (ADS)

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian; Williams, Andrew J.

2016-08-01

We examine the projected ability to reconstruct the mass, scattering, and annihilation cross section of dark matter in the new generation of large underground detectors, XENON-1T, SuperCDMS, and DarkSide-G2, in combination with diffuse gamma radiation from expected 15 years of data from Fermi-LAT observation of 46 local spiral dwarf galaxies and projected CTA sensitivity to a signal from the Galactic Center. To this end we consider several benchmark points spanning a wide range of WIMP mass, different annihilation final states, and large enough event rates to warrant detection in one or more experiments. As previously shown, below some 100 GeV only direct detection experiments will in principle be able to reconstruct WIMP mass well. This may, in case a signal at Fermi-LAT is also detected, additionally help restricting σv and the allowed decay branching rates. In the intermediate range between some 100 GeV and up a few hundred GeV, direct and indirect detection experiments can be used in complementarity to ameliorate the respective determinations, which in individual experiments can at best be rather poor, thus making the WIMP reconstruction in this mass range very challenging. At large WIMP mass, ~ 1 TeV, CTA will have the ability to reconstruct mass, annihilation cross section, and the allowed decay branching rates to very good precision for the τ+τ- or purely leptonic final state, good for the W+W- case, and rather poor for bbar b. A substantial improvement can potentially be achieved by reducing the systematic uncertainties, increasing exposure, or by an additional measurement at Fermi-LAT that would help reconstruct the annihilation cross section and the allowed branching fractions to different final states.

Detection of 16 Gamma-Ray Pulsars Through Blind Frequency Searches Using the Fermi LAT

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-07-02

Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations. In this paper, we report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Finally, direct detection of gamma-raymore » pulsars enables studies of emission mechanisms, population statistics, and the energetics of pulsar wind nebulae and supernova remnants.« less

Radio and gamma-ray properties of extragalactic jets from the TANAMI sample

DOE PAGES

Böck, M.; Kadler, M.; Müller, C.; ...

2016-05-04

The TANAMI program has been observing parsec-scale radio jets of southern (declination south of - 30°) γ-ray bright AGN, simultaneously with Fermi/LAT monitoring of their γ-ray emission, via high-resolution radio imaging with Very Long Baseline Interferometry techniques. In this paper, we present the radio and γ-rayproperties of the TANAMI sources based on one year of contemporaneous TANAMI and Fermi/LAT data. A large fraction (72%) of the TANAMI sample can be associated with bright γ-ray sources for this time range. Association rates differ for different optical classes with all BL Lacs, 76% of quasars, and just 17% of galaxies detected bymore » the LAT. Upper limits were established on the γ-ray flux from TANAMI sources not detected by LAT. This analysis led to the identification of three new Fermi sources whose detection was later confirmed. The γ-ray and radio luminosities are related by L γ ∝ L r 0.89±0.04. The brightness temperatures of the radio cores increase with the average γ-ray luminosity and the presence of brightness temperatures above the inverse Compton limit implies strong Doppler boosting in those sources. The undetected sources have lower γ/radio luminosity ratios and lower contemporaneous brightness temperatures. Finally, unless the Fermi/LAT-undetected blazars are much γ-ray-fainter than the Fermi/LAT-detected sources, their γ-ray luminosity should not be significantly lower than the upper limits calculated here.« less

Functional Polarity of Microvascular Brain Endothelial Cells Supported by Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis

PubMed Central

Taslimifar, Mehdi; Buoso, Stefano; Verrey, Francois; Kurtcuoglu, Vartan

2018-01-01

The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available in vitro and in vivo standard methods so far. To circumvent these limitations, we have incorporated published in vivo data of rat brain into a robust computational model of NVU-LNAA homeostasis, allowing us to evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs across the blood brain barrier (BBB). We show that accounting for functional polarity of MBECs with either asymmetric LAT1 distribution between membranes and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is required to reproduce the experimentally measured brain ISF response to intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of these findings, we have also investigated the effect of IP administrated L-tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and neurons. Finally, the computational model was shown to explain the trans-stimulation of LNAA uptake across the BBB observed upon ISF perfusion with a competitive LAT1 inhibitor. PMID:29593549

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer.

PubMed

Wen, Ning; Guan, Huaiqun; Hammoud, Rabih; Pradhan, Deepak; Nurushev, T; Li, Shidong; Movsas, Benjamin

2007-04-21

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was approximately 4.0 cGy, which was approximately 40% higher than the Rt Lat dose of approximately 2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm x 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370 degrees scan rotation (10 degrees scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of approximately 10-11 cGy while the right hip received approximately 6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than approximately 12% to the table-drop setup.

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer

NASA Astrophysics Data System (ADS)

Wen, Ning; Guan, Huaiqun; Hammoud, Rabih; Pradhan, Deepak; Nurushev, T.; Li, Shidong; Movsas, Benjamin

2007-04-01

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was ~4.0 cGy, which was ~40% higher than the Rt Lat dose of ~2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm × 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370° scan rotation (10° scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of ~10-11 cGy while the right hip received ~6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than ~12% to the table-drop setup.

Reconstructing WIMP properties through an interplay of signal measurements in direct detection, Fermi-LAT, and CTA searches for dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

2016-08-01

We examine the projected ability to reconstruct the mass, scattering, and annihilation cross section of dark matter in the new generation of large underground detectors, XENON-1T, SuperCDMS, and DarkSide-G2, in combination with diffuse gamma radiation from expected 15 years of data from Fermi-LAT observation of 46 local spiral dwarf galaxies and projected CTA sensitivity to a signal from the Galactic Center. To this end we consider several benchmark points spanning a wide range of WIMP mass, different annihilation final states, and large enough event rates to warrant detection in one or more experiments. As previously shown, below some 100 GeVmore » only direct detection experiments will in principle be able to reconstruct WIMP mass well. This may, in case a signal at Fermi-LAT is also detected, additionally help restricting σ v and the allowed decay branching rates. In the intermediate range between some 100 GeV and up a few hundred GeV, direct and indirect detection experiments can be used in complementarity to ameliorate the respective determinations, which in individual experiments can at best be rather poor, thus making the WIMP reconstruction in this mass range very challenging. At large WIMP mass, ∼ 1 TeV, CTA will have the ability to reconstruct mass, annihilation cross section, and the allowed decay branching rates to very good precision for the τ{sup +}τ{sup -} or purely leptonic final state, good for the W {sup +} W {sup -} case, and rather poor for b b-bar . A substantial improvement can potentially be achieved by reducing the systematic uncertainties, increasing exposure, or by an additional measurement at Fermi-LAT that would help reconstruct the annihilation cross section and the allowed branching fractions to different final states.« less

Latency-associated transcript (LAT) exon 1 controls herpes simplex virus species-specific phenotypes: reactivation in the guinea pig genital model and neuron subtype-specific latent expression of LAT.

PubMed

Bertke, Andrea S; Patel, Amita; Imai, Yumi; Apakupakul, Kathleen; Margolis, Todd P; Krause, Philip R

2009-10-01

Herpes simplex virus 1 (HSV-1) and HSV-2 cause similar acute infections but differ in their abilities to reactivate from trigeminal and lumbosacral dorsal root ganglia. During latency, HSV-1 and HSV-2 also preferentially express their latency-associated transcripts (LATs) in different sensory neuronal subtypes that are positive for A5 and KH10 markers, respectively. Chimeric virus studies showed that LAT region sequences influence both of these viral species-specific phenotypes. To further map the LAT region sequences responsible for these phenotypes, we constructed the chimeric virus HSV2-LAT-E1, in which exon 1 (from the LAT TATA to the intron splice site) was replaced by the corresponding sequence from HSV-1 LAT. In intravaginally infected guinea pigs, HSV2-LAT-E1 reactivated inefficiently relative to the efficiency of its rescuant and wild-type HSV-2, but it yielded similar levels of viral DNA, LAT, and ICP0 during acute and latent infection. HSV2-LAT-E1 preferentially expressed the LAT in A5+ neurons (as does HSV-1), while the chimeric viruses HSV2-LAT-P1 (LAT promoter swap) and HSV2-LAT-S1 (LAT sequence swap downstream of the promoter) exhibited neuron subtype-specific latent LAT expression phenotypes more similar to that of HSV-2 than that of HSV-1. Rescuant viruses displayed the wild-type HSV-2 phenotypes of efficient reactivation in the guinea pig genital model and a tendency to express LAT in KH10+ neurons. The region that is critical for HSV species-specific differences in latency and reactivation thus lies between the LAT TATA and the intron splice site, and minor differences in the 5' ends of chimeric sequences in HSV2-LAT-E1 and HSV2-LAT-S1 point to sequences immediately downstream of the LAT TATA.

SENSITIVITY OF BLIND PULSAR SEARCHES WITH THE FERMI LARGE AREA TELESCOPE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dormody, M.; Johnson, R. P.; Atwood, W. B.

2011-12-01

We quantitatively establish the sensitivity to the detection of young to middle-aged, isolated, gamma-ray pulsars through blind searches of Fermi Large Area Telescope (LAT) data using a Monte Carlo simulation. We detail a sensitivity study of the time-differencing blind search code used to discover gamma-ray pulsars in the first year of observations. We simulate 10,000 pulsars across a broad parameter space and distribute them across the sky. We replicate the analysis in the Fermi LAT First Source Catalog to localize the sources, and the blind search analysis to find the pulsars. We analyze the results and discuss the effect ofmore » positional error and spin frequency on gamma-ray pulsar detections. Finally, we construct a formula to determine the sensitivity of the blind search and present a sensitivity map assuming a standard set of pulsar parameters. The results of this study can be applied to population studies and are useful in characterizing unidentified LAT sources.« less

Fermi Large Area Telescope Measurements of the Diffuse Gamma-Ray Emission at Intermediate Galactic Latitudes

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-12-16

We report that the diffuse galactic γ-ray emission is produced by cosmic rays (CRs) interacting with the interstellar gas and radiation field. Measurements by the Energetic Gamma-Ray Experiment Telescope (EGRET) instrument on the Compton Gamma-Ray Observatory indicated excess γ-ray emission ≳1 GeV relative to diffuse galactic γ-ray emission models consistent with directly measured CR spectra (the so-called “EGRET GeV excess”). The Large Area Telescope (LAT) instrument on the Fermi Gamma-Ray Space Telescope has measured the diffuse γ -ray emission with improved sensitivity and resolution compared to EGRET. We report on LAT measurements for energies 100 MeV to 10 GeV andmore » galactic latitudes 10° ≤ | b | ≤ 20°. Finally, the LAT spectrum for this region of the sky is well reproduced by a diffuse galactic γ-ray emission model that is consistent with local CR spectra and inconsistent with the EGRET GeV excess.« less

Latency-Associated Transcript (LAT) Exon 1 Controls Herpes Simplex Virus Species-Specific Phenotypes: Reactivation in the Guinea Pig Genital Model and Neuron Subtype-Specific Latent Expression of LAT▿

PubMed Central

Bertke, Andrea S.; Patel, Amita; Imai, Yumi; Apakupakul, Kathleen; Margolis, Todd P.; Krause, Philip R.

2009-01-01

Herpes simplex virus 1 (HSV-1) and HSV-2 cause similar acute infections but differ in their abilities to reactivate from trigeminal and lumbosacral dorsal root ganglia. During latency, HSV-1 and HSV-2 also preferentially express their latency-associated transcripts (LATs) in different sensory neuronal subtypes that are positive for A5 and KH10 markers, respectively. Chimeric virus studies showed that LAT region sequences influence both of these viral species-specific phenotypes. To further map the LAT region sequences responsible for these phenotypes, we constructed the chimeric virus HSV2-LAT-E1, in which exon 1 (from the LAT TATA to the intron splice site) was replaced by the corresponding sequence from HSV-1 LAT. In intravaginally infected guinea pigs, HSV2-LAT-E1 reactivated inefficiently relative to the efficiency of its rescuant and wild-type HSV-2, but it yielded similar levels of viral DNA, LAT, and ICP0 during acute and latent infection. HSV2-LAT-E1 preferentially expressed the LAT in A5+ neurons (as does HSV-1), while the chimeric viruses HSV2-LAT-P1 (LAT promoter swap) and HSV2-LAT-S1 (LAT sequence swap downstream of the promoter) exhibited neuron subtype-specific latent LAT expression phenotypes more similar to that of HSV-2 than that of HSV-1. Rescuant viruses displayed the wild-type HSV-2 phenotypes of efficient reactivation in the guinea pig genital model and a tendency to express LAT in KH10+ neurons. The region that is critical for HSV species-specific differences in latency and reactivation thus lies between the LAT TATA and the intron splice site, and minor differences in the 5′ ends of chimeric sequences in HSV2-LAT-E1 and HSV2-LAT-S1 point to sequences immediately downstream of the LAT TATA. PMID:19641003

On The Geodynamics In Latvia

NASA Astrophysics Data System (ADS)

Balodis, Janis; Haritonova, Diana; Janpaule, Inese; Normand, Madara; Silabiedis, Gunars; Zarinjsh, Ansis; Rubans, Agusts; Kalinka, Maris; Jumare, Izolde; Lasmane, Ieva

2013-12-01

This paper discusses the research work done in Institute of Geodesy and Geoinformation, University of Latvia, and Department of Geomatics, Riga Technical Univesity, devoted to the geodynamics in Latvia: national geoid model computation, using different methods and data sets, in order to improve its precision; analysis of LatPos and EUPOS®-Riga GNSS permanent station observation data time series for time period of 5 years; development of digital zenith camera for vertical deflection determination.

Fermi LAT Stacking Analysis of Swift Localized GRBs

DOE PAGES

Ackermann, M.; Ajello, M.; Anderson, B.; ...

2016-05-05

In this paper, we perform a comprehensive stacking analysis of data collected by the Fermi Large Area Telescope (LAT) of γ-ray bursts (GRBs) localized by the Swift spacecraft, which were not detected by the LAT but which fell within the instrument's field of view at the time of trigger. We examine a total of 79 GRBs by comparing the observed counts over a range of time intervals to that expected from designated background orbits, as well as by using a joint likelihood technique to model the expected distribution of stacked counts. We find strong evidence for subthreshold emission at MeVmore » to GeV energies using both techniques. This observed excess is detected during intervals that include and exceed the durations typically characterizing the prompt emission observed at keV energies and lasts at least 2700 s after the co-aligned burst trigger. By utilizing a novel cumulative likelihood analysis, we find that although a burst's prompt γ-ray and afterglow X-ray flux both correlate with the strength of the subthreshold emission, the X-ray afterglow flux measured by Swift's X-ray Telescope at 11 hr post trigger correlates far more significantly. Overall, the extended nature of the subthreshold emission and its connection to the burst's afterglow brightness lend further support to the external forward shock origin of the late-time emission detected by the LAT. Finally, these results suggest that the extended high-energy emission observed by the LAT may be a relatively common feature but remains undetected in a majority of bursts owing to instrumental threshold effects.« less

Comparison of Antigen Detection and Nested PCR in CSF Samples of HIV Positive and Negative Patients with Suspected Cryptococcal Meningitis in a Tertiary Care Hospital.

PubMed

Kumari, Sunita; Verma, Rajesh Kumar; Singh, Dharmendra Prasad; Yadav, Ramakant

2016-04-01

The cases of cryptococcal meningitis and other forms of cryptococcosis have increased in recent time and the present scenario of the condition with significant morbidity and mortality is actually posing a serious threat to the community, so an early and prompt diagnosis is necessary to prevent serious complications and thus improving the overall disease outcome. Comparison of diagnostic efficacy of nested Polymerase Chain Reaction (PCR) with Latex Agglutination Test (LAT) in the Cerebro Spinal Fluid (CSF) samples of the cases of meningitis in HIV positive and negative cases. We have compared the diagnostic efficacy of Latex Agglutination Test (LAT) with nested Polymerase Chain Reaction (PCR) in 200 Cerebrospinal Fluid (CSF) samples, including 14 HIV positive also, in the cases of suspected cryptococcal meningitis. Nested PCR was done in all cases reporting positive by LAT and results were then compared with that of India ink and culture on Sabouraud Dextrose Agar (SDA), and the isolates were further identified by urease, nitrate and sugar assimilation tests. Of the 200 cases, including 14 HIV positive, LAT was positive in 46 cases while 154 were negative. Out of these 46 LAT positive cases, nested PCR was positive in 40 cases only, while culture and India ink was positive in 38 and 33 cases respectively. Majority of the cases, 30 (65.2%) were between age group 21-50 years, while 2 (4.3%) in 0-20, and 14 (30.4%) in 51-80 years age group. Although negative staining like India ink and nigrosin are most widely used techniques, but these suffer with subjective error. Rapid method like LAT is available but it always has the scope of false positive and negative results. In such cases nested PCR can help in establishing final diagnosis.

Consolidative local ablative therapy improves the survival of patients with synchronous oligometastatic NSCLC harboring EGFR activating mutation treated with first-line EGFR-TKIs.

PubMed

Xu, Qinghua; Zhou, Fei; Liu, Hui; Jiang, Tao; Li, Xuefei; Xu, Yaping; Zhou, Caicun

2018-05-28

The aim of the current study was to investigate whether consolidative local ablative therapy (LAT) can improve the survival of patients with stage IV EGFR-mutant NSCLC who have oligometastatic disease treated with first-line EGFR-TKI therapy. Patients with stage IV EGFR-mutant NSCLC and no more than five metastases within 2 months of diagnosis were identified. All patients were treated with first-line EGFR-TKIs. Consolidative LAT included radiotherapy, surgery or both. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier curves. From October 2010 to May 2016, 145 patients were enrolled, including 51 (35.2%) who received consolidative LAT to all oligometastatic sites (All-LAT group), 55 (37.9%) who received consolidative LAT to either primary tumor or oligometastatic sites (Part-LAT group), and 39 (26.9%) who did not receive any consolidative LAT (Non-LAT group). The median PFS in All-LAT, Part-LAT, and Non-LAT group were 20.6, 15.6, and 13.9 months, respectively (P<0.001). The median OS in All-LAT, Part-LAT, and Non-LAT group were 40.9, 34.1, and 30.8 months, respectively (P<0.001). The difference was statistically significant between All-LAT group and Part-LAT or Non-LAT group but was not between Part-LAT and Non-LAT group. The median OS was significantly improved with consolidative LAT for primary tumor (40.5 versus 31.5 months, P<0.001), brain metastases (38.2 versus 29.2 months, P=0.002), adrenal metastases (37.1 versus 29.2 months, P =0.032). Adverse events (Grade ≥ 3) due to radiotherapy included pneumonitis (7.7%) and esophagitis (16.9%). The current study demonstrated that consolidative LAT to all metastatic sites was a feasible option for patients with EGFR-mutant oligometastatic NSCLC during first-line EGFR-TKI treatment, with significantly improved PFS and OS compared with consolidative LAT to partial sites or observation alone. Copyright © 2018. Published by Elsevier Inc.

Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohkawa, Mayumi; Ohno, Yoshiya; Masuko, Kazue

Highlights: {yields} We established LAT1 amino-acid transporter-disrupted DT40 cells. {yields} LAT1-disrupted cells showed slow growth and lost the oncogenicity. {yields} siRNA and mAb inhibited human tumor growth in vitro and in vivo. {yields} LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1{supmore » -/-}) cell clones, derived from a heterozygous LAT1{sup +/-} clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1{sup -/-} DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1{sup -/-} cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1{sup -/-} DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1{sup -/-} DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1{sup +/-} DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.« less

Involvement of LAT1 and LAT2 in the high- and low-affinity transport of L-leucine in human retinal pigment epithelial cells (ARPE-19 cells).

PubMed

Yamamoto, Atsushi; Akanuma, Shin-Ichi; Tachikawa, Masanori; Hosoya, Ken-Ichi

2010-05-01

System L, which is encoded by LAT1 and LAT2, is an amino acid transport system that transports neutral amino acids, including several essential amino acids in an Na+-independent manner. Due to its broad substrate selectivity, system L has been proposed to mediate the transport of amino-acid-related drugs across the blood-tissue barriers. We characterized L-leucine transport and its corresponding transporter in a human retinal pigment epithelial cell line (ARPE-19 cells) as an in vitro model of the outer blood-retinal barrier. [3H]L-leucine uptake by ARPE-19 cells took place in an Na+-, Cl(-)-independent and saturable manner with K(m) values of 8.71 and 220 microM. This process was more potently cis-inhibited by substrates of LAT1 than those of LAT2. [3H]L-leucine efflux from ARPE-19 cells was trans-stimulated by substrates of LAT1 and LAT2 through the obligatory exchange mechanism of system L. Although RT-PCR analysis demonstrated that LAT1 and LAT2 mRNA are expressed in ARPE-19 cells, the LAT1 mRNA concentration is 42-fold higher than that of LAT2. Moreover, immunoblot analysis demonstrated that LAT1 is expressed in ARPE-19 cells. In conclusion, although the transport function of LAT1 is greater than that of LAT2, LAT1 and LAT2 are involved in L-leucine transport in ARPE-19 cells.

Seven-year Collection of Well-monitored Fermi -LAT Gamma-Ray Burst Afterglows

DOE PAGES

Panaitescu, Alin-Daniel

2017-02-27

Here we present the light curves and spectra of 24 afterglows that have been monitored by Fermi-LAT at 0.1–100 GeV over more than a decade. All light curves (except 130427) are consistent with a single power law starting from their peaks, which occur in most cases before the burst end. The light curves display a brightness–decay rate correlation, with all but one (130427) of the bright afterglows decaying faster than the dimmer afterglows. We attribute this dichotomy to the quick deposition of relativistic ejecta energy in the external shock for the brighter/faster-decaying afterglows and to an extended energy injection inmore » the afterglow shock for the dimmer/slower-decaying light curves. The spectra of six afterglows (090328, 100414, 110721, 110731, 130427, 140619B) indicate the existence of a harder component above a spectral dip or ankle at energies of 0.3–3 GeV, offering evidence for inverse-Compton emission at higher energies and suggesting that the harder power-law spectra of five other LAT afterglows (130327B, 131231, 150523, 150627, 160509) could also be inverse-Compton, while the remaining, softer LAT afterglows should be synchrotron emission. Finally, marginal evidence for a spectral break and softening at higher energies is found for two afterglows (090902B and 090926).« less

Seven-year Collection of Well-monitored Fermi -LAT Gamma-Ray Burst Afterglows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panaitescu, Alin-Daniel

Here we present the light curves and spectra of 24 afterglows that have been monitored by Fermi-LAT at 0.1–100 GeV over more than a decade. All light curves (except 130427) are consistent with a single power law starting from their peaks, which occur in most cases before the burst end. The light curves display a brightness–decay rate correlation, with all but one (130427) of the bright afterglows decaying faster than the dimmer afterglows. We attribute this dichotomy to the quick deposition of relativistic ejecta energy in the external shock for the brighter/faster-decaying afterglows and to an extended energy injection inmore » the afterglow shock for the dimmer/slower-decaying light curves. The spectra of six afterglows (090328, 100414, 110721, 110731, 130427, 140619B) indicate the existence of a harder component above a spectral dip or ankle at energies of 0.3–3 GeV, offering evidence for inverse-Compton emission at higher energies and suggesting that the harder power-law spectra of five other LAT afterglows (130327B, 131231, 150523, 150627, 160509) could also be inverse-Compton, while the remaining, softer LAT afterglows should be synchrotron emission. Finally, marginal evidence for a spectral break and softening at higher energies is found for two afterglows (090902B and 090926).« less

The vela pulsar: results from the first year of FERMI lat observations

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2010-03-18

Here, we report on analysis of timing and spectroscopy of the Vela pulsar using 11 months of observations with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. The intrinsic brightness of Vela at GeV energies combined with the angular resolution and sensitivity of the LAT allows us to make the most detailed study to date of the energy-dependent light curves and phase-resolved spectra, using a LAT-derived timing model. The light curve consists of two peaks (P1 and P2) connected by bridge emission containing a third peak (P3). We have confirmed the strong decrease of the P1/P2 ratiomore » with increasing energy seen with EGRET and previous Fermi LAT data, and observe that P1 disappears above 20 GeV. The increase with energy of the mean phase of the P3 component can be followed with much greater detail, showing that P3 and P2 are present up to the highest energies of pulsation. We find significant pulsed emission at phases outside the main profile, indicating that magnetospheric emission exists over 80% of the pulsar period. With increased high-energy counts the phase-averaged spectrum is seen to depart from a power law with simple exponential cutoff, and is better fit with a more gradual cutoff. The spectra in fixed-count phase bins are well fit with power laws with exponential cutoffs, revealing a strong and complex phase dependence of the cutoff energy, especially in the peaks. Finally, by combining these results with predictions of the outer magnetosphere models that map emission characteristics to phase, it will be possible to probe the particle acceleration and the structure of the pulsar magnetosphere with unprecedented detail.« less

Identification of a novel herpes simplex virus type 1 transcript and protein (AL3) expressed during latency.

PubMed

Jaber, Tareq; Henderson, Gail; Li, Sumin; Perng, Guey-Chuen; Carpenter, Dale; Wechsler, Steven L; Jones, Clinton

2009-10-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected sensory neurons. In small animal models of infection, expression of the first 1.5 kb of LAT coding sequences is necessary and sufficient for wild-type reactivation from latency. The ability of LAT to inhibit apoptosis is important for reactivation from latency. Within the first 1.5 kb of LAT coding sequences and LAT promoter sequences, additional transcripts have been identified. For example, the anti-sense to LAT transcript (AL) is expressed in the opposite direction to LAT from the 5' end of LAT and LAT promoter sequences. In addition, the upstream of LAT (UOL) transcript is expressed in the LAT direction from sequences in the LAT promoter. Further examination of the first 1.5 kb of LAT coding sequences revealed two small ORFs that are anti-sense with respect to LAT (AL2 and AL3). A transcript spanning AL3 was detected in productively infected cells, mouse neuroblastoma cells stably expressing LAT and trigeminal ganglia (TG) of latently infected mice. Peptide-specific IgG directed against AL3 specifically recognized a protein migrating near 15 kDa in cells stably transfected with LAT, mouse neuroblastoma cells transfected with a plasmid containing the AL3 ORF and TG of latently infected mice. The inability to detect the AL3 protein during productive infection may have been because the 5' terminus of the AL3 transcript was downstream of the first in-frame methionine of the AL3 ORF during productive infection.

Fermi's Motion Produces a Study in Spirograph

NASA Image and Video Library

2013-02-27

Final still from Fermi video [bit.ly/Y2K4LN]. Credit: NASA/DOE/Fermi LAT Collaboration ----- NASA's Fermi Gamma-ray Space Telescope orbits our planet every 95 minutes, building up increasingly deeper views of the universe with every circuit. Its wide-eyed Large Area Telescope (LAT) sweeps across the entire sky every three hours, capturing the highest-energy form of light -- gamma rays -- from sources across the universe. These range from supermassive black holes billions of light-years away to intriguing objects in our own galaxy, such as X-ray binaries, supernova remnants and pulsars. Now a Fermi scientist has transformed LAT data of a famous pulsar into a mesmerizing movie that visually encapsulates the spacecraft's complex motion. Click here to continue reading: 1.usa.gov/WhYwCU NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Fermi-LAT kills dark matter interpretations of AMS-02 data. Or not?

NASA Astrophysics Data System (ADS)

Belotsky, Konstantin; Budaev, Ruslan; Kirillov, Alexander; Laletin, Maxim

2017-01-01

A number of papers attempt to explain the positron anomaly in cosmic rays, observed by PAMELA and AMS-02, in terms of dark matter (DM) decays or annihilations. However, the recent progress in cosmic gamma-ray studies challenges these attempts. Indeed, as we show, any rational DM model explaining the positron anomaly abundantly produces final state radiation and Inverse Compton gamma rays, which inevitably leads to a contradiction with Fermi-LAT isotropic diffuse gamma-ray background measurements. Furthermore, the Fermi-LAT observation of Milky Way dwarf satellites, supposed to be rich in DM, revealed no significant signal in gamma rays. We propose a generic approach in which the major contribution to cosmic rays comes from the dark matter disc and prove that the tension between the DM origin of the positron anomaly and the cosmic gamma-ray observations can be relieved. We consider both a simple model, in which DM decay/annihilate into charged leptons, and a model-independent minimal case of particle production, and we estimate the optimal thickness of DM disk. Possible mechanisms of formation and its properties are briefly discussed.

Region of Herpes Simplex Virus Type 1 Latency-Associated Transcript Sufficient for Wild-Type Spontaneous Reactivation Promotes Cell Survival in Tissue Culture

PubMed Central

Inman, Melissa; Perng, Guey-Chuen; Henderson, Gail; Ghiasi, Homayon; Nesburn, Anthony B.; Wechsler, Steven L.; Jones, Clinton

2001-01-01

The latency-associated transcript (LAT) is the only abundant herpes simplex virus type 1 (HSV-1) transcript expressed during latency. In the rabbit eye model, LAT null mutants do not reactivate efficiently from latency. We recently demonstrated that the LAT null mutant dLAT2903 induces increased levels of apoptosis in trigeminal ganglia of infected rabbits compared to LAT+ strains (G.-C. Perng, C. Jones, J. Ciacci-Zarella, M. Stone, G. Henderson, A. Yokht, S. M. Slanina, F. M. Hoffman, H. Ghiasi, A. B. Nesburn, and C. S. Wechsler, Science 287:1500–1503, 2000).The same study also demonstrated that a plasmid expressing LAT nucleotides 301 to 2659 enhanced cell survival of transfected cells after induction of apoptosis. Consequently, we hypothesized that LAT enhances spontaneous reactivation in part, because it promotes survival of infected neurons. Here we report on the ability of plasmids expressing different portions of the 5′ end of LAT to promote cell survival after induction of apoptosis. A plasmid expressing the first 1.5 kb of LAT (LAT nucleotides 1 to 1499) promoted cell survival in neuro-2A (mouse neuronal) and CV-1 (monkey fibroblast) cells. A plasmid expressing just the first 811 nucleotides of LAT promoted cell survival less efficiently. Plasmids expressing the first 661 nucleotides or less of LAT did not promote cell survival. We previously showed that a mutant expressing just the first 1.5 kb of LAT has wild-type spontaneous reactivation in rabbits, and a mutant expressing just the first 811 nucleotides of LAT has a reactivation frequency higher than that of dLAT2903 but lower than that of wild-type virus. In addition, mutants reported here for the first time, expressing just the first 661 or 76 nucleotides of LAT, had spontaneous reactivation indistinguishable from that of the LAT null mutant dLAT2903. In summary, these studies provide evidence that there is a functional relationship between the ability of LAT to promote cell survival and its ability to enhance spontaneous reactivation. PMID:11264353

Why do intimate partners live apart? Evidence on LAT relationships across Europe

PubMed Central

Liefbroer, Aart C.; Poortman, Anne-Rigt; Seltzer, Judith A.

2015-01-01

BACKGROUND Most research asks whether or not cohabitation has come to rival marriage. Little is known about the meaning of living apart together (LAT) relationships, and whether LAT is an alternative to marriage and cohabitation or a dating relationship. OBJECTIVE We examine across Europe: (1) the prevalence of LAT, (2) the reasons for LAT, and (3) the correlates of (a) LAT relationships vis-à-vis being single, married, or cohabiting, and (b) different types of LAT union. METHODS Using Generations and Gender Survey data from ten Western and Eastern European countries, we present descriptive statistics about LATs and estimate multinominal logistic regression models to assess the correlates of being in different types of LAT unions. RESULTS LAT relationships are uncommon, but they are more common in Western than Eastern Europe. Most people in LAT unions intend to live together but are apart for practical reasons. LAT is more common among young people, those enrolled in higher education, people with liberal attitudes, highly educated people, and those who have previously cohabited or been married. Older people and divorced or widowed persons are more likely to choose LAT to maintain independence. Surprisingly, attitudinal and educational differences are more pronounced in Eastern Europe than in Western Europe. CONCLUSIONS A tentative conclusion is that LAT is more often a stage in the union formation process than an alternative to marriage and cohabitation. Yet some groups do view LAT as substituting for marriage and cohabitation, and these groups differ between East and West. In Eastern Europe a cultural, highly educated elite seems to be the first to resist traditional marriage norms and embrace LAT (and cohabitation) as alternative living arrangements, whereas this is less the case in Western Europe. In Western Europe, LAT unions are mainly an alternative for persons who have been married before or had children in a prior relationship. PMID:26085812

Herpes simplex virus latency-associated transcript sequence downstream of the promoter influences type-specific reactivation and viral neurotropism.

PubMed

Bertke, Andrea S; Patel, Amita; Krause, Philip R

2007-06-01

Herpes simplex virus (HSV) establishes latency in sensory nerve ganglia during acute infection and may later periodically reactivate to cause recurrent disease. HSV type 1 (HSV-1) reactivates more efficiently than HSV-2 from trigeminal ganglia while HSV-2 reactivates more efficiently than HSV-1 from lumbosacral dorsal root ganglia (DRG) to cause recurrent orofacial and genital herpes, respectively. In a previous study, a chimeric HSV-2 that expressed the latency-associated transcript (LAT) from HSV-1 reactivated similarly to wild-type HSV-1, suggesting that the LAT influences the type-specific reactivation phenotype of HSV-2. To further define the LAT region essential for type-specific reactivation, we constructed additional chimeric HSV-2 viruses by replacing the HSV-2 LAT promoter (HSV2-LAT-P1) or 2.5 kb of the HSV-2 LAT sequence (HSV2-LAT-S1) with the corresponding regions from HSV-1. HSV2-LAT-S1 was impaired for reactivation in the guinea pig genital model, while its rescuant and HSV2-LAT-P1 reactivated with a wild-type HSV-2 phenotype. Moreover, recurrences of HSV-2-LAT-S1 were frequently fatal, in contrast to the relatively mild recurrences of the other viruses. During recurrences, HSV2-LAT-S1 DNA increased more in the sacral cord compared to its rescuant or HSV-2. Thus, the LAT sequence region, not the LAT promoter region, provides essential elements for type-specific reactivation of HSV-2 and also plays a role in viral neurotropism. HSV-1 DNA, as quantified by real-time PCR, was more abundant in the lumbar spinal cord, while HSV-2 DNA was more abundant in the sacral spinal cord, which may provide insights into the mechanism for type-specific reactivation and different patterns of central nervous system infection of HSV-1 and HSV-2.

Herpes Simplex Virus Latency-Associated Transcript Sequence Downstream of the Promoter Influences Type-Specific Reactivation and Viral Neurotropism▿

PubMed Central

Bertke, Andrea S.; Patel, Amita; Krause, Philip R.

2007-01-01

Herpes simplex virus (HSV) establishes latency in sensory nerve ganglia during acute infection and may later periodically reactivate to cause recurrent disease. HSV type 1 (HSV-1) reactivates more efficiently than HSV-2 from trigeminal ganglia while HSV-2 reactivates more efficiently than HSV-1 from lumbosacral dorsal root ganglia (DRG) to cause recurrent orofacial and genital herpes, respectively. In a previous study, a chimeric HSV-2 that expressed the latency-associated transcript (LAT) from HSV-1 reactivated similarly to wild-type HSV-1, suggesting that the LAT influences the type-specific reactivation phenotype of HSV-2. To further define the LAT region essential for type-specific reactivation, we constructed additional chimeric HSV-2 viruses by replacing the HSV-2 LAT promoter (HSV2-LAT-P1) or 2.5 kb of the HSV-2 LAT sequence (HSV2-LAT-S1) with the corresponding regions from HSV-1. HSV2-LAT-S1 was impaired for reactivation in the guinea pig genital model, while its rescuant and HSV2-LAT-P1 reactivated with a wild-type HSV-2 phenotype. Moreover, recurrences of HSV-2-LAT-S1 were frequently fatal, in contrast to the relatively mild recurrences of the other viruses. During recurrences, HSV2-LAT-S1 DNA increased more in the sacral cord compared to its rescuant or HSV-2. Thus, the LAT sequence region, not the LAT promoter region, provides essential elements for type-specific reactivation of HSV-2 and also plays a role in viral neurotropism. HSV-1 DNA, as quantified by real-time PCR, was more abundant in the lumbar spinal cord, while HSV-2 DNA was more abundant in the sacral spinal cord, which may provide insights into the mechanism for type-specific reactivation and different patterns of central nervous system infection of HSV-1 and HSV-2. PMID:17409161

Orbiter/payload proximity operations SES Postsim report. Lateral approach and other techniques

NASA Technical Reports Server (NTRS)

Olszewski, O.

1978-01-01

Various approach and stationkeeping simulations (proximity operations) were conducted in the Shuttle engineering simulator (SES). This simulator is the first to dynamically include the Orbiter reaction control system (RCS) plume effects on a payload being recovered after rendezvous operations. A procedure for braking, using the simultaneous firing of both jets, was evaluated and found very useful for proximity operations. However this procedure is very inefficient in the RCS usage and requires modifications to the digital autopilot (DAP) software. A new final approach, the lateral approach technique (LAT), or the momentum vector proximity approach, was also evaluated in the simulations. The LAT, which included a tailfirst approach for braking, was evaluated successfully with both inertial and gravity stabilized payloads.

Expression and functional characterisation of System L amino acid transporters in the human term placenta.

PubMed

Gaccioli, Francesca; Aye, Irving L M H; Roos, Sara; Lager, Susanne; Ramirez, Vanessa I; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

2015-06-09

System L transporters LAT1 (SLC7A5) and LAT2 (SLC7A8) mediate the uptake of large, neutral amino acids in the human placenta. Many System L substrates are essential amino acids, thus representing crucial nutrients for the growing fetus. Both LAT isoforms are expressed in the human placenta, but the relative contribution of LAT1 and LAT2 to placental System L transport and their subcellular localisation are not well established. Moreover, the influence of maternal body mass index (BMI) on placental System L amino acid transport is poorly understood. Therefore the aims of this study were to determine: i) the relative contribution of the LAT isoforms to System L transport activity in primary human trophoblast (PHT) cells isolated from term placenta; ii) the subcellular localisation of LAT transporters in human placenta; and iii) placental expression and activity of System L transporters in response to maternal overweight/obesity. System L mediated leucine uptake was measured in PHT cells after treatment with si-RNA targeting LAT1 and/or LAT2. The localisation of LAT isoforms was studied in isolated microvillous plasma membranes (MVM) and basal membranes (BM) by Western blot analysis. Results were confirmed by immunohistochemistry in sections of human term placenta. Expression and activity System L transporters was measured in isolated MVM from women with varying pre-pregnancy BMI. Both LAT1 and LAT2 isoforms contribute to System L transport activity in primary trophoblast cells from human term placenta. LAT1 and LAT2 transporters are highly expressed in the MVM of the syncytiotrophoblast layer at term. LAT2 is also localised in the basal membrane and in endothelial cells lining the fetal capillaries. Measurements in isolated MVM vesicles indicate that System L transporter expression and activity is not influenced by maternal BMI. LAT1 and LAT2 are present and functional in the syncytiotrophoblast MVM, whereas LAT2 is also expressed in the BM and in the fetal capillary endothelium. In contrast to placental System A and beta amino acid transporters, MVM System L activity is unaffected by maternal overweight/obesity.

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors

PubMed Central

Barollo, Susi; Bertazza, Loris; Watutantrige-Fernando, Sara; Censi, Simona; Cavedon, Elisabetta; Galuppini, Francesca; Pennelli, Gianmaria; Fassina, Ambrogio; Citton, Marilisa; Rubin, Beatrice; Pezzani, Raffaele; Benna, Clara; Opocher, Giuseppe; Iacobone, Maurizio; Mian, Caterina

2016-01-01

Background 6-18F-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC). 18F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC. Methods Real-time PCR and Western blot analyses were used to assess LAT1 and LAT2 gene and protein expression in 32 PHEO, 38 MTC, 16 normal adrenal medulla and 15 normal thyroid tissue samples. Immunohistochemistry method was applied to identify the proteins’ subcellular localization. Results LAT1 and LAT2 were overexpressed in both PHEO and MTC by comparison with normal tissues. LAT1 presented a stronger induction than LAT2, and their greater expression was more evident in PHEO (15.1- and 4.1-fold increases, respectively) than in MTC (9.9- and 4.1-fold increases, respectively). Furthermore we found a good correlation between LAT1/2 and GLUT1 expression levels. A positive correlation was also found between urinary noradrenaline and adrenaline levels and LAT1 gene expression in PHEO. The increased expression of LAT1 is also confirmed at the protein level, in both PHEO and MTC, with a strong cytoplasmic localization. Conclusions The present study is the first to provide experimental evidence of the overexpression in some NET cancers (such as PHEO or MTC) of L-type amino acid transporters, and the LAT1 isoform in particular, giving the molecular basis to explain the increase of the DOPA uptake seen in such tumor cells. PMID:27224648

Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan.

PubMed

Kühne, Annett; Kaiser, Rolf; Schirmer, Markus; Heider, Ulrike; Muhlke, Sabine; Niere, Wiebke; Overbeck, Tobias; Hohloch, Karin; Trümper, Lorenz; Sezer, Orhan; Brockmöller, Jürgen

2007-07-01

Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8). Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension. Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5'-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects. The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.

Cellular FLIP can substitute for the herpes simplex virus type 1 latency-associated transcript gene to support a wild-type virus reactivation phenotype in mice

PubMed Central

Jin, Ling; Carpenter, Dale; Moerdyk-Schauwecker, Megan; Vanarsdall, Adam L; Osorio, Nelson; Hsiang, Chinhui; Jones, Clinton; Wechsler, Steven L

2010-01-01

Latency-associated transcript (LAT) deletion mutants of herpes simplex virus type 1 (HSV-1) have reduced reactivation phenotypes. Thus, LAT plays an essential role in the latency-reactivation cycle of HSV-1. We have shown that LAT has antiapoptosis activity and demonstrated that the chimeric virus, dLAT-cpIAP, resulting from replacing LAT with the baculovirus antiapoptosis gene cpIAP, has a wild-type HSV-1 reactivation phenotype in mice and rabbits. Thus, LAT can be replaced by an alternative antiapoptosis gene, confirming that LAT’s antiapoptosis activity plays an important role in the mechanism by which LAT enhances the virus’ reactivation phenotype. However, because cpIAP interferes with both of the major apoptosis pathways, these studies did not address whether LAT’s proreactivation phenotype function was due to blocking the extrinsic (Fas-ligand–, caspase-8–, or caspase-10–dependent pathway) or the intrinsic (mitochondria-, caspase-9–dependent pathway) pathway, or whether both pathways must be blocked. Here we constructed an HSV-1 LAT(−) mutant that expresses cellular FLIP (cellular FLICE-like inhibitory protein) under control of the LAT promoter and in place of LAT nucleotides 76 to 1667. Mice were ocularly infected with this mutant, designated dLAT-FLIP, and the reactivation phenotype was determined using the trigeminal ganglia explant model. dLAT-FLIP had a reactivation phenotype similar to wild-type virus and significantly higher than the LAT(−) mutant dLAT2903. Thus, the LAT function responsible for enhancing the reactivation phenotype could be replaced with an antiapoptosis gene that primarily blocks the extrinsic signaling apoptosis pathway. PMID:18989818

A Herpes Simplex Virus Type 1 Mutant Expressing a Baculovirus Inhibitor of Apoptosis Gene in Place of Latency-Associated Transcript Has a Wild-Type Reactivation Phenotype in the Mouse

PubMed Central

Jin, Ling; Perng, Guey-Chuen; Mott, Kevin R.; Osorio, Nelson; Naito, Julia; Brick, David J.; Carpenter, Dale; Jones, Clinton; Wechsler, Steven L.

2005-01-01

The latency-associated transcript (LAT) is essential for the wild-type herpes simplex virus type 1 (HSV-1) high-reactivation phenotype since LAT− mutants have a low-reactivation phenotype. We previously reported that LAT can decrease apoptosis and proposed that this activity is involved in LAT's ability to enhance the HSV-1 reactivation phenotype. The first 20% of the primary 8.3-kb LAT transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting this proposal. For this study, we constructed an HSV-1 LAT− mutant that expresses the baculovirus antiapoptosis gene product cpIAP under control of the LAT promoter and in place of the LAT region mentioned above. Mice were ocularly infected with this mutant, designated dLAT-cpIAP, and the reactivation phenotype was determined using the trigeminal ganglion explant model. dLAT-cpIAP had a reactivation phenotype similar to that of wild-type virus and significantly higher than that of (i) the LAT− mutant dLAT2903; (ii) dLAT1.5, a control virus containing the same LAT deletion as dLAT-cpIAP, but with no insertion of foreign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (iii) dLAT-EGFP, a control virus identical to dLAT-cpIAP except that it contained the enhanced green fluorescent protein open reading frame (ORF) in place of the cpIAP ORF, thereby controlling for expression of a random foreign gene instead of the cpIAP gene. These results show that an antiapoptosis gene with no sequence similarity to LAT can efficiently substitute for the LAT function involved in enhancing the in vitro-induced HSV-1 reactivation phenotype in the mouse. PMID:16160155

Ski regulates Hippo and TAZ signaling to suppress breast cancer progression

PubMed Central

Rashidian, Juliet; Le Scolan, Erwan; Ji, Xiaodan; Zhu, Qingwei; Mulvihill, Melinda M.; Nomura, Daniel; Luo, Kunxin

2015-01-01

Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor–β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and subsequent degradation of TAZ. Ski also promoted the degradation of a constitutively active TAZ mutant that is not phosphorylated by Lats, suggesting the existence of a Lats2-independent degradation pathway. Finally, we showed that Ski repressed the transcriptional activity of TAZ by binding to the TAZ partner TEAD and recruiting the transcriptional co-repressor NCoR1 to the TEAD-TAZ complex. Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells. PMID:25670202

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, C. J.; Pletsch, H. J.; Wu, J.

Here, we report the discovery and timing measurements of PSR J1208-6238, a young and highly magnetized gamma-ray pulsar, with a spin period of 440 ms. The pulsar was discovered in gamma-ray photon data from the Fermi Large Area Telescope (LAT) during a blind-search survey of unidentified LAT sources, running on the distributed volunteer computing system Einstein@Home. No radio pulsations were detected in dedicated follow-up searches with the Parkes radio telescope, with a flux density upper limit at 1369 MHz of 30 μJy. Furthermore, by timing this pulsar's gamma-ray pulsations, we measure its braking index over five years of LAT observationsmore » to be n = 2.598 ± 0.001 ± 0.1, where the first uncertainty is statistical and the second estimates the bias due to timing noise. Assuming its braking index has been similar since birth, the pulsar has an estimated age of around 2700 years, making it the youngest pulsar to be found in a blind search of gamma-ray data and the youngest known radio-quiet gamma-ray pulsar. Despite its young age, the pulsar is not associated with any known supernova remnant or pulsar wind nebula. The pulsar's inferred dipolar surface magnetic field strength is 3.8 × 10 13 G, almost 90% of the quantum-critical level. Finally, we investigate some potential physical causes of the braking index deviating from the simple dipole model but find that LAT data covering a longer time interval will be necessary to distinguish between these.« less

A speculated ribozyme site in the herpes simplex virus type 1 latency-associated transcript gene is not essential for a wild-type reactivation phenotype

PubMed Central

Carpenter, Dale; Singh, Sukhpreet; Osorio, Nelson; Hsiang, Chinhui; Jiang, Xianzhi; Jin, Ling; Jones, Clinton; Wechsler, Steven L

2010-01-01

During herpes simplex virus-1 (HSV-1) latency in sensory neurons, LAT (latency-associated transcript) is the only abundantly expressed viral gene. LAT plays an important role in the HSV-1 latency-reactivation cycle, because LAT deletion mutants have a significantly decreased reactivation phenotype. Based solely on sequence analysis, it was speculated that LAT encodes a ribozyme that plays an important role in how LAT enhances the virus’ reactivation phenotype. Because LAT ribozyme activity has never been reported, we decided to test the converse hypothesis, namely, that this region of LAT does not encode a ribozyme function important for LAT’s ability to enhance the reactivation phenotype. We constructed a viral mutant (LAT-Rz) in which the speculated ribozyme consensus sequence was altered such that no ribozyme was encoded. We report here that LAT-Rz had a wild-type reactivation phenotype in mice, confirming the hypothesis that the speculated LAT ribozyme is not a dominant factor in stimulating the latency-reactivation cycle in mice. PMID:18982533

50 CFR 660.72 - Latitude/longitude coordinates defining the 50 fm (91 m) through 75 fm (137 m) depth contours.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... lat., 121°32.88′ W. long.; (132) 35°40.38′ N. lat., 121°22.59′ W. long.; (133) 35°27.74′ N. lat., 121.... long.; (133) 36°45.13′ N. lat., 121°57.06′ W. long.; (134) 36°36.86′ N. lat., 122°00.81′ W. long.; (135...) 39°13.76′ N. lat., 123°54.65′ W. long.; (132) 39°05.21′ N. lat., 123°55.38′ W. long.; (133) 38°57.50...

50 CFR 660.72 - Latitude/longitude coordinates defining the 50 fm (91 m) through 75 fm (137 m) depth contours.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... lat., 121°32.88′ W. long.; (132) 35°40.38′ N. lat., 121°22.59′ W. long.; (133) 35°27.74′ N. lat., 121.... long.; (133) 36°45.13′ N. lat., 121°57.06′ W. long.; (134) 36°36.86′ N. lat., 122°00.81′ W. long.; (135...) 39°13.76′ N. lat., 123°54.65′ W. long.; (132) 39°05.21′ N. lat., 123°55.38′ W. long.; (133) 38°57.50...

Monoterpene glycoside ESK246 from Pittosporum targets LAT3 amino acid transport and prostate cancer cell growth.

PubMed

Wang, Qian; Grkovic, Tanja; Font, Josep; Bonham, Sarah; Pouwer, Rebecca H; Bailey, Charles G; Moran, Anne M; Ryan, Renae M; Rasko, John E J; Jormakka, Mika; Quinn, Ronald J; Holst, Jeff

2014-06-20

The L-type amino acid transporter (LAT) family consists of four members (LAT1-4) that mediate uptake of neutral amino acids including leucine. Leucine is not only important as a building block for proteins, but plays a critical role in mTORC1 signaling leading to protein translation. As such, LAT family members are commonly upregulated in cancer in order to fuel increased protein translation and cell growth. To identify potential LAT-specific inhibitors, we established a function-based high-throughput screen using a prefractionated natural product library. We identified and purified two novel monoterpene glycosides, ESK242 and ESK246, sourced from a Queensland collection of the plant Pittosporum venulosum. Using Xenopus laevis oocytes expressing individual LAT family members, we demonstrated that ESK246 preferentially inhibits leucine transport via LAT3, while ESK242 inhibits both LAT1 and LAT3. We further show in LNCaP prostate cancer cells that ESK246 is a potent (IC50 = 8.12 μM) inhibitor of leucine uptake, leading to reduced mTORC1 signaling, cell cycle protein expression and cell proliferation. Our study suggests that ESK246 is a LAT3 inhibitor that can be used to study LAT3 function and upon which new antiprostate cancer therapies may be based.

Development of nanoscale structure in LAT-based signaling complexes

PubMed Central

2016-01-01

ABSTRACT The adapter molecule linker for activation of T cells (LAT) plays a crucial role in forming signaling complexes induced by stimulation of the T cell receptor (TCR). These multi-molecular complexes are dynamic structures that activate highly regulated signaling pathways. Previously, we have demonstrated nanoscale structure in LAT-based complexes where the adapter SLP-76 (also known as LCP2) localizes to the periphery of LAT clusters. In this study, we show that initially LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR engagement. The segregation of LAT and SLP-76 develops near the end of the spreading process. The local concentration of LAT also increases at the same time. Both changes require TCR activation and an intact actin cytoskeleton. These results demonstrate that the nanoscale organization of LAT-based signaling complexes is dynamic and indicates that different kinds of LAT-based complexes appear at different times during T cell activation. PMID:27875277

78 FR 48300 - Establishment of Class E Airspace; Mahnomen, MN

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... E5 Mahnomen, MN [New] Mahnomen County Airport, MN (Lat. 47[deg]15'38'' N., long. 95[deg]55'41'' W... Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes Class E airspace... safety and management of Instrument Flight Rule (IFR) operations at the airport. DATES: Effective date...

Three Herpes Simplex Virus Type 1 Latency-Associated Transcript Mutants with Distinct and Asymmetric Effects on Virulence in Mice Compared with Rabbits

PubMed Central

Perng, Guey-Chuen; Esmaili, Daniel; Slanina, Susan M.; Yukht, Ada; Ghiasi, Homayon; Osorio, Nelson; Mott, Kevin R.; Maguen, Barak; Jin, Ling; Nesburn, Anthony B.; Wechsler, Steven L.

2001-01-01

Herpes simplex virus type 1 latency-associated transcript (LAT)-null mutants have decreased reactivation but normal virulence in rabbits and mice. We report here on dLAT1.5, a mutant with LAT nucleotides 76 to 1667 deleted. Following ocular infection of rabbits, dLAT1.5 reactivated at a lower rate than its wild-type parent McKrae (6.1 versus 11.8%; P = 0.0025 [chi-square test]). Reactivation was restored in the marker-rescued virus dLAT1.5R (12.6%; P = 0.53 versus wild type), confirming the importance of the deleted region in spontaneous reactivation. Compared with wild-type or marker-rescued virus, dLAT1.5 had similar or slightly reduced virulence in rabbits (based on survival following ocular infection). In contrast, in mice, dLAT1.5 had increased virulence (P < 0.0001). Thus, deletion of LAT nucleotides 76 to 1667 increased viral virulence in mice but not in rabbits. In contrast, we also report here that LAT2.9A, a LAT mutant that we previously reported to have increased virulence in rabbits (G. C. Perng, S. M. Slanina, A. Yuhkt, B. S. Drolet, W. J. Keleher, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 73:920–929, 1999), had decreased virulence in mice (P = 0.03). In addition, we also found that dLAT371, a LAT mutant that we previously reported to have wild-type virulence in rabbits (G. C. Perng, S. M. Slanina, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 70:2014–2018, 1996), had decreased virulence in mice (P < 0.05). Thus, these three mutants, each of which encodes a different LAT RNA, have different virulence phenotypes. dLAT1.5 had wild-type virulence in rabbits but increased virulence in mice. In contrast, LAT2.9A had increased virulence in rabbits but decreased virulence in mice, and dLAT371 had wild-type virulence in rabbits but decreased virulence in mice. Taken together, these results suggest that (i) the 5′ end of LAT and/or a gene that overlaps part of this region is involved in viral virulence, (ii) this virulence appears to have species-specific effects, and (iii) regulation of this virulence may be complex. PMID:11533165

Activated PLC-γ1 is Catalytically Induced at LAT but Activated PLC-γ1 is Localized at both LAT- and TCR-Containing Complexes

PubMed Central

Cruz-Orcutt, Noemi; Vacaflores, Aldo; Connolly, Sean F.; Bunnell, Stephen C.; Houtman, Jon C.D.

2014-01-01

Phospholipase C-γ1 (PLC-γ1) is a key regulator of T cell receptor (TCR)-induced signaling. Activation of the TCR enhances PLC-γ1 enzymatic function, resulting in calcium influx and the activation of PKC family members and RasGRP. The current model is that phosphorylation of LAT tyrosine 132 facilitates the recruitment of PLC-γ1, leading to its activation and function at the LAT complex. In this study, we examined the phosphorylation kinetics of LAT and PLC-γ1 and the cellular localization of activated PLC-γ1. We observed that commencement of the phosphorylation of LAT tyrosine 132 and PLC-γ1 tyrosine 783 occurred simultaneously, supporting the current model. However, once begun, PLC-γ1 activation occurred more rapidly than LAT tyrosine 132. The association of LAT and PLC-γ1 was more transient than the interaction of LAT and Grb2 and a pool of activated PLC-γ1 translocated away from LAT to cellular structures containing the TCR. These studies demonstrate that LAT and PLC-γ1 form transient interactions that catalyze the activation of PLC-γ1, but that activated PLC-γ1 resides in both LAT and TCR clusters. Together, this work highlights that our current model is incomplete and the activation and function of PLC-γ1 in T cells is highly complex. PMID:24412752

The Fermi Large Area Telescope: Optimizing and Then Re-Optimizing the Science Return

NASA Astrophysics Data System (ADS)

Atwood, W. B.

2012-01-01

The general concepts of how to do gamma-ray observations in space were well established and vetted by the early 1990's. In particular, the success of EGRET onboard the Compton Gamma Ray Observatory whetted the appetite for a more ambitious follow on. In parallel, advances in high-energy particle detection, spurred on by plans for the Superconducting Super Collider, provided an unprecedented opportunity for space-based detectors. The GLAST concept, now Fermi-LAT, was born at SLAC in May of 1992 and the instrument was subsequently developed by an international collaboration from France, Italy, Japan, Sweden and the United States. An overview of the original design optimization of the LAT instrument, done with the goal of imposing as few limits as possible on its applications in space, is discussed (along with some of the trials and tribulations of construction along the way to launch!). Now with over 3 years of science operations experience, the lessons-learned will be reviewed and assessed against the expectations. Finally, the ongoing re-optimization of the instrument and plans for how to extend the LAT's science window into the future are discussed.

Fermi-LAT kills dark matter interpretations of AMS-02 data. Or not?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belotsky, Konstantin; Budaev, Ruslan; Kirillov, Alexander

2017-01-01

A number of papers attempt to explain the positron anomaly in cosmic rays, observed by PAMELA and AMS-02, in terms of dark matter (DM) decays or annihilations. However, the recent progress in cosmic gamma-ray studies challenges these attempts. Indeed, as we show, any rational DM model explaining the positron anomaly abundantly produces final state radiation and Inverse Compton gamma rays, which inevitably leads to a contradiction with Fermi-LAT isotropic diffuse gamma-ray background measurements. Furthermore, the Fermi-LAT observation of Milky Way dwarf satellites, supposed to be rich in DM, revealed no significant signal in gamma rays. We propose a generic approachmore » in which the major contribution to cosmic rays comes from the dark matter disc and prove that the tension between the DM origin of the positron anomaly and the cosmic gamma-ray observations can be relieved. We consider both a simple model, in which DM decay/annihilate into charged leptons, and a model-independent minimal case of particle production, and we estimate the optimal thickness of DM disk. Possible mechanisms of formation and its properties are briefly discussed.« less

Diffuse γ-ray emission from misaligned active galactic nuclei

DOE PAGES

Di Mauro, M.; Calore, F.; Donato, F.; ...

2013-12-20

Active galactic nuclei (AGNs) with jets seen at small viewing angles are the most luminous and abundant objects in the γ-ray sky. AGNs with jets misaligned along the line of sight appear fainter in the sky but are more numerous than the brighter blazars. Here, we calculate the diffuse γ-ray emission due to the population of misaligned AGNs (MAGNs) unresolved by the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope (Fermi). Furthermore, a correlation between the γ-ray luminosity and the radio-core luminosity is established and demonstrated to be physical by statistical tests, as well as compatible with uppermore » limits based on Fermi-LAT data for a large sample of radio-loud MAGNs. We constrain the derived γ-ray luminosity function by means of the source-count distribution of the radio galaxies detected by the Fermi-LAT. We finally calculate the diffuse γ-ray flux due to the whole MAGN population. These results demonstrate that MAGNs can contribute from 10% up to nearly the entire measured isotropic gamma-ray background. We evaluate a theoretical uncertainty on the flux of almost an order of magnitude.« less

Identification and expression analyses of two genes encoding putative low-affinity nitrate transporters from Nicotiana plumbaginifolia.

PubMed

Fraisier, V; Dorbe, M F; Daniel-Vedele, F

2001-01-01

Higher plants have both high- and low-affinity nitrate uptake systems (HATS and LATS respectively). Here we report the isolation and characterization of two genes, NpNRT1.1 and NpNRT1.2, from Nicotiana plumbaginifolia whose structural features suggest that they both belong to the NRT1 gene family, which is involved in the LATS. Amino acid sequence alignment showed that the N. plumbaginifolia proteins have greater similarity to their corresponding tomato homologues than to each other. Genomic Southern blot analysis indicates that there are probably more than two members of this family in N. plumbaginifolia. Northern blot analysis shows that NpNRT1.2 expression is restricted strictly to roots, whereas NpNRT1.1, in addition to roots, is expressed at a basal level in all other plant organs. Likewise, differential expression in response to external treatments with various N sources was observed for these two genes: NpNRT1.1 can be considered as a constitutively expressed gene whereas NpNRT1.2 expression is dependent strictly on high nitrate concentrations. Finally, over-expression of a gene involved in the HATS does not lead to any modification of LATS gene expression.

50 CFR 660.73 - Latitude/longitude coordinates defining the 100 fm (183 m) through 150 fm (274 m) depth contours.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... lat., 125°37.25′ W. long.; (7) 48°02.60′ N. lat., 125°34.70′ W. long.; (8) 47°59.00′ N. lat., 125°34....; (309) 32°59.28′ N. lat., 117°19.69′ W. long.; (310) 32°55.36′ N. lat., 117°19.54′ W. long.; (311) 32°53.... long.; (6) 32°47.53′ N. lat., 118°21.76′ W. long.; (7) 32°44.03′ N. lat., 118°24.70′ W. long.; (8) 32...

50 CFR 660.71 - Latitude/longitude coordinates defining the 10-fm (18-m) through 40-fm (73-m) depth contours.

Code of Federal Regulations, 2013 CFR

2013-10-01

...°12.80′ N. lat., 124°43.10′ W. long.; (8) 48°11.10′ N. lat., 124°46.50′ W. long.; (9) 48°10.00′ N. lat...., 124°49.30′ W. long.; (7) 47°37.60′ N. lat., 124°34.30′ W. long.; (8) 47°31.70′ N. lat., 124°32.40′ W.... long.; (7) 46°16.00′ N. lat., 124°12.50′ W. long.; (8) 46°15.99′ N. lat., 124°12.04′ W. long.; (9) 46...

50 CFR 660.71 - Latitude/longitude coordinates defining the 10-fm (18-m) through 40-fm (73-m) depth contours.

Code of Federal Regulations, 2014 CFR

2014-10-01

...°12.80′ N. lat., 124°43.10′ W. long.; (8) 48°11.10′ N. lat., 124°46.50′ W. long.; (9) 48°10.00′ N. lat...., 124°49.30′ W. long.; (7) 47°37.60′ N. lat., 124°34.30′ W. long.; (8) 47°31.70′ N. lat., 124°32.40′ W.... long.; (7) 46°16.00′ N. lat., 124°12.50′ W. long.; (8) 46°15.99′ N. lat., 124°12.04′ W. long.; (9) 46...

50 CFR 660.71 - Latitude/longitude coordinates defining the 10-fm (18-m) through 40-fm (73-m) depth contours.

Code of Federal Regulations, 2012 CFR

2012-10-01

...°12.80′ N. lat., 124°43.10′ W. long.; (8) 48°11.10′ N. lat., 124°46.50′ W. long.; (9) 48°10.00′ N. lat...., 124°49.30′ W. long.; (7) 47°37.60′ N. lat., 124°34.30′ W. long.; (8) 47°31.70′ N. lat., 124°32.40′ W.... long.; (7) 46°16.00′ N. lat., 124°12.50′ W. long.; (8) 46°15.99′ N. lat., 124°12.04′ W. long.; (9) 46...

50 CFR 660.73 - Latitude/longitude coordinates defining the 100 fm (183 m) through 150 fm (274 m) depth contours.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... lat., 125°37.25′ W. long.; (7) 48°02.60′ N. lat., 125°34.70′ W. long.; (8) 47°59.00′ N. lat., 125°34....; (309) 32°59.28′ N. lat., 117°19.69′ W. long.; (310) 32°55.36′ N. lat., 117°19.54′ W. long.; (311) 32°53.... long.; (6) 32°47.53′ N. lat., 118°21.76′ W. long.; (7) 32°44.03′ N. lat., 118°24.70′ W. long.; (8) 32...

50 CFR 660.73 - Latitude/longitude coordinates defining the 100 fm (183 m) through 150 fm (274 m) depth contours.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... lat., 125°37.25′ W. long.; (7) 48°02.60′ N. lat., 125°34.70′ W. long.; (8) 47°59.00′ N. lat., 125°34....; (309) 32°59.28′ N. lat., 117°19.69′ W. long.; (310) 32°55.36′ N. lat., 117°19.54′ W. long.; (311) 32°53.... long.; (6) 32°47.53′ N. lat., 118°21.76′ W. long.; (7) 32°44.03′ N. lat., 118°24.70′ W. long.; (8) 32...

l-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma1

PubMed Central

Lin, Jules; Raoof, Duna A; Thomas, Dafydd G; Greenson, Joel K; Giordano, Thomas J; Robinson, Gregory S; Bourner, Maureen J; Bauer, Christopher T; Orringer, Mark B; Beer, David G

2004-01-01

Abstract The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P < .001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P < .05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P < .001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1. PMID:15068672

Monoterpene Glycoside ESK246 from Pittosporum Targets LAT3 Amino Acid Transport and Prostate Cancer Cell Growth

PubMed Central

2014-01-01

The l-type amino acid transporter (LAT) family consists of four members (LAT1–4) that mediate uptake of neutral amino acids including leucine. Leucine is not only important as a building block for proteins, but plays a critical role in mTORC1 signaling leading to protein translation. As such, LAT family members are commonly upregulated in cancer in order to fuel increased protein translation and cell growth. To identify potential LAT-specific inhibitors, we established a function-based high-throughput screen using a prefractionated natural product library. We identified and purified two novel monoterpene glycosides, ESK242 and ESK246, sourced from a Queensland collection of the plant Pittosporum venulosum. Using Xenopus laevis oocytes expressing individual LAT family members, we demonstrated that ESK246 preferentially inhibits leucine transport via LAT3, while ESK242 inhibits both LAT1 and LAT3. We further show in LNCaP prostate cancer cells that ESK246 is a potent (IC50 = 8.12 μM) inhibitor of leucine uptake, leading to reduced mTORC1 signaling, cell cycle protein expression and cell proliferation. Our study suggests that ESK246 is a LAT3 inhibitor that can be used to study LAT3 function and upon which new antiprostate cancer therapies may be based. PMID:24762008

Limited-angle tomography for analyzer-based phase-contrast X-ray imaging

PubMed Central

Majidi, Keivan; Wernick, Miles N; Li, Jun; Muehleman, Carol; Brankov, Jovan G

2014-01-01

Multiple-Image Radiography (MIR) is an analyzer-based phase-contrast X-ray imaging method (ABI), which is emerging as a potential alternative to conventional radiography. MIR simultaneously generates three planar parametric images containing information about scattering, refraction and attenuation properties of the object. The MIR planar images are linear tomographic projections of the corresponding object properties, which allows reconstruction of volumetric images using computed tomography (CT) methods. However, when acquiring a full range of linear projections around the tissue of interest is not feasible or the scanning time is limited, limited-angle tomography techniques can be used to reconstruct these volumetric images near the central plane, which is the plane that contains the pivot point of the tomographic movement. In this work, we use computer simulations to explore the applicability of limited-angle tomography to MIR. We also investigate the accuracy of reconstructions as a function of number of tomographic angles for a fixed total radiation exposure. We use this function to find an optimal range of angles over which data should be acquired for limited-angle tomography MIR (LAT-MIR). Next, we apply the LAT-MIR technique to experimentally acquired MIR projections obtained in a cadaveric human thumb study. We compare the reconstructed slices near the central plane to the same slices reconstructed by CT-MIR using the full angular view around the object. Finally, we perform a task-based evaluation of LAT-MIR performance for different numbers of angular views, and use template matching to detect cartilage in the refraction image near the central plane. We use the signal-to-noise ratio of this test as the detectability metric to investigate an optimum range of tomographic angles for detecting soft tissues in LAT-MIR. Both results show that there is an optimum range of angular view for data acquisition where LAT-MIR yields the best performance, comparable to CT-MIR only if one considers volumetric images near the central plane and not the whole volume. PMID:24898008

Limited-angle tomography for analyzer-based phase-contrast x-ray imaging

NASA Astrophysics Data System (ADS)

Majidi, Keivan; Wernick, Miles N.; Li, Jun; Muehleman, Carol; Brankov, Jovan G.

2014-07-01

Multiple-image radiography (MIR) is an analyzer-based phase-contrast x-ray imaging method, which is emerging as a potential alternative to conventional radiography. MIR simultaneously generates three planar parametric images containing information about scattering, refraction and attenuation properties of the object. The MIR planar images are linear tomographic projections of the corresponding object properties, which allows reconstruction of volumetric images using computed tomography (CT) methods. However, when acquiring a full range of linear projections around the tissue of interest is not feasible or the scanning time is limited, limited-angle tomography techniques can be used to reconstruct these volumetric images near the central plane, which is the plane that contains the pivot point of the tomographic movement. In this work, we use computer simulations to explore the applicability of limited-angle tomography to MIR. We also investigate the accuracy of reconstructions as a function of number of tomographic angles for a fixed total radiation exposure. We use this function to find an optimal range of angles over which data should be acquired for limited-angle tomography MIR (LAT-MIR). Next, we apply the LAT-MIR technique to experimentally acquired MIR projections obtained in a cadaveric human thumb study. We compare the reconstructed slices near the central plane to the same slices reconstructed by CT-MIR using the full angular view around the object. Finally, we perform a task-based evaluation of LAT-MIR performance for different numbers of angular views, and use template matching to detect cartilage in the refraction image near the central plane. We use the signal-to-noise ratio of this test as the detectability metric to investigate an optimum range of tomographic angles for detecting soft tissues in LAT-MIR. Both results show that there is an optimum range of angular view for data acquisition where LAT-MIR yields the best performance, comparable to CT-MIR only if one considers volumetric images near the central plane and not the whole volume.

The Herpes Simplex Virus Type 1 Latency-Associated Transcript Inhibits Phenotypic and Functional Maturation of Dendritic Cells

PubMed Central

Dervillez, Xavier; Dasgupta, Gargi; Nguyen, Chelsea; Kabbara, Khaled W.; Jiang, Xianzhi; Nesburn, Anthony B.; Wechsler, Steven L.

2012-01-01

Abstract We recently found that the herpes simplex virus-1 (HSV-1) latency-associated transcript (LAT) results in exhaustion of virus-specific CD8+ T cells in latently-infected trigeminal ganglia (TG). In this study we sought to determine if this impairment may involve LAT directly and/or indirectly interfering with DC maturation. We found that a small number of HSV-1 antigen-positive DCs are present in the TG of latently-infected CD11c/eYFP mice; however, this does not imply that these DCs are acutely or latently infected. Some CD8+ T cells are adjacent to DCs, suggesting possible interactions. It has previously been shown that wild-type HSV-1 interferes with DC maturation. Here we show for the first time that this is associated with LAT expression, since compared to LAT(−) virus: (1) LAT(+) virus interfered with expression of MHC class I and the co-stimulatory molecules CD80 and CD86 on the surface of DCs; (2) LAT(+) virus impaired DC production of the proinflammatory cytokines IL-6, IL-12, and TNF-α; and (3) DCs infected in vitro with LAT(+) virus had significantly reduced the ability to stimulate HSV-specific CD8+ T cells. While a similar number of DCs was found in LAT(+) and LAT(−) latently-infected TG of CD11c/eYFP transgenic mice, more HSV-1 Ag-positive DCs and more exhausted CD8 T cells were seen with LAT(+) virus. Consistent with these findings, HSV-specific cytotoxic CD8+ T cells in the TG of mice latently-infected with LAT(+) virus produced less IFN-γ and TNF-α than those from TG of LAT(−)-infected mice. Together, these results suggest a novel immune-evasion mechanism whereby the HSV-1 LAT increases the number of HSV-1 Ag-positive DCs in latently-infected TG, and interferes with DC phenotypic and functional maturation. The effect of LAT on TG-resident DCs may contribute to the reduced function of HSV-specific CD8+ T cells in the TG of mice latently infected with LAT(+) virus. PMID:22512280

Identification of two small RNAs within the first 1.5-kb of the herpes simplex virus type 1-encoded latency-associated transcript.

PubMed

Peng, Weiping; Vitvitskaia, Olga; Carpenter, Dale; Wechsler, Steven L; Jones, Clinton

2008-01-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected neurons. In the rabbit or mouse ocular models of infection, expression of the first 1.5 kb of LAT coding sequences is sufficient for and necessary for wild-type levels of spontaneous reactivation from latency. The antiapoptosis functions of LAT, which maps to the same 1.5 kb of LAT, are important for the latency-reactivation cycle because replacement of LAT with other antiapoptosis genes (the baculovirus IAP gene or the bovine herpesvirus type 1 latency-related gene) restores wild-type levels of reactivation to a LAT null mutant. A recent study identified a micro-RNA within LAT that can inhibit apoptosis (Gupta et al, Nature 442: 82-85). In this study, the authors analyzed the first 1.5 kb of LAT for additional small RNAs that may have regulatory functions. Two LAT-specific small RNAs were detected in productively infected human neuroblastoma cells within the first 1.5 kb of LAT, in a region that is important for inhibiting apoptosis. Although these small RNAs possess extensive secondary structure and a stem-loop structure, bands migrating near 23 bases were not detected suggesting these small RNAs are not true micro-RNAs. Both of the small LAT-specific RNAs have the potential to base pair with the ICP4 mRNA. These two small LAT RNAs may play a role in the latency-reactivation cycle by reducing apoptosis and/or by reducing ICP4 RNA expression.

Herpes Simplex Virus 2 Latency-Associated Transcript (LAT) region mutations do not identify a role for LAT-Associated Micro RNAs in viral reactivation in the Guinea Pig Genital Model.

PubMed

Kawamura, Yoshiki; Bosch-Marce, Marta; Tang, Shuang; Patel, Amita; Krause, Philip R

2018-05-02

Despite the long-standing observation that herpes simplex virus (HSV) Latency-Associated Transcript (LAT) promoter-deletion viruses show impaired recurrence phenotypes in relevant animal models, the mechanism by which these sequences exert this phenotypic effect is unknown. We constructed and evaluated four mutant HSV-2 viruses with targeted mutations in the LAT promoter and LAT-associated miRNAs affecting (1) the LAT TATA box, (2) the LAT ICP4-binding site, (3) miR-I and miR-II (miR-I/II), which both target ICP34.5, and (4) miR-III, which targets ICP0. While the LAT-TATA box mutant caused milder acute infections than wild-type (WT), there was no difference in recurrence phenotype between these viruses. LAT and miRNA expression during latency were not impaired by this mutation, suggesting that other promoter elements may be more important for latent HSV-2 LAT expression. Mutation of the LAT ICP4-binding site also did not cause an in vivo phenotypic difference between mutant and WT viruses. Acute infection and reactivation from latency of the miR-I/II mutant was similar to that of its rescuant, although slightly reduced in severity relative to the wild-type virus. The miR-III mutant also exhibited WT phenotypes in acute and recurrent phases of infection. While not ruling out an effect of these elements in human latency or reactivation, these findings do not identify a specific role for LAT or LAT-associated miRNAs in the HSV-2 LAT promoter deletion phenotype in guinea pigs. Thus, other sequences in this region may play a more important role in the long-studied LAT-associated phenotype in animals. IMPORTANCE While it has been known for several decades that specific HSV-1 and HSV-2 sequences near the LAT promoter are required for efficient viral reactivation in animal models, the mechanism is still not known. We constructed four mutant viruses with the goal of identifying critical sequence elements and of specifically testing the hypothesis that microRNAs that are expressed during latency play a role. Determination that specific LAT promoter sequences and miRNA sequences do not influence viral reactivation of HSV-2 helps to narrow down the search for the mechanism by which the virus controls its latency and recurrence phenotype. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

The braking index of a radio-quiet gamma-ray pulsar

DOE PAGES

Clark, C. J.; Pletsch, H. J.; Wu, J.; ...

2016-11-16

Here, we report the discovery and timing measurements of PSR J1208-6238, a young and highly magnetized gamma-ray pulsar, with a spin period of 440 ms. The pulsar was discovered in gamma-ray photon data from the Fermi Large Area Telescope (LAT) during a blind-search survey of unidentified LAT sources, running on the distributed volunteer computing system Einstein@Home. No radio pulsations were detected in dedicated follow-up searches with the Parkes radio telescope, with a flux density upper limit at 1369 MHz of 30 μJy. Furthermore, by timing this pulsar's gamma-ray pulsations, we measure its braking index over five years of LAT observationsmore » to be n = 2.598 ± 0.001 ± 0.1, where the first uncertainty is statistical and the second estimates the bias due to timing noise. Assuming its braking index has been similar since birth, the pulsar has an estimated age of around 2700 years, making it the youngest pulsar to be found in a blind search of gamma-ray data and the youngest known radio-quiet gamma-ray pulsar. Despite its young age, the pulsar is not associated with any known supernova remnant or pulsar wind nebula. The pulsar's inferred dipolar surface magnetic field strength is 3.8 × 10 13 G, almost 90% of the quantum-critical level. Finally, we investigate some potential physical causes of the braking index deviating from the simple dipole model but find that LAT data covering a longer time interval will be necessary to distinguish between these.« less

Coregulatory Interactions among CD8α Dendritic Cells, the Latency-Associated Transcript, and Programmed Death 1 Contribute to Higher Levels of Herpes Simplex Virus 1 Latency

PubMed Central

Mott, Kevin R.; Allen, Sariah J.; Zandian, Mandana

2014-01-01

ABSTRACT The latency-associated transcript (LAT) of herpes simplex virus 1 (HSV-1), CD8α+ dendritic cells (DCs), and programmed death 1 (PD-1) have all been implicated in the HSV-1 latency-reactivation cycle. It is not known, however, whether an interaction between LAT and CD8α+ DCs regulates latency and T-cell exhaustion. To address this question, we used LAT-expressing [LAT(+)] and LAT-negative [LAT(−)] viruses. Depletion of DCs in mice ocularly infected with LAT(+) virus resulted in a reduction in the number of T cells expressing PD-1 in the trigeminal ganglia (TG), whereas depletion of DCs in mice similarly infected with LAT(−) virus did not alter PD-1 expression. CD8α+ DCs, but not CD4+ DCs, infected with LAT(+) virus had higher levels of ICP0, ICP4, thymidine kinase (TK), and PD-1 ligand 1 (PD-L1) transcripts than those infected with LAT(−) virus. Coculture of infected bone marrow (BM)-derived DCs from wild-type (WT) mice, but not infected DCs from CD8α−/− mice, with WT naive T cells contributed to an increase in PD-1 expression. Transfer of bone marrow from WT mice but not CD8α−/− mice to recipient Rag1−/− mice increased the number of latent viral genomes in reconstituted mice infected with the LAT(+) virus. Collectively, these data indicated that a reduction in latency correlated with a decline in the levels of CD8α+ DCs and PD-1 expression. In summary, our results demonstrate an interaction among LAT, PD-1, and CD11c CD8α+ cells that regulates latency in the TG of HSV-1-infected mice. IMPORTANCE Very little is known regarding the interrelationship of LAT, PD-1, and CD8α+ DCs and how such interactions might contribute to relative numbers of latent viral genomes. We show here that (i) in both in vivo and in vitro studies, deficiency of CD8α+ DCs significantly reduced T-cell exhaustion in the presence of LAT(+) virus but not LAT(−) virus; (ii) HSV-1 infectivity was significantly lower in LAT(−)-infected DCs than in their LAT(+)-infected counterparts; and (iii) adoptive transfer of bone marrow (BM) from WT but not CD8α−/− mice to recipient Rag1−/− mice restored latency to the level in WT mice following infection with LAT(+) virus. These studies point to a key role for CD8α+ DCs in T-cell exhaustion in the presence of LAT, which leads to larger numbers of latent viral genomes. Thus, altering this negative function of CD8α+ DCs can potentially be used to generate a more effective vaccine against HSV infection. PMID:24672046

Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast

PubMed Central

Cleal, J K; Glazier, J D; Ntani, G; Crozier, S R; Day, P E; Harvey, N C; Robinson, S M; Cooper, C; Godfrey, K M; Hanson, M A; Lewis, R M

2011-01-01

Fetal growth depends on placental transfer of amino acids from maternal to fetal blood. The mechanisms of net amino acid efflux across the basal membrane (BM) of the placental syncytiotrophoblast to the fetus, although vital for amino acid transport, are poorly understood. We examined the hypothesis that facilitated diffusion by the amino acid transporters TAT1, LAT3 and LAT4 plays an important role in this process, with possible effects on fetal growth. Amino acid transfer was measured in isolated perfused human placental cotyledons (n= 5 per experiment) using techniques which distinguish between different transport processes. Placental TAT1, LAT3 and LAT4 proteins were measured, and mRNA expression levels (measured using real-time quantitative-PCR) were related to fetal and neonatal anthropometry and dual-energy X-ray absorptiometry measurements of neonatal lean mass in 102 Southampton Women's Survey (SWS) infants. Under conditions preventing transport by amino acid exchangers, all amino acids appearing in the fetal circulation were substrates of TAT1, LAT3 or LAT4. Western blots demonstrated the presence of TAT1, LAT3 and LAT4 in placental BM preparations. Placental TAT1 and LAT3 mRNA expression were positively associated with measures of fetal growth in SWS infants (P < 0.05). We provide evidence that the efflux transporters TAT1, LAT3 and LAT4 are present in the human placental BM, and may play an important role in the net efflux of amino acids to the fetus. Unlike other transporters they can increase fetal amino acid concentrations. Consistent with a role in placental amino acid transfer capacity and fetal growth TAT1 and LAT3 mRNA expression showed positive associations with infant size at birth. PMID:21224231

77 FR 43181 - Proposed Establishment of Class E Airspace; Coaldale, NV

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... airspace extending upward from 1,200 feet above the surface bounded by a line beginning at lat. 38[deg]55... lat. 38[deg]16'55'' N., long. 118[deg]13'39'' W.; to lat. 38[deg]02'23'' N., long. 117[deg]56'00'' W.... 117[deg]54'28'' W.; to lat. 37[deg]55'00'' N., long. 118[deg]10'30'' W.; to lat. 38[deg]04'06'' N...

New Gener. High-Energy Spectra of the Blazar 3C 279 with XMM-Newton and GLAST

NASA Astrophysics Data System (ADS)

Collmar, Werner

2007-10-01

We propose two 20 ksec XMM-Newton observations of the X-ray bright gamma-ray blazar 3C~279 simultaneous with GLAST/LAT. The main goal is to measure its X-ray properties (spectrum, variability) in order to (1) improve our knowledge on the X-ray emission of the blazar, and (2) to supplement and correlate them to simultaneous GLAST/LAT Gamma-ray observations (30 MeV-300 GeV). Simultaneous GLAST observations of 3C 279 are guaranteed (assuming proper operation then). The high-energy data will be supplemented by ground-based measurements, adding finally up to multifrequency spectra which have unprecedented accuracy and will extend up to high-energy gamma-rays. Such high-quality SEDs will provide severe constraints on their modeling and have the potential to discriminate among models.

Cooperation of Antiporter LAT2/CD98hc with Uniporter TAT1 for Renal Reabsorption of Neutral Amino Acids.

PubMed

Vilches, Clara; Boiadjieva-Knöpfel, Emilia; Bodoy, Susanna; Camargo, Simone; López de Heredia, Miguel; Prat, Esther; Ormazabal, Aida; Artuch, Rafael; Zorzano, Antonio; Verrey, François; Nunes, Virginia; Palacín, Manuel

2018-04-02

Background Reabsorption of amino acids (AAs) across the renal proximal tubule is crucial for intracellular and whole organism AA homeostasis. Although the luminal transport step is well understood, with several diseases caused by dysregulation of this process, the basolateral transport step is not understood. In humans, only cationic aminoaciduria due to malfunction of the basolateral transporter y + LAT1/CD98hc (SLC7A7/SLC3A2), which mediates the export of cationic AAs, has been described. Thus, the physiologic roles of basolateral transporters of neutral AAs, such as the antiporter LAT2/CD98hc (SLC7A8/SLC3A2), a heterodimer that exports most neutral AAs, and the uniporter TAT1 (SLC16A10), which exports only aromatic AAs, remain unclear. Functional cooperation between TAT1 and LAT2/CD98hc has been suggested by in vitro studies but has not been evaluated in vivo Methods To study the functional relationship of TAT1 and LAT2/CD98hc in vivo , we generated a double-knockout mouse model lacking TAT1 and LAT2, the catalytic subunit of LAT2/CD98hc (dKO LAT2-TAT1 mice). Results Compared with mice lacking only TAT1 or LAT2, dKO LAT2-TAT1 mice lost larger amounts of aromatic and other neutral AAs in their urine due to a tubular reabsorption defect. Notably, dKO mice also displayed decreased tubular reabsorption of cationic AAs and increased expression of y + LAT1/CD98hc. Conclusions The LAT2/CD98hc and TAT1 transporters functionally cooperate in vivo , and y + LAT1/CD98hc may compensate for the loss of LAT2/CD98hc and TAT1, functioning as a neutral AA exporter at the expense of some urinary loss of cationic AAs. Cooperative and compensatory mechanisms of AA transporters may explain the lack of basolateral neutral aminoacidurias in humans. Copyright © 2018 by the American Society of Nephrology.

Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.

PubMed

Segawa, H; Fukasawa, Y; Miyamoto, K; Takeda, E; Endou, H; Kanai, Y

1999-07-09

We have isolated a cDNA from rat small intestine that encodes a novel Na+-independent neutral amino acid transporter with distinctive characteristics in substrate selectivity and transport property. The encoded protein, designated L-type amino acid transporter-2 (LAT-2), shows amino acid sequence similarity to the system L Na+-independent neutral amino acid transporter LAT-1 (Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) J. Biol. Chem. 273, 23629-23632) (50% identity) and the system y+L transporters y+LAT-1 (47%) and KIAA0245/y+LAT-2 (45%) (Torrents, D., Estevez, R., Pineda, M., Fernandez, E., Lloberas, J., Shi, Y.-B., Zorzano, A., and Palacin, M. (1998) J. Biol. Chem. 273, 32437-32445). LAT-2 is a nonglycosylated membrane protein. It requires 4F2 heavy chain, a type II membrane glycoprotein, for its functional expression in Xenopus oocytes. LAT-2-mediated transport is not dependent on Na+ or Cl- and is inhibited by a system L-specific inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), indicating that LAT-2 is a second isoform of the system L transporter. Compared with LAT-1, which prefers large neutral amino acids with branched or aromatic side chains, LAT-2 exhibits remarkably broad substrate selectivity. It transports all of the L-isomers of neutral alpha-amino acids. LAT-2 exhibits higher affinity (Km = 30-50 microM) to Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower affinity (Km = 180-300 microM) to His, Ala, Met, and Gly. In addition, LAT-2 mediates facilitated diffusion of substrate amino acids, as distinct from LAT-1, which mediates amino acid exchange. LAT-2-mediated transport is increased by lowering the pH level, with peak activity at pH 6.25, because of the decrease in the Km value without changing the Vmax value. Because of these functional properties and a high level of expression of LAT-2 in the small intestine, kidney, placenta, and brain, it is suggested that the heterodimeric complex of LAT-2 and 4F2 heavy chain is involved in the trans-cellular transport of neutral amino acids in epithelia and blood-tissue barriers.

Research at the Hamburgische Schiffbau Versuchsanstalt Relating to Pressure Actuated Mines

DTIC Science & Technology

1945-10-01

I. ± z f± -, i*.!.."..... .... I .... 4 ... * . ... ; .. 1 • ’ #,, PIEZOMETER NUMBE VAIU WED7E ND LAT ARRA NLEMENTS SPEED OF MODEL 2.50 Is/ 1 ...IS NAVAL*TECHNICAL* MISSION-IN.E PE 0O UL NCLASS-[ ED, I T~~~CHNIC" 1 RIERT No. 424..45 RESEARCH ,.T THE H-IWURGISCHE SCHIFFLU VERXCHSINSTLT RELTING...Rol-tting to 2russuro Actuatud Mines - For-marding of’. Miclosuros: (A) (H.’’) Oric ( 1 ) eorwoloto coiy of’ sub jact report * as listod in di

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

PubMed

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

Recent Results on SNRs and PWNe from the Fermi Large Area Telescope

NASA Technical Reports Server (NTRS)

Hays, Elizabeth A.

2010-01-01

Topics include: Fermi LAT Collaboration groups; galactic results from LAT; a GeV, wide-field instrument; the 1FGL catalog, the Fermi LAT 1FGL source catalog, unidentified gamma-ray sources; variability in 1FGL sources; curvature in 1FGL sources; spectral-variability classification; gamma-ray pulsars and MSPs; GeV PWN - where to look; Crab pulsar and nebula; Vela X nebular of Vela pulsar; MSH 15-52; GeV PWNe spectra; GeV nebula limits; Nebula search of LAT pulsars; supernova remnants; SNR: GeV morphology; SNR: molecular connection; SNR: GeV breaks; SNR: young vs. old. The summary includes slides about the Large Area Telescope (LAT) and LAT sensitivity with time.

50 CFR 660.74 - Latitude/longitude coordinates defining the 180 fm (329 m) through 250 fm (457 m) depth contours.

Code of Federal Regulations, 2012 CFR

2012-10-01

....00′ N. lat., 124°52.36′ W. long.; (132) 42°49.43′ N. lat., 124°52.03′ W. long.; (133) 42°47.68′ N...°41.90′ W. long.; (132) 40°31.30′ N. lat., 124°41.00′ W. long.; (133) 40°30.16′ N. lat., 124°37.91′ W....28′ N. lat., 124°31.35′ W. long.; (132) 40°16.29′ N. lat., 124°34.50′ W. long.; (133) 40°14.00′ N...

50 CFR 660.74 - Latitude/longitude coordinates defining the 180 fm (329 m) through 250 fm (457 m) depth contours.

Code of Federal Regulations, 2013 CFR

2013-10-01

....00′ N. lat., 124°52.36′ W. long.; (132) 42°49.43′ N. lat., 124°52.03′ W. long.; (133) 42°47.68′ N...°40.18′ W. long.; (132) 40°32.90′ N. lat., 124°41.90′ W. long.; (133) 40°31.30′ N. lat., 124°41.00′ W....; (132) 40°16.29′ N. lat., 124°34.50′ W. long.; (133) 40°14.00′ N. lat., 124°33.02′ W. long.; (134) 40°10...

Canine Lat1: molecular structure, distribution and its expression in cancer samples.

PubMed

Ochiai, Hideharu; Morishita, Taiki; Onda, Ken; Sugiyama, Hiroki; Maruo, Takuya

2012-07-01

A full-length cDNA sequence of canine L-type amino acid transporter 1 (Lat1) was determined from a canine brain. The sequence was 1828 bp long and was predicted to encode 485 amino acid polypeptides. The deduced amino acid sequence of canine Lat1 showed 93.2% and 91.1% similarities to those of humans and rats, respectively. Northern blot analysis detected Lat1 expression in the cerebellum at 4 kb, and Western blot analysis showed a single band at 40 kDa. RT-PCR analysis revealed a distinct expression of Lat1 in the pancreas and testis in addition to the cerebrum and cerebellum. Notably, Lat1 expression was observed in the tissues of thyroid cancer, melanoma and hemangiopericytoma. Although the cancer samples examined were not enough, Lat1 may serve as a useful biomarker of cancer cells in veterinary clinic.

Increased neurovirulence and reactivation of the herpes simplex virus type 1 latency associated transcript (LAT) negative mutant dLAT2903 with a disrupted LAT miR-H2

PubMed Central

Jiang, Xianzhi; Brown, Don; Osorio, Nelson; Hsiang, Chinhui; BenMohamed, Lbachir; Wechsler, Steven L.

2015-01-01

At least six microRNAs (miRNAs) appear to be encoded by the latency associated transcript (LAT) of herpes simplex virus type 1 (HSV-1). The gene for ICP0, an important immediate early (IE) viral protein, is antisense to, and overlaps with, the region of LAT from which miRNA H2 (miR-H2) is derived. We recently reported that a mutant (McK-ΔH2) disrupted for miR-H2 on the wild type HSV-1 strain McKrae genomic background has increased ICP0 expression, increased neurovirulence, and slightly more rapid reactivation. We report here that HSV-1 mutants deleted for the LAT promoter nonetheless make significant amounts of miR-H2 during lytic tissue culture infection, presumably via readthrough transcription from an upstream promoter. To determine if miR-H2 might also play a role in the HSV-1 latency-reactivation cycle of a LAT negative mutant, we constructed dLAT-ΔH2, in which miR-H2 is disrupted in dLAT2903 without altering the predicted amino acid sequence of the overlapping ICP0 open reading frame. Similar to McK-ΔH2, dLAT-ΔH2 expressed more ICP0, was more neurovirulent, and had increased reactivation in the mouse TG explant induced reactivation model of HSV-1 compared to its parental virus. Interestingly, although the increased reactivation of McK-ΔH2 compared to its parental wt virus was subtle and only detected at very early times after explant TG induced reactivation, the increased reactivation of dLAT-ΔH2 compared to its dLAT2903 parental virus appeared more robust and was significantly increased even at late times after induction. These results confirm that miR-H2 plays a role in modulating the HSV-1 reactivation phenotype. PMID:26069184

The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1▿

PubMed Central

Allen, Sariah J.; Hamrah, Pedram; Gate, David; Mott, Kevin R.; Mantopoulos, Dimosthenis; Zheng, Lixin; Town, Terrence; Jones, Clinton; von Andrian, Ulrich H.; Freeman, Gordon J.; Sharpe, Arlene H.; BenMohamed, Lbachir; Ahmed, Rafi; Wechsler, Steven L.; Ghiasi, Homayon

2011-01-01

Herpes simplex virus (HSV) infection is a classic example of latent viral infection in humans and experimental animal models. The HSV-1 latency-associated transcript (LAT) plays a major role in the HSV-1 latency reactivation cycle and thus in recurrent disease. Whether the presence of LAT leads to generation of dysfunctional T cell responses in the trigeminal ganglia (TG) of latently infected mice is not known. To address this issue, we used LAT-positive [LAT(+)] and LAT-deficient [LAT(−)] viruses to evaluate the effect of LAT on CD8 T cell exhaustion in TG of latently infected mice. The amount of latency as determined by quantitative reverse transcription-PCR (qRT-PCR) of viral DNA in total TG extracts was 3-fold higher with LAT(+) than with LAT(−) virus. LAT expression and increased latency correlated with increased mRNA levels of CD8, PD-1, and Tim-3. PD-1 is both a marker for exhaustion and a primary factor leading to exhaustion, and Tim-3 can also contribute to exhaustion. These results suggested that LAT(+) TG contain both more CD8+ T cells and more CD8+ T cells expressing the exhaustion markers PD-1 and Tim-3. This was confirmed by flow cytometry analyses of expression of CD3/CD8/PD-1/Tim-3, HSV-1, CD8+ T cell pentamer (specific for a peptide derived from residues 498 to 505 of glycoprotein B [gB498–505]), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α). The functional significance of PD-1 and its ligands in HSV-1 latency was demonstrated by the significantly reduced amount of HSV-1 latency in PD-1- and PD-L1-deficient mice. Together, these results may suggest that both PD-1 and Tim-3 are mediators of CD8+ T cell exhaustion and latency in HSV-1 infection. PMID:21307196

A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn

2013-09-13

Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transportermore » recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P < 0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [{sup 3}H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM.« less

Two open reading frames (ORF1 and ORF2) within the 2.0-kilobase latency-associated transcript of herpes simplex virus type 1 are not essential for reactivation from latency.

PubMed Central

Fareed, M U; Spivack, J G

1994-01-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcripts (LATs) are dispensable for establishment and maintenance of latent infection. However, the LATs have been implicated in reactivation of the virus from its latent state. Since the reported LAT deletion and/or insertion variants that are reactivation impaired contain deletions in the putative LAT promoter, it is not known which LAT sequences are involved in reactivation. To examine the role of the 2.0-kb LAT in the process of reactivation and the functional importance of the putative open reading frames (ORF1 and ORF2) contained within the 2.0-kb LAT, we have constructed an HSV-1 variant that contains a precise deletion and insertion within the LAT-specific DNA sequences using site-directed mutagenesis. The HSV-1 variant FS1001K contains an 1,186-bp deletion starting precisely from the 5' end of the 2.0-kb LAT and, for identification, a XbaI restriction endonuclease site insertion. The FS1001K genome contains no other deletions and/or insertions as analyzed by a variety of restriction endonucleases. The deletion in FS1001K removes the entire 556-bp intron within the 2.0-kb LAT, the first 229 nucleotides of ORF1, and the first 159 nucleotides of ORF2 without having an affect on the RL2 (ICP0) gene. Explant cocultivation reactivation assays indicated that this deletion had a minimal effect on reactivation of the variant FS1001K compared with the parental wild-type virus using a mouse eye model. As expected, Northern (RNA) blot analyses have shown that the variant virus (FS1001K) does not produce the 2.0-kb LAT or the 1.45- to 1.5-kb LAT either in vitro or in vivo; however, FS1001K produces an intact RL2 transcript in tissue culture. These data suggest that the 2.0-kb LAT putative ORF1 and ORF2 (or the first 1,186 bp of the 2.0-kb LAT) are dispensable for explant reactivation of latent HSV-1. Images PMID:7966597

FERMI LAT Discovery of Extended Gamma-Ray Emission in the Direction of Supernova Remnant W51C

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-10-27

In this paper, the discovery of bright gamma-ray emission coincident with supernova remnant (SNR) W51C is reported using the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope. W51C is a middle-aged remnant (~10 4 yr) with intense radio synchrotron emission in its shell and known to be interacting with a molecular cloud. The gamma-ray emission is spatially extended, broadly consistent with the radio and X-ray extent of SNR W51C. The energy spectrum in the 0.2-50 GeV band exhibits steepening toward high energies. The luminosity is greater than 1 × 10 36 erg s –1 given the distance constraint of D > 5.5 kpc, which makes this object one of the most luminous gamma-ray sources in our Galaxy. The observed gamma-rays can be explained reasonably by a combination of efficient acceleration of nuclear cosmic rays at supernova shocks and shock-cloud interactions. The decay of neutral π mesons produced in hadronic collisions provides a plausible explanation for the gamma-ray emission. The product of the average gas density and the total energy content of the accelerated protons amounts tomore » $$\\bar{n}_{\\rm H}W_p \\simeq 5\\times 10^{51}\\ (D/6\\ {\\rm kpc})^2\\ \\rm erg\\ cm^{-3}$$. Electron density constraints from the radio and X-ray bands render it difficult to explain the LAT signal as due to inverse Compton scattering. Finally, the Fermi LAT source coincident with SNR W51C sheds new light on the origin of Galactic cosmic rays.« less

The Herpes Simplex Virus Type 1 Latency-Associated Transcript Can Protect Neuron-Derived C1300 and Neuro2A Cells from Granzyme B-Induced Apoptosis and CD8 T-Cell Killing▿

PubMed Central

Jiang, Xianzhi; Alami Chentoufi, Aziz; Hsiang, Chinhui; Carpenter, Dale; Osorio, Nelson; BenMohamed, Lbachir; Fraser, Nigel W.; Jones, Clinton; Wechsler, Steven L.

2011-01-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is the only HSV-1 gene transcript abundantly expressed throughout latency. LAT null mutants have a significantly reduced reactivation phenotype. LAT's antiapoptosis activity is the major LAT factor involved in supporting the wild-type reactivation phenotype. During HSV-1 latency, some ganglionic neurons are surrounded by CD8 T cells, and it has been proposed that these CD8 T cells help maintain HSV-1 latency by suppressing viral reactivations. Surprisingly, despite injection of cytotoxic lytic granules by these CD8 T cells into latently infected neurons, neither apoptosis nor neuronal cell death appears to occur. We hypothesized that protection of latently infected neurons against cytotoxic CD8 T-cell killing is due to LAT's antiapoptosis activity. Since CD8 T-cell cytotoxic lytic granule-mediated apoptosis is critically dependent on granzyme B (GrB), we examined LAT's ability to block GrB-induced apoptosis. We report here that (i) LAT can interfere with GrB-induced apoptosis in cell cultures, (ii) LAT can block GrB-induced cleavage (activation) of caspase-3 both in cell culture and in a cell-free in vitro cell extract assay, and (iii) LAT can protect C1300 and Neuro2A cells from cytotoxic CD8 T-cell killing in vitro. These findings support the hypothesis that LAT's antiapoptosis activity can protect latently infected neurons from being killed by CD8 T-cell lytic granules in vivo. PMID:21177822

Biophysical studies and NMR structure of YAP2 WW domain - LATS1 PPxY motif complexes reveal the basis of their interaction

PubMed Central

Verma, Apoorva; Jing-Song, Fan; Finch-Edmondson, Megan L.; Velazquez-Campoy, Adrian; Balasegaran, Shanker; Sudol, Marius; Sivaraman, Jayaraman

2018-01-01

YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1. PMID:29487715

Biophysical studies and NMR structure of YAP2 WW domain - LATS1 PPxY motif complexes reveal the basis of their interaction.

PubMed

Verma, Apoorva; Jing-Song, Fan; Finch-Edmondson, Megan L; Velazquez-Campoy, Adrian; Balasegaran, Shanker; Sudol, Marius; Sivaraman, Jayaraman

2018-01-30

YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1. We solved the NMR structures of these complexes and identified several conserved residues that play a critical role in binding. We further created a YAP2 mutant by swapping the WW domains, and found that YAP2 phosphorylation at S127 by LATS1 is not affected by the spatial configuration of its WW domains. This is likely because the region between the PPxY motifs of LATS1 is unstructured, even upon binding with its partner. Based on our observations, we propose possible models for the interaction between YAP2 and LATS1.

Recent Results on SNRs and PWNe from the Fermi Large Area Telescope

NASA Technical Reports Server (NTRS)

Hays, Elizabeth

2010-01-01

Topics include: Fermi LAT Collaboration groups; galactic results from LAT; a GeV, wide-field instrument; the 1FGL catalog, the Fermi LAT 1FGL source catalog, unidentified gamma-ray sources; variability in 1FGL sources; curvature in 1FGL sources; spectral-variability classification; pulsars and their wind nebulae; gamma-ray pulsars and MSPs; GeV PWN search; Crab pulsar and nebula; Vela X nebular of Vela pulsar; MSH 15-52; supernova remnants, resolved GeV sources, galactic transients, LAT unassociated transient detections; gamma rays from a nova; V407 Cyngi - a symbiotic nova; V407 Cygni: a variable star; and March 11 - a nova. Summary slides include pulsars everywhere, blazars, LAT as an electron detector, cosmic ray spectrum, the Large Area Telescope, the Fermi Observatory, LAT sensitivity with time, candidate gamma-ray events, on-orbit energy calibration and rate, a 1 year sky map, LAT automated science processing, reported GeV flares, early activity and spectacular flare, gamma-ray transients near the galactic plane , two early unassociated transients, counter part search - Fermi J0910-5404; counterpart search 3EG J0903-3531, and a new LAT transient - J1057-6027.

Herpes simplex virus 1 microRNAs expressed abundantly during latent infection are not essential for latency in mouse trigeminal ganglia

PubMed Central

Kramer, Martha F.; Jurak, Igor; Pesola, Jean M.; Boissel, Sandrine; Knipe, David M.; Coen, Donald M.

2013-01-01

Several herpes simplex virus 1 microRNAs are encoded within or near the latency associated transcript (LAT) locus, and are expressed abundantly during latency. Some of these microRNAs can repress the expression of important viral proteins and are hypothesized to play important roles in establishing and/or maintaining latent infections. We found that in lytically infected cells and in acutely infected mouse ganglia, expression of LAT-encoded microRNAs was weak and unaffected by a deletion that includes the LAT promoter. In mouse ganglia latently infected with wild type virus, the microRNAs accumulated to high levels, but deletions of the LAT promoter markedly reduced expression of LAT-encoded microRNAs and also miR-H6, which is encoded upstream of LAT and can repress expression of ICP4. Because these LAT deletion mutants establish and maintain latent infections, these microRNAs are not essential for latency, at least in mouse trigeminal ganglia, but may help promote it. PMID:21782205

Comparison of the Defense Meteorological Satellite Program (DMSP) and the NOAA Polar-Orbiting Operational Environmental Satellite (POES) Program,

DTIC Science & Technology

1985-10-01

grid points on 1 /20 lat /long meshI 4 c. SST global scale analysis ( 1 or 100 km lat /long grid) .. d. SST climatic scale analysis (50 or 500 km lat ...long grid) e. SST monthly means (2 1 /20 or 250 km lat /long grid) 3. Analog Sea Surface Temperature Product Set ’-%". V" " a. GOSSTCOMP charts - weekly...Mercator contour charts, each a ., 500 by 500 lat /long segment, 1 °C contour interval b. Regional charts - set of three charts covering the U.S

A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels.

PubMed

Perng, Guey-Chuen; Maguen, Barak; Jin, Ling; Mott, Kevin R; Osorio, Nelson; Slanina, Susan M; Yukht, Ada; Ghiasi, Homayon; Nesburn, Anthony B; Inman, Melissa; Henderson, Gail; Jones, Clinton; Wechsler, Steven L

2002-02-01

After ocular herpes simplex virus type 1 (HSV-1) infection, the virus travels up axons and establishes a lifelong latent infection in neurons of the trigeminal ganglia. LAT (latency-associated transcript), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. The LAT function responsible for this reactivation phenotype is not known. Recently, we showed that LAT can block programmed cell death (apoptosis) in neurons of the trigeminal ganglion in vivo and in tissue culture cells in vitro (G.-C. Perng et al., Science 287:1500-1503, 2000; M. Inman et al., J. Virol. 75:3636-3646, 2001). Consequently, we proposed that this antiapoptosis function may be a key to the mechanism by which LAT enhances reactivation. To study this further, we constructed a recombinant HSV-1 virus in which the HSV-1 LAT gene was replaced by an alternate antiapoptosis gene. We used the bovine herpes virus 1 (BHV-1) latency-related (LR) gene, which was previously shown to have antiapoptosis activity, for this purpose. The resulting chimeric virus, designated CJLAT, contains two complete copies of the BHV-1 LR gene (one in each viral long repeat) in place of the normal two copies of the HSV-1 LAT, on an otherwise wild-type HSV-1 strain McKrae genomic background. We report here that in both rabbits and mice reactivation of CJLAT was significantly greater than the LAT null mutant dLAT2903 (P < 0.0004 and P = 0.001, respectively) and was at least as efficient as wild-type McKrae. This strongly suggests that a BHV-1 LR gene function was able to efficiently substitute for an HSV-1 LAT gene function involved in reactivation. Although replication of CJLAT in rabbits and mice was similar to that of wild-type McKrae, CJLAT killed more mice during acute infection and caused more corneal scarring in latently infected rabbits. This suggested that the BHV-1 LR gene and the HSV-1 LAT gene are not functionally identical. However, LR and LAT both have antiapoptosis activity. These studies therefore strongly support the hypothesis that replacing LAT with an antiapoptosis gene restores the wild-type reactivation phenotype to a LAT null mutant of HSV-1 McKrae.

Aryl hydrocarbon receptor (AHR) regulation of L-Type Amino Acid Transporter 1 (LAT-1) expression in MCF-7 and MDA-MB-231 breast cancer cells.

PubMed

Tomblin, Justin K; Arthur, Subha; Primerano, Donald A; Chaudhry, Ateeq R; Fan, Jun; Denvir, James; Salisbury, Travis B

2016-04-15

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is regulated by environmental toxicants that function as AHR agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). L-Type Amino Acid Transporter 1 (LAT1) is a leucine transporter that is overexpressed in cancer. The regulation of LAT1 by AHR in MCF-7 and MDA-MB-231 breast cancer cells (BCCs) was investigated in this report. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and molecular transport. Overlapping the TCDD-RNA-Seq dataset obtained in this study with a published TCDD-ChIP-seq dataset identified LAT1 as a primary target of AHR-dependent TCDD induction. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed that TCDD-stimulated increases in LAT1 mRNA and protein required AHR expression. TCDD-stimulated increases in LAT1 mRNA were also inhibited by the AHR antagonist CH-223191. Upregulation of LAT1 by TCDD coincided with increases in leucine uptake by MCF-7 cells in response to TCDD. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays revealed increases in AHR, AHR nuclear translocator (ARNT) and p300 binding and histone H3 acetylation at an AHR binding site in the LAT1 gene in response to TCDD. In MCF-7 and MDA-MB-231 cells, endogenous levels of LAT1 mRNA and protein were reduced in response to knockdown of AHR expression. Knockdown experiments demonstrated that proliferation of MCF-7 and MDA-MB-231 cells is dependent on both LAT1 and AHR. Collectively, these findings confirm the dependence of cancer cells on leucine uptake and establish a mechanism for extrinsic and intrinsic regulation of LAT1 by AHR. Copyright © 2016 Elsevier Inc. All rights reserved.

Lateral spine densitometry in obese women.

PubMed

Brooks, E R; Heltz, D; Wozniak, P; Partington, C; Lovejoy, J C

1998-08-01

The lateral (LAT) spine scan has been suggested as a more sensitive measure than posterior-anterior (PA) scanning for assessing age-related bone loss in normal-weight postmenopausal women. The measurement error of PA and LAT bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) has also been shown to rise with incremental increases in fat and from large variance in fat thickness, respectively. The purpose of this cross-sectional study was to determine specific affects of obesity on paired PA and LAT lumbar (L2-L4) BMD and Z score (BMD of patient versus age-matched reference data-base) correlation in 30 obese postmenopausal women (mean BMI +/- SD = 33.3 +/- 4.06). The mean PA and LAT BMD +/- SD were 0.946 +/- 0.123 and 0.749 +/- 0.134, respectively. The mean PA and LAT Z scores were -0.17 +/- 1.15 and 0.80 +/- 1.7. The correlation between PA and LAT BMD was significantly lower (r = 0.55; P < 0.05) than previously reported, and PA and LAT Z score correlation was (r = 0.57; P = 0.0016). After adjusting for body mass index (BMI), percent body fat, fat mass, and truncal fat by DXA, waist:hip ratio (WHR) and visceral and subcutaneous abdominal fat by computerized axial tomography (CT), PA and LAT Z score correlation increased to r = 0.62; P = 0.0065. In our subjects, the mean LAT Z score was 4.6 times higher than the mean AP Z, contrary to previous observations in normal-weight postmenopausal women. Our findings may be due to increased soft tissue composition and fat inhomogeneity in the LAT scanning field resulting in increased X-ray attenuation in obesity.

Characterization of a spliced exon product of herpes simplex type-1 latency-associated transcript in productively infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Wen; Mukerjee, Ruma; Gartner, Jared J.

2006-12-20

The latency-associated transcripts (LATs) of herpes simplex virus type-1 (HSV-1) are the only viral RNAs accumulating during latent infections in the sensory ganglia of the peripheral nervous system. The major form of LAT that accumulates in latently infected neurons is a 2 kb intron, spliced from a much less abundant 8.3 primary transcript. The spliced exon mRNA has been hard to detect. However, in this study, we have examined the spliced exon RNA in productively infected cells using ribonuclease protection (RPA), and quantitative RT-PCR (q-PCR) assays. We were able to detect the LAT exon RNA in productively infected SY5Y cellsmore » (a human neuronal cell line). The level of the LAT exon RNA was found to be approximately 5% that of the 2 kb intron RNA and thus is likely to be relatively unstable. Quantitative RT-PCR (q-PCR) assays were used to examine the LAT exon RNA and its properties. They confirmed that the LAT exon mRNA is present at a very low level in productively infected cells, compared to the levels of other viral transcripts. Furthermore, experiments showed that the LAT exon mRNA is expressed as a true late gene, and appears to be polyadenylated. In SY5Y cells, in contrast to most late viral transcripts, the LAT exon RNA was found to be mainly nuclear localized during the late stage of a productive infection. Interestingly, more LAT exon RNA was found in the cytoplasm in differentiated compared to undifferentiated SY5Y cells, suggesting the nucleocytoplasmic distribution of the LAT exon RNA and its related function may be influenced by the differentiation state of cells.« less

Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation

PubMed Central

BenMohamed, Lbachir; Osorio, Nelson; Srivastava, Ruchi; Khan, Arif A.; Simpson, Jennifer L.; Wechsler, Steven L.

2015-01-01

Blinding ocular herpetic disease in humans is due to herpes simplex virus type 1 (HSV-1) reactivations from latency, rather than to primary acute infection. The cellular and molecular mechanisms that control the HSV-1 latency-reactivation cycle remain to be fully elucidated. The aim of this study was to determine if reactivation of the HSV-1 latency associated transcript (LAT) deletion mutant (dLAT2903) was impaired in this model, as it is in the rabbit model of induced and spontaneous reactivation and in the explant TG induced reactivation model in mice. The eyes of mice latently infected with wild type HSV-1 strain McKrae (LAT(+) virus) or dLAT2903 (LAT(−) virus) were irradiated with UV-B and reactivation was determined. We found that compared to LAT(−) virus, LAT(+) virus reactivated at a higher rate as determined by shedding of virus in tears on days 3 to 7 after UV-B treatment. Thus, the UV-B induced reactivation model of HSV-1 appears to be a useful small animal model for studying the mechanisms involved in how LAT enhances the HSV-1 reactivation phenotype. The utility of the model for investigating the immune evasion mechanisms regulating the HSV-1 latency/reactivation cycle and for testing the protective efficacy of candidate therapeutic vaccines and drugs are discussed. PMID:26002839

Quantitative insight into the design of compounds recognized by the L-type amino acid transporter 1 (LAT1).

PubMed

Ylikangas, Henna; Malmioja, Kalle; Peura, Lauri; Gynther, Mikko; Nwachukwu, Emmanuel O; Leppänen, Jukka; Laine, Krista; Rautio, Jarkko; Lahtela-Kakkonen, Maija; Huttunen, Kristiina M; Poso, Antti

2014-12-01

L-Type amino acid transporter 1 (LAT1) is a transmembrane protein expressed abundantly at the blood-brain barrier (BBB), where it ensures the transport of hydrophobic acids from the blood to the brain. Due to its unique substrate specificity and high expression at the BBB, LAT1 is an intriguing target for carrier-mediated transport of drugs into the brain. In this study, a comparative molecular field analysis (CoMFA) model with considerable statistical quality (Q(2) =0.53, R(2) =0.75, Q(2) SE=0.77, R(2) SE=0.57) and good external predictivity (CCC=0.91) was generated. The model was used to guide the synthesis of eight new prodrugs whose affinity for LAT1 was tested by using an in situ rat brain perfusion technique. This resulted in the creation of a novel LAT1 prodrug with L-tryptophan as the promoiety; it also provided a better understanding of the molecular features of LAT1-targeted high-affinity prodrugs, as well as their promoiety and parent drug. The results obtained will be beneficial in the rational design of novel LAT1-binding prodrugs and other compounds that bind to LAT1. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developing the Second Generation CMORPH: A Prototype

NASA Astrophysics Data System (ADS)

Xie, Pingping; Joyce, Robert

2014-05-01

A prototype system of the second generation CMORPH is being developed at NOAA Climate Prediction Center (CPC) to produce global analyses of 30-min precipitation on a 0.05deg lat/lon grid over the entire globe from pole to pole through integration of information from satellite observations as well as numerical model simulations. The second generation CMORPH is built upon the Kalman Filter based CMORPH algorithm of Joyce and Xie (2011). Inputs to the system include rainfall and snowfall rate retrievals from passive microwave (PMW) measurements aboard all available low earth orbit (LEO) satellites, estimates derived from infrared (IR) observations of geostationary (GEO) as well as LEO platforms, and precipitation simulations from numerical global models. First, precipitation estimation / retrievals from various sources are mapped onto a global grid of 0.05deg lat/lon and calibrated against a common reference field to ensure consistency in their precipitation rate PDF structures. The motion vectors for the precipitating cloud systems are then defined using information from both satellite IR observations and precipitation fields generated by the NCEP Climate Forecast System Reanalysis (CFSR). To this end, motion vectors are first computed from CFSR hourly precipitation fields through cross-correlation analysis of consecutive hourly precipitation fields on the global T382 (~35 km) grid. In a similar manner, separate processing is also performed on satellite IR-based precipitation estimates to derive motion vectors from observations. A blended analysis of precipitating cloud motion vectors is then constructed through the combination of CFSR and satellite-derived vectors with an objective analysis technique. Fine resolution mapped PMW precipitation retrievals are then separately propagated along the motion vectors from their respective observation times to the target analysis time from both forward and backward directions. The CMORPH high resolution precipitation analyses are finally constructed through the combination of propagated PMW retrievals with the IR based estimates for the target analysis time. This Kalman Filter based CMORPH processing is performed for rainfall and snowfall fields separately with the same motion vectors. Experiments have been conducted for two periods of two months each, July - August 2009, and January - February 2010, to explore the development of an optimal algorithm that generates global precipitation for summer and winter situations. Preliminary results demonstrated technical feasibility to construct global rainfall and snowfall analyses through the integration of information from multiple sources. More work is underway to refine various technical components of the system for operational applications of the system. Detailed results will be reported at the EGU meeting.

Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

PubMed

Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

2017-04-01

Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Don't trust an(t)ybody - Pitfalls during investigation of candidate proteins for methylmercury transport at the placental interface.

PubMed

Ellinger, Isabella; Chatuphonprasert, Waranya; Reiter, Martin; Voss, Agnes; Kemper, Jost; Straka, Elisabeth; Scheinast, Matthias; Zeisler, Harald; Salzer, Hans; Gundacker, Claudia

2016-07-01

While investigating placental mercury transport, we validated specificity of commercial antibodies against four candidate transporters (Large neutral amino acids transporter (LAT)1, LAT2, 4F2 cell-surface antigen heavy chain (4F2hc), and multidrug resistance-associated protein (MRP)2) by immunoblotting and small interfering RNA (siRNA)-mediated protein knockdown. An anti-4F2hc- and one anti-LAT1-antibody were specific. Another anti-LAT1-antibody reacted with LAT2. Two anti-LAT2-antibodies detected mainly albumin in placental lysates. A specific anti-MRP2-antibody hardly detected MRP2 in human placentas, contradicting published data. We recommend testing any unknown antibody by western blotting for 1/specificity for the protein of interest using e.g. siRNA knockdown and 2/cross-reactivity with albumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

PSR J1838–0537: Discovery of a young, energetic gamma-ray pulsar

DOE PAGES

Pletsch, H. J.; Guillemot, L.; Allen, B.; ...

2012-07-27

Here, we report the discovery of PSR J1838–0537, a gamma-ray pulsar found through a blind search of data from the Fermi Large Area Telescope (LAT). The pulsar has a spin frequency of 6.9 Hz and a frequency derivative of –2.2 × 10 –11 Hz s–1, implying a young characteristic age of 4970 yr and a large spin-down power of 5.9 × 1036 erg s–1. Follow-up observations with radio telescopes detected no pulsations; thus PSR J1838–0537 appears radio-quiet as viewed from Earth. In 2009 September the pulsar suffered the largest glitch so far seen in any gamma-ray-only pulsar, causing a relativemore » increase in spin frequency of about 5.5 × 10–6. After the glitch, during a putative recovery period, the timing analysis is complicated by the sparsity of the LAT photon data, the weakness of the pulsations, and the reduction in average exposure from a coincidental, contemporaneous change in LAT's sky-survey observing pattern. Furthermore, the pulsar's sky position is coincident with the spatially extended TeV source HESS J1841–055 detected by the High Energy Stereoscopic System (H.E.S.S.). Finally, the inferred energetics suggest that HESS J1841–055 contains a pulsar wind nebula powered by the pulsar.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Eileen T.; Breiding, Peter; Georganopoulos, Markos

The Chandra X-ray observatory has discovered several dozen anomalously X-ray-bright jets associated with powerful quasars. A popular explanation for the X-ray flux from the knots in these jets is that relativistic synchrotron-emitting electrons inverse-Compton scatter cosmic microwave background (CMB) photons to X-ray energies (the IC/CMB model). This model predicts a high gamma-ray flux that should be detectable by the Fermi /Large Area Telescope (LAT) for many sources. GeV-band upper limits from Fermi /LAT for the well-known anomalous X-ray jet in PKS 0637−752 were previously shown in Meyer et al. to violate the predictions of the IC/CMB model. Previously, measurements ofmore » the jet synchrotron spectrum, important for accurately predicting the gamma-ray flux level, were lacking between radio and infrared wavelengths. Here, we present new Atacama Large Millimeter/submillimeter Array (ALMA) observations of the large-scale jet at 100, 233, and 319 GHz, which further constrain the synchrotron spectrum, supporting the previously published empirical model. We also present updated limits from the Fermi /LAT using the new “Pass 8” calibration and approximately 30% more time on source. With these deeper limits, we rule out the IC/CMB model at the 8.7 σ level. Finally, we demonstrate that complete knowledge of the synchrotron SED is critical in evaluating the IC/CMB model.« less

A Search for Transitions between States in Redbacks and Black Widows Using Seven Years of Fermi-LAT Observations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres, Diego F.; Ji, Long; Li, Jian

Considering about seven years of Fermi-Large Area Telescope (LAT) data, we present a systematic search for variability that is possibly related to transitions between states in redbacks and black widow systems. In addition, the transitions are characterized by sudden and significant changes in the gamma-ray flux that persist on a timescale that is much larger than the orbital period. This phenomenology was already detected in the case of two redback systems, PSR J1023+0038 and PSR J1227-4853, which we present here. We show the existence of only one transition for each of these systems over the past seven years. We determinemore » their spectra, establishing high-energy cutoffs at a few GeV for the high gamma-ray state of PSR J1023+0038, and for both states of PSR J1227-4853. The surveying capability of the Fermi-LAT allows further study of whether similar phenomenology has occurred in other sources. Although we have not found any evidence of a state transition for most of the studied pulsars, we note two black-widow systems, PSR J2234+0944 and PSR J1446-4701, whose apparent variabilities are reminiscent of the transitions in PSR J1023+0038 and PSR J1227-4853. Finally, for the other systems, we set limits on potential transitions in their measured gamma-ray light curves.« less

New Fermi-LAT event reconstruction reveals more high-energy gamma rays from gamma-ray bursts

DOE PAGES

Atwood, W. B.; Baldini, L.; Bregeon, J.; ...

2013-08-19

Here, based on the experience gained during the four and a half years of the mission, the Fermi-LAT Collaboration has undertaken a comprehensive revision of the event-level analysis going under the name of Pass 8. Although it is not yet finalized, we can test the improvements in the new event reconstruction with the special case of the prompt phase of bright gamma-ray bursts (GRBs), where the signal-to-noise ratio is large enough that loose selection cuts are sufficient to identify gamma rays associated with the source. Using the new event reconstruction, we have re-analyzed 10 GRBs previously detected by the Largemore » Area Telescope (LAT) for which an X-ray/optical follow-up was possible and found four new gamma rays with energies greater than 10 GeV in addition to the seven previously known. Among these four is a 27.4 GeV gamma ray from GRB 080916C, which has a redshift of 4.35, thus making it the gamma ray with the highest intrinsic energy (~147 GeV) detected from a GRB. We present here the salient aspects of the new event reconstruction and discuss the scientific implications of these new high-energy gamma rays, such as constraining extragalactic background light models, Lorentz invariance violation tests, the prompt emission mechanism, and the bulk Lorentz factor of the emitting region.« less

A Search for Transitions between States in Redbacks and Black Widows Using Seven Years of Fermi-LAT Observations

DOE PAGES

Torres, Diego F.; Ji, Long; Li, Jian; ...

2017-02-08

Considering about seven years of Fermi-Large Area Telescope (LAT) data, we present a systematic search for variability that is possibly related to transitions between states in redbacks and black widow systems. In addition, the transitions are characterized by sudden and significant changes in the gamma-ray flux that persist on a timescale that is much larger than the orbital period. This phenomenology was already detected in the case of two redback systems, PSR J1023+0038 and PSR J1227-4853, which we present here. We show the existence of only one transition for each of these systems over the past seven years. We determinemore » their spectra, establishing high-energy cutoffs at a few GeV for the high gamma-ray state of PSR J1023+0038, and for both states of PSR J1227-4853. The surveying capability of the Fermi-LAT allows further study of whether similar phenomenology has occurred in other sources. Although we have not found any evidence of a state transition for most of the studied pulsars, we note two black-widow systems, PSR J2234+0944 and PSR J1446-4701, whose apparent variabilities are reminiscent of the transitions in PSR J1023+0038 and PSR J1227-4853. Finally, for the other systems, we set limits on potential transitions in their measured gamma-ray light curves.« less

Constraints on cosmological dark matter annihilation from the Fermi-LAT isotropic diffuse gamma-ray measurement

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2010-04-01

The first published Fermi large area telescope (Fermi-LAT) measurement of the isotropic diffuse gamma-ray emission is in good agreement with a single power law, and is not showing any signature of a dominant contribution from dark matter sources in the energy range from 20 to 100 GeV. Here, we use the absolute size and spectral shape of this measured flux to derive cross section limits on three types of generic dark matter candidates: annihilating into quarks, charged leptons and monochromatic photons. Predicted gamma-ray fluxes from annihilating dark matter are strongly affected by the underlying distribution of dark matter, and bymore » using different available results of matter structure formation we assess these uncertainties. We also quantify how the dark matter constraints depend on the assumed conventional backgrounds and on the Universe's transparency to high-energy gamma-rays. In reasonable background and dark matter structure scenarios (but not in all scenarios we consider) it is possible to exclude models proposed to explain the excess of electrons and positrons measured by the Fermi-LAT and PAMELA experiments. Derived limits also start to probe cross sections expected from thermally produced relics (e.g. in minimal supersymmetry models) annihilating predominantly into quarks. Finally, for the monochromatic gamma-ray signature, the current measurement constrains only dark matter scenarios with very strong signals.« less

The Herpes Simplex Virus Latency-Associated Transcript Gene Is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits

PubMed Central

Srivastava, Ruchi; Dervillez, Xavier; Khan, Arif A.; Chentoufi, Aziz A.; Chilukuri, Sravya; Shukr, Nora; Fazli, Yasmin; Ong, Nicolas N.; Afifi, Rasha E.; Osorio, Nelson; Geertsema, Roger; Nesburn, Anthony B.

2016-01-01

ABSTRACT Persistent pathogens, such as herpes simplex virus 1 (HSV-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host's immune system. A dynamic cross talk appears to occur between the HSV-1 latency-associated transcript (LAT), the only viral gene that is abundantly transcribed during latency, and the CD8+ T cells that reside in HSV-1 latently infected human and rabbit trigeminal ganglia (TG). The reactivation phenotype of TG that are latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT+ TG) is significantly higher than TG latently infected with LAT-null mutant (i.e., LAT− TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8+ T cells in LAT+ TG is unknown. In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8+ T cells specific to 40 epitopes derived from HSV-1 gB, gD, VP11/12, and VP13/14 proteins, in human leukocyte antigen (HLA-A*0201) transgenic rabbits infected ocularly with LAT+ versus LAT– virus. Compared to CD8+ T cells from LAT– TG, CD8+ T cells from LAT+ TG (i) recognized a broader selection of nonoverlapping HSV-1 epitopes, (ii) expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tumor necrosis factor alpha, gamma interferon, and granzyme B. These results suggest a novel immune evasion mechanism by which the HSV-1 LAT may contribute to the shaping of a broader repertoire of exhausted HSV-specific CD8+ T cells in latently infected TG, thus allowing for increased viral reactivation. IMPORTANCE A significantly larger repertoire of dysfunctional (exhausted) HSV-specific CD8+ T cells were found in the TG of HLA transgenic rabbits latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT+ TG) than in a more restricted repertoire of functional HSV-specific CD8+ T cells in the TG of HLA transgenic rabbits latently infected with LAT-null mutant (i.e., LAT– TG). These findings suggest that the HSV-1 LAT locus interferes with the host cellular immune response by shaping a broader repertoire of exhausted HSV-specific CD8+ T cells within the latency/reactivation TG site. PMID:26842468

Understanding Optimal Decision-Making

DTIC Science & Technology

2015-06-01

Task (IGT) (Bechara, Damasio, Damasio, & Anderson,1994), a very common test of reinforcement learning that has been used in hundreds of psychology ... psychology task that elicits reinforcement learning (Bechara et al., 1994) and has been used in hundreds of studies (Krain et al., 2006). Subjects...34) 70 # LatByTrial<- LatByTrial+geom_line(data=player,aes(x=trial,y=ewma),linetype=1, colour ="grey8 8") # LatByTrial<- LatByTrial+geom_point

Lidocaine attenuation testing: An in vivo investigation of putative LQT3-associated variants in the SCN5A-encoded sodium channel.

PubMed

Anderson, Heather N; Bos, J Martijn; Kapplinger, Jamie D; Meskill, Jana M; Ye, Dan; Ackerman, Michael J

2017-08-01

Long QT syndrome type 3 (LQT3) accounts for 5%-10% of long QT syndrome and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Approximately 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential. The purpose of this study was to assess the use of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3. We reviewed the LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant. The LAT involved a loading dose of 1 mg/kg of intravenous lidocaine followed by continuous infusion at 50 μg/(kg⋅min) for 20 minutes. If the corrected QT interval shortened by ≥30 ms, the LAT was defined as positive. Sixteen patients (64%) had a positive LAT, 6 of which demonstrated the E1784K variant. A positive LAT correlated in 86% of cases with abnormal in vitro channel function (mean corrected QT interval attenuation 43 ± 3 ms vs 25 ± 5 ms for wild-type variants; P = .03). Four of 5 patients (80%) with a VUS had a positive LAT (T1304M [2 patients], L1786P, and R800L). The T1304M variant demonstrated abnormal in vitro function and a positive LAT, opening the door for a potential variant promotion from VUS to likely pathogenic. The LAT may help distinguish true LQT3-causative mutations from an otherwise noncontributory VUS. Given that lidocaine acts as a late sodium current blocker, a positive LAT may enable the early identification of a pathological accentuation of the late sodium current that could be targeted therapeutically. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Cerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation

PubMed Central

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M.; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2 -/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3′-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3′-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development. PMID:24819605

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

PubMed

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

The Herpes Simplex Virus 1 Latency-Associated Transcript Promotes Functional Exhaustion of Virus-Specific CD8+ T Cells in Latently Infected Trigeminal Ganglia: a Novel Immune Evasion Mechanism▿

PubMed Central

Chentoufi, Aziz A.; Kritzer, Elizabeth; Tran, Michael V.; Dasgupta, Gargi; Lim, Chang Hyun; Yu, David C.; Afifi, Rasha E.; Jiang, Xianzhi; Carpenter, Dale; Osorio, Nelson; Hsiang, Chinhui; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

2011-01-01

Following ocular herpes simplex virus 1 (HSV-1) infection of C57BL/6 mice, HSV-specific (HSV-gB498–505 tetramer+) CD8+ T cells are induced, selectively retained in latently infected trigeminal ganglia (TG), and appear to decrease HSV-1 reactivation. The HSV-1 latency-associated transcript (LAT) gene, the only viral gene that is abundantly transcribed during latency, increases reactivation. Previously we found that during latency with HSV-1 strain McKrae-derived viruses, more of the total TG resident CD8 T cells expressed markers of exhaustion with LAT+ virus compared to LAT− virus. Here we extend these findings to HSV-1 strain 17syn+-derived LAT+ and LAT− viruses and to a virus expressing just the first 20% of LAT. Thus, the previous findings were not an artifact of HSV-1 strain McKrae, and the LAT function involved mapped to the first 1.5 kb of LAT. Importantly, to our knowledge, we show here for the first time that during LAT+ virus latency, most of the HSV-1-specific TG resident CD8 T cells were functionally exhausted, as judged by low cytotoxic function and decreased gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. This resulted in LAT− TG having more functional HSV-gB498–505 tetramer+ CD8+ T cells compared to LAT+ TG. In addition, LAT expression, in the absence of other HSV-1 gene products, appeared to be able to directly or indirectly upregulate both PD-L1 and major histocompatibility complex class I (MHC-I) on mouse neuroblastoma cells (Neuro2A). These findings may constitute a novel immune evasion mechanism whereby the HSV-1 LAT directly or indirectly promotes functional exhaustion (i.e., dysfunction) of HSV-specific CD8+ T cells in latently infected TG, resulting in increased virus reactivation. PMID:21715478

LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma.

PubMed

Strazisar, Mojca; Mlakar, Vid; Glavac, Damjan

2009-06-01

LATS2 is a new member of the LATS tumour suppressor family. The human LATS2 gene is located at chromosome 13q11-12, a hot spot (67%) for loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). We screened 129 non-small cell lung cancer samples and 13 lung cancer cell lines, initially for mutations in the LATS2 gene and subsequently for mutations in P53 and K-RAS genes. Either polymorphisms or mutations were identified in over 50 percent of analysed tumours. A novel missense mutation, S1073R, and a large deletion of 8 amino acids in the PAPA-repeat region were detected in 9 and 2 NSCLC tumours, respectively. Those mutations were not identified in the 13 lung cancer cell lines. Mutations were tumour specific and were absent from adjacent normal tissue and healthy controls. Down-regulation of the LATS2 gene was observed in most NSCLC tumours but was not related to any mutation or polymorphism. Tumours with a LATS2 mutation often also harbour a P53 but not K-RAS gene mutation and were mostly in an advanced stage of development, with regional lymph node involvement.

Fermi-LAT Gamma-ray Bursts and Insight from Swift

NASA Technical Reports Server (NTRS)

Racusin, Judith L.

2011-01-01

A new revolution in GRB observation and theory has begun over the last 3 years since the launch of the Fermi gamma-ray space telescope. The new window into high energy gamma-rays opened by the Fermi-LAT is providing insight into prompt emission mechanisms and possibly also afterglow physics. The LAT detected GRBs appear to be a new unique subset of extremely energetic and bright bursts. In this talk I will discuss the context and recent discoveries from these LAT GRBs and the large database of broadband observations collected by Swift over the last 7 years and how through comparisons between the Swift, GBM, and LAT GRB samples, we can learn about the unique characteristics and relationships between each population.

Localization of the lysine epsilon-aminotransferase (lat) and delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (pcbAB) genes from Streptomyces clavuligerus and production of lysine epsilon-aminotransferase activity in Escherichia coli.

PubMed Central

Tobin, M B; Kovacevic, S; Madduri, K; Hoskins, J A; Skatrud, P L; Vining, L C; Stuttard, C; Miller, J R

1991-01-01

Lysine epsilon-aminotransferase (LAT) in the beta-lactam-producing actinomycetes is considered to be the first step in the antibiotic biosynthetic pathway. Cloning of restriction fragments from Streptomyces clavuligerus, a beta-lactam producer, into Streptomyces lividans, a nonproducer that lacks LAT activity, led to the production of LAT in the host. DNA sequencing of restriction fragments containing the putative lat gene revealed a single open reading frame encoding a polypeptide with an approximately Mr 49,000. Expression of this coding sequence in Escherichia coli led to the production of LAT activity. Hence, LAT activity in S. clavuligerus is derived from a single polypeptide. A second open reading frame began immediately downstream from lat. Comparison of this partial sequence with the sequences of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D valine (ACV) synthetases from Penicillium chrysogenum and Cephalosporium acremonium and with nonribosomal peptide synthetases (gramicidin S and tyrocidine synthetases) found similarities among the open reading frames. Since mapping of the putative N and C termini of S. clavuligerus pcbAB suggests that the coding region occupies approximately 12 kbp and codes for a polypeptide related in size to the fungal ACV synthetases, the molecular characterization of the beta-lactam biosynthetic cluster between pcbC and cefE (approximately 25 kbp) is nearly complete. Images PMID:1917855

The GeV Excess Shining Through: Background Systematics for the Inner Galaxy Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calore, Francesca; Cholis, Ilias; Weniger, Christoph

2015-02-10

Recently, a spatially extended excess of gamma rays collected by the Fermi-LAT from the inner region of the Milky Way has been detected by different groups and with increasingly sophisticated techniques. Yet, any final conclusion about the morphology and spectral properties of such an extended diffuse emission are subject to a number of potentially critical uncertainties, related to the high density of cosmic rays, gas, magnetic fields and abundance of point sources. We will present a thorough study of the systematic uncertainties related to the modelling of diffuse background and to the propagation of cosmic rays in the inner partmore » of our Galaxy. We will test a large set of models for the Galactic diffuse emission, generated by varying the propagation parameters within extreme conditions. By using those models in the fit of Fermi-LAT data as Galactic foreground, we will show that the gamma-ray excess survives and we will quantify the uncertainties on the excess emission morphology and energy spectrum.« less

S5 0716+714: GeV variability study

DOE PAGES

Rani, B.; Krichbaum, T. P.; Lott, B.; ...

2013-02-19

The GeV observations by Fermi-LAT give us the opportunity to characterize the high-energy emission (100 MeV–300 GeV) variability properties of the BL Lac object S5 0716+714. In this study, we performed flux and spectral analysis of more than 3 year long (August 2008 to April 2012) Fermi-LAT data of the source. During this period, the source exhibits two different modes of flux variability with characteristic timescales of ~75 and ~140 days, respectively. In addition, we also notice that the flux variations are characterized by a weak spectral hardening. The GeV spectrum of the source shows a clear deviation from amore » simple power law, and is better explained by a broken power law. Similar to other bright Fermi blazars, the break energy does not vary with the source flux during the different activity states. Finally, we discuss several possible scenarios to explain the observed spectral break.« less

S5 0716+714: GeV variability study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rani, B.; Krichbaum, T. P.; Lott, B.

The GeV observations by Fermi-LAT give us the opportunity to characterize the high-energy emission (100 MeV–300 GeV) variability properties of the BL Lac object S5 0716+714. In this study, we performed flux and spectral analysis of more than 3 year long (August 2008 to April 2012) Fermi-LAT data of the source. During this period, the source exhibits two different modes of flux variability with characteristic timescales of ~75 and ~140 days, respectively. In addition, we also notice that the flux variations are characterized by a weak spectral hardening. The GeV spectrum of the source shows a clear deviation from amore » simple power law, and is better explained by a broken power law. Similar to other bright Fermi blazars, the break energy does not vary with the source flux during the different activity states. Finally, we discuss several possible scenarios to explain the observed spectral break.« less

Fermi Observations of GRB 090510: A Short Hard Gamma-Ray Burst with an Additional, Hard Power-Law Component from 10 keV to GeV Energies

DOE PAGES

Ackermann, M.; Asano, K.; Atwood, W. B.; ...

2010-05-27

We present detailed observations of the bright short-hard gamma-ray burst GRB 090510 made with the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi observatory. GRB 090510 is the first burst detected by the LAT that shows strong evidence for a deviation from a Band spectral fitting function during the prompt emission phase. The time-integrated spectrum is fit by the sum of a Band function with E peak = 3.9 ± 0.3 MeV, which is the highest yet measured, and a hard power-law component with photon index –1.62 ± 0.03 that dominates the emission below ≈20more » keV and above ≈100 MeV. The onset of the high-energy spectral component appears to be delayed by ~0.1 s with respect to the onset of a component well fit with a single Band function. A faint GBM pulse and a LAT photon are detected 0.5 s before the main pulse. During the prompt phase, the LAT detected a photon with energy 30.5 +5.8 –2.6 GeV, the highest ever measured from a short GRB. Observation of this photon sets a minimum bulk outflow Lorentz factor, Γ≳ 1200, using simple γγ opacity arguments for this GRB at redshift z = 0.903 and a variability timescale on the order of tens of ms for the ≈100 keV-few MeV flux. Stricter high confidence estimates imply Γ ≳ 1000 and still require that the outflows powering short GRBs are at least as highly relativistic as those of long-duration GRBs. Finally, implications of the temporal behavior and power-law shape of the additional component on synchrotron/synchrotron self-Compton, external-shock synchrotron, and hadronic models are considered.« less

A robotic system for researching social integration in honeybees.

PubMed

Griparić, Karlo; Haus, Tomislav; Miklić, Damjan; Polić, Marsela; Bogdan, Stjepan

2017-01-01

In this paper, we present a novel robotic system developed for researching collective social mechanisms in a biohybrid society of robots and honeybees. The potential for distributed coordination, as observed in nature in many different animal species, has caused an increased interest in collective behaviour research in recent years because of its applicability to a broad spectrum of technical systems requiring robust multi-agent control. One of the main problems is understanding the mechanisms driving the emergence of collective behaviour of social animals. With the aim of deepening the knowledge in this field, we have designed a multi-robot system capable of interacting with honeybees within an experimental arena. The final product, stationary autonomous robot units, designed by specificaly considering the physical, sensorimotor and behavioral characteristics of the honeybees (lat. Apis mallifera), are equipped with sensing, actuating, computation, and communication capabilities that enable the measurement of relevant environmental states, such as honeybee presence, and adequate response to the measurements by generating heat, vibration and airflow. The coordination among robots in the developed system is established using distributed controllers. The cooperation between the two different types of collective systems is realized by means of a consensus algorithm, enabling the honeybees and the robots to achieve a common objective. Presented results, obtained within ASSISIbf project, show successful cooperation indicating its potential for future applications.

Searching for Dark Matter Signatures in the GLAST LAT Electron Flux

NASA Technical Reports Server (NTRS)

Moiseev, Alexander; Profumo, Stefano

2008-01-01

We explored several viable scenarios of how LAT might observe DM, when the spectral feature is predicted to be observed in the HE electron flux It has been demonstrated elsewhere that LAT will be capable to detect HE electrons flux in energy range from 20 GeV to - 1 TeV with 520% energy resolution and good statistics If there is a DM-caused feature in the HE electron flux (in the range 20 GeV - 1 TeV), LAT will be the best current instrument to observe it!

Influence of Herpes Simplex Virus Latency-Associated Transcript (LAT) on the Distribution of Latently Infected Neurons

DTIC Science & Technology

2007-03-20

part of my life, who knows more about herpesviruses than any 8-year-old should, for making me tea and snacks when I was studying or writing, for...of latency (2, 13, 36, 45, 76, 77, 81). However, HSV-2 LAT has not been shown to inhibit apoptosis of neuronal cells. HSV has several anti ...apoptotic genes, including ICP27, ICP22, US3, US5, ICP4, and HSV-1 LAT (4). Only LAT is expressed during latency, suggesting that its anti -apoptotic

Fermi LAT Observations of Cosmic-Ray Electrons

NASA Technical Reports Server (NTRS)

Moiseev, Alexander

2011-01-01

Designed as a gamma-ray instrument, the LAT is a capable detector of high energy cosmic ray electrons. The LAT is composed of a 4x4 array of identical towers. Each tower has a Tracker and a Calorimeter module. Entire LAT is covered by segmented Anti-Coincidence Detector (ACD). The electron data analysis is based on that developed for photons. The main challenge is to identify and separate electrons from all other charged species, mainly CR protons (for gamma-ray analysis this is provided by the Anti-Coincidence Detector)

The Fermi LAT Very Important Project (VIP) List of Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Thompson, David J.; Fermi Large Area Telescope Collaboration

2018-01-01

Using nine years of Fermi Gamma-ray Space Telescope Large Area Telescope (LAT) observations, we have identified 30 projects for Active Galactic Nuclei (AGN) that appear to provide strong prospects for significant scientific advances. This Very Important Project (VIP) AGN list includes AGNs that have good multiwavelength coverage, are regularly detected by the Fermi LAT, and offer scientifically interesting timing or spectral properties. Each project has one or more LAT scientists identified who are actively monitoring the source. They will be regularly updating the LAT results for these VIP AGNs, working together with multiwavelength observers and theorists to maximize the scientific return during the coming years of the Fermi mission. See https://confluence.slac.stanford.edu/display/GLAMCOG/VIP+List+of+AGNs+for+Continued+Study

Interactions between Herpesvirus Entry Mediator (TNFRSF14) and Latency-Associated Transcript during Herpes Simplex Virus 1 Latency

PubMed Central

Allen, Sariah J.; Rhode-Kurnow, Antje; Mott, Kevin R.; Jiang, Xianzhi; Carpenter, Dale; Rodriguez-Barbosa, J. Ignacio; Jones, Clinton; Wechsler, Steven L.; Ware, Carl F.

2014-01-01

Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune responses and can also increase cell survival. Interestingly, latency-associated transcript (LAT), the only viral gene consistently expressed during neuronal latency, enhances latency and reactivation by promoting cell survival and by helping the virus evade the host immune response. However, the mechanisms of these LAT activities are not well understood. We show here for the first time that one mechanism by which LAT enhances latency and reactivation appears to be by upregulating HVEM expression. HSV-1 latency/reactivation was significantly reduced in Hvem−/− mice, indicating that HVEM plays a significant role in HSV-1 latency/reactivation. Furthermore, LAT upregulated HVEM expression during latency in vivo and also when expressed in vitro in the absence of other viral factors. This study suggests a mechanism whereby LAT upregulates HVEM expression potentially through binding of two LAT small noncoding RNAs to the HVEM promoter and that the increased HVEM then leads to downregulation of immune responses in the latent microenvironment and increased survival of latently infected cells. Thus, one of the mechanisms by which LAT enhances latency/reactivation appears to be through increasing expression of HVEM. PMID:24307582

The use of longitudinal 18F-FET MicroPET imaging to evaluate response to irinotecan in orthotopic human glioblastoma multiforme xenografts.

PubMed

Nedergaard, Mette K; Kristoffersen, Karina; Michaelsen, Signe R; Madsen, Jacob; Poulsen, Hans S; Stockhausen, Marie-Thérése; Lassen, Ulrik; Kjaer, Andreas

2014-01-01

Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared. Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens. The relative tumor-to-brain (T/B) ratio of SUV max was significantly lower after one week (123 ± 6%, n = 7 vs. 147 ± 6%, n = 7; p = 0.018) and after two weeks (142 ± 8%, n = 5 vs. 204 ± 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = -0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts. 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.

In vivo Knock-down of the HSV-1 Latency-Associated Transcript Reduces Reactivation from Latency.

PubMed

Watson, Zachary L; Washington, Shannan D; Phelan, Dane M; Lewin, Alfred S; Tuli, Sonal S; Schultz, Gregory S; Neumann, Donna M; Bloom, David C

2018-06-06

During Herpes Simplex Virus (HSV) latency, most viral genes are silenced with the exception of one region of the genome encoding the latency-associated transcript (LAT). This long non-coding RNA was originally described as having a role in enhancing HSV-1 reactivation. However, subsequent evidence showing that the LAT blocked apoptosis and promoted efficient establishment of latency suggested that its effects on reactivation were secondary to establishment. Here, we utilize an Adeno-associated Virus (AAV) vector to deliver a LAT-targeting hammerhead ribozyme to HSV-1-infected neurons of rabbits after the establishment of HSV-1 latency. The rabbits were then induced to reactivate latent HSV-1. Using this model, we show that decreasing LAT levels in neurons following the establishment of latency reduced the ability of the virus to reactivate. This demonstrates that the HSV-1 LAT RNA has a role in reactivation that is independent of its function in establishment of latency. In addition these results suggest the potential of AAV vectors expressing LAT-targeting ribozymes as a potential therapy for recurrent HSV disease such as herpes stromal keratitis, a leading cause of infectious blindness. Importance Herpes Simplex Virus (HSV) establishes a life long infection and remains dormant (latent) in our nerve cells. Occasionally HSV reactivates to cause disease, with HSV-1 typically causing cold sores whereas HSV-2 is the most common cause of genital herpes. The details of how HSV reactivates are largely unknown. Most of HSV's genes are silent during latency with the exception of RNAs made from the latency-associated transcript (LAT) region. While viruses that make less LAT do not reactivate efficiently, these viruses also do not establish latency as efficiently. Here we deliver a ribozyme that can degrade the LAT to the nerve cells of latently infected rabbits using a gene therapy vector. We show that this treatment blocks reactivation in the majority of the rabbits. This work shows that the LAT RNA is important for reactivation and the suggests the potential of this treatment as a therapy for treating HSV infections. Copyright © 2018 American Society for Microbiology.

Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

PubMed Central

Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

2018-01-01

The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family. PMID:29558430

Fermi large area telescope second source catalog

DOE PAGES

Nolan, P. L.; Abdo, A. A.; Ackermann, M.; ...

2012-03-28

Here, we present the second catalog of high-energy γ-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), derived from data taken during the first 24 months of the science phase of the mission, which began on 2008 August 4. Source detection is based on the average flux over the 24 month period. The second Fermi-LAT catalog (2FGL) includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms of power-law, exponentially cutoff power-law, or log-normal forms. Also included are fluxmore » measurements in five energy bands and light curves on monthly intervals for each source. Twelve sources in the catalog are modeled as spatially extended. Furthermore, we provide a detailed comparison of the results from this catalog with those from the first Fermi-LAT catalog (1FGL). Although the diffuse Galactic and isotropic models used in the 2FGL analysis are improved compared to the 1FGL catalog, we attach caution flags to 162 of the sources to indicate possible confusion with residual imperfections in the diffuse model. Finally, the 2FGL catalog contains 1873 sources detected and characterized in the 100 MeV to 100 GeV range of which we consider 127 as being firmly identified and 1171 as being reliably associated with counterparts of known or likely γ-ray-producing source classes.« less

The high-energy γ -ray emission of AP Librae

DOE PAGES

Abramowski, A.; Aharonian, F.; Ait Benkhali, F.; ...

2014-12-10

In this paper, the γ-ray spectrum of the low-frequency-peaked BL Lac (LBL) object AP Librae is studied, following the discovery of very-high-energy (VHE; E> 100 GeV) γ-ray emission up to the TeV range by the H.E.S.S. experiment. This makes AP Librae one of the few VHE emitters of the LBL type. The measured spectrum yields a flux of (8.8 ± 1.5 stat ± 1.8 sys) × 10 -12 cm -2 s -1 above 130 GeV and a spectral index of Γ = 2.65 ± 0.19 stat ± 0.20 sys. This study also makes use of Fermi-LAT observations in the highmore » energy (HE, E> 100 MeV) range, providing the longest continuous light curve (5 years) ever published on this source. The source underwent a flaring event between MJD 56 306–56 376 in the HE range, with a flux increase of a factor of 3.5 in the 14 day bin light curve and no significant variation in spectral shape with respect to the low-flux state. While the H.E.S.S. and (low state) Fermi-LAT fluxes are in good agreement where they overlap, a spectral curvature between the steep VHE spectrum and the Fermi-LAT spectrum is observed. Finally, the maximum of the γ-ray emission in the spectral energy distribution is located below the GeV energy range.« less

The SLC3 and SLC7 families of amino acid transporters.

PubMed

Fotiadis, Dimitrios; Kanai, Yoshikatsu; Palacín, Manuel

2013-01-01

Amino acids are necessary for all living cells and organisms. Specialized transporters mediate the transfer of amino acids across plasma membranes. Malfunction of these proteins can affect whole-body homoeostasis giving raise to diverse human diseases. Here, we review the main features of the SLC3 and SLC7 families of amino acid transporters. The SLC7 family is divided into two subfamilies, the cationic amino acid transporters (CATs), and the L-type amino acid transporters (LATs). The latter are the light or catalytic subunits of the heteromeric amino acid transporters (HATs), which are associated by a disulfide bridge with the heavy subunits 4F2hc or rBAT. These two subunits are glycoproteins and form the SLC3 family. Most CAT subfamily members were functionally characterized and shown to function as facilitated diffusers mediating the entry and efflux of cationic amino acids. In certain cells, CATs play an important role in the delivery of L-arginine for the synthesis of nitric oxide. HATs are mostly exchangers with a broad spectrum of substrates and are crucial in renal and intestinal re-absorption and cell redox balance. Furthermore, the role of the HAT 4F2hc/LAT1 in tumor growth and the application of LAT1 inhibitors and PET tracers for reduction of tumor progression and imaging of tumors are discussed. Finally, we describe the link between specific mutations in HATs and the primary inherited aminoacidurias, cystinuria and lysinuric protein intolerance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Signs of magnetic acceleration and multizone emission in GRB 080825C

DOE PAGES

Moretti, Elena; Axelsson, Magnus

2016-03-03

One of the major results from the study of gamma-ray bursts with the Fermi Gamma-ray Space Telescope has been the confirmation that several emission components can be present in the energy spectrum. In this paper, we reanalyse the spectrum of GRB 080825C using data from the Fermi-Large Area Telescope (LAT) and Gamma-ray Burst Monitor instruments. Although fairly weak, it is the first gamma-ray burst detected by the Fermi-LAT. We improve on the original analysis by using the LAT Low Energy events covering the 30–100 MeV band. We find evidence of an additional component above the main emission peak (modelled usingmore » a Band function) with a significance of 3.5σ in two out of the four time bins. The component is well fitted by a Planck function, but shows unusual behaviour: the peak energy increases in the prompt emission phase, reaching energies of several MeV. This is the first time such a trend has been seen, and implies that the origin of this component is different from those previously detected. We suggest that the two spectral components likely arise in different regions of the outflow, and that strong constraints can be achieved by assuming one of them originates from the photosphere. Finally, the most promising model appears to be that the high-energy peak is the result of photospheric emission in a Poynting flux dominated outflow where the magnetization increases with time.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moretti, Elena; Axelsson, Magnus

One of the major results from the study of gamma-ray bursts with the Fermi Gamma-ray Space Telescope has been the confirmation that several emission components can be present in the energy spectrum. In this paper, we reanalyse the spectrum of GRB 080825C using data from the Fermi-Large Area Telescope (LAT) and Gamma-ray Burst Monitor instruments. Although fairly weak, it is the first gamma-ray burst detected by the Fermi-LAT. We improve on the original analysis by using the LAT Low Energy events covering the 30–100 MeV band. We find evidence of an additional component above the main emission peak (modelled usingmore » a Band function) with a significance of 3.5σ in two out of the four time bins. The component is well fitted by a Planck function, but shows unusual behaviour: the peak energy increases in the prompt emission phase, reaching energies of several MeV. This is the first time such a trend has been seen, and implies that the origin of this component is different from those previously detected. We suggest that the two spectral components likely arise in different regions of the outflow, and that strong constraints can be achieved by assuming one of them originates from the photosphere. Finally, the most promising model appears to be that the high-energy peak is the result of photospheric emission in a Poynting flux dominated outflow where the magnetization increases with time.« less

Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

PubMed

Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

2018-03-20

The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

TOMOGRAPHY OF THE FERMI-LAT γ-RAY DIFFUSE EXTRAGALACTIC SIGNAL VIA CROSS CORRELATIONS WITH GALAXY CATALOGS

DOE PAGES

Xia, Jun-Qing; Cuoco, Alessandro; Branchini, Enzo; ...

2015-03-24

Building on our previous cross-correlation analysis (Xia et al. 2011) between the isotropic γ-ray background (IGRB) and different tracers of the large-scale structure of the universe, we update our results using 60 months of data from the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi). For this study, we perform a cross-correlation analysis both in configuration and spherical harmonics space between the IGRB and objects that may trace the astrophysical sources of the IGRB: QSOs in the Sloan Digital Sky Survey (SDSS) DR6, the SDSS DR8 Main Galaxy Sample, luminous red galaxies (LRGs) in the SDSS catalog, infrared-selected galaxies in the Two Micron All Sky Survey (2MASS), and radio galaxies in the NRAO VLA Sky Survey (NVSS). The benefit of correlating the Fermi-LAT signal with catalogs of objects at various redshifts is to provide tomographic information on the IGRB, which is crucial in separating the various contributions and clarifying its origin. The main result is that, unlike in our previous analysis, we now observe a significant (>3.5σ) cross-correlation signal on angular scales smaller than 1° in the NVSS, 2MASS, and QSO cases and, at lower statistical significance (~3.0σ), with SDSS galaxies. The signal is stronger in two energy bands, E > 0.5 GeV and E > 1 GeV, but it is also seen at E > 10 GeV. No cross-correlation signal is detected between Fermi data and the LRGs. These results are robust against the choice of the statistical estimator, estimate of errors, map cleaning procedure, and instrumental effects. Finally, we test the hypothesis that the IGRB observed by Fermi-LAT originates from the summed contributions of three types of unresolved extragalactic sources: BL Lacertae objects (BL Lacs), flat spectrum radio quasars (FSRQs), and star-forming galaxies (SFGs). Finally, we find that a model in which the IGRB is mainly produced by SFGs (more » $$72_{-37}^{+23}$$% with 2σ errors), with BL Lacs and FSRQs giving a minor contribution, provides a good fit to the data. We also consider a possible contribution from misaligned active galactic nuclei, and we find that, depending on the details of the model and its uncertainty, they can also provide a substantial contribution, partly degenerate with the SFG one.« less

Pulsar simulations for the Fermi Large Area Telescope

DOE PAGES

Razzano, M.; Harding, Alice K.; Baldini, L.; ...

2009-05-21

Pulsars are among the prime targets for the Large Area Telescope (LAT) aboard the recently launched Fermi observatory. The LAT will study the gamma-ray Universe between 20 MeV and 300 GeV with unprecedented detail. Increasing numbers of gamma-ray pulsars are being firmly identified, yet their emission mechanisms are far from being understood. To better investigate and exploit the LAT capabilities for pulsar science, a set of new detailed pulsar simulation tools have been developed within the LAT collaboration. The structure of the pulsar simulator package ( PulsarSpectrum) is presented here. Starting from photon distributions in energy and phase obtained frommore » theoretical calculations or phenomenological considerations, gamma-rays are generated and their arrival times at the spacecraft are determined by taking into account effects such as barycentric effects and timing noise. Pulsars in binary systems also can be simulated given orbital parameters. As a result, we present how simulations can be used for generating a realistic set of gamma-rays as observed by the LAT, focusing on some case studies that show the performance of the LAT for pulsar observations.« less

Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells.

PubMed

Januchowski, Radosław; Jagodzinski, Paweł P

2007-02-01

We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA) effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the signal transduction pathway from T cell receptor to nucleus. Using reverse transcription real-time quantitative PCR and Western blotting analysis we observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down-regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9 and 1.7 h, respectively. Employing the protein biosynthesis inhibitor cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP-70, LAT and SLP-76 content in T cells confirms an immunosuppressive effect by TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of autoimmune diseases.

A PLC-γ1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

PubMed Central

Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Markegard, Evan; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P.; Blumberg, Peter M.; Samelson, Lawrence E.; Sommers, Connie L.

2012-01-01

Mice expressing a germline mutation in the PLC-γ1 binding site of LAT (linker for activation of T cells) show progressive lymphoproliferation and ultimately die at 4–6 months of age. The hyper-activated T cells in these mice show defective TCR-induced calcium flux, but enhanced Ras/ERK activation that is critical for disease progression. Despite the loss of LAT-dependent PLC-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major RasGEF responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4+ T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, PKCθ, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

Structural basis for Mob1-dependent activation of the core Mst–Lats kinase cascade in Hippo signaling

DOE PAGES

Ni, Lisheng; Zheng, Yonggang; Hara, Mayuko; ...

2015-06-24

The Mst–Lats kinase cascade is central to the Hippo tumor-suppressive pathway that controls organ size and tissue homeostasis. The adaptor protein Mob1 promotes Lats activation by Mst, but the mechanism remains unknown. Here, we show that human Mob1 binds to autophosphorylated docking motifs in active Mst2. This binding enables Mob1 phosphorylation by Mst2. Phosphorylated Mob1 undergoes conformational activation and binds to Lats1. We determine the crystal structures of phospho-Mst2–Mob1 and phospho-Mob1–Lats1 complexes, revealing the structural basis of both phosphorylation-dependent binding events. Further biochemical and functional analyses demonstrate that Mob1 mediates Lats1 activation through dynamic scaffolding and allosteric mechanisms. Thus, Mob1more » acts as a phosphorylation-regulated coupler of kinase activation by virtue of its ability to engage multiple ligands. We propose that stepwise, phosphorylation-triggered docking interactions of nonkinase elements enhance the specificity and robustness of kinase signaling cascades.« less

Laser-assisted tympanostomy (LAT) in adult individuals

NASA Astrophysics Data System (ADS)

Prokopakis, E. P.; Lachanas, V. A.; Helidonis, Emmanuel S.; Velegrakis, G.

2004-06-01

Objectives: To assess outcome, in adult individuals undergone Laser Assisted Tympanostomy (LAT) without ventilation tube placement. Method: LAT was performed on a total of 95 ears (72 individuals). Indications included serous otitis media with effusion (44 ears/31 patients), eustachian tube dysfunction (32 ears/24 patients), acute otitis media (13 ears/11 patients), and endoscopic visualization of the middle ear (6 ears/6 patients). Results: Middle ear disease was resolved after the closure of tympanostomy in 48% of patients with serous otitis media with effusion. In 78% of patients with Eustachian tube dysfunction symptoms were diminished. All patients with acute otitis media had a satisfactory outcome. LAT was found quite effective in patients undergoing middle ear endoscopy. Conclusion: LAT without ventilation tubes provides a safe alternative surgical option in adult patients in certain cases. The selection criteria for this procedure are addressed in detail.

Advantages of Efficacy and Safety of Fixed-Dose Tafluprost/Timolol Combination Over Fixed-Dose Latanoprost/Timolol Combination.

PubMed

Fuwa, Masahiro; Ueda, Kenji; Akaishi, Takahiro; Yamashita, Naoko; Kirihara, Tomoko; Shimazaki, Atsushi; Mano, Hidetoshi; Kawazu, Kouichi

2016-01-01

To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity. The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated. The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs. Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.

Advantages of Efficacy and Safety of Fixed-Dose Tafluprost/Timolol Combination Over Fixed-Dose Latanoprost/Timolol Combination

PubMed Central

Fuwa, Masahiro; Ueda, Kenji; Akaishi, Takahiro; Yamashita, Naoko; Kirihara, Tomoko; Shimazaki, Atsushi; Mano, Hidetoshi; Kawazu, Kouichi

2016-01-01

Purpose To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity. Methods The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1–30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated. Results The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4–8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24–30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24–30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs. Conclusion Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC. PMID:27383260

Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo.

PubMed

Kalia, Neena; Auger, Jocelyn M; Atkinson, Ben; Watson, Steve P

2008-05-01

The role of collagen receptor complex GPVI-FcR gamma-chain, PLCgamma2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLCgamma2 and thrombin. Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLCgamma2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Significantly reduced thrombus formation was observed in FcR gamma-chain and PLCgamma2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. GPVI-FcR gamma-chain, LAT and PLCgamma2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.

Characterization of herpes simplex virus 2 primary microRNA Transcript regulation.

PubMed

Tang, Shuang; Bosch-Marce, Marta; Patel, Amita; Margolis, Todd P; Krause, Philip R

2015-05-01

In order to understand factors that may influence latency-associated transcription and latency-associated transcript (LAT) phenotypes, we studied the expression of the herpes simplex virus 2 (HSV-2) LAT-associated microRNAs (miRNAs). We mapped the transcription initiation sites of all three primary miRNA transcripts and identified the ICP4-binding sequences at the transcription initiation sites of both HSV-2 LAT (pri-miRNA for miR-I and miR-II, which target ICP34.5, and miR-III, which targets ICP0) and L/ST (a pri-miRNA for miR-I and miR-II) but not at that of the primary miR-H6 (for which the target is unknown). We confirmed activity of the putative HSV-2 L/ST promoter and found that ICP4 trans-activates the L/ST promoter when the ICP4-binding site at its transcription initiation site is mutated, suggesting that ICP4 may play a dual role in regulating transcription of L/ST and, consequently, of miR-I and miR-II. LAT exon 1 (containing LAT enhancer sequences), together with the LAT promoter region, comprises a bidirectional promoter required for the expression of both LAT-encoded miRNAs and miR-H6 in latently infected mouse ganglia. The ability of ICP4 to suppress ICP34.5-targeting miRNAs and to activate lytic viral genes suggests that ICP4 could play a key role in the switch between latency and reactivation. The HSV-2 LAT and viral miRNAs expressed in the LAT region are the most abundant viral transcripts during HSV latency. The balance between the expression of LAT and LAT-associated miRNAs and the expression of lytic viral transcripts from the opposite strand appears to influence whether individual HSV-infected neurons will be latently or productively infected. The outcome of neuronal infection may thus depend on regulation of gene expression of the corresponding primary miRNAs. In the present study, we characterize promoter sequences responsible for miRNA expression, including identification of the primary miRNA 5' ends and evaluation of ICP4 response. These findings provide further insight into the virus' strategy to tightly control expression of lytic cycle genes (especially the neurovirulence factor, ICP34.5) and suggest a mechanism (via ICP4) for the transition from latency to reactivated productive infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Characterization of Herpes Simplex Virus 2 Primary MicroRNA Transcript Regulation

PubMed Central

Bosch-Marce, Marta; Patel, Amita; Margolis, Todd P.

2015-01-01

ABSTRACT In order to understand factors that may influence latency-associated transcription and latency-associated transcript (LAT) phenotypes, we studied the expression of the herpes simplex virus 2 (HSV-2) LAT-associated microRNAs (miRNAs). We mapped the transcription initiation sites of all three primary miRNA transcripts and identified the ICP4-binding sequences at the transcription initiation sites of both HSV-2 LAT (pri-miRNA for miR-I and miR-II, which target ICP34.5, and miR-III, which targets ICP0) and L/ST (a pri-miRNA for miR-I and miR-II) but not at that of the primary miR-H6 (for which the target is unknown). We confirmed activity of the putative HSV-2 L/ST promoter and found that ICP4 trans-activates the L/ST promoter when the ICP4-binding site at its transcription initiation site is mutated, suggesting that ICP4 may play a dual role in regulating transcription of L/ST and, consequently, of miR-I and miR-II. LAT exon 1 (containing LAT enhancer sequences), together with the LAT promoter region, comprises a bidirectional promoter required for the expression of both LAT-encoded miRNAs and miR-H6 in latently infected mouse ganglia. The ability of ICP4 to suppress ICP34.5-targeting miRNAs and to activate lytic viral genes suggests that ICP4 could play a key role in the switch between latency and reactivation. IMPORTANCE The HSV-2 LAT and viral miRNAs expressed in the LAT region are the most abundant viral transcripts during HSV latency. The balance between the expression of LAT and LAT-associated miRNAs and the expression of lytic viral transcripts from the opposite strand appears to influence whether individual HSV-infected neurons will be latently or productively infected. The outcome of neuronal infection may thus depend on regulation of gene expression of the corresponding primary miRNAs. In the present study, we characterize promoter sequences responsible for miRNA expression, including identification of the primary miRNA 5′ ends and evaluation of ICP4 response. These findings provide further insight into the virus' strategy to tightly control expression of lytic cycle genes (especially the neurovirulence factor, ICP34.5) and suggest a mechanism (via ICP4) for the transition from latency to reactivated productive infection. PMID:25673716

Chandra and Swift Observations of Unidentified Fermi-LAT Objects

NASA Astrophysics Data System (ADS)

Donato, Davide; Cheung, T.; Gehrels, N.

2010-03-01

In the last year we targeted some of the unidentified Fermi-LAT objects (UFOs) at high Galactic latitude with Chandra and Swift in order to determine the basic properties (positions, fluxes, hardness ratios) of all X-ray sources within the Fermi-LAT localization circles. These satellites enable us to detect the X-ray conterparts with a flux limit that is at least an order of magnitude lower than achieved in extant RASS data and to further follow-up at other wavelengths, with the ultimate goal to reveal the nature of these enigmatic gamma-ray sources. Here we present the results obtained with 5 Chandra pointings of high Galactic latitude UFOs in the Fermi-LAT 3-months bright source list. The association of detected X-ray sources within the improved 11-months Fermi-LAT localization circles with available optical and radio observations is discussed.

Fermi-LAT Gamma-Ray Detections of Classical Novae V1369 Centauri 2013 and V5668 Sagittarii 2015

NASA Astrophysics Data System (ADS)

Cheung, C. C.; Jean, P.; Shore, S. N.; Stawarz, Ł.; Corbet, R. H. D.; Knödlseder, J.; Starrfield, S.; Wood, D. L.; Desiante, R.; Longo, F.; Pivato, G.; Wood, K. S.

2016-08-01

We report the Fermi Large Area Telescope (LAT) detections of high-energy (>100 MeV) γ-ray emission from two recent optically bright classical novae, V1369 Centauri 2013 and V5668 Sagittarii 2015. At early times, Fermi target-of-opportunity observations prompted by their optical discoveries provided enhanced LAT exposure that enabled the detections of γ-ray onsets beginning ˜2 days after their first optical peaks. Significant γ-ray emission was found extending to 39-55 days after their initial LAT detections, with systematically fainter and longer-duration emission compared to previous γ-ray-detected classical novae. These novae were distinguished by multiple bright optical peaks that encompassed the time spans of the observed γ-rays. The γ-ray light curves and spectra of the two novae are presented along with representative hadronic and leptonic models, and comparisons with other novae detected by the LAT are discussed.

The First FERMI-LAT Gamma-Ray Burst Catalog

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Asano, K.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.;

The first Fermi-LAT Gamma-Ray burst catalog

DOE PAGES

Ackermann, M.; Ajello, M.; Asano, K.; ...

2013-10-23

In three years of observations since the beginning of nominal science operations in 2008 August, the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope has observed high-energy (gsim 20 MeV) γ-ray emission from 35 gamma-ray bursts (GRBs). Among these, 28 GRBs have been detected above 100 MeV and 7 GRBs above ~20 MeV. The first Fermi-LAT catalog of GRBs is a compilation of these detections and provides a systematic study of high-energy emission from GRBs for the first time. To generate the catalog, we examined 733 GRBs detected by the Gamma-Ray Burst Monitor (GBM) on Fermi andmore » processed each of them using the same analysis sequence. Details of the methodology followed by the LAT collaboration for the GRB analysis are provided. Here, we summarize the temporal and spectral properties of the LAT-detected GRBs. We also discuss characteristics of LAT-detected emission such as its delayed onset and longer duration compared with emission detected by the GBM, its power-law temporal decay at late times, and the fact that it is dominated by a power-law spectral component that appears in addition to the usual Band model.« less

Multiscale Pigment Analysis of Medieval Illuminated Manuscripts

NASA Astrophysics Data System (ADS)

Sestak, Erica; Manukyan, Khachatur; Wiescher, Michael; Gura, David

2017-09-01

Three medieval illuminated manuscripts (codd. Lat. b. 1; Lat. b. 2; Lat. e. 4), housed at the University of Notre Dame's Hesburgh Library, vary in style, pigments, scribes, and regions, despite all three being Psalters used in the Late Middle Ages. XRF and Raman spectroscopy, which provided the elemental and molecular composition of the pigments, respectively, were used to analyze the pigments' compositions in an attempt to narrow further the manuscripts' possible origins. This experimental investigation emphasizes the importance of understanding the history of the manuscript through their pigments. Codd. Lat. b. 1 and Lat. b. 2 are Latinate German Psalters from the fifteenth century likely used in Katharinenkloster in Nuremberg. While there are visible differences in style within each Psalter, the variations in some of the pigment compositions, such as the inconstant presence of zinc, suggest different admixtures. Cod. Lat. e. 4 is a Latinate English Psalter from the fourteenth century, and it was written by two scribes and illuminated by two distinct painters. It is currently being tested to determine whether there are any correlations between the scribes and painters. These physical analyses will clarify the origins and provenances of the manuscripts.

First light from the Vela pulsar with the Fermi Gamma-ray Space Telescope

NASA Astrophysics Data System (ADS)

Razzano, M.

2009-04-01

The Fermi Gamma-ray Space Telescope, launched in June 2008, is an international space mission entirely devoted to the study of the high-energy gamma rays from the Universe. The main instrument aboard Fermi is the Large Area Telescope (LAT), a pair conversion telescope equipped with the state-of-the art in gamma-ray detectors technology. Thanks to its large field of view and effective area, combined with its excellent timing capability, Fermi-LAT is a perfect instrument for probing physics of gamma-ray emission in pulsars. LAT is expected to discover tens of new pulsars, both radio-loud and radio-quiet (Geminga-like). Moreover, LAT will observe with unprecedented statistics the brightest pulsars, investigating the details of magnetospheric emission. The first two months of the mission have been focused on the commissioning and first light, during which the LAT firmly detected the six previously known EGRET gamma-ray pulsars. One of the main sources of interest during our first light observations has been the Vela pulsar, the brightest persistent source in the whole gamma-ray sky. Thanks to its brightness, the Vela pulsar is an ideal candidate for calibrating the LAT and testing its performance. In addition, observations of Vela will help answer many questions related to the physics of pulsar emission processes. We present here some recent results obtained by the LAT on the Vela pulsar, using high-quality timing solutions provided by radio observations carried out within the Fermi pulsar radio timing campaign.

Water and sediment dynamics in the Red River mouth and adjacent coastal zone

NASA Astrophysics Data System (ADS)

van Maren, D. S.

2007-02-01

The coastline of the Red River Delta is characterized by alternating patterns of rapid accretion and severe erosion. The main branch of the Red River, the Ba Lat, is presently expanding seaward with a main depositional area several km downstream and offshore the Ba Lat River mouth. Sediment deposition rates are approximately 6 m in the past 50 years. Field measurements were done to determine the processes that regulate marine dispersal and deposition of sediment supplied by the Ba Lat. These measurements reveal that the waters surrounding the Ba Lat delta are strongly stratified with a pronounced southward-flowing surface layer. This southward-flowing surface layer is a coastal current which is generated by river plumes that flow into the coastal zone north of the Ba Lat. However, outflow of turbid river water is not continuous and most sediment enters the coastal zone when the alongshore surface velocities are low. As a consequence, most sediment settles from suspension close to the river mouth. In addition to the southward surface flow, the southward near-bottom currents are also stronger than northward currents. Contrasting with the residual flow near-surface, this southward flow component near-bottom is caused by tidal asymmetry. Because most sediment is supplied by the Ba Lat when wave heights are low, sediment is able to consolidate and therefore the long-term deposition is southward of, but still close to, the Ba Lat mouth.

78 FR 48293 - Amendment of Class D and Class E Airspace; San Marcos, TX

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

..., TX [Amended] San Marcos Municipal Airport, TX (Lat. 29[deg]53'34'' N., long. 97[deg]51'47'' W.) That...] San Marcos Municipal Airport, TX (Lat. 29[deg]53'34'' N., long. 97[deg]51'47'' W.) Lockhart Municipal Airport, TX (Lat. 29[deg]51'01'' N., long. 97[deg]40'21'' W.) That airspace extending upward from 700 feet...

76 FR 15825 - Amendment of Class E Airspace; Pueblo, CO

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

... [Modified] Pueblo Memorial Airport, CO (Lat. 38[deg]17'21'' N., long. 104[deg]29'47'' W.) That airspace... within the 28.8-mile radius of Pueblo Memorial Airport clockwise between the 070[deg] and 133[deg... lat. 37[deg]37'26'' N., long. 105[deg]00'02'' W.; to lat. 38[deg]09'25'' N., long. 105[deg]08'06'' W...

78 FR 33263 - Proposed Amendment of Class D and Class E Airspace; San Marcos, TX

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

...] San Marcos Municipal Airport, TX (Lat. 29[deg]53'34'' N., long. 97[deg]51'47'' W.) That airspace... [Amended] San Marcos Municipal Airport, TX (Lat. 29[deg]53[min]34[sec] N., long. 97[deg]51'47'' W.) Lockhart Municipal Airport, TX (Lat. 29[deg]51'01'' N., long. 97[deg]40'21'' W.) That airspace extending...

Fermi-LAT detection of increased gamma-ray activity of TXS 0506+056, located inside the IceCube-170922A error region.

NASA Astrophysics Data System (ADS)

Tanaka, Yasuyuki T.; Buson, Sara; Kocevski, Daniel

2017-09-01

We searched for Fermi-LAT sources inside the extremely high-energy (EHE) IceCube-170922A neutrino event error region (https://gcn.gsfc.nasa.gov/gcn3/21916.gcn3, see also ATels 10773, 10787) with all-sky survey data from the Large Area Telescope (LAT), on board the Fermi Gamma-ray Space Telescope.

75 FR 32865 - Proposed Revision of Class E Airspace; Unalakleet, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

...] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57'' W.) Unalakleet Localizer (Lat. 63[deg]52'52'' N., long. 160[deg]47'42'' W.) Within a 4.2-mile radius of the Unalakleet Airport, AK, and.... * * * * * AAL AK E5 Unalakleet, AK [Revised] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57...

75 FR 62459 - Revision of Class E Airspace; Unalakleet, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

...] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57'' W.) Unalakleet Localizer (Lat. 63[deg]52'52'' N., long. 160[deg]47'42'' W.) Within a 4.2-mile radius of the Unalakleet Airport, AK, and.... * * * * * AAL AK E5 Unalakleet, AK [Revised] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57...

Herpes Simplex Virus 2 MicroRNA miR-H6 Is a Novel Latency-Associated Transcript-Associated MicroRNA, but Reduction of Its Expression Does Not Influence the Establishment of Viral Latency or the Recurrence Phenotype▿

PubMed Central

Tang, Shuang; Bertke, Andrea S.; Patel, Amita; Margolis, Todd P.; Krause, Philip R.

2011-01-01

The herpes simplex virus 2 (HSV-2) viral microRNA (miRNA) designated miR-H6 is located upstream of the latency-associated transcript (LAT) promoter region on the strand opposite the LAT. Deletion of the LAT promoter and part of LAT exon 1 abolished HSV-2 miR-H6 expression in acutely and latently infected guinea pig dorsal root ganglia (DRG), suggesting that this region is needed both for the expression of LAT-encoded miRNAs and for miR-H6 expression in vivo. Relative to cells infected with a viral rescuant, miR-H6 expression was significantly reduced in cells infected with a mutant HSV-2 virus, NotPolyA, with an insertion of a simian virus (SV40) polyadenylation signal sequence between the LAT promoter and miR-H6 sequences. In addition, expression of miR-H6, but not LAT or viral DNA, was significantly reduced in both mouse trigeminal ganglia (TG) and guinea pig DRG latently infected with the NotPolyA mutant. Guinea pigs infected with NotPolyA experienced reduced neurological complications of acute infection relative to those infected with the rescuant, but the recurrence phenotype of the NotPolyA mutant was similar to those of its rescuant and wild-type HSV-2, indicating that reduction of miR-H6 expression is not by itself able to alter the establishment of latency for the wild-type virus or the recurrence phenotype. Furthermore, the mutation in NotPolyA did not affect the propensity of wild-type HSV-2 to establish latency in neurons positive for subtype marker KH10. In contrast to published reports regarding its HSV-1 homolog, HSV-2 miR-H6 did not affect ICP4 expression in transfected or infected cells. We hypothesize that viral miRNAs associated with LAT expression are likely to work collectively, contributing to the phenotype attributed to the LAT. PMID:21325410

The X-Ray Counterpart to LAT PSR J2021+4026 and Its Interesting Spectrum

NASA Technical Reports Server (NTRS)

Weisskopf, Martin C.; Becker, W.; Carraminana, A.; De Luca, A.; Dormandy, M.; Harding, A.; Kanbach, G.; O'Dell, S. L.; Parkinson, P. Saz; Ray, P.;

Search for Spatially Extended Fermi-LAT Sources Using Two Years of Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lande, Joshua; Ackermann, Markus; Allafort, Alice

2012-07-13

Spatial extension is an important characteristic for correctly associating {gamma}-ray-emitting sources with their counterparts at other wavelengths and for obtaining an unbiased model of their spectra. We present a new method for quantifying the spatial extension of sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi). We perform a series of Monte Carlo simulations to validate this tool and calculate the LAT threshold for detecting the spatial extension of sources. We then test all sources in the second Fermi -LAT catalog (2FGL) for extension. We report the detection of sevenmore » new spatially extended sources.« less

Three millisecond pulsars in FERMI LAT unassociated bright sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ransom, S. M.; Ray, P. S.; Camilo, F.

2010-12-23

We searched for radio pulsars in 25 of the non-variable, unassociated sources in the Fermi LAT Bright Source List with the Green Bank Telescope at 820 MHz. Here, we report the discovery of three radio and γ-ray millisecond pulsars (MSPs) from a high Galactic latitude subset of these sources. All of the pulsars are in binary systems, which would have made them virtually impossible to detect in blind γ-ray pulsation searches. They seem to be relatively normal, nearby (≤2 kpc) MSPs. These observations, in combination with the Fermi detection of γ-rays from other known radio MSPs, imply that most, ifmore » not all, radio MSPs are efficient γ-ray producers. The γ-ray spectra of the pulsars are power law in nature with exponential cutoffs at a few GeV, as has been found with most other pulsars. The MSPs have all been detected as X-ray point sources. Finally, their soft X-ray luminosities of ~10 30-10 31 erg s –1 are typical of the rare radio MSPs seen in X-rays.« less

Fermi Large Area Telescope observations of PSR J1836+5925

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2010-03-11

The discovery of the γ-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25° off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1 × 10 34 erg s –1, and a large off-peak (OP) emission component, making it quite unusual among the known γ-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results, and a long-term lightmore » curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the OP emission indicate it is likely magnetospheric. Finally, analysis of recent XMM-Newton observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.« less

Discovery of a GeV blazar shining through the galactic plane

DOE PAGES

Vandenbroucke, J.; Buehler, R.; Ajello, M.; ...

2010-07-14

The Fermi Large Area Telescope (LAT) discovered a new gamma-ray source near the Galactic plane, Fermi J0109+6134, when it flared brightly in 2010 February. The low Galactic latitude (b = –1more » $$ο\\atop{.}$$2) indicated that the source could be located within the Galaxy, which motivated rapid multi-wavelength follow-up including radio, optical, and X-ray observations. Here, we report the results of analyzing all 19 months of LAT data for the source, and of X-ray observations with both Swift and the Chandra X-ray Observatory. We determined the source redshift, z = 0.783, using a Keck Low-Resolution Imaging Spectrometer observation. Finally, we compiled a broadband spectral energy distribution (SED) from both historical and new observations contemporaneous with the 2010 February flare. The redshift, SED, optical line width, X-ray absorption, and multi-band variability indicate that this new GeV source is a blazar seen through the Galactic plane. Because several of the optical emission lines have equivalent width >5 Å, this blazar belongs in the flat-spectrum radio quasar category.« less

Characteristics of Gamma-Ray Loud Blazars in the VLBA Imaging and Polarimetry Survey

NASA Technical Reports Server (NTRS)

Linford, J. D.; Taylor, G. B.; Romani, R. W.; Healey, S. E.; Helmboldt, J. F.; Readhead, A. C.; Reeves, R.; Richards, J. L.; Cotter, G.

2010-01-01

The radio properties of blazars detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope have been observed as part of the VLBA Imaging and Polarimetry Survey. This large, flux-limited sample of active galactic nuclei (AGNs) provides insights into the mechanism that produces strong gamma-ray emission. At lower flux levels, radio flux density does not directly correlate with gamma-ray flux. We find that the LAT-detected BL Lac objects tend to be similar to the non-LAT BL Lac objects, but that the LAT-detected FSRQs are often significantly different from the non-LAT FSRQs. The differences between the gamma-ray loud and quiet FSRQS can be explained by Doppler boosting; these objects appear to require larger Doppler factors than those of the BL Lac objects. It is possible that the gamma-ray loud FSRQs are fundamentally different from the gamma-ray quiet FSRQs. Strong polarization at the base of the jet appears to be a signature for gamma-ray loud AGNs.

Fermi-LAT Gamma-Ray Bursts and Insights from Swift

NASA Technical Reports Server (NTRS)

Racusin, Judith L.

2010-01-01

A new revolution in Gamma-ray Burst (GRB) observations and theory has begun over the last two years since the launch of the Fermi Gamma-ray Space Telescope. The new window into high energy gamma-rays opened by the Fermi-Large Area Telescope (LAT) is providing insight into prompt emission mechanisms and possibly also afterglow physics. The LAT detected GRBs appear to be a new unique subset of extremely energetic and bright bursts compared to the large sample detected by Swift over the last 6 years. In this talk, I will discuss the context and recent discoveries from these LAT GRBs and the large database of broadband observations collected by the Swift X-ray Telescope (XRT) and UV/Optical Telescope (UVOT). Through comparisons between the GRBs detected by Swift-BAT, G8M, and LAT, we can learn about the unique characteristics, physical differences, and the relationships between each population. These population characteristics provide insight into the different physical parameters that contribute to the diversity of observational GRB properties.

Zyxin-Siah2–Lats2 axis mediates cooperation between Hippo and TGF-β signalling pathways

PubMed Central

Ma, Biao; Cheng, Hongcheng; Gao, Ruize; Mu, Chenglong; Chen, Ling; Wu, Shian; Chen, Quan; Zhu, Yushan

2016-01-01

The evolutionarily conserved Hippo pathway is a regulator that controls organ size, cell growth and tissue homeostasis. Upstream signals of the Hippo pathway have been widely studied, but how microenvironmental factors coordinately regulate this pathway remains unclear. In this study, we identify LIM domain protein Zyxin, as a scaffold protein, that in response to hypoxia and TGF-β stimuli, forms a ternary complex with Lats2 and Siah2 and stabilizes their interaction. This interaction facilitates Lats2 ubiquitination and degradation, Yap dephosphorylation and subsequently activation. We show that Zyxin is required for TGF-β and hypoxia-induced Lats2 downregulation and deactivation of Hippo signalling in MDA-MB-231 cells. Depletion of Zyxin impairs the capability of cell migration, proliferation and tumourigenesis in a xenograft model. Zyxin is upregulated in human breast cancer and positively correlates with histological stages and metastasis. Our study demonstrates that Zyxin-Lats2–Siah2 axis may serve as a potential therapeutic target in cancer treatment. PMID:27030211

Gamma-ray activity of Seyfert galaxies and constraints on hot accretion flows

NASA Astrophysics Data System (ADS)

Wojaczyński, Rafał; Niedźwiecki, Andrzej; Xie, Fu-Guo; Szanecki, Michał

2015-12-01

Aims: We check how the Fermi/LAT data constrain the physics of hot accretion flows that are most likely present in low-luminosity AGNs. Methods: Using a precise model of emission from hot flows, we studied the flow γ-ray emission resulting from proton-proton interactions. We explored the dependence of the γ-ray luminosity on the accretion rate, the black hole spin, the magnetic field strength, the electron heating efficiency, and the particle distribution. Then, we compared the hadronic γ-ray luminosities predicted by the model for several nearby Seyfert 1 galaxies with the results of our analysis of 6.4 years of Fermi/LAT observations of these AGNs. Results: In agreement with previous studies, we find a significant γ-ray detection in NGC 6814. We were only able to derive upper limits for the remaining objects, although we report marginally significant (~3σ) signals at the positions of NGC 4151 and NGC 4258. The derived upper limits for the flux above 1 GeV allow us to constrain the proton acceleration efficiency in flows with heating of electrons dominated by Coulomb interactions, which case is favored by the X-ray spectral properties. In these flows, at most ~10% of the accretion power can be used for a relativistic acceleration of protons. Upper limits for the flux below 1 GeV can constrain the magnetic field strength and black hole spin value; we find these constraints for NGC 7213 and NGC 4151. We also note that the spectral component above ~4 GeV previously found in the Fermi/LAT data of Centaurus A may be due to hadronic emission from a flow within the above constraint. We rule out this origin of the γ-ray emission for NGC 6814. For models with a strong magnetohydrodynamic heating of electrons, the hadronic γ-ray fluxes are below the Fermi/LAT sensitivity even for the closest AGNs. In these models, nonthermal Compton radiation may dominate in the γ-ray range if electrons are efficiently accelerated and the acceleration index is hard; for the index ≃2, the LAT upper limits constrain the fraction of accretion power used for such an acceleration to at most ~5%. Finally, we note that the three Seyfert 2 galaxies with high starburst activity NGC 4595, NGC 1068, and Circinus show an interesting correlation of their γ-ray luminosities with properties of their active nuclei, and we discuss this in the context of the hot flow model.

Suenos Indocumentados: Using LatCrit to Explore the Testimonios of Undocumented and U.S. Born Chicana College Students on Discourses of Racist Nativism in Education

ERIC Educational Resources Information Center

Huber, Lindsay Perez

2010-01-01

Latina/o critical race theory (LatCrit) is used as an overarching framework that examines the intersectionality of race, class, and gender while also acknowledging the unique forms of subordination within the Latina/o community based on immigration status, language, phenotype, and ethnicity. LatCrit allows for the specific examination of race and…

78 FR 16823 - Proposed Establishment of Class E Airspace; Tuba City, AZ

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

...., long. 109[deg]35'55'' W.; to lat. 37[deg]04'41'' N., long. 109[deg]38'16'' W.; to lat. 36[deg]57'10'' N...., long. 110[deg]38'05'' W.; to lat. 39[deg]03'55'' N., long. 110[deg]37'49'' W.; thence to the point of... Air Navigational Aid (VORTAC), Tuba City, AZ to facilitate vectoring of Instrument Flight Rules (IFR...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (largemore » tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.« less

Latrunculin A can improve the birth rate of cloned mice and simplify the nuclear transfer protocol by gently inhibiting actin polymerization.

PubMed

Terashita, Yukari; Wakayama, Sayaka; Yamagata, Kazuo; Li, Chong; Sato, Eimei; Wakayama, Teruhiko

2012-06-01

Although animal cloning is becoming more practicable, there are many abnormalities in cloned embryos, and the success rate of producing live animals by cloning has been low. Here, we focused on the procedure for preventing pseudo-second polar body extrusion from somatic cell nuclear transfer (SCNT)-derived oocytes. Typically, reconstructed oocytes are treated with cytochalasin B (CB), but here latrunculin A (LatA) was used instead of CB to prevent pseudo-second polar body extrusion by inhibiting actin polymerization. CB caps F-actin, LatA binds G-actin, and both drugs prevent their polymerization. When the localization of F-actin was examined using phalloidin staining, it was abnormally scattered in the cytoplasm of CB-treated 1-cell embryos, but this was not detected in LatA-treated or in vitro fertilization-derived control embryos. The spindle was larger in CB-treated oocytes than in LatA-treated or untreated control oocytes. LatA treatment also doubled the rate of full-term development after embryo transfer. These results suggest that cloning efficiency in mice can be improved by optimizing each step of the SCNT procedure. Moreover, by using LatA, we could simplify the procedure with a higher birth rate of cloned mice compared with our original method.

Effect of postactivation treatment with latrunculin A on in vitro and in vivo development of cloned embryos derived from kidney fibroblasts of an aged Clawn miniature boar.

PubMed

Himaki, Takehiro; Mizobe, Yamato; Tsuda, Kenichirou; Suetomo, Masashi; Yamakuchi, Hiroshi; Miyoshi, Kazuchika; Takao, Sonshin; Yoshida, Mitsutoshi

2012-01-01

The objective of this study was to examine the effect of postactivation treatment with latrunculin A (LatA), an actin polymerization inhibitor, on in vitro and in vivo development of somatic cell nuclear transfer (SCNT) embryos derived from kidney fibroblasts of an aged Clawn miniature boar (12 years old). After electric activation, SCNT embryos were treated with 0, 0.5 or 1 μM LatA and cultured in vitro. The rate of blastocyst formation was significantly higher (P<0.05) in SCNT embryos treated with 0.5 μM LatA (38%) than those in control (14%). When cloned embryos treated with 0.5 μM LatA were transferred into the oviducts of two recipient miniature gilts to assess their development in vivo, both recipients became pregnant; one maintained pregnancy to term, and a live piglet (weighing 220 g) was delivered by Caesarean section. The results of this study indicated that the postactivation treatment with LatA was effective in improving in vitro developmental capacity of SCNT miniature pig embryos derived from kidney fibroblasts of an aged animal and that miniature pig cloned embryos treated with LatA had the ability to develop to term.

Fermi-LAT Observations of the LIGO Event GW150914

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Albert, A.; Anderson, B.; Arimoto, M.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.;

Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran.

PubMed

Fisher, Katherine H; Stec, Wojciech; Brown, Stephen; Zeidler, Martin P

2016-02-01

Transmembrane receptors interact with extracellular ligands to transduce intracellular signaling cascades, modulate target gene expression, and regulate processes such as proliferation, apoptosis, differentiation, and homeostasis. As a consequence, aberrant signaling events often underlie human disease. Whereas the vertebrate JAK/STAT signaling cascade is transduced via multiple receptor combinations, the Drosophila pathway has only one full-length signaling receptor, Domeless (Dome), and a single negatively acting receptor, Eye Transformer/Latran (Et/Lat). Here we investigate the molecular mechanisms underlying Et/Lat activity. We demonstrate that Et/Lat negatively regulates the JAK/STAT pathway activity and can bind to Dome, thus reducing Dome:Dome homodimerization by creating signaling-incompetent Dome:Et/Lat heterodimers. Surprisingly, we find that Et/Lat is able to bind to both JAK and STAT92E but, despite the presence of putative cytokine-binding motifs, does not detectably interact with pathway ligands. We find that Et/Lat is trafficked through the endocytic machinery for lysosomal degradation but at a much slower rate than Dome, a difference that may enhance its ability to sequester Dome into signaling-incompetent complexes. Our data offer new insights into the molecular mechanism and regulation of Et/Lat in Drosophila that may inform our understanding of how short receptors function in other organisms. © 2016 Fisher et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu; Weickhardt, Andrew J.; Scheier, Benjamin

Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progressionmore » meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.« less

A significant hardening and rising shape detected in the MeV/GeV νF ν spectrum from the recently discovered very-high-energy blazar S4 0954+65 during the bright optical flare in 2015 February

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Yasuyuki T.; Becerra Gonzalez, Josefa; Itoh, Ryosuke

2016-05-23

In this paper, we report on Fermi Large Area Telescope (LAT) and multi-wavelength results on the recently discovered very-high-energy (VHE, E > 100 GeV) blazar S4 0954+65 (z = 0.368) during an exceptionally bright optical flare in 2015 February. During the time period (2015 February 13/14, or MJD 57067) when the MAGIC telescope detected VHE γ-ray emission from the source, the Fermi-LAT data indicated a significant spectral hardening at GeV energies, with a power-law photon index of 1.8 ± 0.1—compared with the 3FGL (The Fermi LAT 4-Year Point Source Catalog) value (averaged over four years of observation) of 2.34 ±more » 0.04. In contrast, Swift X-Ray Telescope data showed a softening of the X-ray spectrum, with a photon index of 1.72 ± 0.08 (compared with 1.38 ± 0.03 averaged during the flare from MJD 57066 to 57077), possibly indicating a modest contribution of synchrotron photons by the highest-energy electrons superposed on the inverse Compton component. Fitting of the quasi-simultaneous (<1 d) broad-band spectrum with a one-zone synchrotron plus inverse-Compton model revealed that GeV/TeV emission could be produced by inverse-Compton scattering of external photons from the dust torus. Finally, we emphasize that a flaring blazar showing high flux of ≳1.0 × 10 -6 photons cm -2s -1 (E > 100 MeV) and a hard spectral index of ΓGeV < 2.0 detected by Fermi-LAT on daily timescales is a promising target for TeV follow-up by ground-based Cherenkov telescopes to discover high-redshift blazars, investigate their temporal variability and spectral features in the VHE band, and also constrain the intensity of the extragalactic background light.« less

Fermi LAT detection of a GeV flare from blazar TXS 0943+105

NASA Astrophysics Data System (ADS)

Ciprini, S.

2014-07-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed gamma-ray flaring activity from a source positionally consistent with the flat spectrum radio quasar TXS 0943+105, also known as GB6 J0946+1016, MG1 J094636+1017 and 2FGL J0946.5+1015 in the second Fermi LAT catalog (2FGL, Nolan et al. ...

Cosmic Ray Studies with the Fermi Gamma-ray Space Telescope Large Area Telescope

NASA Technical Reports Server (NTRS)

Thompson, David J.; Baldini, L.; Uchiyama, Y.

2012-01-01

The Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope provides both direct and indirect measurements of galactic cosmic rays (CR). The LAT high-statistics observations of the 7 GeV - 1 TeV electron plus positron spectrum and limits on spatial anisotropy constrain models for this cosmic-ray component. On a galactic scale, the LAT observations indicate that cosmic-ray sources may be more plentiful in the outer Galaxy than expected or that the scale height of the cosmic-ray diffusive halo is larger than conventional models. Production of cosmic rays in supernova remnants (SNR) is supported by the LAT gamma-ray studies of several of these, both young SNR and those interacting with molecular clouds.

Cosmic Ray Studies with the Fermi Gamma-ray Space Telescope Large Area Telescope

NASA Technical Reports Server (NTRS)

Thompson, D. J.; Baldini, L.; Uchiyama, Y.

2011-01-01

The Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope provides both direct and indirect measurements of Galactic cosmic rays (CR). The LAT high-statistics observations of the 7 GeV - 1 TcV electron plus positron spectrum and limits on spatial anisotropy constrain models for this cosmic-ray component. On a Galactic scale, the LAT observations indicate that cosmic-ray sources may be more plentiful in the outer Galaxy than expected or that the scale height of the cosmic-ray diffusive halo is larger than conventional models. Production of cosmic rays in supernova remnants (SNR) is supported by the LAT gamma-ray studies of several of these, both young SNR and those interacting with molecular clouds.

Identification of herpes simplex virus type 1 proteins encoded within the first 1.5 kb of the latency-associated transcript.

PubMed

Henderson, Gail; Jaber, Tareq; Carpenter, Dale; Wechsler, Steven L; Jones, Clinton

2009-09-01

Expression of the first 1.5 kb of the latency-associated transcript (LAT) that is encoded by herpes simplex virus type 1 (HSV-1) is sufficient for wild-type (wt) levels of reactivation from latency in small animal models. Peptide-specific immunoglobulin G (IgG) was generated against open reading frames (ORFs) that are located within the first 1.5 kb of LAT coding sequences. Cells stably transfected with LAT or trigeminal ganglionic neurons of mice infected with a LAT expressing virus appeared to express the L2 or L8 ORF. Only L2 ORF expression was readily detected in trigeminal ganglionic neurons of latently infected mice.

Final Technical Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glasser, Alan H.

Final technical report on DE-SC0016106. This is the final technical report for a portion of the multi-institutional CEMM project. This report is centered around 3 publications and a seminar presentation, which have been submitted to E-Link.

10 CFR 52.157 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2013 CFR

2013-01-01

...; technical information in final safety analysis report. The application must contain a final safety analysis...) Information sufficient to demonstrate compliance with the applicable requirements regarding testing, analysis... 10 Energy 2 2013-01-01 2013-01-01 false Contents of applications; technical information in final...

10 CFR 52.157 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2012 CFR

2012-01-01

...; technical information in final safety analysis report. The application must contain a final safety analysis...) Information sufficient to demonstrate compliance with the applicable requirements regarding testing, analysis... 10 Energy 2 2012-01-01 2012-01-01 false Contents of applications; technical information in final...

10 CFR 52.157 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2014 CFR

2014-01-01

...; technical information in final safety analysis report. The application must contain a final safety analysis...) Information sufficient to demonstrate compliance with the applicable requirements regarding testing, analysis... 10 Energy 2 2014-01-01 2014-01-01 false Contents of applications; technical information in final...

10 CFR 52.157 - Contents of applications; technical information in final safety analysis report.

Code of Federal Regulations, 2011 CFR

2011-01-01

...; technical information in final safety analysis report. The application must contain a final safety analysis...) Information sufficient to demonstrate compliance with the applicable requirements regarding testing, analysis... 10 Energy 2 2011-01-01 2011-01-01 false Contents of applications; technical information in final...

Comparative evaluation of recombinant LigB protein and heat-killed antigen-based latex agglutination test with microscopic agglutination test for diagnosis of bovine leptospirosis.

PubMed

Nagalingam, Mohandoss; Thirumalesh, Sushma Rahim Assadi; Kalleshamurthy, Triveni; Niharika, Nakkala; Balamurugan, Vinayagamurthy; Shome, Rajeswari; Sengupta, Pinaki Prasad; Shome, Bibek Ranjan; Prabhudas, Krishnamsetty; Rahman, Habibur

2015-10-01

This study aimed to develop latex agglutination test (LAT) using recombinant leptospiral immunoglobulin-like protein (LigB) (rLigB) antigen and compare its diagnostic efficacy with LAT using conventional heat-killed leptospiral antigen and microscopic agglutination test (MAT) in diagnosing bovine leptospirosis. The PCR-amplified 1053-bp ligB gene sequences from Leptospira borgpetersenii Hardjo serovar were cloned in pET 32 (a) vector at EcoRI and NotI sites and expressed in BL21 E. coli cells as fusion protein with thioredoxin (-57 kDa) and characterized by SDS-PAGE and immunoblot. Out of 390 serum samples [cattle (n = 214), buffaloes (n = 176)] subjected to MAT, 115 samples showed reciprocal titre≥100 up to 1600 against one or more serovars. For recombinant LigB protein/antigen-based LAT, agglutination was observed in the positive sample, while no agglutination was observed in the negative sample. Similarly, heat-killed leptospiral antigen was prepared from and used in LAT for comparison with MAT. A two-sided contingency table was used for analysis of LAT using both the antigens separately against MAT for 390 serum samples. The sensitivity, specificity and positive and negative predictive values of recombinant LigB LAT were found to be 75.65, 91.27, 78.38 and 89.96 %, respectively, and that of heat-killed antigen-based LAT were 72.17, 89.82, 74.77 and 88.53 %, respectively, in comparison with MAT. This developed test will be an alternative/complementary to the existing battery of diagnostic assays/tests for specific detection of pathogenic Leptospira infection in bovine population.

The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex.

PubMed

Quiñones, Henry; Collazo, Roberto; Moe, Orson W

2004-07-01

The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na(+) homeostasis. l-Dihydroxyphenylalanine (l-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule l-DOPA uptake has not been characterized. Renal cortical poly-A(+) RNA injected into Xenopus laevis oocytes induced l-DOPA uptake in a time- and dose-dependent fashion with biphasic K(m)s in the millimolar and micromolar range and independent of inward Na(+), K(+), or H(+) gradients, suggesting the presence of low- and high-affinity l-DOPA carriers. Complementary RNA from two amino acid transporters yielded l-DOPA uptake significantly above water-injected controls the rBAT/b(0,+)AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A(+), l-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with K(m)s in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced l-DOPA transport and cortical poly-A(+)-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A(+)-induced l-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited l-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral l-DOPA uptake into the proximal tubule, respectively. Additional l-DOPA transport mechanisms exist in the renal cortex that remain to be identified.

Left atrial thrombus and dense spontaneous echocardiographic contrast in patients on continuous direct oral anticoagulant therapy undergoing catheter ablation of atrial fibrillation: Comparison of dabigatran, rivaroxaban, and apixaban.

PubMed

Wu, Michael; Gabriels, James; Khan, Mohammad; Shaban, Nada; D'Amato, Salvatore; Liu, Christopher F; Markowitz, Steven M; Ip, James E; Thomas, George; Singh, Parmanand; Lerman, Bruce; Patel, Apoor; Cheung, Jim W

2018-04-01

Left atrial thrombus (LAT) and dense spontaneous echocardiographic contrast (SEC) detected by transesophageal echocardiography (TEE) in patients on continuous direct oral anticoagulants (DOAC) therapy before catheter ablation of atrial fibrillation (AF) or atrial flutter (AFL) have been described. We sought to compare rates of TEE-detected LAT and dense SEC among patients taking different DOACs. We evaluated 609 consecutive patients from 3 tertiary hospitals (median age 65 years; interquartile range 58-71 years; 436 (72%) men) who were on ≥4 weeks of continuous DOAC therapy (dabigatran, n = 166 [27%]; rivaroxaban, n = 257 [42%]; or apixaban, n = 186 [31%]) undergoing TEE before catheter ablation of AF/AFL. Demographic, clinical, and TEE data were collected for each patient. Despite ≥4 weeks of continuous DOAC therapy, 17 patients (2.8%) had LAT and 15 patients (2.5%) had dense SEC detected by TEE. The rates of LAT were 3.0%, 3.5%, and 1.6% for patients on dabigatran, rivaroxaban, and apixaban, respectively (P = .482). The rates of dense SEC were 1.2%, 3.5%, and 2.2% for patients on dabigatran, rivaroxaban, and apixaban, respectively (P = .299). Congestive heart failure (odds ratio 4.4; 95% confidence interval 1.6-12; P = .003) and moderate/severe left atrial enlargement (odds ratio 3.1; 95% confidence interval 1.1-8.6; P = .026) were independent predictors of LAT. In this study, ∼3% of patients on continuous DOAC therapy had LAT detected before catheter ablation of AF/AFL. Specific DOAC therapy did not significantly affect the rates of LAT detection. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Laser ablation and 131-iodine: a 24-month pilot study of combined treatment for large toxic nodular goiter.

PubMed

Chianelli, M; Bizzarri, G; Todino, V; Misischi, I; Bianchini, A; Graziano, F; Guglielmi, R; Pacella, C M; Gharib, H; Papini, E

2014-07-01

It is normally recognized that the preferred treatment in large toxic thyroid nodules should be thyroidectomy. The aim of the study was to assess the efficacy of combined laser ablation treatment (LAT) and radioiodine 131 (131I) treatment of large thyroid toxic nodules with respect to rapidity of control of local symptoms, of hyperthyroidism, and of reduction of administered 131I activity in patients at refusal or with contraindications to surgery. We conducted a pilot study at a single center specializing in thyroid care. Fifteen patients were treated with LAT, followed by 131I (group A), and a series of matched consecutive patients were treated by 131I only (group B). Laser energy was delivered with an output power of 3 W (1800 J per fiber per treatment) through two 75-mm, 21-gauge spinal needles. Radioiodine activity was calculated to deliver 200 Gy to the hyperfunctioning nodule. Thyroid function, thyroid peroxidase antibody, thyroglobulin antibody, ultrasound, and local symptoms were measured at baseline and up to 24 months. Nodule volume reduction at 24 months was: 71.3 ± 13.4 vs 47.4 ± 5.5%, group A (LAT+131I) vs group B (131I), respectively; P < .001). In group A (LAT+131I), a reduction in radioiodine-administered activity was obtained (-21.1 ± 8.1%). Local symptom score demonstrated a more rapid reduction in group A (LAT+131I). In three cases, no 131I treatment was needed after LAT. In this pilot study, combined LAT/131I treatment induced faster and greater improvement of local and systemic symptoms compared to 131I only. This approach seems a possible alternative to thyroidectomy in patients at refusal of surgery.

Patient-Reported Outcomes in Latin America: Implementation in Research and Role in Emerging HTA Systems.

PubMed

Winnette, Randall; Zárate, Victor; Machnicki, Gerardo; DeMuro, Carla; Gawlicki, Mary; Gnanasakthy, Ari

2015-12-01

Patient-reported outcomes (PROs) are increasingly used to demonstrate the value of interventions and support health technology assessment (HTA). The objective of this work was to analyze trends regarding PROs in Latin America (LatAm), highlight challenges in the application of PROs in this region, and suggest solutions. A team of researchers with expertise in PROs conducted a nonsystematic PubMed literature search pertaining to the use of PROs in LatAm. The experts also drew on their experience working with PROs to assess the application of PROs in LatAm. The literature search yielded more than 4000 publications, with an increasing publication rate in recent years. PROs are being used in LatAm in various study types: instrument validation, phase III international clinical trials, health service research. A large Inter-American Development Bank study demonstrates the growing importance of PROs in the region. The growth in local value sets for the EuroQol five-dimensional questionnaire in LatAm reflects the regional emergence of HTA systems. Operational challenges relate to ensuring the use of good-quality questionnaires that, at a minimum, have undergone appropriate cultural adaptation and ideally have established psychometric properties. PROs are increasingly important in LatAm. Future efforts should aim to strengthen the operational and research infrastructure around PROs in the region. Innovation should be encouraged, including studying alternative methods of eliciting health utilities for economic evaluation. A wider scope around PRO uses for decision making by HTA bodies is an international trend with potential positive prospects in LatAm. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

EPA Office of Water (OW): SDWIS - HUC12 Densities for Public Surface Water and Groundwater Sources

EPA Pesticide Factsheets

Public Water System location points, based on information from the Safe Drinking Water Act Information System (SDWIS/Federal) for a 2010 third quarter (SDWIS_2010Q3) baseline period, were applied to relate system latitude and longitude coordinates (LatLongs) to Watershed Boundary Dataset subwatershed polygons (HUC12s). This HUC12 table can be mapped through setting up appropriate table relationships on the attribute HUC_12 with the HUC12 GIS layer that is part of EPA's Reach Address Database (RAD) Version 3. At the present time, the RAD Version 3 contains HUC12 polygons for the conterminous United States (CONUS), Hawaii, Puerto Rico, and the U.S. Virgin Islands (materials for Alaska or for other territories and dependencies are not available as of February, 2010). The records in this table are based on a special QUERY created by the EPA Office of Ground Water and Drinking Water (OGWDW) from the primary SDWIS/FED information to provide a robust point representation for a PWS system. PWS points are selected based on the following prioritization: 1. If the system has a treatment plant with LatLongs and MAD codes; 2. If the system has a treatment plant with LatLongs but without MAD codes; 3. If the system has a well with LatLongs and MAD codes; 4. If the system has a well with LatLongs but without MAD codes; 5. If the system has an intake with LatLongs and MAD codes; 6. If the system has an intake with LatLongs but without MAD codes; 7. If the system has any source

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism.

PubMed

Badziong, Julia; Ting, Saskia; Synoracki, Sarah; Tiedje, Vera; Brix, Klaudia; Brabant, Georg; Moeller, Lars Christian; Schmid, Kurt Werner; Fuhrer, Dagmar; Zwanziger, Denise

2017-09-01

Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n  = 19), follicular adenoma (FA, n  = 44), follicular thyroid carcinoma (FTC, n  = 45), papillary thyroid carcinoma (PTC, n  = 40), anaplastic thyroid carcinoma (ATC, n  = 40) and Graves' disease (GD, n  = 50) by calculating the 'hybrid' (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions. MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation. Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8. © 2017 European Society of Endocrinology.

Integrated tracking of components by engineering and logistics utilizing logistics asset tracking system

NASA Technical Reports Server (NTRS)

Renfroe, Michael B.; Mcdonald, Edward J.; Bradshaw, Kimberly

1988-01-01

The Logistics Asset Tracking System (LATS) devised by NASA contains data on Space Shuttle LRUs that are daily updated to reflect such LRU status changes as repair due to failure or modification due to changing engineering requirements. The implementation of LATS has substantially increased personnel responsiveness, preventing costly delays in Space Shuttle processing and obviating hardware cannibalization. An evaluation is presented of LATS achievements in the direction of an integrated logistical support posture.

Applications of Aerodynamic Forces for Spacecraft Orbit Maneuverability in Operationally Responsive Space and Space Reconstitution Needs

DTIC Science & Technology

2012-03-01

observation re = the radius of the Earth at the equator Pn = the Legendre polynomial 26 L = the geocentric latitude, sin The acceleration can then...atmospheric density at an altitude above an %% oblate earth given the position vector in the Geocentric Equatorial %% frame. The position vector is in...Diff between Delta and Geocentric lat rad %% GeoDtLat - Geodetic Latitude -Pi/2 to Pi/2 rad %% GeoCnLat

Fermi Sees the Gamma Ray Sky

NASA Image and Video Library

2009-10-30

This view of the gamma-ray sky constructed from one year of Fermi LAT observations is the best view of the extreme universe to date. The map shows the rate at which the LAT detects gamma rays with energies above 300 million electron volts -- about 120 million times the energy of visible light -- from different sky directions. Brighter colors equal higher rates. Credit: NASA/DOE/Fermi LAT Collaboration Full story: www.nasa.gov/mission_pages/GLAST/news/first_year.html

Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells.

PubMed

Myers, Darienne R; Lau, Tannia; Markegard, Evan; Lim, Hyung W; Kasler, Herbert; Zhu, Minghua; Barczak, Andrea; Huizar, John P; Zikherman, Julie; Erle, David J; Zhang, Weiguo; Verdin, Eric; Roose, Jeroen P

2017-05-23

CD4 + T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4 + T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (T H 2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4 + T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4 + T cell proliferation and uncover a suppressive role for Irf4 in T H 2 polarization; halving Irf4 gene-dosage leads to increases in GATA3 + and IL-4 + cells. Our studies reveal that naive CD4 + T cells are dynamically tuned by tonic LAT-HDAC7 signals. Published by Elsevier Inc.

Amniotic membrane transplantation with conjunctival autograft for recurrent pterygium.

PubMed

Shimazaki, Jun; Kosaka, Koichi; Shimmura, Shigeto; Tsubota, Kazuo

2003-01-01

To study the effect of amniotic membrane transplantation (AMT) combined with either limbal autograft transplantation (LAT) or conjunctival autograft transplantation (CAT) in recurrent pterygium. Retrospective, noncomparative, interventional case series. Twenty-seven eyes of 27 patients with recurrent pterygium. The mean number of prior surgeries was 3.1 (range, 1-10). Fifteen eyes each had restriction of ocular movement and symblepharon before surgery. Patients were treated by AMT with either LAT (n = 15) or CAT (n = 12). Recurrence of pterygium, improvement in ocular movement, and symblepharon formation. Twenty-three (85.2%) of 27 eyes showed no recurrence with a mean observation period of 67.0 weeks. Fourteen eyes (93.3%) each showed improvement in ocular movement restriction and symblepharon after AMT. In four eyes that developed recurrence, three had LAT and one had CAT combined with AMT, suggesting that there was no difference in surgical outcome between LAT and CAT. AMT with CAT is a safe and effective method for recurrent pterygium, especially that associated with ocular movement restriction and symblepharon. Considering the potential adverse effects associated with limbal excision, AMT plus CAT may be preferred over AMT plus LAT.

Fermi LAT detection of enhanced gamma-ray emission from the Crab Nebula region

NASA Astrophysics Data System (ADS)

Ojha, Roopesh; Buehler, Rolf; Hays, Elizabeth; Dutka, Michael

2012-07-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed a significant increase in the gamma-ray activity from a source positionally consistent with the Crab Nebula on July 3, 2012. Preliminary LAT analysis indicates that the daily-averaged gamma-ray emission (E >100 MeV) from the direction of the Crab doubled from (2.4 +/- 0.5) x 10^-6 ph/cm2/sec (statistical errors only) on July 2nd to (5.5 +/- 0.7) x 10^-6 ph/cm2/sec on July 3rd, a factor of 2 greater than the average flux of (2.75 +/- 0.10) x 10^-6 ph/cm2/sec reported in the second Fermi LAT catalog (2FGL, Nolan et al.

A tool to estimate the Fermi Large Area Telescope background for short-duration observations

DOE PAGES

Vasileiou, Vlasios

2013-07-25

Here, the proper estimation of the background is a crucial component of data analyses in astrophysics, such as source detection, temporal studies, spectroscopy, and localization. For the case of the Large Area Telescope (LAT) on board the Fermi spacecraft, approaches to estimate the background for short (≲1000 s duration) observations fail if they ignore the strong dependence of the LAT background on the continuously changing observational conditions. We present a (to be) publicly available background-estimation tool created and used by the LAT Collaboration in several analyses of Gamma Ray Bursts. This tool can accurately estimate the expected LAT background formore » any observational conditions, including, for example, observations with rapid variations of the Fermi spacecraft’s orientation occurring during automatic repointings.« less

50 CFR 622.35 - Atlantic EEZ seasonal and/or area closures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... artificial reefs and surrounding areas as follows: (i) Paradise Reef is bounded on the north by 33°31.59′ N....85′ W. long. (ii) Ten Mile Reef is bounded on the north by 33°26.65′ N. lat.; on the south by 33°24... Island Reef is bounded on the north by 33°26.58′ N. lat.; on the south by 33°25.76′ N. lat.; on the east...

50 CFR 622.35 - Atlantic EEZ seasonal and/or area closures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... artificial reefs and surrounding areas as follows: (i) Paradise Reef is bounded on the north by 33°31.59′ N....85′ W. long. (ii) Ten Mile Reef is bounded on the north by 33°26.65′ N. lat.; on the south by 33°24... Island Reef is bounded on the north by 33°26.58′ N. lat.; on the south by 33°25.76′ N. lat.; on the east...

50 CFR Table 3 (north) to Part 660... - 2010 Trip Limits for Open Access Gears North of 40°10′ N. Lat.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2010 Trip Limits for Open Access Gears North of 40°10â² N. Lat. 3 Table 3 (North) to Part 660, Subpart F Wildlife and Fisheries FISHERY... Limits for Open Access Gears North of 40°10′ N. Lat. ER01OC10.020 ER01OC10.021 ...

50 CFR Table 3 (south) to Part 660... - 2010 Trip Limits for Open Access Gears South of 40°10′ N. Lat.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2010 Trip Limits for Open Access Gears South of 40°10â² N. Lat. 3 Table 3 (South) to Part 660, Subpart F Wildlife and Fisheries FISHERY... Limits for Open Access Gears South of 40°10′ N. Lat. ER01OC10.022 ER01OC10.023 ...

YAP Tyrosine Phosphorylation and Nuclear Localization in Cholangiocarcinoma Cells is Regulated by LCK and Independent of LATS Activity.

PubMed

Sugihara, Takaaki; Werneburg, Nathan W; Hernandez, Matthew C; Yang, Lin; Kabashima, Ayano; Hirsova, Petra; Yohanathan, Lavanya; Sosa, Carlos; Truty, Mark Joseph; Vasmatzis, George; Gores, Gregory J; Smoot, Rory L

2018-06-14

The hippo pathway effector, Yes-associated protein (YAP) is a transcriptional co-activator implicated in cholangiocarcinoma (CCA) pathogenesis. YAP is known to be regulated by a serine/threonine kinase relay module (MST1/2 - LATS1/2) culminating in phosphorylation of YAP at Serine 127 (S127) and cytoplasmic sequestration. However, YAP also undergoes tyrosine phosphorylation, and the role of tyrosine phosphorylation in YAP regulation remains unclear. Herein, YAP regulation by tyrosine phosphorylation was examined in human and mouse CCA cells, as well as patient-derived xenograft (PDX) models. YAP was phosphorylated on tyrosine 357 (Y357) in CCA cell lines and PDX models. SRC family kinase (SFK) inhibition with dasatinib resulted in loss of YAPY357 phosphorylation, promoted its translocation from the nucleus to the cytoplasm, and reduced YAP target gene expression; including cell lines expressing a LATS1/2-resistant YAP mutant in which all serine residues were mutated to alanine. Consistent with these observations, precluding YAPY357 phosphorylation by site-directed mutagenesis (YAPY357F) excluded YAP from the nucleus. Targeted siRNA experiments identified LCK as the SFK that most potently mediated YAPY357 phosphorylation. Likewise, inducible CRISPR/Cas9-targeted LCK deletion decreased YAPY357 phosphorylation and its nuclear localization. The importance of LCK in CCA biology was demonstrated by clinical observations suggesting LCK expression levels were associated with early tumor recurrence following resection of CCA. Finally, dasatinib displayed therapeutic efficacy in PDX models. Demonstration of targetable, LCK-mediated YAP tyrosine phosphorylation in CCA regulating YAP's nuclear retention and oncogenic activity. Copyright ©2018, American Association for Cancer Research.

The soft γ-ray pulsar population: a high-energy overview

NASA Astrophysics Data System (ADS)

Kuiper, L.; Hermsen, W.

2015-06-01

At high-energy γ-rays (>100 MeV), the Large Area Telescope (LAT) on the Fermi satellite already detected more than 145 rotation-powered pulsars (RPPs), while the number of pulsars seen at soft γ-rays (20 keV-30 MeV) remained small. We present a catalogue of 18 non-recycled RPPs from which presently non-thermal pulsed emission has been securely detected at soft γ-rays above 20 keV, and characterize their pulse profiles and energy spectra. For 14 of them, we report new results, (re)analysing mainly data from RXTE, INTEGRAL, XMM-Newton and Chandra. The soft γ-pulsars are all fast rotators and on average ˜9.3 times younger and ˜43 times more energetic than the Fermi LAT sample. The majority (11 members) exhibits broad, structured single pulse profiles, and only six have double (or even multiple, Vela) pulses. 15 soft γ-ray pulsar show hard power-law spectra in the hard X-ray band and reach maximum luminosities typically in the MeV range. For only 7 of the 18 soft γ-ray pulsars, pulsed emission has also been detected by the LAT, but 12 have a pulsar wind nebula (PWN) detected at TeV energies. For six pulsars with PWNe, we present also the spectra of the total emissions at hard X-rays, and for IGR J18490-0000, associated with HESS J1849-000 and PSR J1849-0001, we used our Chandra data to resolve and characterize the contributions from the point source and PWN. Finally, we also discuss a sample of 15 pulsars which are candidates for future detection of pulsed soft γ-rays, given their characteristics at other wavelengths.

Search for Gamma-Ray Emission from Local Primordial Black Holes with the Fermi Large Area Telescope

DOE PAGES

Ackermann, M.; Atwood, W. B.; Baldini, L.; ...

2018-04-10

Black holes with masses below approximately 10 15 g are expected to emit gamma-rays with energies above a few tens of MeV, which can be detected by the Fermi Large Area Telescope (LAT). Although black holes with these masses cannot be formed as a result of stellar evolution, they may have formed in the early universe and are therefore called primordial black holes (PBHs). Previous searches for PBHs have focused on either short-timescale bursts or the contribution of PBHs to the isotropic gamma-ray emission. We show that, in cases of individual PBHs, the Fermi-LAT is most sensitive to PBHs with temperatures above approximately 16 GeV and masses 6 × 10 11 g, which it can detect out to a distance of about 0.03 pc. These PBHs have a remaining lifetime of months to years at the start of the Fermi mission. They would appear as potentially moving point sources with gamma-ray emission that become spectrally harder and brighter with time until the PBH completely evaporates. In this paper, we develop a new algorithm to detect the proper motion of gamma-ray point sources, and apply it to 318 unassociated point sources at a high galactic latitude in the third Fermi-LAT source catalog. None of the unassociated point sources with spectra consistent with PBH evaporation show significant proper motion. Finally, using the nondetection of PBH candidates, we derive a 99% confidence limit on the PBH evaporation rate in the vicinity of Earth,more » $${\\dot{\\rho }}_{\\mathrm{PBH}}\\lt 7.2\\times {10}^{3}\\ {\\mathrm{pc}}^{-3}\\,{\\mathrm{yr}}^{-1}$$. This limit is similar to the limits obtained with ground-based gamma-ray observatories.« less

Search for Gamma-Ray Emission from Local Primordial Black Holes with the Fermi Large Area Telescope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackermann, M.; Atwood, W. B.; Baldini, L.

Black holes with masses below approximately 10 15 g are expected to emit gamma-rays with energies above a few tens of MeV, which can be detected by the Fermi Large Area Telescope (LAT). Although black holes with these masses cannot be formed as a result of stellar evolution, they may have formed in the early universe and are therefore called primordial black holes (PBHs). Previous searches for PBHs have focused on either short-timescale bursts or the contribution of PBHs to the isotropic gamma-ray emission. We show that, in cases of individual PBHs, the Fermi-LAT is most sensitive to PBHs with temperatures above approximately 16 GeV and masses 6 × 10 11 g, which it can detect out to a distance of about 0.03 pc. These PBHs have a remaining lifetime of months to years at the start of the Fermi mission. They would appear as potentially moving point sources with gamma-ray emission that become spectrally harder and brighter with time until the PBH completely evaporates. In this paper, we develop a new algorithm to detect the proper motion of gamma-ray point sources, and apply it to 318 unassociated point sources at a high galactic latitude in the third Fermi-LAT source catalog. None of the unassociated point sources with spectra consistent with PBH evaporation show significant proper motion. Finally, using the nondetection of PBH candidates, we derive a 99% confidence limit on the PBH evaporation rate in the vicinity of Earth,more » $${\\dot{\\rho }}_{\\mathrm{PBH}}\\lt 7.2\\times {10}^{3}\\ {\\mathrm{pc}}^{-3}\\,{\\mathrm{yr}}^{-1}$$. This limit is similar to the limits obtained with ground-based gamma-ray observatories.« less

Eszopiclone and Zolpidem Do Not Affect the Prevalence of the Low Arousal Threshold Phenotype

PubMed Central

Smith, Patrick R.; Sheikh, Karen L.; Costan-Toth, Camille; Forsthoefel, Derek; Bridges, Edward; Andrada, Teotimo F.; Holley, Aaron B.

2017-01-01

Study Objectives: We sought to determine whether non benzodiazepine sedative hypnotics (NBSH) reduce the occurrence of the low arousal threshold (LAT) phenotype. Methods: Consecutive patients with suspected obstructive sleep apnea (OSA) referred for polysomnography (PSG) had demographic and PSG data abstracted. LAT was estimated using PSG criteria. After adjusting for pretest probability (PTP) for OSA, we calculated the effect that premedication with NBSHs has on LAT prevalence. Results: Five hundred seventy-nine patients with a mean age and body mass index of 42.2 ± 10.1 y and 28.9 ± 4.5 kg/m2, respectively, had data available for analysis. Most patients (444, or 80.9%) had a LAT, and administering a NBSH (zolpidem or eszopiclone) on the same night as the PSG did not change LAT prevalence (NBSH: 339 (83.3%) versus no drug: 100 (80.6%); p = 0.50). Adjusting for PTP, neither administration of eszopiclone (odds ratio 0.80 (95% confidence interval: 0.33–2.0); 0.69) nor zolpidem (odds ratio 1.65 (95% confidence interval: 0.8–3.5); p = 0.19) reduced the odds that a patient had a LAT. NBSHs did not change the mean SpO2 nadir, percentage hypopneas, or apnea-hypopnea index. There was no association between zolpidem or eszopiclone dosing and SpO2 nadir (zolpidem: β = −0.69, p = 0.80; eszopiclone: β = −1.53, p = 0.68), percentage hypopneas (zolpidem: β = 2.2, p = 0.43; eszopiclone β = −6.2, p = 0.46), or apnea-hypopnea index (zolpidem: β = 3.1, p = 0.22; eszopiclone: β = 2.6, p = 0.39). Conclusions: The LAT is common in our population and NBSH premedication does not alter its occurrence. Further studies are needed to determine how the LAT can be optimally managed to improve OSA treatment. Citation: Smith PR, Sheikh KL, Costan-Toth C, Forsthoefel D, Bridges E, Andrada TF, Holley AB. Eszopiclone and zolpidem do not affect the prevalence of the low arousal threshold phenotype. J Clin Sleep Med. 2017;13(1):115–119. PMID:27784413

LatY136F knock-in mouse model for human IgG4-related disease.

PubMed

Yamada, Kazunori; Zuka, Masahiko; Ito, Kiyoaki; Mizuguchi, Keishi; Kakuchi, Yasushi; Onoe, Tamehito; Suzuki, Yasunori; Yamagishi, Masakazu; Izui, Shozo; Malissen, Marie; Malissen, Bernard; Kawano, Mitsuhiro

2018-01-01

The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD). LatY136F knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed. Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment. LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse strain to represent a promising model for human IgG4-RD.

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

PubMed

Suzuki, Katsuyoshi; Otsuka, Naomi; Hizaki, Hiroko; Hashimoto, Masayo; Kuwayama, Yasuaki

2018-06-05

This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM). This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire. In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4-6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group. TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores. UMIN Clinical Trials Registry Identifier, UMIN000023862. Santen Pharmaceutical Co., Ltd., Osaka, Japan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, A.; Veres, P.; Burns, E.

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger (BBH) event GW170104. No candidate electromagnetic counterparts was detected by either GBM or LAT. A detailed analysis of the GBM and LAT data over timescales from seconds to days covering the LIGO localization region is presented. The resulting ux upper bound from the GBM is (5.2{9.4) 10 -7 erg cm -2 s -1 in the 10-1000 keV range and from the LAT is (0.2{13) 10 -9 erg cm -2 s -1 in the 0.1{1 GeV range. We also describemore » the improvements to our automated pipelines and analysis techniques for searching for and characterizing the potential electromagnetic counterparts for future gravitational wave events from Advanced LIGO/VIRGO.« less

Multi-station investigation of spread F over Europe during low to high solar activity

NASA Astrophysics Data System (ADS)

Paul, Krishnendu Sekhar; Haralambous, Haris; Oikonomou, Christina; Paul, Ashik; Belehaki, Anna; Ioanna, Tsagouri; Kouba, Daniel; Buresova, Dalia

2018-04-01

Spread F is an ionospheric phenomenon which has been reported and analyzed extensively over equatorial regions on the basis of the Rayleigh-Taylor (R-T) instability. It has also been investigated over midlatitude regions, mostly over the Southern Hemisphere with its generation attributed to the Perkins instability mechanism. Over midlatitudes it has also been correlated with geomagnetic storms through the excitation of travelling ionospheric disturbances (TIDs) and subsequent F region uplifts. The present study deals with the occurrence rate of nighttime spread F events and their diurnal, seasonal and solar cycle variation observed over three stations in the European longitude sector namely Nicosia (geographic Lat: 35.29 °N, Long: 33.38 °E geographic: geomagnetic Lat: 29.38 °N), Athens (geographic Lat: 37.98 °N, Long: 23.73 °E geographic: geomagnetic Lat: 34.61 °N) and Pruhonice (geographic Lat: 50.05 °N, Long: 14.41 °E geographic: geomagnetic Lat: 47.7 °N) during 2009, 2015 and 2016 encompassing periods of low, medium and high solar activity, respectively. The latitudinal and longitudinal variation of spread F occurrence was examined by considering different instability triggering mechanisms and precursors which past literature identified as critical to the generation of spread F events. The main findings of this investigation is an inverse solar cycle and annual temporal dependence of the spread F occurrence rate and a different dominant spread F type between low and high European midlatitudes.

Prostate Cancer Cells in Different Androgen Receptor Status Employ Different Leucine Transporters.

PubMed

Otsuki, Hideo; Kimura, Toru; Yamaga, Takashi; Kosaka, Takeo; Suehiro, Jun-Ichi; Sakurai, Hiroyuki

2017-02-01

Leucine stimulates cancer cell proliferation through the mTOR pathway, therefore, inhibiting leucine transporters may be a novel therapeutic target for cancer. L-type amino acid transporter (LAT) 1, a Na + -independent amino acid transporter, is highly expressed in many tumor cells. However, leucine transporter(s) in different stages of prostate cancer, particularly in the stages of castration resistance with androgen receptor (AR) expression, is unclear. LNCaP and DU145 and PC-3 cell lines were used as a model of androgen dependent, and metastatic prostate cancer. A new "LN-cr" cell line was established after culturing LNCaP cells for 6 months under androgen-free conditions, which is considered a model of castration resistant prostate cancer (CRPC) with androgen AR expression. The expression of leucine transporters was investigated with quantitative PCR and immunofluorescence. Uptake of 14 C Leucine was examined in the presence or absence of BCH (a pan-LAT inhibitor), JPH203 (an LAT1-specific inhibitor), or Na + . Cell growth was assessed with MTT assay. siRNA studies were performed to evaluate the indispensability of y + LAT2 on leucine uptake and cell viability in LN-cr. Cell viability showed a 90% decrease in the absence of leucine in all four cell lines. LNCaP cells principally expressed LAT3, and their leucine uptake was more than 90% Na + -independent. BCH, but not JPH203, inhibited leucine uptake, and cell proliferation (IC 50BCH :15 mM). DU145 and PC-3 cells predominantly expressed LAT1. Leucine uptake and cell growth were suppressed by BCH or JPH203 in a dose-dependent manner (IC 50BCH : ∼20 mM, IC 50JPH203 : ∼5 µM). In LN-cr cells, Na + -dependent uptake of leucine was 3.8 pmol/mgprotein/min, while, Na + -independent uptake was only 0.52 (P < 0.05). Leucine uptake of LN-cr was largely (∼85%) Na + -dependent. y + LAT2 expression was confirmed in LN-cr. Knockdown of y + LAT2 lead to significant leucine uptake inhibition (40%) and cell growth inhibition (20%). New CRPC cell line with increased expression of y + LAT2 as a leucine transporter was established in vitro. Anti-leucine transporter therapy could be an important option against prostate cancer. Prostate 77:222-233, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

East Pacific Rise at lat 19°S: Evidence for a recent ridge jump

NASA Astrophysics Data System (ADS)

Morton, Janet L.; Ballard, Robert D.

1986-02-01

A detailed ANGUS (Acoustically Navigated Geological Undersea Surveyor) photographic and bathymetric survey of the East Pacific Rise (EPR) near lat 19°S reveals a small jump of the ridge axis to the west. The axial block in this region consists of two parallel ridges 3 km apart and separated by a 200-m-deep valley. South of lat 19°06‧S the plate boundary is a single, narrow (<1 km) ridge. The eastern ridge near lat 19°S is shallower than the western ridge and is morphologically a continuation of the narrow, active ridge axis to the south. ANGUS photographs along both ridges and in the intervening valley, however, show that the western ridge is the currently active plate boundary. We suggest that spreading shifted westward from the eastern ridge to its present position within the past 40 000 yr. The EPR in the general region has been characterized by asymmetric spreading for the past 2.4 m.y. The sense of the ridge jump near lat 19°S is consistent with the asymmetric spreading, which could have been produced by a series of such jumps.

Searching the Gamma-Ray Sky for Counterparts to Gravitational Wave Sources Fermi Gamma-Ray Burst Monitor and Large Area Telescope Observations of LVT151012 and GW151226

NASA Technical Reports Server (NTRS)

Racusin, J. L.; Burns, E.; Goldstein, A.; Connaughton, V.; Wilson-Hodge, C. A.; Jenke, P.; Blackburn, L.; Briggs, M. S.; Broida, J.; Camp, J.;

The Fermi Large Area Telescope on Orbit: Event Classification, Instrument Response Functions, and Calibration

DOE PAGES

Ackermann, M.; Ajello, M.; Albert, A.; ...

2012-10-12

The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy γ-ray telescope, covering the energy range from 20 MeV to more than 300 GeV. During the first years of the mission, the LAT team has gained considerable insight into the in-flight performance of the instrument. Accordingly, we have updated the analysis used to reduce LAT data for public release as well as the instrument response functions (IRFs), the description of the instrument performance provided for data analysis. In this study, we describe the effects thatmore » motivated these updates. Furthermore, we discuss how we originally derived IRFs from Monte Carlo simulations and later corrected those IRFs for discrepancies observed between flight and simulated data. We also give details of the validations performed using flight data and quantify the residual uncertainties in the IRFs. In conclusion, we describe techniques the LAT team has developed to propagate those uncertainties into estimates of the systematic errors on common measurements such as fluxes and spectra of astrophysical sources.« less

2FHL: The Second Catalog of Hard Fermi-LAT Sources

DOE PAGES

Ackermann, M.; Ajello, M.; Atwood, W. B.; ...

2016-01-14

We present a catalog of sources detected above 50 GeV by the Fermi-Large Area Telescope (LAT) in 80 months of data. The newly delivered Pass 8 event-level analysis allows the detection and characterization of sources in the 50 GeV–2TeV energy range. In this energy band, Fermi - LAT has detected 360 sources, which constitute the second catalog of hard Fermi -LAT sources (2FHL). The improved angular resolution enables the precise localization of point sources (~1.'7 radius at 68 % C. L.) and the detection and characterization of spatially extended sources. We find that 86% of the sources can be associatedmore » with counterparts at other wavelengths, of which the majority (75%) are active galactic nuclei and the rest (11%) are Galactic sources. Only 25% of the 2FHL sources have been previously detected by Cherenkov telescopes, implying that the 2FHL provides a reservoir of candidates to be followed up at very high energies. This work closes the energy gap between the observations performed at GeV energies by Fermi -LAT on orbit and the observations performed at higher energies by Cherenkov telescopes from the ground.« less

2FHL- The Second Catalog of Hard Fermi-LAT Sources

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Atwood, W. B.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Gonzalez, J. Becerra; Bellazzini, R.; Bissaldi, E.;

2FHL: The Second Catalog of Hard Fermi-LAT Sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackermann, M.; Ajello, M.; Atwood, W. B.

We present a catalog of sources detected above 50 GeV by the Fermi-Large Area Telescope (LAT) in 80 months of data. The newly delivered Pass 8 event-level analysis allows the detection and characterization of sources in the 50 GeV–2TeV energy range. In this energy band, Fermi - LAT has detected 360 sources, which constitute the second catalog of hard Fermi -LAT sources (2FHL). The improved angular resolution enables the precise localization of point sources (~1.'7 radius at 68 % C. L.) and the detection and characterization of spatially extended sources. We find that 86% of the sources can be associatedmore » with counterparts at other wavelengths, of which the majority (75%) are active galactic nuclei and the rest (11%) are Galactic sources. Only 25% of the 2FHL sources have been previously detected by Cherenkov telescopes, implying that the 2FHL provides a reservoir of candidates to be followed up at very high energies. This work closes the energy gap between the observations performed at GeV energies by Fermi -LAT on orbit and the observations performed at higher energies by Cherenkov telescopes from the ground.« less

Detection and characterization of latent HSV RNA by in situ and northern blot hybridization in guinea pigs.

PubMed

Burke, R L; Hartog, K; Croen, K D; Ostrove, J M

1991-04-01

Following intravaginal infection of guinea pigs, herpes simplex virus establishes a latent infection in the sensory lumbosacral ganglia. Using the techniques of in situ and Northern blot hybridization, we have characterized this latent HSV-2 virus and compared it to latent HSV-1 at the same anatomical site. For HSV-2, a single 1.8-kb latency-associated transcript (LAT) was detected. In contrast, as described for latent HSV-1 in the trigeminal ganglia of rabbits and mice, two HSV-1 LAT species were detected in the lumbosacral ganglia, an abundant transcript of 1.8 kb and a less abundant transcript of 1.55 kb. Despite these differences in LAT expression, the clinical course of the acute and recurrent genital disease was similar for both viruses. LAT was detected in 0.3-6.0% of the sensory neurons of sacral but not in lumbar ganglia. The abundance of LAT correlated with the severity of the initial infection, but not with the frequency of recurrent disease. Thus, vaccination strategies that substantially reduced or eliminated symptomatic disease following challenge infection appeared to block the establishment of a latent infection.

SEARCHING THE GAMMA-RAY SKY FOR COUNTERPARTS TO GRAVITATIONAL WAVE SOURCES: FERMI GAMMA-RAY BURST MONITO R AND LARGE AREA TELESCOPE OBSERVATIONS OF LVT151012 AND GW151226

DOE Office of Scientific and Technical Information (OSTI.GOV)

Racusin, J. L.; Camp, J.; Singer, L.

2017-01-20

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger event GW151226 and candidate LVT151012. At the time of the LIGO triggers on LVT151012 and GW151226, GBM was observing 68% and 83% of the localization regions, and LAT was observing 47% and 32%, respectively. No candidate electromagnetic counterparts were detected by either the GBM or LAT. We present a detailed analysis of the GBM and LAT data over a range of timescales from seconds to years, using automated pipelines and new techniques for characterizing the flux upper bounds acrossmore » large areas of the sky. Due to the partial GBM and LAT coverage of the large LIGO localization regions at the trigger times for both events, differences in source distances and masses, as well as the uncertain degree to which emission from these sources could be beamed, these non-detections cannot be used to constrain the variety of theoretical models recently applied to explain the candidate GBM counterpart to GW150914.« less

Fitting the Fermi-LAT GeV excess: On the importance of including the propagation of electrons from dark matter

NASA Astrophysics Data System (ADS)

Lacroix, Thomas; BÅ`hm, Céline; Silk, Joseph

2014-08-01

An excess of gamma rays at GeV energies has been pointed out in the Fermi-LAT data. This signal comes from a narrow region centred around the Galactic center and has been interpreted as possible evidence for light dark matter particles annihilating either into a mixture of leptons-antileptons and bb ¯ or into bb ¯ only. Focusing on the prompt gamma-ray emission, previous works found that the best fit to the data corresponds to annihilations proceeding predominantly into bb ¯. However, here we show that omitting the photon emission originating from primary and secondary electrons produced in dark matter annihilations, and undergoing diffusion through the Galactic magnetic field, can actually lead to the wrong conclusion. Accounting for this emission, we find that not only are annihilations of ˜10 GeV particles into a purely leptonic final state allowed, but the democratic scenario actually provides a better fit to the spectrum of the excess than the pure bb ¯ channel. We conclude our work with a discussion on constraints on these leptophilic scenarios based on the AMS data and the morphology of the excess.

On possible interpretations of the high energy electron–positron spectrum measured by the Fermi Large Area Telescope

DOE PAGES

Grasso, D.; Profumo, S.; Strong, A. W.; ...

2009-07-11

The Fermi-LAT experiment recently reported high precision measurements of the spectrum of cosmic-ray electrons-plus-positrons (CRE) between 20 GeV and 1 TeV. The spectrum shows no prominent spectral features, and is significantly harder than that inferred from several previous experiments. In this paper, we discuss several interpretations of the Fermi results based either on a single large scale Galactic CRE component or by invoking additional electron–positron primary sources, e.g. nearby pulsars or particle dark matter annihilation. We show that while the reported Fermi-LAT data alone can be interpreted in terms of a single component scenario, when combined with other complementary experimentalmore » results, specifically the CRE spectrum measured by H.E.S.S. and especially the positron fraction reported by PAMELA between 1 and 100 GeV, that class of models fails to provide a consistent interpretation. Rather, we find that several combinations of parameters, involving both the pulsar and dark matter scenarios, allow a consistent description of those results. Finally, we also briefly discuss the possibility of discriminating between the pulsar and dark matter interpretations by looking for a possible anisotropy in the CRE flux.« less

CTCF Occupation of the Herpes Simplex Virus 1 Genome Is Disrupted at Early Times Postreactivation in a Transcription-Dependent Manner

PubMed Central

Ertel, Monica K.; Cammarata, Amy L.; Hron, Rebecca J.

2012-01-01

In herpes simplex virus 1 (HSV-1), binding clusters enriched in CTCF during latency have been previously identified. We hypothesized that CTCF binding to CTCF clusters in HSV-1 would be disrupted in a reactivation event. To investigate, CTCF occupation of three CTCF binding clusters in HSV-1 was analyzed following sodium butyrate (NaB)- and explant-induced reactivation in the mouse. Our data show that the CTCF domains positioned within the HSV-1 genome, specifically around the latency-associated transcript (LAT) and ICP0 and ICP4 regions of the genome, lose CTCF occupancy following the application of reactivation stimuli in wild-type virus. We also found that CTCF binding clusters upstream of the ICP0 and ICP4 promoters both function as classical insulators capable of acting as enhancer blockers of the LAT enhancer. Finally, our results suggest that CTCF occupation of domains in HSV-1 may be differentially regulated both during latency and at early times following reactivation by the presence of lytic transcripts and further implicate epigenetic regulation of HSV-1 as a critical component of the latency-reactivation transition. PMID:22973047

Henry Taube and Coordination Chemistry

Science.gov Websites

Shifts Caused by Cr++ in Aqueous Solutions, DOE Technical Report, 1962 Reactions of Solvated Ions Final Report, DOE Technical Report, 1962 Isotopic Discrimination of Some Solutes in Liquid Ammonia, DOE Technical Report, 1966 Final Technical Report of Research, DOE Technical Report, 1972 Top Additional Web

George A. Olah, Carbocation and Hydrocarbon Chemistry

Science.gov Websites

. Final Technical Report. [HF:BF{sub 2}/H{sub 2}] , DOE Technical Report, 1980 Superacid Catalyzed Coal Conversion Chemistry. 1st and 2nd Quarterly Technical Progress Reports, September 1, 1983-March 30, 1984 , DOE Technical Report, 1984 Superacid Catalyzed Coal Conversion Chemistry. Final Technical Report

Fermi LAT detection of a GeV flare from blazar S5 1217+71

NASA Astrophysics Data System (ADS)

Ciprini, Stefano

2013-03-01

The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed gamma-ray flaring activity from a source positionally consistent with the flat spectrum radio quasar S5 1217+71, also known as TXS 1217+713 and 2FGL J1219.2+7107 in the second Fermi LAT catalog (2FGL, Nolan et al. 2012, ApJS, 199, 31) with VLBI coordinates, (J2000.0), R.A: 185.015118 deg, Dec.: +71.091981 deg (Petrov et al.

ensembleBMA: An R Package for Probabilistic Forecasting using Ensembles and Bayesian Model Averaging

DTIC Science & Technology

2007-08-15

library is used to allow addition of the legend and map outline to the plot. > bluescale <- function(n) hsv (4/6, s = seq(from = 1 /8, to = 1 , length = n...v = 1 ) > plotBMAforecast( probFreeze290104, lon=srftGridData$lon, lat =srftGridData$ lat , type="image", col=bluescale(100)) > title("Probability of...probPrecip130103) # used to determine zlim in plots [ 1 ] 0.02832709 0.99534860 > plotBMAforecast( probPrecip130103[,Ŕ"], lon=prcpGridData$lon, lat

Multispectral Bathymetry Programs: A Users Guide

DTIC Science & Technology

1991-01-01

LAT,LON,NEAST,NORTH,ID, NCTM ,NRTM, + (INTENSET(N) ,N=1,5) ,NCSPOT,NRSPOT, + (INTENSES(N) ,N~=1, 3) 10 FORMAT(5I8,12I4) DO WHILE (NEAST .NE. 0) IF...LCALL .EQ. 1) THEN IF (INTENSET(1) .GT. 0 ..AND. INTENSES~l) .GT. 0> THEN NP = NP + 1 IMAGE(NP,l) = NCTM IMAGE(NP,2) = NRTM IMAGE(NP,3) = ID IMAGE(NP,4...LAT,LON,NEAST,NORTH,ID, NCTM ,NRTM, + (INTENSET(N) ,N=1,5) ,NCSPOT,NRSPOT, + (INTENSES(N) ,N=1, 3) READ(7,1O) LAT,LON,NEAST,NORTH,ID, NCTM ,NRTM

Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression.

PubMed

Zhang, Jing; Liu, Hui; Hou, Lidan; Wang, Ge; Zhang, Rui; Huang, Yanxia; Chen, Xiaoyu; Zhu, Jinshui

2017-09-11

Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gastric cancer (GC). But, the underlying molecular mechanisms by which ncRNAs modulate LATS1 expression in GC remain undetermined. The correlation of LATS1 and has-miR-424-5p (miR-424) expression with clinicopathological characteristics and prognosis of GC patients was analyzed by TCGA RNA-sequencing data. A novel circular RNA_LARP4 (circLARP4) was identified to sponge miR-424 by circRNA expression profile and bioinformatic analysis. The binding site between miR-424 and LATS1 or circLARP4 was verified using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The expression and localization of circLARP4 in GC tissues were investigated by fluorescence in situ hybridization (FISH). MTT, colony formation, Transwell and EdU assays were performed to assess the effects of miR-424 or circLARP4 on cell proliferation and invasion. Increased miR-424 expression or decreased LATS1 expression was associated with pathological stage and unfavorable prognosis of GC patients. Ectopic expression of miR-424 promoted proliferation and invasion of GC cells by targeting LATS1 gene. Furthermore, circLARP4 was mainly localized in the cytoplasm and inhibited biological behaviors of GC cells by sponging miR-424. The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients. circLARP4 may act as a novel tumor suppressive factor and a potential biomarker in GC.

Sensitivity projections for dark matter searches with the Fermi large area telescope

NASA Astrophysics Data System (ADS)

Charles, E.; Sánchez-Conde, M.; Anderson, B.; Caputo, R.; Cuoco, A.; Di Mauro, M.; Drlica-Wagner, A.; Gomez-Vargas, G. A.; Meyer, M.; Tibaldo, L.; Wood, M.; Zaharijas, G.; Zimmer, S.; Ajello, M.; Albert, A.; Baldini, L.; Bechtol, K.; Bloom, E. D.; Ceraudo, F.; Cohen-Tanugi, J.; Digel, S. W.; Gaskins, J.; Gustafsson, M.; Mirabal, N.; Razzano, M.

2016-06-01

The nature of dark matter is a longstanding enigma of physics; it may consist of particles beyond the Standard Model that are still elusive to experiments. Among indirect search techniques, which look for stable products from the annihilation or decay of dark matter particles, or from axions coupling to high-energy photons, observations of the γ-ray sky have come to prominence over the last few years, because of the excellent sensitivity of the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope mission. The LAT energy range from 20 meV to above 300 GeV is particularly well suited for searching for products of the interactions of dark matter particles. In this report we describe methods used to search for evidence of dark matter with the LAT, and review the status of searches performed with up to six years of LAT data. We also discuss the factors that determine the sensitivities of these searches, including the magnitudes of the signals and the relevant backgrounds, considering both statistical and systematic uncertainties. We project the expected sensitivities of each search method for 10 and 15 years of LAT data taking. In particular, we find that the sensitivity of searches targeting dwarf galaxies, which provide the best limits currently, will improve faster than the square root of observing time. Current LAT limits for dwarf galaxies using six years of data reach the thermal relic level for masses up to 120 GeV for the b b ¯ annihilation channel for reasonable dark matter density profiles. With projected discoveries of additional dwarfs, these limits could extend to about 250 GeV. With as much as 15 years of LAT data these searches would be sensitive to dark matter annihilations at the thermal relic cross section for masses to greater than 400 GeV (200 GeV) in the b b ¯ (τ+τ-) annihilation channels.

Comparison of fracture strength and failure mode of different ceramic implant abutments.

PubMed

Elsayed, Adham; Wille, Sebastian; Al-Akhali, Majed; Kern, Matthias

2017-04-01

The whitish color of zirconia (ZrO 2 ) abutments offers favorable esthetics compared with the grayish color of titanium (Ti) abutments. Nonetheless, ZrO 2 has greater opacity, making it difficult to achieve natural tooth color. Therefore, lithium disilicate (LaT) abutments have been suggested to replace metal abutments. The purpose of this in vitro study was to evaluate the fracture strength and failure mode of single-tooth implant restorations using ZrO 2 and LaT abutments, and to compare them with titanium (Ti) abutments. Five different types of abutments, Ti; ZrO 2 with no metal base; ZrO 2 with a metal base (ZrT); LaT; and LaT combination abutment and crown (LcT) were assembled on 40 Ti implants and restored with LaT crowns. Specimens were subjected to quasistatic loading using a universal testing machine, until the implant-abutment connection failed. As bending of the metal would be considered a clinical failure, the values of force (N) at which the plastic deformation of the metal occurred were calculated, and the rate of deformation was analyzed. Statistical analysis was done using the Mann-Whitney U test (α=.05). Group ZrO 2 revealed the lowest resistance to failure with a mean of 202 ±33 N. Groups ZrT, LaT, and LaC withstood higher forces without fracture or debonding of the ceramic suprastructure, and failure was due to deformation of metal bases, with no statistically significant differences between these groups regarding the bending behavior. Within the limitations of this in vitro study, it was concluded that LaT abutments have the potential to withstand the physiological occlusal forces that occur in the anterior region and that ZrO 2 abutments combined with Ti inserts have much higher fracture strength than pure ZrO 2 abutments. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Sensitivity projections for dark matter dearches with the Fermi large area telescope

DOE PAGES

Charles, E.; M. Sanchez-Conde; Anderson, B.; ...

2016-05-20

The nature of dark matter is a longstanding enigma of physics; it may consist of particles beyond the Standard Model that are still elusive to experiments. Among indirect search techniques, which look for stable products from the annihilation or decay of dark matter particles, or from axions coupling to high-energy photons, observations of themore » $$\\gamma$$-ray sky have come to prominence over the last few years, because of the excellent sensitivity of the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope mission. The LAT energy range from 20 MeV to above 300 GeV is particularly well suited for searching for products of the interactions of dark matter particles. In this report we describe methods used to search for evidence of dark matter with the LAT, and review the status of searches performed with up to six years of LAT data. We also discuss the factors that determine the sensitivities of these searches, including the magnitudes of the signals and the relevant backgrounds, considering both statistical and systematic uncertainties. We project the expected sensitivities of each search method for 10 and 15 years of LAT data taking. In particular, we find that the sensitivity of searches targeting dwarf galaxies, which provide the best limits currently, will improve faster than the square root of observing time. Current LAT limits for dwarf galaxies using six years of data reach the thermal relic level for masses up to 120 GeV for the $$b\\bar{b}$$ annihilation channel for reasonable dark matter density profiles. With projected discoveries of additional dwarfs, these limits could extend to about 250 GeV. With as much as 15 years of LAT data these searches would be sensitive to dark matter annihilations at the thermal relic cross section for masses to greater than 400 GeV (200 GeV) in the $$b\\bar{b}$$ ($$\\tau^+ \\tau^-$$) annihilation channels.« less

Sensitivity projections for dark matter dearches with the Fermi large area telescope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charles, E.; M. Sanchez-Conde; Anderson, B.

The nature of dark matter is a longstanding enigma of physics; it may consist of particles beyond the Standard Model that are still elusive to experiments. Among indirect search techniques, which look for stable products from the annihilation or decay of dark matter particles, or from axions coupling to high-energy photons, observations of themore » $$\\gamma$$-ray sky have come to prominence over the last few years, because of the excellent sensitivity of the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope mission. The LAT energy range from 20 MeV to above 300 GeV is particularly well suited for searching for products of the interactions of dark matter particles. In this report we describe methods used to search for evidence of dark matter with the LAT, and review the status of searches performed with up to six years of LAT data. We also discuss the factors that determine the sensitivities of these searches, including the magnitudes of the signals and the relevant backgrounds, considering both statistical and systematic uncertainties. We project the expected sensitivities of each search method for 10 and 15 years of LAT data taking. In particular, we find that the sensitivity of searches targeting dwarf galaxies, which provide the best limits currently, will improve faster than the square root of observing time. Current LAT limits for dwarf galaxies using six years of data reach the thermal relic level for masses up to 120 GeV for the $$b\\bar{b}$$ annihilation channel for reasonable dark matter density profiles. With projected discoveries of additional dwarfs, these limits could extend to about 250 GeV. With as much as 15 years of LAT data these searches would be sensitive to dark matter annihilations at the thermal relic cross section for masses to greater than 400 GeV (200 GeV) in the $$b\\bar{b}$$ ($$\\tau^+ \\tau^-$$) annihilation channels.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, A.; Cleveland, W. H.; Connaughton, V.

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger (BBH) event GW170104. No candidate electromagnetic counterpart was detected by either GBM or LAT. A detailed analysis of the GBM and LAT data over timescales from seconds to days covering the Laser Interferometer Gravitational-wave Observatory (LIGO) localization region is presented. The resulting flux upper bound from the GBM is (5.2–9.4) × 10{sup −7} erg cm{sup −2} s{sup −1} in the 10–1000 keV range and from the LAT is (0.2–90) × 10{sup −9} erg cm{sup −2} s{sup −1} in themore » 0.1–1 GeV range. We also describe the improvements to our automated pipelines and analysis techniques for searching for and characterizing the potential electromagnetic counterparts for future gravitational-wave events from Advanced LIGO/Virgo.« less

GUST LAT Multiwavelength Planning

NASA Technical Reports Server (NTRS)

Thompson, D. J.

2004-01-01

Because gamma-ray astrophysics profits in powerful ways from multi-wavelength studies, the GLAST Large Area Telescope (LAT) Collaboration has started multiwavelength planning well before the scheduled 2007 launch. Many aspects of this program are of direct interest to observers using VERITAS and other atmospheric Cerenkov telescopes, whose capabilities complement those of GLAST. This talk with describe some of the current developmental concepts for GLAST LAT multiwavelength work, including release of data for transient sources, nearly-continuous monitoring of selected time-variable sources, pulsar timing, follow-on observations for source identification, coordinated blazar campaigns, and cross-calibration with other high-energy telescopes. Although few details are firm at this stage of preparation for GLAST, the LAT Collaboration looks forward to cooperation with a broad cross-section of the multiwave-length community. The GLAST Large Area Telescope is an international effort, with U.S. funding provided by the Department of Energy and NASA.

A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis.

PubMed

Azad, T; Janse van Rensburg, H J; Lightbody, E D; Neveu, B; Champagne, A; Ghaffari, A; Kay, V R; Hao, Y; Shen, H; Yeung, B; Croy, B A; Guan, K L; Pouliot, F; Zhang, J; Nicol, C J B; Yang, X

2018-03-13

The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings.

Fermi Observations of the LIGO Event GW170104

DOE PAGES

Goldstein, A.; Veres, P.; Burns, E.; ...

2017-08-28

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger (BBH) event GW170104. No candidate electromagnetic counterparts was detected by either GBM or LAT. A detailed analysis of the GBM and LAT data over timescales from seconds to days covering the LIGO localization region is presented. The resulting ux upper bound from the GBM is (5.2{9.4) 10 -7 erg cm -2 s -1 in the 10-1000 keV range and from the LAT is (0.2{13) 10 -9 erg cm -2 s -1 in the 0.1{1 GeV range. We also describemore » the improvements to our automated pipelines and analysis techniques for searching for and characterizing the potential electromagnetic counterparts for future gravitational wave events from Advanced LIGO/VIRGO.« less

Air Weather Service Model Output Statistics Systems.

DTIC Science & Technology

1983-10-01

LAT LONG 57^43’N 3°20’W 58°27’N 3°05*W 57°12’N 2°12’W 54051’N 4°57’W 54O05’N 4°38*W 54018’N 1 °32’W 53°29’N 1 °00’W LAT LONG 53^10’N...Region 4 LAT LONG 51°56*N "PTF’W 51°37’N 1 °05’W 51°58’N 0°30’E 51°23’N 1 °17’W 51°10’N 1 °45’W 51°15’N 0°57’W 51°17’N 0°45’W NUMBER ICAO... 1 LAT 47^46’N

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

NASA Astrophysics Data System (ADS)

MAGIC Collaboration; Ahnen, M. L.; Ansoldi, S.; Antonelli, L. A.; Antoranz, P.; Babic, A.; Banerjee, B.; Bangale, P.; Barres de Almeida, U.; Barrio, J. A.; Becerra González, J.; Bednarek, W.; Bernardini, E.; Biasuzzi, B.; Biland, A.; Blanch, O.; Bonnefoy, S.; Bonnoli, G.; Borracci, F.; Bretz, T.; Carmona, E.; Carosi, A.; Chatterjee, A.; Clavero, R.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; Da Vela, P.; Dazzi, F.; De Angelis, A.; De Lotto, B.; de Oña Wilhelmi, E.; Delgado Mendez, C.; Di Pierro, F.; Dominis Prester, D.; Dorner, D.; Doro, M.; Einecke, S.; Eisenacher Glawion, D.; Elsaesser, D.; Fernández-Barral, A.; Fidalgo, D.; Fonseca, M. V.; Font, L.; Frantzen, K.; Fruck, C.; Galindo, D.; García López, R. J.; Garczarczyk, M.; Garrido Terrats, D.; Gaug, M.; Giammaria, P.; Godinović, N.; González Muñoz,; A.; Guberman, D.; Hahn, A.; Hanabata, Y.; Hayashida, M.; Herrera, J.; Hose, J.; Hrupec, D.; Hughes, G.; Idec, W.; Kodani, K.; Konno, Y.; Kubo, H.; Kushida, J.; La Barbera, A.; Lelas, D.; Lindfors, E.; Lombardi, S.; Longo, F.; López-Coto, M. López R.; López-Oramas, A.; Lorenz, E.; Majumdar, P.; Makariev, M.; Mallot, K.; Maneva, G.; Manganaro, M.; Mannheim, K.; Maraschi, L.; Marcote, B.; Mariotti, M.; Martínez, M.; Mazin, D.; Menzel, U.; Miranda, J. M.; Mirzoyan, R.; Moralejo, A.; Moretti, E.; Nakajima, D.; Neustroev, V.; Niedzwiecki, A.; Nievas Rosillo, M.; Nilsson, K.; Nishijima, K.; Noda, K.; Orito, R.; Overkemping, A.; Paiano, S.; Palacio, J.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Paredes-Fortuny, X.; Persic, M.; Poutanen, J.; Prada Moroni, P. G.; Prandini, E.; Puljak, I.; Rhode, W.; Ribó, M.; Rico, J.; Rodriguez Garcia, J.; Saito, T.; Satalecka, K.; Schultz, C.; Schweizer, T.; Shore, S. N.; Sillanpää, A.; Sitarek, J.; Snidaric, I.; Sobczynska, D.; Stamerra, A.; Steinbring, T.; Strzys, M.; Takalo, L.; Takami, H.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Thaele, J.; Torres, D. F.; Toyama, T.; Treves, A.; Verguilov, V.; Vovk, I.; Ward, J. E.; Will, M.; Wup, M. H.; Zanins, R.; Aleksić, J.; Wood, M.; Anderson, B.; Bloom, E. D.; Cohen-Tanugi, J.; Drlica-Wagner, A.; Mazziotta, M. N.; Sánchez-Condeai, M.; Strigarian, L.

2016-02-01

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV—the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.

Constraints on dark matter annihilation in clusters of galaxies with the Fermi large area telescope

DOE PAGES

Ackermann, M.; Ajello, M.; Allafort, A.; ...

2010-05-20

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~ 200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits excludemore » large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~ 5 over a smooth-halo assumption. Here, we also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. Finally, in this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.« less

77 FR 46306 - Fluxapyroxad; Pesticide Tolerances Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

...; Pesticide Tolerances Technical Amendment AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule; technical amendment. SUMMARY: EPA issued a final rule in the Federal Register of May 14, 2012, concerning.... Inadvertently, the terminology for the oilseed crop group and for dried plums was incorrect. This technical...

miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Mingjun; Wang, Xiaolei; Li, Wanhu

Although a series of oncogenes and tumor suppressors were identified in the pathological development of gastric adenocarcinoma (GAC), the underlying molecule mechanism were still not fully understood. The current study explored the expression profile of miR-107 and miR-25 in GAC patients and their downstream regulative network. qRT-PCR analysis was performed to quantify the expression of these two miRNAs in serum samples from both patients and healthy controls. Dual luciferase assay was conducted to verify their putative bindings with LATS2. MTT assay, cell cycle assay and transwell assay were performed to explore how miR-107 and miR-25 regulate proliferation and invasion ofmore » gastric cancer cells. Findings of this study demonstrated that total miR-107 or miR-25 expression might be overexpressed in gastric cancer patients and they can simultaneously and synchronically regulate LATS2 expression, thereby affecting gastric cancer cell growth and invasion. Therefore, the miR-25/miR-107-LATS2 axis might play an important role in proliferation and invasion of the gastric cancer cells. - Highlights: • Total miR-107 and miR-25 expression is significantly increased in GAC patients. • Both miR-107 and miR-25 can promote proliferation and invasion of GAC cells. • Both miR-107 and miR-25 can target LATS2 and regulate its expression. • miR-107 and miR-25 regulate proliferation and invasion of GAC cells though LATS2.« less

Theoretical Interpretation of Pass 8 Fermi -LAT e + + e - Data

DOE PAGES

Di Mauro, M.; Manconi, S.; Vittino, A.; ...

2017-08-17

The flux of positrons and electrons (e + + e -) has been measured by the Fermi Large Area Telescope (LAT) in the energy range between 7 GeV and 2 TeV. Here, we discuss a number of interpretations of Pass 8 Fermi-LAT e + + e - spectrum, combining electron and positron emission from supernova remnants (SNRs) and pulsar wind nebulae (PWNe), or produced by the collision of cosmic rays (CRs) with the interstellar medium. We also found that the Fermi-LAT spectrum is compatible with the sum of electrons from a smooth SNR population, positrons from cataloged PWNe, and amore » secondary component. If we include in our analysis constraints from the AMS-02 positron spectrum, we obtain a slightly worse fit to the e + + e - Fermi-LAT spectrum, depending on the propagation model. As an additional scenario, we replace the smooth SNR component within 0.7 kpc with the individual sources found in Green's catalog of Galactic SNRs. We find that separate consideration of far and near sources helps to reproduce the e + + e - Fermi-LAT spectrum. However, we show that the fit degrades when the radio constraints on the positron emission from Vela SNR (which is the main contributor at high energies) are taken into account. We find that a break in the power-law injection spectrum at about 100 GeV can also reproduce the measured e + + e -spectrum and, among the CR propagation models that we consider, no reasonable break of the power-law dependence of the diffusion coefficient can modify the electron flux enough to reproduce the observed shape.« less

Fermi-LAT Search for Pulsar Wind Nebulae around gamma-ray Pulsars

DOE PAGES

Ackermann, M.; Ajello, M.; Baldini, L.; ...

2010-12-13

The high sensitivity of the Fermi-LAT (Large Area Telescope) offers the first opportunity to study faint and extended GeV sources such as pulsar wind nebulae (PWNe). After one year of observation the LAT detected and identified three PWNe: the Crab Nebula, Vela-X, and the PWN inside MSH 15-52. In the meantime, the list of LAT detected pulsars increased steadily. These pulsars are characterized by high energy loss rates (more » $$\\dot{E}$$) from ~3 × 10 33 erg s –1 to 5 × 10 38 erg s –1 and are therefore likely to power a PWN. This paper summarizes the search for PWNe in the off-pulse windows of 54 LAT-detected pulsars using 16 months of survey observations. Ten sources show significant emission, seven of these likely being of magnetospheric origin. The detection of significant emission in the off-pulse interval offers new constraints on the γ-ray emitting regions in pulsar magnetospheres. The three other sources with significant emission are the Crab Nebula, Vela-X, and a new PWN candidate associated with the LAT pulsar PSR J1023–5746, coincident with the TeV source HESS J1023–575. Here, we further explore the association between the HESS and the Fermi source by modeling its spectral energy distribution. Lastly, flux upper limits derived for the 44 remaining sources are used to provide new constraints on famous PWNe that have been detected at keV and/or TeV energies.« less

Theoretical Interpretation of Pass 8 Fermi -LAT e + + e - Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Mauro, M.; Manconi, S.; Vittino, A.

The flux of positrons and electrons (e + + e -) has been measured by the Fermi Large Area Telescope (LAT) in the energy range between 7 GeV and 2 TeV. Here, we discuss a number of interpretations of Pass 8 Fermi-LAT e + + e - spectrum, combining electron and positron emission from supernova remnants (SNRs) and pulsar wind nebulae (PWNe), or produced by the collision of cosmic rays (CRs) with the interstellar medium. We also found that the Fermi-LAT spectrum is compatible with the sum of electrons from a smooth SNR population, positrons from cataloged PWNe, and amore » secondary component. If we include in our analysis constraints from the AMS-02 positron spectrum, we obtain a slightly worse fit to the e + + e - Fermi-LAT spectrum, depending on the propagation model. As an additional scenario, we replace the smooth SNR component within 0.7 kpc with the individual sources found in Green's catalog of Galactic SNRs. We find that separate consideration of far and near sources helps to reproduce the e + + e - Fermi-LAT spectrum. However, we show that the fit degrades when the radio constraints on the positron emission from Vela SNR (which is the main contributor at high energies) are taken into account. We find that a break in the power-law injection spectrum at about 100 GeV can also reproduce the measured e + + e -spectrum and, among the CR propagation models that we consider, no reasonable break of the power-law dependence of the diffusion coefficient can modify the electron flux enough to reproduce the observed shape.« less

Expression of Herpes Simplex Virus 1-Encoded MicroRNAs in Human Trigeminal Ganglia and Their Relation to Local T-Cell Infiltrates ▿

PubMed Central

Held, Kathrin; Junker, Andreas; Dornmair, Klaus; Meinl, Edgar; Sinicina, Inga; Brandt, Thomas; Theil, Diethilde; Derfuss, Tobias

2011-01-01

Herpes simplex type 1 (HSV-1) is a neurotropic virus which establishes lifelong latency in human trigeminal ganglia (TG). Currently, two nonexclusive control mechanisms of HSV-1 latency are discussed: antiviral CD8+ T cells and viral microRNAs (miRNAs) encoded by the latency associated transcript (LAT). We investigate here to what extent these mechanisms may contribute to the maintenance of HSV-1 latency. We show that only a small proportion of LAT+ neurons is surrounded by T cells in human TG. This indicates that viral latency in human TG might be controlled by other mechanisms such as viral miRNAs. Therefore, we assessed TG sections for the presence of HSV-1 miRNA, DNA, and mRNA by combining LAT in situ hybridization, T-cell immunohistochemistry, and single cell analysis of laser-microdissected sensory neurons. Quantitative reverse transcription-PCR (RT-PCR) revealed that LAT+ neurons with or without surrounding T cells were always positive for HSV-1 miRNAs and DNA. Furthermore, ICP0 mRNA could rarely be detected only in LAT+ neurons, as analyzed by single-cell RT-PCR. In contrast, in LAT− neurons that were surrounded by T cells, neither miRNAs nor the DNA of HSV-1, HSV-2, or varicella-zoster virus could be detected. These data indicate that the majority of LAT+ neurons is not directly controlled by T cells. However, miRNA expression in every latently infected neuron would provide an additional checkpoint before viral replication is initiated. PMID:21795359

Enhanced gravitropism of roots with a disrupted cap actin cytoskeleton

NASA Technical Reports Server (NTRS)

Hou, Guichuan; Mohamalawari, Deepti R.; Blancaflor, Elison B.

2003-01-01

The actin cytoskeleton has been proposed to be a major player in plant gravitropism. However, understanding the role of actin in this process is far from complete. To address this problem, we conducted an analysis of the effect of Latrunculin B (Lat B), a potent actin-disrupting drug, on root gravitropism using various parameters that included detailed curvature kinetics, estimation of gravitropic sensitivity, and monitoring of curvature development after extended clinorotation. Lat B treatment resulted in a promotion of root curvature after a 90 degrees reorientation in three plant species tested. More significantly, the sensitivity of maize (Zea mays) roots to gravity was enhanced after actin disruption, as determined from a comparison of presentation time of Lat B-treated versus untreated roots. A short 10-min gravistimulus followed by extended rotation on a 1-rpm clinostat resulted in extensive gravitropic responses, manifested as curvature that often exceeded 90 degrees. Application of Lat B to the cap or elongation zone of maize roots resulted in the disruption of the actin cytoskeleton, which was confined to the area of localized Lat B application. Only roots with Lat B applied to the cap displayed the strong curvature responses after extended clinorotation. Our study demonstrates that disrupting the actin cytoskeleton in the cap leads to the persistence of a signal established by a previous gravistimulus. Therefore, actin could function in root gravitropism by providing a mechanism to regulate the proliferation of a gravitropic signal originating from the cap to allow the root to attain its correct orientation or set point angle.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Jun-Qing; Cuoco, Alessandro; Branchini, Enzo

Building on our previous cross-correlation analysis (Xia et al. 2011) between the isotropic γ-ray background (IGRB) and different tracers of the large-scale structure of the universe, we update our results using 60 months of data from the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi). For this study, we perform a cross-correlation analysis both in configuration and spherical harmonics space between the IGRB and objects that may trace the astrophysical sources of the IGRB: QSOs in the Sloan Digital Sky Survey (SDSS) DR6, the SDSS DR8 Main Galaxy Sample, luminous red galaxies (LRGs) in the SDSS catalog, infrared-selected galaxies in the Two Micron All Sky Survey (2MASS), and radio galaxies in the NRAO VLA Sky Survey (NVSS). The benefit of correlating the Fermi-LAT signal with catalogs of objects at various redshifts is to provide tomographic information on the IGRB, which is crucial in separating the various contributions and clarifying its origin. The main result is that, unlike in our previous analysis, we now observe a significant (>3.5σ) cross-correlation signal on angular scales smaller than 1° in the NVSS, 2MASS, and QSO cases and, at lower statistical significance (~3.0σ), with SDSS galaxies. The signal is stronger in two energy bands, E > 0.5 GeV and E > 1 GeV, but it is also seen at E > 10 GeV. No cross-correlation signal is detected between Fermi data and the LRGs. These results are robust against the choice of the statistical estimator, estimate of errors, map cleaning procedure, and instrumental effects. Finally, we test the hypothesis that the IGRB observed by Fermi-LAT originates from the summed contributions of three types of unresolved extragalactic sources: BL Lacertae objects (BL Lacs), flat spectrum radio quasars (FSRQs), and star-forming galaxies (SFGs). Finally, we find that a model in which the IGRB is mainly produced by SFGs (more » $$72_{-37}^{+23}$$% with 2σ errors), with BL Lacs and FSRQs giving a minor contribution, provides a good fit to the data. We also consider a possible contribution from misaligned active galactic nuclei, and we find that, depending on the details of the model and its uncertainty, they can also provide a substantial contribution, partly degenerate with the SFG one.« less

West Central U.S. Imagery (GOES-WEST) - Satellite Services Division /

Science.gov Websites

Single Image Java Loop Flash Loops HTML5 Loops With Lat/Lon No Lat/Lon Standard Standard Enhanced Same Sector from GOES East Flash Loop Note: Standard - usually 12-15 images many static overlays

Drainage Areas of Streams at Selected Locations in Kentucky

DTIC Science & Technology

1981-01-01

23󈧸", Long 82 ° 17󈧇" 195 LICK CREEK .2 .3 .70 1 .81 03207995 Levisa Fork (Fishtrap Lake ) near Millard--Lat 37°26󈧄", Long 82 ° 24󈧾" 195 MILLARD...130 .1 209 .3 392 1,015 (Area in Kentucky) 84 .6 219 (Area outside Kentucky) 308 798 03208000 Levisa Fork (below Fishtrap Lake ) near Millard--Lat 37...547 1,417 Elkhorn Creek Basin--at Russell Fork mile 12 .3 Little Elkhorn Creek at Jenkins--Lat 37 ° 10󈧊", Long 82°38󈧊", at Elkhorn Lake outlet

Fermi/LAT Observations of Swift/BAT Seyfert Galaxies: On the Contribution of Radio-Quiet Active Galactic Nuclei to the Extragalactic gamma-Ray Background

NASA Technical Reports Server (NTRS)

Teng, Stacy H.; Mushotzky, Richard F.; Sambruna, Rita M.; Davis, David S.; Reynolds, Christopher S.

2011-01-01

We present the analysis of 2.1 years of Fermi Large Area Telescope (LAT) data on 491 Seyfert galaxies detected by the Swift Burst Alert Telescope (BAT) survey. Only the two nearest objects, NGC 1068 and NGC 4945, which were identified in the Fermi first year catalog, are detected. Using Swift/BAT and radio 20 cm fluxes, we define a new radio-loudness parameter R(sub X,BAT) where radio-loud objects have logR(sub X,BAT) > -4.7. Based on this parameter, only radio-loud sources are detected by Fermi/LAT. An upper limit to the flux of the undetected sources is derived to be approx.2x10(exp -11) photons/sq cm/s, approximately seven times lower than the observed flux of NGC 1068. Assuming a median redshift of 0.031, this implies an upper limit to the gamma-ray (1-100 GeV) luminosity of < approx.3x10(exp 41) erg/s. In addition, we identified 120 new Fermi/LAT sources near the Swift/BAT Seyfert galaxies with significant Fermi/LAT detections. A majority of these objects do not have Swift/BAT counterparts, but their possible optical counterparts include blazars, flat-spectrum radio quasars, and quasars.

NuLat: 3D Event Reconstruction of a ROL Detector for Neutrino Detection and Background Rejection

NASA Astrophysics Data System (ADS)

Yokley, Zachary; NuLat Collaboration

2015-04-01

NuLat is a proposed very-short baseline reactor antineutrino experiment that employs a unique detector design, a Ragahavan Optical Lattice (ROL), developed for the LENS solar neutrino experiment. The 3D lattice provides high spatial and temporal resolution and allows for energy deposition in each voxel to be determined independently of other voxels, as well as the time sequence associated with each voxel energy deposition. This unique feature arises from two independent means to spatially locate energy deposits: via timing and via optical channeling. NuLat, the first application of a ROL detector targeting physics results, will measure the reactor antineutrino flux at very short baselines via inverse beta decay (IBD). The ROL design of NuLat makes possible the reconstruction of positron energy with little contamination due to the annihilation gammas which smear the positron energy resolution in a traditional detector. IBD events are cleanly tagged via temporal and spatial coincidence of neutron capture in the vertex voxel or nearest neighbors. This talk will present work on IBD event reconstruction in NuLat and its likely impact on sterile neutrino detection via operation in higher background locations enabled by its superior rejection of backgrounds. This research has been funded in part by the National Science Foundation on Award Numbers 1001394 and 1001078.

Ciculating miRNA-21 as a Biomarker Predicts Polycystic Ovary Syndrome (PCOS) in Patients.

PubMed

Jiang, Liyan; Li, Wei; Wu, Minmin; Cao, Sifan

2015-01-01

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, hyperinsulinemia, and infertility. In PCOS, abnormal regulation of relevant genes is required for follicular development. By binding to the 3' untranslated region (3'URT), microRNAs (miRNAs) are widely involved in posttranscriptional gene regulation. However, few studies have been conducted on circulating miRNA expression in PCOS. This study aims to describe altered expression of circulating miR-21 in PCOS. The expression of serum miRNAs of PCOS patients were explored using the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays. The protein level of LATS1 was determined using Western blot. To validate whether miR-21 targeted LATS1, the luciferase assay was applied. In comparison with normal subjects, the circulating level of miRNA-21 was significantly enhanced in PCOS patients. In PCOS patients, the expression levels of MST1/2, LATS1/2, TAZ were much lower than the control subjects. Luciferase reporter assay revealed that LATS1 was a downstream target of miR-21. In comparison with normal subjects, serum miR-21 is obviously increased in PCOS patients. Through targeting LATS1, miR-21 could prompt PCOS progression and could act as a novel non-invasive biomarker for diagnosis of PCOS.

CONSTRAINTS ON THE INTERGALACTIC MAGNETIC FIELD WITH GAMMA-RAY OBSERVATIONS OF BLAZARS

DOE PAGES

Finke, Justin D.; Reyes, Luis C.; Georganopoulos, Markos; ...

2015-11-12

Distant BL Lacertae objects emit γ rays which interact with the extragalactic background light (EBL), creating electron-positron pairs, and reducing the flux measured by ground-based imaging atmospheric Cherenkov telescopes (IACTs) at very-high energies (VHE). These pairs can Comptonscatter the cosmic microwave background, creating a γ-ray signature at slightly lower energies observable by the Fermi Large Area Telescope (LAT). This signal is strongly dependent on the intergalactic magnetic field (IGMF) strength (B) and its coherence length (LB). We use IACT spectra taken from the literature for 5 VHE-detected BL Lac objects, and combine it with LAT spectra for these sources tomore » constrain these IGMF parameters. Low B values can be ruled out by the constraint that the cascade flux cannot exceed that observed by the LAT. High values of B can be ruled out from the constraint that the EBL-deabsorbed IACT spectrum cannot be greater than the LAT spectrum extrapolated into the VHE band, unless the cascade spectrum contributes a sizable fraction of the LAT flux. We rule out low B values (B . 10 -19 G for LB ≥ 1 Mpc) at > 5σ in all trials with different EBL models and data selection, except when« less

Characteristics of L-citrulline transport through blood-brain barrier in the brain capillary endothelial cell line (TR-BBB cells).

PubMed

Lee, Kyeong-Eun; Kang, Young-Sook

2017-05-10

L -Citrulline is a neutral amino acid and a major precursor of L -arginine in the nitric oxide (NO) cycle. Recently it has been reported that L -citrulline prevents neuronal cell death and protects cerebrovascular injury, therefore, L -citrulline may have a neuroprotective effect to improve cerebrovascular dysfunction. Therefore, we aimed to clarify the brain transport mechanism of L -citrulline through blood-brain barrier (BBB) using the conditionally immortalized rat brain capillary endothelial cell line (TR-BBB cells), as an in vitro model of the BBB. The uptake study of [ 14 C] L-citrulline, quantitative real-time polymerase chain reaction (PCR) analysis, and rLAT1, system b 0,+ , and CAT1 small interfering RNA study were performed in TR-BBB cells. The uptake of [ 14 C] L -citrulline was a time-dependent, but ion-independent manner in TR-BBB cells. The transport process involved two saturable components with a Michaelis-Menten constant of 30.9 ± 1.0 μM (Km 1 ) and 1.69 ± 0.43 mM (Km 2 ). The uptake of [ 14 C] L -citrulline in TR-BBB cells was significantly inhibited by neutral and cationic amino acids, but not by anionic amino acids. In addition, [ 14 C] L -citrulline uptake in the cells was markedly inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), which is the inhibitor of the large neutral amino acid transporter 1 (LAT1), B 0 , B 0,+ and harmaline, the inhibitor of system b 0,+ . Gabapentin and L -dopa as the substrates of LAT1 competitively inhibited the uptake of [ 14 C] L -citrulline. IC 50 values for L -dopa, gabapentin, L -phenylalanine and L -arginine were 501 μM, 223 μM, 68.9 μM and 33.4 mM, respectively. The expression of mRNA for LAT1 was predominantly increased 187-fold in comparison with that of system b 0,+ in TR-BBB cells. In the studies of LAT1, system b 0,+ and CAT1 knockdown via siRNA transfection into TR-BBB cells, the transcript level of LAT1 and [ 14 C] L -citrulline uptake by LAT1 siRNA were significantly reduced compared with those by control siRNA in TR-BBB cells. Our results suggest that transport of L -citrulline is mainly mediated by LAT1 in TR-BBB cells. Delivery strategy for LAT1-mediated transport and supply of L-citrulline to the brain may serve as therapeutic approaches to improve its neuroprotective effect in patients with cerebrovascular disease.

The StreamCat Dataset: Accumulated Attributes for NHDPlusV2 Catchments (Version 2.1) for the Conterminous United States: Dam Density and Storage Volume

EPA Pesticide Factsheets

This dataset represents the dam density and storage volumes within individual, local NHDPlusV2 catchments and upstream, contributing watersheds based on National Inventory of Dams (NID) data. Attributes were calculated for every local NHDPlusV2 catchment and accumulated to provide watershed-level metrics.(See Supplementary Info for Glossary of Terms) The NID database contains information about the dam??s location, size, purpose, type, last inspection, regulatory facts, and other technical data. Structures on streams reduce the longitudinal and lateral hydrologic connectivity of the system. For example, impoundments above dams slow stream flow, cause deposition of sediment and reduce peak flows. Dams change both the discharge and sediment supply of streams, causing channel incision and bed coarsening downstream. Downstream areas are often sediment deprived, resulting in degradation, i.e., erosion of the stream bed and stream banks. This database was improved upon by locations verified by work from the USGS National Map (Jeff Simley Group). It was observed that some dams, some of them major and which do exist, were not part of the 2009 NID, but were represented in the USGS National Map dataset, and had been in the 2006 NID. Approximately 1,100 such dams were added, based on the USGS National Map lat/long and the 2006 NID attributes (dam height, storage, etc.) Finally, as clean-up, a) about 600 records with duplicate NIDID were removed, and b) about 300 reco

76 FR 11978 - Proposed Amendment of Federal Airways; Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... Federal airways in Alaska. Due to construction of wind turbines on Fire Island, AK, the Anchorage VOR is... NDB/DME (Lat. 56[deg]57'15'' N., long. 158[deg]38'51'' W.) BATTY Fix (Lat. 59[deg]03'57'' N., long...

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shikai; Song, Lili, E-mail: commasll@163.com; Zhang, Liang

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervicalmore » cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.« less

Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids.

PubMed

Subbaiah, P V; Liu, M

1996-05-31

Oxidation of lipoproteins results in the formation of several polar phospholipids with pro-inflammatory and pro-atherogenic properties. To examine the possible role of lecithin/cholesterol acyltransferase (LCAT) in the metabolism of these oxidized phospholipids, we oxidized whole plasma with either Cu(2+) or a free-radical generator, and determined the various activities of LCAT. Oxidation caused a reduction in plasma phosphatidylcholine (PC), an increase in a short-chain polar PC (SCP-PC), and an inhibition of the transfer of long-chain acyl groups to cholesterol (LCAT activity) or to lyso PC (lysolecithin acyltransferase (LAT) I activity). However, the transfer of short-chain acyl groups from SCP-PC to lyso PCLAT II activity) was stimulated several fold, in direct correlation with the degree of oxidation. LAT II activity was not stimulated by oxidation in LCAT-deficient plasma, showing that it is carried out by LCAT. Oxidized normal plasma exhibited low LCAT activity even in the presence of exogenous proteoliposome substrate, indicating that the depletion of substrate PC was not responsible for the loss of activity. Oxidation of isolated LDL or HDL abolished their ability to support LCAT and LAT I activities of exogenous enzyme, but promoted the LAT II activity. Purified LCAT lost its LCAT and LAT I functions, but not its LAT II function, when oxidized in vitro. These results show that while oxidation of plasma causes a loss of LCAT's ability to transfer long-chain acyl groups, its ability to transfer short-chain acyl groups, from SCP-PC is retained, and even stimulated, suggesting that LCAT may have a physiological role in the metabolism of oxidized PC in plasma.

Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs.

PubMed

Napolitano, Lara; Scalise, Mariafrancesca; Koyioni, Maria; Koutentis, Panayiotis; Catto, Marco; Eberini, Ivano; Parravicini, Chiara; Palazzolo, Luca; Pisani, Leonardo; Galluccio, Michele; Console, Lara; Carotti, Angelo; Indiveri, Cesare

2017-11-01

The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [ 3 H]histidine in exchange with intraliposomal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100µM concentration, were subjected to dose-response analysis. Two of them exhibited IC 50 lower than 1µM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular docking of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Conventional tracheal tubes for intubation through the intubating laryngeal mask airway.

PubMed

Kundra, Pankaj; Sujata, N; Ravishankar, M

2005-01-01

The laryngeal mask airway (LMA)-Fastrach silicone wire-reinforced tracheal tube (FTST) was specially designed for tracheal intubation through the intubating LMA (ILMA). However, conventional tracheal tubes have been successfully used to accomplish tracheal intubation. We designed this study to evaluate the success rate of blind tracheal intubation through the ILMA by using the FTST, the Rusch polyvinyl chloride tube (PVCT), and the Rusch latex armored tube (LAT). One-hundred-fifty healthy adults of ASA physical status I and II who were undergoing elective surgery under general anesthesia were randomly allocated into three groups. FTST (n=50), prewarmed PVCT (n=50), and LAT (n=50) were used for tracheal intubation. Ease of tracheal intubation was assessed by the time taken, the number of attempts, and the number of maneuvers required for success. In addition, numbers of failed intubation attempts and times taken for ILMA removal were also recorded. After surgery, the incidence of trauma, sore throat, and hoarseness was noted. Significantly more frequent success in tracheal intubation was achieved with the PVCT and FTST (96%) compared with the LAT (82%) (P <0.05). Tracheal intubation on the first attempt was similar with the PVCT and FTST (86%) and was significantly more frequent than with the LAT (52%) (P <0.05). Esophageal placement was significantly more frequent with the LAT (29.7%) when compared with the PVCT and FTST (1.8% and 7.4%, respectively) (P <0.05). The authors conclude that a prewarmed PVCT can be used as successfully as the FTST for blind tracheal intubation through the ILMA, whereas the LAT is associated with more frequent failure and esophageal intubation.

Theoretical Interpretation of Pass 8 Fermi -LAT e {sup +} + e {sup −} Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Mauro, M.; Manconi, S.; Donato, F.

The flux of positrons and electrons ( e {sup +} + e {sup −}) has been measured by the Fermi Large Area Telescope (LAT) in the energy range between 7 GeV and 2 TeV. We discuss a number of interpretations of Pass 8 Fermi -LAT e {sup +} + e {sup −} spectrum, combining electron and positron emission from supernova remnants (SNRs) and pulsar wind nebulae (PWNe), or produced by the collision of cosmic rays (CRs) with the interstellar medium. We find that the Fermi -LAT spectrum is compatible with the sum of electrons from a smooth SNR population, positronsmore » from cataloged PWNe, and a secondary component. If we include in our analysis constraints from the AMS-02 positron spectrum, we obtain a slightly worse fit to the e {sup +} + e {sup −} Fermi -LAT spectrum, depending on the propagation model. As an additional scenario, we replace the smooth SNR component within 0.7 kpc with the individual sources found in Green’s catalog of Galactic SNRs. We find that separate consideration of far and near sources helps to reproduce the e {sup +} + e {sup −} Fermi -LAT spectrum. However, we show that the fit degrades when the radio constraints on the positron emission from Vela SNR (which is the main contributor at high energies) are taken into account. We find that a break in the power-law injection spectrum at about 100 GeV can also reproduce the measured e {sup +} + e {sup −} spectrum and, among the CR propagation models that we consider, no reasonable break of the power-law dependence of the diffusion coefficient can modify the electron flux enough to reproduce the observed shape.« less

FERMI Large Area Telescope Gamma-Ray Detection of the Radio Galaxy M87

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-11-17

Here, we report the Fermi Large Area Telescope (LAT) discovery of high-energy (MeV/GeV) γ-ray emission positionally consistent with the center of the radio galaxy M87, at a source significance of over 10σ in 10 months of all-sky survey data. Following the detections of Cen A and Per A, this makes M87 the third radio galaxy seen with the LAT. The faint point-like γ-ray source has a >100 MeV flux of 2.45 (±0.63) × 10 –8 photons cm –2 s –1 (photon index = 2.26 ± 0.13) with no significant variability detected within the LAT observation. This flux is comparable withmore » the previous EGRET upper limit (<2.18 × 10 –8 photons cm –2 s –1, 2σ), thus there is no evidence for a significant MeV/GeV flare on decade timescales. Contemporaneous Chandra and Very Long Baseline Array data indicate low activity in the unresolved X-ray and radio core relative to previous observations, suggesting M87 is in a quiescent overall level over the first year of Fermi-LAT observations. The LAT γ-ray spectrum is modeled as synchrotron self-Compton (SSC) emission from the electron population producing the radio-to-X-ray emission in the core. The resultant SSC spectrum extrapolates smoothly from the LAT band to the historical-minimum TeV emission. Lastly, alternative models for the core and possible contributions from the kiloparsec-scale jet in M87 are considered, and cannot be excluded.« less

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2014 CFR

2014-07-01

... How is the final performance report to be sent to the Defense Technical Information Center? (a... 32 National Defense 1 2014-07-01 2014-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of...

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2011 CFR

2011-07-01

... How is the final performance report to be sent to the Defense Technical Information Center? (a... 32 National Defense 1 2011-07-01 2011-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of...

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2013 CFR

2013-07-01

... How is the final performance report to be sent to the Defense Technical Information Center? (a... 32 National Defense 1 2013-07-01 2013-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of...

32 CFR 37.895 - How is the final performance report to be sent to the Defense Technical Information Center?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false How is the final performance report to be sent to the Defense Technical Information Center? 37.895 Section 37.895 National Defense Department of... How is the final performance report to be sent to the Defense Technical Information Center? (a...

Fermi-LAT Bright Gamma-ray Detection of Nova ASASSN-18fv

NASA Astrophysics Data System (ADS)

Jean, P.; Cheung, C. C.; Ojha, R.; van Zyl, P.; Angioni, R.

2018-04-01

The Large Area Telescope (LAT), one of two instruments on the Fermi Gamma-ray Space Telescope, has observed bright gamma-ray emission from a source positionally consistent with the bright optical nova ASASSN-18fv (ATel #11454, #11456, #11460, #11467, #11508).

Anti-Coincidence Detector for GLAST

NASA Technical Reports Server (NTRS)

Moiseev, Alexander A.; Hartman, R. C.; Johnson, Thomas E.; Ormes, Jonathan F.; Thompson, D. J.

2004-01-01

The Anti-Coincidence Detector (ACD) is the outermost detector layer in the GLAST Large Area Telescope (LAT), surrounding the top and sides of the tracker. The purpose of the ACD is to detect and veto incident cosmic ray charged particles, which outnumber cosmic gamma rays by 3-5 orders of magnitude. The challenge in ACD design is that it has to have high (0.9997) detection efficiency for relativistic charged particles, but must have low sensitivity to backsplash photons. These are products of high energy interactions in the LAT calorimeter, and can cause a veto signal in the ACD resulting in degradation of the LAT efficiency for high energy (>10 GeV) gamma-rays. The ACD requirement is that backsplash shall not reduce the LAT sensitivity by more than 20% for gamma rays of 300 GeV. To solve this problem, the ACD is divided into 89 scintillating tiles, with wave-length shifting fiber readout. The detector design and its characteristics are given in this paper.

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

DOE Office of Scientific and Technical Information (OSTI.GOV)

MAGIC Collaboration

2016-02-01

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV—the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of twomore » at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.« less

Fermi and Swift Gamma-Ray Burst Afterglow Population Studies

NASA Technical Reports Server (NTRS)

Racusin, J. L.; Oates, S. R.; Schady, P.; Burrows, D. N.; de Pasquale, M.; Donato, D.; Gehrels, N.; Koch, S.; McEnery, J.; Piran, T.;

Fermi and Swift Gamma-Ray Burst Afterglow Population Studies

NASA Technical Reports Server (NTRS)

Racusin, Judith I.

2011-01-01

The new and extreme population of GRBs detected by Fermi-LAT shows several new features in high energy gamma-rays that are providing interesting and unexpected clues into GRB prompt and afterglow emission mechanisms. Over the last 6 years, it has been Swift that has provided the robust data set of UV/optical and X-ray afterglow observations that opened many windows into components of GRB emission structure. The relationship between the LAT GRBs and the well studied, fainter, less energetic GRBs detected by Swift-BAT is only beginning to be explored by multi-wavelength studies. We explore the large sample of GRBs detected by BAT only, BAT and Fermi-GBM, and GBM and LAT, focusing on these samples separately in order to search for statistically significant differences between the populations, using only those GRBs with measured redshifts in order to physically characterize these objects. We disentangle which differences are instrumental selection effects versus intrinsic properties, in order to better understand the nature of the special characteristics of the LAT bursts.

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

DOE PAGES

Ahnen, M. L.

2016-02-16

Here, we present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to amore » factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.« less

Afterglow Population Studies from Swift Follow-Up Observations of Fermi LAT GRBs

NASA Technical Reports Server (NTRS)

Racusin, Judith L.; Oates, S. R.; McEnery, J.; Vasileiou, V.; Troja, E.; Gehrels, N.

2010-01-01

The small population of Fermi LAT detected GRBs discovered over the last year has been providing interesting and unexpected clues into GRB prompt and afterglow emission mechanisms. Over the last 5 years, it has been Swift that has provided the robust data set of UV/optical and X-ray afterglow observations that opened many windows into other components of GRB emission structure. We explore the new ability to utilize both of these observatories to study the same GRBs over 10 orders of magnitude in energy, although not always concurrently. Almost all LAT GRBs that have been followed-up by Swift within 1-day have been clearly detected and carefully observed. We will present the context of the lower-energy afterglows of this special subset of GRBs that has > 100 MeV emission compared to the hundreds in the Swift database that may or may not have been observed by LAT, and theorize upon the relationship between these properties and the origin of the high energy gamma-ray emission.

Fermi and Swift Gamma-Ray Burst Afterglow Population Studies

NASA Technical Reports Server (NTRS)

Racusin, Judith L.; Oates, S. R.; Schady, P.; Burrows, D. N.; dePasquale, M.; Donato, D.; Gehrels, N.; Koch, S.; McEnery, J.; Piran, T.;

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor.

PubMed

Tang, Shuang; Bertke, Andrea S; Patel, Amita; Wang, Kening; Cohen, Jeffrey I; Krause, Philip R

2008-08-05

Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma.

PubMed

Guo, Qingping; Wang, Jiale; Cao, Zeyu; Tang, Yongchang; Feng, Chao; Huang, Feizhou

2018-06-05

Despite advances in surgery and chemotherapy, the prognosis of patients with hepatocellular carcinoma (HCC) remains poor. In the present study, the role of S100A1 in the progression of HCC was investigated. Immunohistochemical staining was used to measure the expression of S100A1 in HCC tissues. S100A1 was knocked down by siRNA. A battery of experiments was used to evaluate the biology functions of S100A1. It was found that S100A1 was upregulated in HCC tissues, and its upregulation was associated with a large tumor size, low differentiation and shorter survival time. The biological experiments demonstrated that S100A1 functions as an oncogene in HCC. It was also found that S100A1 knockdown enhanced the inhibitory effects of cisplatin on HCC cells. The results showed that the downregulation of S100A1 induced the phosphorylation of yes‑associated protein (YAP), and treatment with CHX demonstrated that the downregulation of S100A1 accelerated YAP protein degradation. The downregulation of S100A1 did not alter the expression of mammalian sterile 20‑like kinase (MST)1/2 or phosphorylated MST1/2, but upregulated the phosphorylation of large tumor suppressor kinase 1 (LATS1). It was further confirmed that S100A1 interacted with LATS1. LATS1 depletion significantly reduced the effects of S100A1 on cell growth rate and apoptosis, and there was a positive correlation between phosphorylated LATS1 and S100A1 in clinical samples, indicating that LATS1 was responsible for the S100A1-induced changes in cancer cell growth and Hippo signaling. In conclusion, the results of the present study indicated that S100A1 functions as an oncogene and may be a biomarker for the prognosis of patients with HCC. S100A1 exerted its oncogenic function by interacting with LATS1 and activating YAP. S100A1 may serve as a target for novel therapies in HCC.

LAT region factors mediating differential neuronal tropism of HSV-1 and HSV-2 do not act in trans.

PubMed

Bertke, Andrea S; Apakupakul, Kathleen; Ma, AyeAye; Imai, Yumi; Gussow, Anne M; Wang, Kening; Cohen, Jeffrey I; Bloom, David C; Margolis, Todd P

2012-01-01

After HSV infection, some trigeminal ganglion neurons support productive cycle gene expression, while in other neurons the virus establishes a latent infection. We previously demonstrated that HSV-1 and HSV-2 preferentially establish latent infection in A5+ and KH10+ sensory neurons, respectively, and that exchanging the latency-associated transcript (LAT) between HSV-1 and HSV-2 also exchanges the neuronal preference. Since many viral genes besides the LAT are functionally interchangeable between HSV-1 and HSV-2, we co-infected HSV-1 and HSV-2, both in vivo and in vitro, to determine if trans-acting viral factors regulate whether HSV infection follows a productive or latent pattern of gene expression in sensory neurons. The pattern of HSV-1 and HSV-2 latent infection in trigeminal neurons was no different following co-infection than with either virus alone, consistent with the hypothesis that a trans-acting viral factor is not responsible for the different patterns of latent infection of HSV-1 and HSV-2 in A5+ and KH10+ neurons. Since exchanging the LAT regions between the viruses also exchanges neuronal preferences, we infected transgenic mice that constitutively express 2.8 kb of the LAT region with the heterologous viral serotype. Endogenous expression of LAT did not alter the pattern of latent infection after inoculation with the heterologous serotype virus, demonstrating that the LAT region does not act in trans to direct preferential establishment of latency of HSV-1 and HSV-2. Using HSV1-RFP and HSV2-GFP in adult trigeminal ganglion neurons in vitro, we determined that HSV-1 and HSV-2 do not exert trans-acting effects during acute infection to regulate neuron specificity. Although some neurons were productively infected with both HSV-1 and HSV-2, no A5+ or KH10+ neurons were productively infected with both viruses. Thus, trans-acting viral factors do not regulate preferential permissiveness of A5+ and KH10+ neurons for productive HSV infection and preferential establishment of latent infection.

LAT Region Factors Mediating Differential Neuronal Tropism of HSV-1 and HSV-2 Do Not Act in Trans

PubMed Central

Bertke, Andrea S.; Apakupakul, Kathleen; Ma, AyeAye; Imai, Yumi; Gussow, Anne M.; Wang, Kening; Cohen, Jeffrey I.; Bloom, David C.; Margolis, Todd P.

2012-01-01

After HSV infection, some trigeminal ganglion neurons support productive cycle gene expression, while in other neurons the virus establishes a latent infection. We previously demonstrated that HSV-1 and HSV-2 preferentially establish latent infection in A5+ and KH10+ sensory neurons, respectively, and that exchanging the latency-associated transcript (LAT) between HSV-1 and HSV-2 also exchanges the neuronal preference. Since many viral genes besides the LAT are functionally interchangeable between HSV-1 and HSV-2, we co-infected HSV-1 and HSV-2, both in vivo and in vitro, to determine if trans-acting viral factors regulate whether HSV infection follows a productive or latent pattern of gene expression in sensory neurons. The pattern of HSV-1 and HSV-2 latent infection in trigeminal neurons was no different following co-infection than with either virus alone, consistent with the hypothesis that a trans-acting viral factor is not responsible for the different patterns of latent infection of HSV-1 and HSV-2 in A5+ and KH10+ neurons. Since exchanging the LAT regions between the viruses also exchanges neuronal preferences, we infected transgenic mice that constitutively express 2.8 kb of the LAT region with the heterologous viral serotype. Endogenous expression of LAT did not alter the pattern of latent infection after inoculation with the heterologous serotype virus, demonstrating that the LAT region does not act in trans to direct preferential establishment of latency of HSV-1 and HSV-2. Using HSV1-RFP and HSV2-GFP in adult trigeminal ganglion neurons in vitro, we determined that HSV-1 and HSV-2 do not exert trans-acting effects during acute infection to regulate neuron specificity. Although some neurons were productively infected with both HSV-1 and HSV-2, no A5+ or KH10+ neurons were productively infected with both viruses. Thus, trans-acting viral factors do not regulate preferential permissiveness of A5+ and KH10+ neurons for productive HSV infection and preferential establishment of latent infection. PMID:23300908

Geomagnetic and solar activity dependence of ionospheric upflowing O+: FAST observations

NASA Astrophysics Data System (ADS)

Zhao, K.; Jiang, Y.; Chen, K. W.; Huang, L. F.

2016-09-01

This paper investigates the dependence of the occurrence frequency of ionospheric upflowing oxygen (O+) ions on the sunspot cycle and geomagnetic activity. We examine the upflows response to the geomagnetic disturbances as well as the influence of the ion energy factor in controlling the magnitude of the occurrence frequency and the net energy flux. We discuss the spatial distribution of the upflow occurrence frequency and construct a regression model as a function of the magnetic latitude. The results show an overall enhancement of the upflow occurrence frequency during magnetically disturbed periods and indicate that the high-occurrence area spreads out from the source regions during magnetically quiet periods. The high-occurrence areas are located at 70° magnetic latitude (mLat) in the dayside auroral oval zone and between 76-80° mLat in the dayside polar cusp region. In the nightside auroral oval zone, these areas are near 60° mLat, penetrating further equatorward to 55° mLat during magnetically disturbed periods. High energy (≥1 keV) upflowing ions are common in the nightside auroral oval zone while low energy (<1 keV) upflowing ions are found escaping from the high latitude dayside cusp region. A Gaussian function is shown to be a good fit to the occurrence frequency over the magnetic latitude. For high energy upflowing O+ ions, the occurrence frequency exhibits a single peak located at about 60° mLat in the nightside auroral oval zone while for low energy upflowing O+ ions, it exhibits two peaks, one near 60° mLat in the auroral oval zone and the other near 78° mLat in the cusp region. We study the solar activity dependence by analyzing the relationship between the upflow occurrence frequency and the sunspot number (RZ). The statistical result shows that the frequency decreases with declining solar activity level, from ˜30 % at solar maximum to ˜5 % at solar minimum. In addition, the correlation coefficient between the occurrence frequency and RZ is 0.9.

VizieR Online Data Catalog: Fermi-LAT flaring gamma-ray sources from FAVA (Ackermann+, 2013)

NASA Astrophysics Data System (ADS)

Ackermann, M.; Ajello, M.; Albert, A.; Allafort, A.; Antolini, E.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Bottacini, E.; Bouvier, A.; Brandt, T. J.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Caraveo, P. A.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Chiaro, G.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Conrad, J.; Cutini, S.; Dalton, M.; D'Ammando, F.; de Angelis, A.; de Palma, F.; Dermer, C. D.; di Venere, L.; Drell, P. S.; Drlica-Wagner, A.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Franckowiak, A.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Germani, S.; Giglietto, N.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guiriec, S.; Hadasch, D.; Hanabata, Y.; Harding, A. K.; Hayashida, M.; Hays, E.; Hewitt, J.; Hill, A. B.; Horan, D.; Hou, X.; Hughes, R. E.; Inoue, Y.; Jackson, M. S.; Jogler, T.; Johannesson, G.; Johnson, W. N.; Kamae, T.; Kataoka, J.; Kawano, T.; Knodlseder, J.; Kuss, M.; Lande, J.; Larsson, S.; Latronico, L.; Lemoine-Goumard, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Mayer, M.; Mazziotta, M. N.; McEnery, J. E.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nemmen, R.; Nuss, E.; Ohsugi, T.; Okumura, A.; Omodei, N.; Orienti, M.; Orlando, E.; Ormes, J. F.; Paneque, D.; Panetta, J. H.; Perkins, J. S.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Porter, T. A.; Raino, S.; Rando, R.; Razzano, M.; Reimer, A.; Reimer, O.; Romoli, C.; Roth, M.; Sanchez-Conde, M.; Scargle, J. D.; Schulz, A.; Sgro, C.; Siskind, E. J.; Spandre, G.; Spinelli, P.; Suson, D. J.; Takahashi, H.; Takeuchi, Y.; Thayer, J. G.; Thayer, J. B.; Thompson, D. J.; Tibaldo, L.; Tinivella, M.; Torres, D. F.; Tosti, G.; Troja, E.; Tronconi, V.; Usher, T. L.; Vandenbroucke, J.; Vasileiou, V.; Vianello, G.; Vitale, V.; Winer, B. L.; Wood, K. S.; Wood, M.; Yang, Z.

2015-01-01

We applied FAVA (Fermi All-sky Variability Analysis) to the first 47 months of Fermi/LAT observations (2008 August 4 to 2012 July 16 UTC), in weekly time intervals. The total number of weeks is 206. We considered two ranges of gamma-ray energy, E>100MeV and E>800MeV, to increase the sensitivity for spectrally soft and hard flares, respectively. We generate measured and expected count maps with a resolution of 0.25deg2 per pixel. We found LAT counterparts for 192 of the 215 FAVA sources. Most of the associated sources, 177, are AGNs. (2 data files).

50 CFR 622.406 - Areas closed to lobster trap gear.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Trap Gear Closed Area 37. Point North lat. West long. A 25°07′51.156″ 80°17′27.910″ B 25°07′35.857″ 80... Trap Gear Closed Area 51. Point North lat. West long. A 25°16′33.006″ 80°13′30.001″ B 25°16′33.006″ 80... Closed Area 55. Point North lat. West long. A 25°21′45.004″ 80°09′51.998″ B 25°21′38.124″ 80°09′56.722″ C...

50 CFR 622.406 - Areas closed to lobster trap gear.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Trap Gear Closed Area 37. Point North lat. West long. A 25°07′51.156″ 80°17′27.910″ B 25°07′35.857″ 80... Trap Gear Closed Area 51. Point North lat. West long. A 25°16′33.006″ 80°13′30.001″ B 25°16′33.006″ 80... Closed Area 55. Point North lat. West long. A 25°21′45.004″ 80°09′51.998″ B 25°21′38.124″ 80°09′56.722″ C...

50 CFR 640.22 - Gear and diving restrictions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Area 37. Point North Lat. West Long. A 25°07′51.156″ 80°17′27.910″ B 25°07′35.857″ 80°17′37.091″ C 25...) Lobster Trap Gear Closed Area 51. Point North Lat. West Long. A 25°16′33.006″ 80°13′30.001″ B 25°16′33.006... Gear Closed Area 55. Point North Lat. West Long. A 25°21′45.004″ 80°09′51.998″ B 25°21′38.124″ 80°09′56...

Identifying Unidentified Fermi-LAT Objects (UFOs) at High-Latitude

NASA Astrophysics Data System (ADS)

Cheung, Chi Teddy

2009-09-01

We propose a Chandra study of 8 high Galactic latitude gamma-ray sources in the Fermi-LAT bright source list. These sources are currently unidentified, i.e., they are not clearly associated with established classes of gamma-ray emitters like blazars and pulsars. The proposed observations will determine the basic properties (fluxes, positions, hardness ratio/spectra) of all X-ray sources down to a 0.3-10 keV flux limit of 1.5e-14 erg/cm2/s within the Fermi-LAT localization circles. This will enable further follow-up at other wavelengths, with the ultimate goal to reveal the nature of these enigmatic gamma-ray sources.

Fermi-LAT Gamma-ray Observations of Nova Lupus 2016 (ASASSN-16kt)

NASA Astrophysics Data System (ADS)

Cheung, C. C.; Jean, P.; Shore, S. N.; Fermi Large Area Telescope Collaboration

2016-10-01

The Fermi Gamma-ray Space Telescope performed a ~6-day Target of Opportunity (ToO) observation of Nova Lupus 2016 (ATel #9538, #9539, CBET #4322) that commenced on September 28. Considering earlier all-sky survey Large Area Telescope (LAT) observations as well, preliminary analysis indicates gamma-ray emission at ~2 sigma was detected around 1 to 2 days after the optical peak on September 25th (pre-validated AAVSO visual lightcurve; ATel #9550, CBET #4322) when the optical spectra show opaque ejecta, similar to previous gamma-ray detected novae (Fermi-LAT collaboration, 2014 Science 345, 554; Cheung et al. 2016 ApJ 826, 142).

Comparing posteroanterior with lateral and anteroposterior chest radiography in the initial detection of parapneumonic effusions.

PubMed

Moffett, Bryan K; Panchabhai, Tanmay S; Nakamatsu, Raul; Arnold, Forest W; Peyrani, Paula; Wiemken, Timothy; Guardiola, Juan; Ramirez, Julio A

2016-12-01

It is unclear whether anteroposterior (AP) or posteroanterior with lateral (PA/Lat) chest radiographs are superior in the early detection of clinically relevant parapneumonic effusions (CR-PPEs). The objective of this study was to identify which technique is preferred for detection of PPEs using chest computed tomography (CCT) as a reference standard. A secondary analysis of a pneumonia database was conducted to identify patients who received a CCT within 24 hours of presentation and also received AP or PA/Lat chest radiographs within 24 hours of CCT. Sensitivity and specificity were then calculated by comparing the radiographic diagnosis of PPEs of both types of radiographs compared with CCT by using the existing attending radiologist interpretation. Clinical relevance of effusions was determined by CCT effusion measurement of >2.5 cm or presence of loculation. There was a statistically significant difference between the sensitivity of AP (67.3%) and PA/Lat (83.9%) chest radiography for the initial detection of CR-PPE. Of 16 CR-PPEs initially missed by AP radiography, 7 either required drainage initially or developed empyema within 30 days, whereas no complicated PPE or empyema was found in those missed by PA/Lat radiography. PA/Lat chest radiography should be the initial imaging of choice in pneumonia patients for detection of PPEs because it appears to be statistically superior to AP chest radiography. Published by Elsevier Inc.

Downstream of human NDR kinases: impacting on c-myc and p21 protein stability to control cell cycle progression.

PubMed

Cornils, Hauke; Kohler, Reto S; Hergovich, Alexander; Hemmings, Brian A

2011-06-15

The mammalian genome encodes four members of the NDR/LATS kinase family: NDR1 (STK38), NDR2 (STK38L), LATS1 and LATS2, which are highly conserved from yeast to man. Members of the NDR/LATS kinase family have been implicated in a variety of biological processes ranging from cell division and morphology to apoptosis and tumor suppression. In mammals, LATS1/2 function as central parts of the HIPPO tumor suppressor pathway by restricting the activity of the YAP/TAZ proto-oncogenes. Recent evidence suggested that NDR1/2 are also part of an extended HIPPO tumor suppressor pathway. Apart from functions in apoptosis signaling and tumor suppression, NDR1/2 have been implicated in controlling centrosome duplication and mitotic chromosome alignment downstream of the HIPPO kinase homologs MST1 and MST2. Significantly, we also reported recently that NDR1/2 are controlling G 1/S transition downstream of a third MST family member MST3. Intriguingly, this newly described MST3-NDR1/2 axis promotes G 1 progression by stabilizing c-myc and preventing p21 accumulation, indicating a potential pro-tumorigenic role for NDR kinases. Here, we discuss these novel cell cycle functions of NDR kinases in a broader context and elaborate on possible explanations for the opposing functions of NDR kinases in normal and tumor biology.

Constraints on the Intergalactic Magnetic Field with Gamma-Ray Observations of Blazars

NASA Astrophysics Data System (ADS)

Finke, Justin D.; Reyes, Luis C.; Georganopoulos, Markos; Reynolds, Kaeleigh; Ajello, Marco; Fegan, Stephen J.; McCann, Kevin

2015-11-01

Distant BL Lacertae objects emit γ-rays that interact with the extragalactic background light (EBL), creating electron-positron pairs, and reducing the flux measured by ground-based imaging atmospheric Cherenkov telescopes (IACTs) at very-high energies (VHE). These pairs can Compton-scatter the cosmic microwave background, creating a γ-ray signature at slightly lower energies that is observable by the Fermi Large Area Telescope (LAT). This signal is strongly dependent on the intergalactic magnetic field (IGMF) strength (B) and its coherence length (LB). We use IACT spectra taken from the literature for 5 VHE-detected BL Lac objects and combine them with LAT spectra for these sources to constrain these IGMF parameters. Low B values can be ruled out by the constraint that the cascade flux cannot exceed that observed by the LAT. High values of B can be ruled out from the constraint that the EBL-deabsorbed IACT spectrum cannot be greater than the LAT spectrum extrapolated into the VHE band, unless the cascade spectrum contributes a sizable fraction of the LAT flux. We rule out low B values (B ≲ 10-19 G for LB ≥ 1 Mpc) at >5σ in all trials with different EBL models and data selection, except when using >1 GeV spectra and the lowest EBL models. We were not able to constrain high values of B.

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1.

PubMed

Liu, Shikai; Song, Lili; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

2015-04-17

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3'-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling.

PubMed

Brdicka, Tomás; Imrich, Martin; Angelisová, Pavla; Brdicková, Nadezda; Horváth, Ondrej; Spicka, Jirí; Hilgert, Ivan; Lusková, Petra; Dráber, Petr; Novák, Petr; Engels, Niklas; Wienands, Jürgen; Simeoni, Luca; Osterreicher, Jan; Aguado, Enrique; Malissen, Marie; Schraven, Burkhart; Horejsí, Václav

2002-12-16

A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non-T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcgamma- and Fc epsilon -receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non-T cells.

Studying the SGR 1806-20/Cl* 1806-20 Region Using the Fermi Large Area Telescope

NASA Astrophysics Data System (ADS)

Yeung, Paul K. H.; Kong, Albert K. H.; Tam, P. H. Thomas; Lin, Lupin C. C.; Hui, C. Y.; Hu, Chin-Ping; Cheng, K. S.

2016-08-01

The region around SGR 1806-20 and its host stellar cluster Cl* 1806-20 is a potentially important site of particle acceleration. The soft γ-ray repeater and Cl* 1806-20, which also contains several very massive stars including a luminous blue variable hypergiant LBV 1806-20, are capable of depositing a large amount of energy to the surroundings. Using the data taken with the Fermi Large Area Telescope (LAT), we identified an extended LAT source to the southwest of Cl* 1806-20. The centroid of the 1-50 GeV emission is consistent with that of HESS J1808-204 (until now unidentified). The LAT spectrum is best-fit by a broken power law with the break energy {E}{{b}}=297+/- 15 {MeV}. The index above E b is 2.60 ± 0.04 and is consistent with the flux and spectral index above 100 GeV for HESS J1808-204, suggesting an association between the two sources. Meanwhile, the interacting supernova remnant SNR G9.7-0.0 is also a potential contributor to the LAT flux. A tentative flux enhancement at the MeV band during a 45 day interval (2011 January 21-March 7) is also reported. We discuss possible origins of the extended LAT source in the context of both leptonic and hadronic scenarios.

Fermi's Motion Produces a Study in Spirograph

NASA Image and Video Library

2017-12-08

The LAT's sensitivity to gamma rays is greatest in the center of its wide field of view and decreases toward the edge. LAT scientists regard the effective limit of the instrument's field of view to be 78.5 degrees (red circle) from its center. View a video of this here: bit.ly/Y2K4LN. Credit: NASA/DOE/Fermi LAT Collaboration ----- NASA's Fermi Gamma-ray Space Telescope orbits our planet every 95 minutes, building up increasingly deeper views of the universe with every circuit. Its wide-eyed Large Area Telescope (LAT) sweeps across the entire sky every three hours, capturing the highest-energy form of light -- gamma rays -- from sources across the universe. These range from supermassive black holes billions of light-years away to intriguing objects in our own galaxy, such as X-ray binaries, supernova remnants and pulsars. Now a Fermi scientist has transformed LAT data of a famous pulsar into a mesmerizing movie that visually encapsulates the spacecraft's complex motion. Click here to continue reading: 1.usa.gov/WhYwCU NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

FERMI/LAT OBSERVATIONS OF SWIFT/BAT SEYFERT GALAXIES: ON THE CONTRIBUTION OF RADIO-QUIET ACTIVE GALACTIC NUCLEI TO THE EXTRAGALACTIC {gamma}-RAY BACKGROUND

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teng, Stacy H.; Mushotzky, Richard F.; Reynolds, Christopher S.

2011-12-01

We present the analysis of 2.1 years of Fermi Large Area Telescope (LAT) data on 491 Seyfert galaxies detected by the Swift Burst Alert Telescope (BAT) survey. Only the two nearest objects, NGC 1068 and NGC 4945, which were identified in the Fermi first year catalog, are detected. Using Swift/BAT and radio 20 cm fluxes, we define a new radio-loudness parameter R{sub X,BAT} where radio-loud objects have log R{sub X,BAT} > -4.7. Based on this parameter, only radio-loud sources are detected by Fermi/LAT. An upper limit to the flux of the undetected sources is derived to be {approx}2 Multiplication-Sign 10{supmore » -11} photons cm{sup -2} s{sup -1}, approximately seven times lower than the observed flux of NGC 1068. Assuming a median redshift of 0.031, this implies an upper limit to the {gamma}-ray (1-100 GeV) luminosity of {approx}< 3 Multiplication-Sign 10{sup 41} erg s{sup -1}. In addition, we identified 120 new Fermi/LAT sources near the Swift/BAT Seyfert galaxies with significant Fermi/LAT detections. A majority of these objects do not have Swift/BAT counterparts, but their possible optical counterparts include blazars, flat-spectrum radio quasars, and quasars.« less

Searching for high-energy gamma-ray counterparts to gravitational-wave sources with Fermi-LAT: A needle in a haystack

DOE PAGES

Vianello, G.; Omodei, N.; Chiang, J.; ...

2017-05-20

At least a fraction of gravitational-wave (GW) progenitors are expected to emit an electromagnetic (EM) signal in the form of a short gamma-ray burst (sGRB). Discovering such a transient EM counterpart is challenging because the LIGO/VIRGO localization region is much larger (several hundreds of square degrees) than the field of view of X-ray, optical, and radio telescopes. The Fermi Large Area Telescope (LAT) has a wide field of view (~2.4 sr) and detects ~2–3 sGRBs per year above 100 MeV. It can detect them not only during the short prompt phase, but also during their long-lasting high-energy afterglow phase. If other wide-field, high-energy instruments such as Fermi-GBM, Swift-BAT, or INTEGRAL-ISGRI cannot detect or localize with enough precision an EM counterpart during the prompt phase, the LAT can potentially pinpoint it withmore » $$\\lesssim 10$$ arcmin accuracy during the afterglow phase. This routinely happens with gamma-ray bursts. Moreover, the LAT will cover the entire localization region within hours of any triggers during normal operations, allowing the γ-ray flux of any EM counterpart to be measured or constrained. As a result, we illustrate two new ad hoc methods to search for EM counterparts with the LAT and their application to the GW candidate LVT151012.« less

Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.

PubMed

Brahmajothi, Mulugu V; Mason, S Nicholas; Whorton, A Richard; McMahon, Timothy J; Auten, Richard L

2010-07-15

The pathway by which inhaled NO gas enters pulmonary alveolar epithelial cells has not been directly tested. Although the expected mechanism is diffusion, another route is the formation of S-nitroso-L-cysteine, which then enters the cell through the L-type amino acid transporter (LAT). To determine if NO gas also enters alveolar epithelium this way, we exposed alveolar epithelial-rat type I, type II, L2, R3/1, and human A549-cells to NO gas at the air liquid interface in the presence of L- and D-cysteine+/-LAT competitors. NO gas exposure concentration dependently increased intracellular NO and S-nitrosothiol levels in the presence of L- but not D-cysteine, which was inhibited by LAT competitors, and was inversely proportional to diffusion distance. The effect of L-cysteine on NO uptake was also concentration dependent. Without preincubation with L-cysteine, NO uptake was significantly reduced. We found similar effects using ethyl nitrite gas in place of NO. Exposure to either gas induced activation of soluble guanylyl cylase in a parallel manner, consistent with LAT dependence. We conclude that NO gas uptake by alveolar epithelium achieves NO-based signaling predominantly by forming extracellular S-nitroso-L-cysteine that is taken up through LAT, rather than by diffusion. Augmenting extracellular S-nitroso-L-cysteine formation may augment pharmacological actions of inhaled NO gas. Copyright 2010 Elsevier Inc. All rights reserved.

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC).

PubMed

Strazisar, Mojca; Mlakar, Vid; Glavac, Damjan

2009-01-01

Several studies have reported different expression levels of certain genes in NSCLC, mostly related to the stage and advancement of the tumours. We investigated 65 stage I-III NSCLC tumours: 32 adenocarcinomas (ADC), 26 squamous cell carcinomas (SCC) and 7 large cell carcinomas (LCC). Using the real-time reverse transcription polymerase chain reaction (RT-PCR), we analysed the expression of the COX-2, hTERT, MDM2, LATS2 and S100A2 genes and researched the relationships between the NSCLC types and the differences in expression levels. The differences in the expression levels of the LATS2, S100A2 and hTERT genes in different types of NSCLC are significant. hTERT and COX-2 were over-expressed and LATS2 under-expressed in all NSCLC. We also detected significant relative differences in the expression of LATS2 and MDM2, hTERT and MDM2 in different types of NSCLC. There was a significant difference in the average expression levels in S100A2 for ADC and SCC. Our study shows differences in the expression patterns within the NSCLC group, which may mimic the expression of the individual NSCLC type, and also new relationships in the expression levels for different NSCLC types.

Searching for high-energy gamma-ray counterparts to gravitational-wave sources with Fermi-LAT: A needle in a haystack

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vianello, G.; Omodei, N.; Chiang, J.

At least a fraction of gravitational-wave (GW) progenitors are expected to emit an electromagnetic (EM) signal in the form of a short gamma-ray burst (sGRB). Discovering such a transient EM counterpart is challenging because the LIGO/VIRGO localization region is much larger (several hundreds of square degrees) than the field of view of X-ray, optical, and radio telescopes. The Fermi Large Area Telescope (LAT) has a wide field of view (~2.4 sr) and detects ~2–3 sGRBs per year above 100 MeV. It can detect them not only during the short prompt phase, but also during their long-lasting high-energy afterglow phase. If other wide-field, high-energy instruments such as Fermi-GBM, Swift-BAT, or INTEGRAL-ISGRI cannot detect or localize with enough precision an EM counterpart during the prompt phase, the LAT can potentially pinpoint it withmore » $$\\lesssim 10$$ arcmin accuracy during the afterglow phase. This routinely happens with gamma-ray bursts. Moreover, the LAT will cover the entire localization region within hours of any triggers during normal operations, allowing the γ-ray flux of any EM counterpart to be measured or constrained. As a result, we illustrate two new ad hoc methods to search for EM counterparts with the LAT and their application to the GW candidate LVT151012.« less

76 FR 18624 - Research, Technical Assistance and Training Programs: Notice of Final Circular

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... to FTA Circular 6100.1D, Research and Technical Assistance Training Program: Application Instructions... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Research, Technical Assistance and Training Programs: Notice of Final Circular AGENCY: Federal Transit Administration (FTA), DOT. ACTION...

The Roles of NDR Protein Kinases in Hippo Signalling.

PubMed

Hergovich, Alexander

2016-05-18

The Hippo tumour suppressor pathway has emerged as a critical regulator of tissue growth through controlling cellular processes such as cell proliferation, death, differentiation and stemness. Traditionally, the core cassette of the Hippo pathway includes the MST1/2 protein kinases, the LATS1/2 protein kinases, and the MOB1 scaffold signal transducer, which together regulate the transcriptional co-activator functions of the proto-oncoproteins YAP and TAZ through LATS1/2-mediated phosphorylation of YAP/TAZ. Recent research has identified additional kinases, such as NDR1/2 (also known as STK38/STK38L) and MAP4Ks, which should be considered as novel members of the Hippo core cassette. While these efforts helped to expand our understanding of Hippo core signalling, they also began to provide insights into the complexity and redundancy of the Hippo signalling network. Here, we focus on summarising our current knowledge of the regulation and functions of mammalian NDR kinases, discussing parallels between the NDR pathways in Drosophila and mammals. Initially, we provide a general overview of the cellular functions of NDR kinases in cell cycle progression, centrosome biology, apoptosis, autophagy, DNA damage signalling, immunology and neurobiology. Finally, we put particular emphasis on discussing NDR1/2 as YAP kinases downstream of MST1/2 and MOB1 signalling in Hippo signalling.

Determination of the Point-Spread Function for the FERMI Large Area Telescope from On-Orbit Data and Limits on Pair Halos of Active Galactic Nuclei

DOE PAGES

Ackermann, M.; Ajello, M.; Allafort, A.; ...

2013-02-15

We present the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope is a pair-conversion telescope designed to detect photons with energies from ≈20 MeV to >300 GeV. The pre-launch response functions of the LAT were determined through extensive Monte Carlo simulations and beam tests. The point-spread function (PSF) characterizing the angular distribution of reconstructed photons as a function of energy and geometry in the detector is determined here from two years of on-orbit data by examining the distributions of γ rays from pulsars and active galactic nuclei (AGNs). Above 3 GeV, the PSF is found to be broadermore » than the pre-launch PSF. We checked for dependence of the PSF on the class of γ-ray source and observation epoch and found none. We also investigated several possible spatial models for pair-halo emission around BL Lac AGNs. Finally, we found no evidence for a component with spatial extension larger than the PSF and set upper limits on the amplitude of halo emission in stacked images of low- and high-redshift BL Lac AGNs and the TeV blazars 1ES0229+200 and 1ES0347–121.« less

Spectral Topography Generation for Arbitrary Grids

NASA Astrophysics Data System (ADS)

Oh, T. J.

2015-12-01

A new topography generation tool utilizing spectral transformation technique for both structured and unstructured grids is presented. For the source global digital elevation data, the NASA Shuttle Radar Topography Mission (SRTM) 15 arc-second dataset (gap-filling by Jonathan de Ferranti) is used and for land/water mask source, the NASA Moderate Resolution Imaging Spectroradiometer (MODIS) 30 arc-second land water mask dataset v5 is used. The original source data is coarsened to a intermediate global 2 minute lat-lon mesh. Then, spectral transformation to the wave space and inverse transformation with wavenumber truncation is performed for isotropic topography smoothness control. Target grid topography mapping is done by bivariate cubic spline interpolation from the truncated 2 minute lat-lon topography. Gibbs phenomenon in the water region can be removed by overwriting ocean masked target coordinate grids with interpolated values from the intermediate 2 minute grid. Finally, a weak smoothing operator is applied on the target grid to minimize the land/water surface height discontinuity that might have been introduced by the Gibbs oscillation removal procedure. Overall, the new topography generation approach provides spectrally-derived, smooth topography with isotropic resolution and minimum damping, enabling realistic topography forcing in the numerical model. Topography is generated for the cubed-sphere grid and tested on the KIAPS Integrated Model (KIM).

Light higgsino dark matter from non-thermal cosmology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aparicio, Luis; Cicoli, Michele; Dutta, Bhaskar

We study the scenario of higgsino dark matter in the context of a non-standard cosmology with a period of matter domination prior to Big Bang nucleosynthesis. Matter domination changes the dark matter relic abundance if it ends via reheating to a temperature below the higgsino thermal freeze-out temperature. We perform a model independent analysis of the higgsino dark matter production in such scenario. We show that light higgsino-type dark matter is possible for reheating temperatures close to 1 GeV. We study the impact of dark matter indirect detection and collider physics in this context. We show that Fermi-LAT data rulemore » out non-thermal higgsinos with masses below 300 GeV. A future indirect dark matter searches from Fermi-LAT and CTA will be able to cover essentially the full parameter space. Contrary to the thermal case, collider signals from a 100 TeV collider could fully test the non-thermal higgsino scenario. In the second part of the paper we discuss the motivation of such non-thermal cosmology from the perspective of string theory with late-time decaying moduli for both KKLT and LVS moduli stabilisation mechanisms. Finally, we describe the impact of embedding higgsino dark matter in these scenarios.« less

Light higgsino dark matter from non-thermal cosmology

DOE PAGES

Aparicio, Luis; Cicoli, Michele; Dutta, Bhaskar; ...

2016-11-01

We study the scenario of higgsino dark matter in the context of a non-standard cosmology with a period of matter domination prior to Big Bang nucleosynthesis. Matter domination changes the dark matter relic abundance if it ends via reheating to a temperature below the higgsino thermal freeze-out temperature. We perform a model independent analysis of the higgsino dark matter production in such scenario. We show that light higgsino-type dark matter is possible for reheating temperatures close to 1 GeV. We study the impact of dark matter indirect detection and collider physics in this context. We show that Fermi-LAT data rulemore » out non-thermal higgsinos with masses below 300 GeV. A future indirect dark matter searches from Fermi-LAT and CTA will be able to cover essentially the full parameter space. Contrary to the thermal case, collider signals from a 100 TeV collider could fully test the non-thermal higgsino scenario. In the second part of the paper we discuss the motivation of such non-thermal cosmology from the perspective of string theory with late-time decaying moduli for both KKLT and LVS moduli stabilisation mechanisms. Finally, we describe the impact of embedding higgsino dark matter in these scenarios.« less

Enhanced lines and box-shaped features in the gamma-ray spectrum from annihilating dark matter in the NMSSM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cerdeño, D.G.; Peiró, M.; Robles, S., E-mail: davidg.cerdeno@gmail.com, E-mail: miguel.peiro@uam.es, E-mail: sandra.robles@uam.es

2016-04-01

We study spectral features in the gamma-ray emission from dark matter (DM) annihilation in the Next-to-Minimal Supersymmetric Standard Model (NMSSM), with either neutralino or right-handed (RH) sneutrino DM . We perform a series of scans over the NMSSM parameter space, compute the DM annihilation cross section into two photons and the contribution of box-shaped features, and compare them with the limits derived from the Fermi-LAT search for gamma-ray lines using the latest Pass 8 data. We implement the LHC bounds on the Higgs sector and on the masses of supersymmetric particles as well as the constraints on low-energy observables. Wemore » also consider the recent upper limits from the Fermi-LAT satellite on the continuum gamma-ray emission from dwarf spheroidal galaxies (dSphs). We show that in the case of the RH sneutrino the constraint on gamma-ray spectral features can be more stringent than the dSph bounds. This is due to the Breit-Wigner enhancement near the ubiquitous resonances with a CP even Higgs and the contribution of scalar and pseudoscalar Higgs final states to box-shaped features. By contrast, for neutralino DM, the di-photon final state is only enhanced in the resonance with a Z boson and box-shaped features are even more suppressed. Therefore, the observation of spectral features could constitute a discriminating factor between both models. In addition, we compare our results with direct DM searches, including the SuperCDMS and LUX limits on the elastic DM-nucleus scattering cross section and show that some of these scenarios would be accessible to next generation experiments. Thus, our findings strengthen the idea of complementarity among distinct DM search strategies.« less

Explaining low energy γ-ray excess from the galactic centre using a two-component dark matter model

NASA Astrophysics Data System (ADS)

Biswas, Anirban

2016-06-01

Over the past few years, there has been a hint of the γ-ray excess observed by the Fermi-LAT satellite-borne telescope from the regions surrounding the galactic centre (GC) at an energy range of ˜1-3 GeV. The nature of this excess γ-ray spectrum is found to be consistent with the γ-ray emission expected from dark matter (DM) annihilation at the GC while disfavouring other known astrophysical sources as the possible origin of this phenomena. It is also reported that the spectrum and morphology of this excess γ-rays can well be explained by the DM particles having mass in the range 30{--}40 {{GeV}} annihilating significantly into b\\bar{b} final state with an annihilation cross section σ v˜ (1.4-2.0)× {10}-26 cm{}3 {{{s}}}-1 at the GC. In this work, we propose a two-component DM model where two different types of DM particles, namely a complex scalar and a Dirac fermion are considered. The stability of both the dark sector particles are maintained by virtue of an additional local {{U}}{(1)}X gauge symmetry. We find that our proposed scenario can provide a viable explanation for this anomalous excess γ-rays besides satisfying all the existing relevant theoretical as well as experimental and observational bounds from LHC, PLANCK and LUX collaborations. The allowed range of ‘effective annihilation cross section’ of lighter DM particle for the b\\bar{b} annihilation channel thus obtained is finally compared with the limits reported by the Fermi-LAT and DES collaborations using data from various dwarf spheroidal galaxies.

Bright gamma-ray emission from TCP J04432130+4721280 (V392 Per) detected by Fermi-LAT

NASA Astrophysics Data System (ADS)

Li, Kwan-Lok; Chomiuk, Laura; Strader, Jay

2018-05-01

We report the Fermi-LAT detection of the optical transient TCP J04432130+4721280 (V392 Per), which was discovered by Yuji Nakamura on 2018-04-29.4740 (CBET #4515) and later identified as a Galactic nova by Wagner et al. (ATel #11588).

(18)F-FBPA as a tumor specific tracer of L-type amino acid transporter 1 (LAT1): PET evaluation in tumor and inflammation compared to (18)F-FDG and (11)C-methionine.

PubMed

Watabe, Tadashi; Hatazawa, Jun

2015-01-01

(18)F-FDG-PET is used worldwide for oncology patients. However, we sometimes encounter false positive cases of (18)F-FDG PET, such as moderate uptake in the inflammatory lesion, because (18)F-FDG accumulates not only in the cancer cells but also in the inflammatory cells (macrophage, granulation tissue, etc). To overcome this limitation of (18)F-FDG, we started to use (4-borono-2- [(18)F]fluoro-L-phenylalanine) (18)F-FBPA, an artificial amino acid tracer which is focusing attention as a tumor specific PET tracer. Physiological accumulation of (18)F-FBPA is limited in the kidney and urinary tract in humans, which enable preferable evaluation of uptake in the abdominal organs compared to (11)C-methionine ((11)C-MET). The purpose of this study was to evaluate (18)F-FBPA as a tumor specific tracer by in vitro cellular uptake analysis focusing on the selectivity of L-type amino acid transporter 1 (LAT1), which is specifically expressed in tumor cells, and in vivo PET analysis in rat xenograft and inflammation models compared to (18)F-FDG and (11)C-methionine. Uptake inhibition and efflux experiments were performed in HEK293-LAT1 and LAT2 cells using cold BPA, cold (18)F-FBPA, and hot (18)F-FBPA to evaluate LAT affinity and transport capacity. Position emission tomography studies were performed in rat xenograft model of C6 glioma 2 weeks after the implantation (n=9, body weight=197±10.5g) and subcutaneous inflammation model 4 days after the injection of turpentine oil (n=9, body weight=197±14.4g). Uptake on static PET images were compared among (18)F-FBPA at 60-70min post injection, (18)F-FDG at 60-70min, and (11)C-MET at 20-30min in the tumors and the inflammatory lesions by maximum standardized uptake value (SUVmax). Cellular uptake analysis showed no significant difference in inhibitory effect and efflux of LAT1 between cold (18)F-FBPA and cold BPA, suggesting the same affinity and transport capacity via LAT1. Uptake of (18)F-FBPA via LAT1 was superior to LAT2 by the concentration dependent uptake analysis. Position emission tomography analysis using SUVmax showed significantly higher accumulation of (18)F-FDG in the tumor and the inflammatory lesions (7.19±2.11 and 4.66±0.63, respectively) compared to (18)F-FBPA (3.23±0.40 and 1.86±0.19, respectively) and (11)C-MET (3.39±0.43 and 1.63±0.11, respectively) (P<0.01 by Tukey test). No significant difference was observed between (18)F-FBPA and (11)C-MET. (18)F-FBPA showed high selectivity of LAT1 by in vitro cellular uptake analysis, suggesting the potential as a tumor-specific substrate. In vivo PET analysis showed significantly lower uptake of (18)F-FBPA and (11)C-MET in the inflammatory lesions compared to (18)F-FDG, suggesting comparable utility of (18)F-FBPA PET to (11)C-MET PET in differentiating between the tumor and the inflammation.

Minnesota Deaf-Blind Technical Assistance Project. Final Report.

ERIC Educational Resources Information Center

Kloos, Eric

This final report describes activities and accomplishments of the 3-year federally supported Minnesota Deaf-Blind Technical Assistance Project. The project provided training and technical assistance, information sharing, and support services to families of children with deaf-blindness. Activities and accomplishments included: collaboration with…

75 FR 56857 - Pilot, Flight Instructor, and Pilot School Certification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

... of part 141. Discussion of Technical Amendment Section 141.5(d) establishes the quality of training... Certification AGENCY: Federal Aviation Administration, DOT. ACTION: Final rule; technical amendment. SUMMARY: The Federal Aviation Administration (FAA) is making minor technical changes to a final rule published...

Suzaku observations of γ-ray bright radio galaxies: Origin of the x-ray emission and broadband modeling

DOE PAGES

Fukazawa, Yasushi; Finke, Justin; Stawarz, Łukasz; ...

2014-12-24

Here, we performed a systematic X-ray study of eight nearby γ-ray bright radio galaxies with Suzaku in order to understand the origins of their X-ray emissions. The Suzaku spectra for five of those have been presented previously, while the remaining three (M87, PKS 0625–354, and 3C 78) are presented here for the first time. Based on the Fe-K line strength, X-ray variability, and X-ray power-law photon indices, and using additional information on the [O III] line emission, we argue for a jet origin of the observed X-ray emission in these three sources. We also analyzed five years of Fermi Largemore » Area Telescope (LAT) GeV gamma-ray data on PKS 0625–354 and 3C 78 to understand these sources within the blazar paradigm. We found significant γ-ray variability in the former object. Overall, we note that the Suzaku spectra for both PKS 0625–354 and 3C 78 are rather soft, while the LAT spectra are unusually hard when compared with other γ-ray detected low-power (FR I) radio galaxies. We demonstrate that the constructed broadband spectral energy distributions of PKS 0625–354 and 3C 78 are well described by a one-zone synchrotron/synchrotron self-Compton model. The results of the modeling indicate lower bulk Lorentz factors compared to those typically found in other BL Lacertae (BL Lac) objects, but consistent with the values inferred from modeling other LAT-detected FR I radio galaxies. Interestingly, the modeling also implies very high peak (~10 16 Hz) synchrotron frequencies in the two analyzed sources, contrary to previously suggested scenarios for Fanaroff-Riley (FR) type I/BL Lac unification. Finally, we discuss the implications of our findings in the context of the FR I/BL Lac unification schemes.« less

Search for Gamma-Ray Emission from Galactic Novae using Fermi-LAT Pass 8

NASA Astrophysics Data System (ADS)

Buson, Sara; Franckowiak, Anna; Cheung, Teddy; Jean, Pierre; Fermi-LAT Collaboration

2016-01-01

Recently Galactic novae have been identified as a new class of GeV gamma-ray emitters, with 6 detected so far with the Fermi Large Area Telescope (Fermi-LAT) data. Based on optical observations we have compiled a catalog of ~70 Galactic novae, which peak (in optical) during the operations of the Fermi mission. Based on the properties of known gamma-ray novae we developed a search procedure that we apply to all novae in the catalog to detect these slow transient sources or set flux upper limits using the Fermi-LAT Pass 8 data set. This is the first time a large sample of Galactic novae has been uniformly studied.

77 FR 29247 - Federal Motor Vehicle Safety Standards; Occupant Crash Protection

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

...). ACTION: Final rule; technical amendments. SUMMARY: This final rule makes technical amendments to Federal... advanced air bag requirements. As written now, the general warning label requirements contain an explicit... equipment requirements for restraint systems. This document makes technical amendments to several of the...

77 FR 45238 - Amendment of Class E Airspace; Montgomery, AL

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... and publication of conforming amendments. FOR FURTHER INFORMATION CONTACT: John Fornito, Operations....) Maxwell AFB (Lat. 32[deg]22'45''N., long. 86[deg]21'45''W.) Prattville-Grouby Field Airport (Lat. 32[deg..., and within a 7-mile radius of Maxwell AFB, and within a 7-mile radius of Prattville-Grouby [[Page...

Point Cloud Storage and Access on a Global Scale

DTIC Science & Technology

2015-01-01

coordinates. These Geodetic values are appended to the list of parameters and are re-projected into WGS84 Geocentric (ECEF X,Y,Z), replacing the original...Append Lon,Lat,Alt to point parameters Re-project point with Proj.4 from Geodetic (Lon,Lat,Alt) -> Geocentric (X,Y,Z) Insert point into

Optical polarimetry of TXS 0506+056 (possible counterpart of IceCube-170922A)

NASA Astrophysics Data System (ADS)

Steele, I. A.; Jermak, H.; Copperwheat, C.

2018-03-01

ATel #11419 reports enhanced Gamma Ray Activity of TXS 0506+056 detected by Fermi-LAT on 2018 March 13. A previous Fermi-LAT high state of this source in the period 2017 Sept 15-27 was potentially associated with the Ice Cube Neutrino detection 170922A (ATel #10791).

New Results on High Energy Cosmic Ray Electrons Observed with Fermi LAT and Their Implications on the Models of Pulsars

NASA Technical Reports Server (NTRS)

Moiseev, Alexander

2010-01-01

This viewgraph presentation describes, in detail, the Fermi Large Area Telescope (LAT) and GLAST Burst Monitor (GBM). Observations made from the June 11, 2008 launch and a discussion of observations made of high energy cosmic ray electrons is also presented.

Fermi-LAT detection of ongoing gamma-ray activity from the new gamma-ray source Fermi J1654-1055 (PMN J1632-1052)

NASA Astrophysics Data System (ADS)

Kocevski, D.; Ajello, M.; Buson, S.; Buehler, R.; Giomi, M.

2016-02-01

During the week between February 8 and 15, 2016, the Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, observed gamma-ray activity from a new transient source, Fermi J1654-1055.

T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2

PubMed Central

Dong, Shen; Corre, Béatrice; Foulon, Eliane; Dufour, Evelyne; Veillette, André; Acuto, Oreste; Michel, Frédérique

2006-01-01

Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance. PMID:17043143

New Theoretical Estimates of the Contribution of Unresolved Star-Forming Galaxies to the Extragalactic Gamma-Ray Background (EGB) as Measured by EGRET and the Fermi-LAT

NASA Technical Reports Server (NTRS)

Venters, Tonia M.

2011-01-01

We present new theoretical estimates of the contribution of unresolved star-forming galaxies to the extragalactic gamma-ray background (EGB) as measured by EGRET and the Fermi-LAT. We employ several methods for determining the star-forming galaxy contribution the the EGB, including a method positing a correlation between the gamma-ray luminosity of a galaxy and its rate of star formation as calculated from the total infrared luminosity, and a method that makes use of a model of the evolution of the galaxy gas mass with cosmic time. We find that depending on the model, unresolved star-forming galaxies could contribute significantly to the EGB as measured by the Fermi-LAT at energies between approx. 300 MeV and approx. few GeV. However, the overall spectrum of unresolved star-forming galaxies can explain neither the EGRET EGB spectrum at energies between 50 and 200 MeV nor the Fermi-LAT EGB spectrum at energies above approx. few GeV.

De-novo NAD+ synthesis regulates SIRT1-FOXO1 apoptotic pathway in response to NQO1 substrates in lung cancer cells.

PubMed

Liu, Huiying; Xing, Rong; Cheng, Xuefang; Li, Qingran; Liu, Fang; Ye, Hui; Zhao, Min; Wang, Hong; Wang, Guangji; Hao, Haiping

2016-09-20

Tryptophan metabolism is essential in diverse kinds of tumors via regulating tumor immunology. However, the direct role of tryptophan metabolism and its signaling pathway in cancer cells remain largely elusive. Here, we establish a mechanistic link from L-type amino acid transporter 1 (LAT1) mediated transport of tryptophan and the subsequent de-novo NAD+ synthesis to SIRT1-FOXO1 regulated apoptotic signaling in A549 cells in response to NQO1 activation. In response to NQO1 activation, SIRT1 is repressed leading to the increased cellular accumulation of acetylated FOXO1 that transcriptionally activates apoptotic signaling. Decreased uptake of tryptophan due to the downregulation of LAT1 coordinates with PARP-1 hyperactivation to induce rapid depletion of NAD+ pool. Particularly, the LAT1-NAD+-SIRT1 signaling is activated in tumor tissues of patients with non-small cell lung cancer. Because NQO1 activation is characterized with oxidative challenge induced DNA damage, these results suggest that LAT1 and de-novo NAD+ synthesis in NSCLC cells may play essential roles in sensing excessive oxidative stress.

Status and Prospects for Indirect Dark Matter Searches with the Fermi Large Area Telescope

NASA Astrophysics Data System (ADS)

Charles, Eric; Fermi-LAT Collaboration

2014-01-01

During the first five years of operation of the Fermi Large Area Telescope (LAT) the LAT collaboration has performed numerous searches for signatures of Dark Matter interactions in both gamma-ray and cosmic-ray data. These searches feature many different target types, including dwarf spheroidal galaxies, galaxy clusters, the Milky Way halo and inner Galaxy and unassociated LAT sources. They make use of a variety of techniques, and have been performed in both the spatial and spectral domains, as well as via less conventional strategies such as examining the potential Dark Matter contribution to both large scale and small scale anisotropies. To date no clear gamma-ray or cosmic-ray signal from dark matter annihilation or decay has been observed, and the deepest current limits for annihilation exclude many Dark Matter particle models with the canonical thermal relic cross section and masses up to 30 GeV. In this contribution we will briefly review the status of each of the searches by the LAT collaboration. We will also discuss the limiting factors for the various search strategies and examine the prospects for the future.

Role of low density lipoprotein in the activation of plasma lysolecithin acyltransferase activity. Effect of chemical and enzymatic modifications of the lipoprotein on enzyme activity.

PubMed

Subbaiah, P V; Chen, C H; Bagdade, J D; Albers, J J

1985-01-01

The effect of various chemical and enzymatic modifications of low density lipoprotein (LDL) on its ability to activate the isolated human plasma lysolecithin acyltransferase (LAT) was studied. Removal of all lipids from LDL resulted in the complete loss of LAT activation. Removal of only neutral lipids by extraction with heptane retained up to 50% of the original activity, which was not increased further by reconstitution of the LDL with the extracted lipids. Hydrolysis of the diacylphosphoglycerides of the LDL with phospholipases resulted in complete loss of LAT activation which was partially restored by the addition of egg lecithin. Hydrolysis of more than 4% of LDL protein by trypsin led to a linear decrease in activity with complete loss of activity occurring when about 25% of the LDL protein is hydrolyzed. Modification of the arginine groups of LDL reversibly inhibited the activation of LAT. Modification of lysine residues of LDL by acetylation, acetoacetylation or succinylation also abolished its ability to activate lysolecithin acylation.

An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor

PubMed Central

Tang, Shuang; Bertke, Andrea S.; Patel, Amita; Wang, Kening; Cohen, Jeffrey I.; Krause, Philip R.

2008-01-01

Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression. PMID:18678906

Milagro Observations of Potential TeV Emitters

NASA Technical Reports Server (NTRS)

Abdo, A. A.; Abeysekara, A. U.; Allen, B. T.; Aune, T.; Barber, A. S.; Berley, D.; Braun, J.; Chen, C.; Christopher, G. E.; DeYoung, T.;

In-Flight Measurement of the Absolute Energy Scale of the Fermi Large Area Telescope

NASA Technical Reports Server (NTRS)

Ackermann, M.; Ajello, M.; Allafort, A.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Barbielini, G; Bastieri, D.; Bechtol, K.; Bellazzini, R.;

Estimation of skin entrance doses (SEDs) for common medical X-ray diagnostic examinations in India and proposed diagnostic reference levels (DRLs).

PubMed

Sonawane, A U; Shirva, V K; Pradhan, A S

2010-02-01

Skin entrance doses (SEDs) were estimated by carrying out measurements of air kerma from 101 X-ray machines installed in 45 major and selected hospitals in the country by using a silicon detector-based dose Test-O-Meter. 1209 number of air kerma measurements of diagnostic projections for adults have been analysed for seven types of common diagnostic examinations, viz. chest (AP, PA, LAT), lumbar spine (AP, LAT), thoracic spine (AP, LAT), abdomen (AP), pelvis (AP), hip joints (AP) and skull (PA, LAT) for different film-screen combinations. The values of estimated diagnostic reference levels (DRLs) (third quartile values of SEDs) were compared with guidance levels/DRLs of doses published by the IAEA-BSS-Safety Series No. 115, 1996; HPA (NRPB) (2000 and 2005), UK; CRCPD/CDRH (USA), European Commission and other national values. The values of DRLs obtained in this study are comparable with the values published by the IAEA-BSS-115 (1996); HPA (NRPB) (2000 and 2005) UK; EC and CRCPD/CDRH, USA including values obtained in previous studies in India.

Thermal anomaly mapping from night MODIS imagery of USA, a tool for environmental assessment.

PubMed

Miliaresis, George Ch

2013-02-01

A method is presented for elevation, latitude and longitude decorrelation stretch of multi-temporal MODIS MYD11C3 imagery (monthly average night land surface temperature (LST) across USA and Mexico). Multiple linear regression analysis of principal components images (PCAs) quantifies the variance explained by elevation (H), latitude (LAT), and longitude (LON). The multi-temporal LST imagery is reconstructed from the residual images and selected PCAs by taking into account the portion of variance that is not related to H, LAT, LON. The reconstructed imagery presents the magnitude the standardized LST value per pixel deviates from the H, LAT, LON predicted. LST anomaly is defined as a region that presents either positive or negative reconstructed LST value. The environmental assessment of USA indicated that only for the 25 % of the study area (Mississippi drainage basin), the LST is predicted by the H, LAT, LON. Regions with milled climatic pattern were identified in the West Coast while the coldest climatic pattern is observed for Mid USA. Positive season invariant LST anomalies are identified in SW (Arizona, Sierra Nevada, etc.) and NE USA.

FERMI observations of high-energy gamma-ray emission from GRB 090217A

DOE PAGES

Ackermann, M.; Ajello, M.; Baldini, L.; ...

2010-06-22

The Fermi observatory is advancing our knowledge of gamma-ray bursts (GRBs) through pioneering observations at high energies, covering more than seven decades in energy with the two on-board detectors, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). Here, we report on the observation of the long GRB 090217A which triggered the GBM and has been detected by the LAT with a significance greater than 9σ. We present the GBM and LAT observations and on-ground analyses, including the time-resolved spectra and the study of the temporal profile from 8 keV up to ~1 GeV. All spectra are wellmore » reproduced by a Band model. We compare these observations to the first two LAT-detected, long bursts GRB 080825C and GRB 080916C. These bursts were found to have time-dependent spectra and exhibited a delayed onset of the high-energy emission, which are not observed in the case of GRB 090217A. We discuss some theoretical implications for the high-energy emission of GRBs.« less

In-Flight Measurement of the Absolute Energy Scale of the Fermi Large Area Telescope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackermann, M.; /Stanford U., HEPL /SLAC /KIPAC, Menlo Park; Ajello, M.

The Large Area Telescope (LAT) on-board the Fermi Gamma-ray Space Telescope is a pair-conversion telescope designed to survey the gamma-ray sky from 20 MeV to several hundreds of GeV. In this energy band there are no astronomical sources with sufficiently well known and sharp spectral features to allow an absolute calibration of the LAT energy scale. However, the geomagnetic cutoff in the cosmic ray electron-plus-positron (CRE) spectrum in low Earth orbit does provide such a spectral feature. The energy and spectral shape of this cutoff can be calculated with the aid of a numerical code tracing charged particles in themore » Earth's magnetic field. By comparing the cutoff value with that measured by the LAT in different geomagnetic positions, we have obtained several calibration points between {approx}6 and {approx}13 GeV with an estimated uncertainty of {approx}2%. An energy calibration with such high accuracy reduces the systematic uncertainty in LAT measurements of, for example, the spectral cutoff in the emission from gamma ray pulsars.« less

Latex agglutination using the periplasmic proteins antigen of Brucella melitensis is a successful, rapid, and specific serodiagnostic test for ovine brucellosis

PubMed Central

Ismael, Alaa Bassuny; Swelum, Ayman Abdel-Aziz; Mostafa, Salama A-H; Alhumiany, Abdel-Rahman A

2016-01-01

Brucellosis, especially caused by Brucella melitensis, is considered the most-widespread zoonosis in the world, particularly in developing countries. This study was planned to develop an accurate test for diagnosis of ovine brucellosis using a specific hot saline extracted soluble Brucella melitensis periplasmic proteins (SBPPs). The efficacy of the latex agglutination test (LAT) using SBPPs compared to the Rose Bengal test (RBT), buffered plate agglutination test (BPAT), serum agglutination test (SAT), and an indirect enzyme-linked immunosorbent assay (i-ELISA) was evaluated in the field diagnosis of ovine brucellosis. The test performance was evaluated by estimating sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), disease prevalence (DP), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) using test agreement and bacteriological culture in 1777 samples. The false-positive result was significantly (P ⩽0.05) lower in LAT than RBT, BPAT, SAT, and i-ELISA. With reference to test agreement, the Se, Sp, PPV, and PLR were highest (P ⩽0.05) in LAT 99.33%, 99.88%, 98.68%, and 827.25%, respectively. With reference to bacteriological culture, the LAT and i-ELISA tests showed a significant difference in Se with SAT. However, no significant difference in specificity was detected. The DP was 8.44% in the five tests. In conclusion, LAT using SBPPs of B. melitensis could be a suitable serodiagnostic field test for ovine brucellosis, with high sensitivity and specificity. PMID:27207442

Spermine modulates the expression of two probable polyamine transporter genes and determines growth responses to cadaverine in Arabidopsis.

PubMed

Sagor, G H M; Berberich, Thomas; Kojima, Seiji; Niitsu, Masaru; Kusano, Tomonobu

2016-06-01

Two genes, LAT1 and OCT1 , are likely to be involved in polyamine transport in Arabidopsis. Endogenous spermine levels modulate their expression and determine the sensitivity to cadaverine. Arabidopsis spermine (Spm) synthase (SPMS) gene-deficient mutant was previously shown to be rather resistant to the diamine cadaverine (Cad). Furthermore, a mutant deficient in polyamine oxidase 4 gene, accumulating about twofold more of Spm than wild type plants, showed increased sensitivity to Cad. It suggests that endogenous Spm content determines growth responses to Cad in Arabidopsis thaliana. Here, we showed that Arabidopsis seedlings pretreated with Spm absorbs more Cad and has shorter root growth, and that the transgenic Arabidopsis plants overexpressing the SPMS gene are hypersensitive to Cad, further supporting the above idea. The transgenic Arabidopsis overexpressing L-Amino acid Transporter 1 (LAT1) absorbed more Cad and showed increased Cad sensitivity, suggesting that LAT1 functions as a Cad importer. Recently, other research group reported that Organic Cation Transporter 1 (OCT1) is a causal gene which determines the Cad sensitivity of various Arabidopsis accessions. Furthermore, their results suggested that OCT1 is involved in Cad efflux. Thus we monitored the expression of OCT1 and LAT1 during the above experiments. Based on the results, we proposed a model in which the level of Spm content modulates the expression of OCT1 and LAT1, and determines Cad sensitivity of Arabidopsis.

Latex agglutination using the periplasmic proteins antigen of Brucella melitensis is a successful, rapid, and specific serodiagnostic test for ovine brucellosis.

PubMed

Ismael, Alaa Bassuny; Swelum, Ayman Abdel-Aziz; Mostafa, Salama A-H; Alhumiany, Abdel-Rahman A

2016-09-01

Brucellosis, especially caused by Brucella melitensis, is considered the most-widespread zoonosis in the world, particularly in developing countries. This study was planned to develop an accurate test for diagnosis of ovine brucellosis using a specific hot saline extracted soluble Brucella melitensis periplasmic proteins (SBPPs). The efficacy of the latex agglutination test (LAT) using SBPPs compared to the Rose Bengal test (RBT), buffered plate agglutination test (BPAT), serum agglutination test (SAT), and an indirect enzyme-linked immunosorbent assay (i-ELISA) was evaluated in the field diagnosis of ovine brucellosis. The test performance was evaluated by estimating sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), disease prevalence (DP), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) using test agreement and bacteriological culture in 1777 samples. The false-positive result was significantly (P ⩽0.05) lower in LAT than RBT, BPAT, SAT, and i-ELISA. With reference to test agreement, the Se, Sp, PPV, and PLR were highest (P ⩽0.05) in LAT 99.33%, 99.88%, 98.68%, and 827.25%, respectively. With reference to bacteriological culture, the LAT and i-ELISA tests showed a significant difference in Se with SAT. However, no significant difference in specificity was detected. The DP was 8.44% in the five tests. In conclusion, LAT using SBPPs of B. melitensis could be a suitable serodiagnostic field test for ovine brucellosis, with high sensitivity and specificity. © The Author(s) 2016.

Emotion recognition through static faces and moving bodies: a comparison between typically developed adults and individuals with high level of autistic traits

PubMed Central

Actis-Grosso, Rossana; Bossi, Francesco; Ricciardelli, Paola

2015-01-01

We investigated whether the type of stimulus (pictures of static faces vs. body motion) contributes differently to the recognition of emotions. The performance (accuracy and response times) of 25 Low Autistic Traits (LAT group) young adults (21 males) and 20 young adults (16 males) with either High Autistic Traits or with High Functioning Autism Spectrum Disorder (HAT group) was compared in the recognition of four emotions (Happiness, Anger, Fear, and Sadness) either shown in static faces or conveyed by moving body patch-light displays (PLDs). Overall, HAT individuals were as accurate as LAT ones in perceiving emotions both with faces and with PLDs. Moreover, they correctly described non-emotional actions depicted by PLDs, indicating that they perceived the motion conveyed by the PLDs per se. For LAT participants, happiness proved to be the easiest emotion to be recognized: in line with previous studies we found a happy face advantage for faces, which for the first time was also found for bodies (happy body advantage). Furthermore, LAT participants recognized sadness better by static faces and fear by PLDs. This advantage for motion kinematics in the recognition of fear was not present in HAT participants, suggesting that (i) emotion recognition is not generally impaired in HAT individuals, (ii) the cues exploited for emotion recognition by LAT and HAT groups are not always the same. These findings are discussed against the background of emotional processing in typically and atypically developed individuals. PMID:26557101

Emotion recognition through static faces and moving bodies: a comparison between typically developed adults and individuals with high level of autistic traits.

PubMed

Actis-Grosso, Rossana; Bossi, Francesco; Ricciardelli, Paola

2015-01-01

We investigated whether the type of stimulus (pictures of static faces vs. body motion) contributes differently to the recognition of emotions. The performance (accuracy and response times) of 25 Low Autistic Traits (LAT group) young adults (21 males) and 20 young adults (16 males) with either High Autistic Traits or with High Functioning Autism Spectrum Disorder (HAT group) was compared in the recognition of four emotions (Happiness, Anger, Fear, and Sadness) either shown in static faces or conveyed by moving body patch-light displays (PLDs). Overall, HAT individuals were as accurate as LAT ones in perceiving emotions both with faces and with PLDs. Moreover, they correctly described non-emotional actions depicted by PLDs, indicating that they perceived the motion conveyed by the PLDs per se. For LAT participants, happiness proved to be the easiest emotion to be recognized: in line with previous studies we found a happy face advantage for faces, which for the first time was also found for bodies (happy body advantage). Furthermore, LAT participants recognized sadness better by static faces and fear by PLDs. This advantage for motion kinematics in the recognition of fear was not present in HAT participants, suggesting that (i) emotion recognition is not generally impaired in HAT individuals, (ii) the cues exploited for emotion recognition by LAT and HAT groups are not always the same. These findings are discussed against the background of emotional processing in typically and atypically developed individuals.

A Tribute to Professor Steven L. Wechsler (1948-2016): The Man and the Scientist.

PubMed

Nesburn, Anthony B; BenMohamed, Lbachir

2017-01-01

Professor Steven L. Wechsler, a world-renowned eye researcher and virologist, passed away unexpectedly on June 12, 2016 at the age of 68. Many scientists came to know Professor Wechsler as a gifted researcher in the field of ocular Herpes Simplex Virus (HSV-1) latency, reactivation, and pathogenesis. Professor Wechsler published over 150 peer-reviewed scientific papers during his career, pushing forward the frontiers of his field eye research. His colleagues would say, 'Steve literally wrote the book on herpes latency and reactivation.' He was the first to show that the HSV-1 latency-associated transcript (LAT) is essential for the HSV-1 high spontaneous reactivation phenotype and that LAT has anti-apoptosis activity. This discovery of LAT's anti-apoptosis activity, which is a key factor in how the LAT gene enhances reactivation, was published in Science in 2000 and created a new paradigm that greatly increased understanding of HSV-1 latency and reactivation. In collaboration with Professor Lbachir BenMohamed, an immunologist, they later demonstrated that LAT also acts as an immune evasion gene. He was a caring scientist who truly enjoyed working and sharing his experience and expertise with young researchers. He will be remembered as a significant pillar within scientific and ocular herpes research communities worldwide. Professor Wechsler's dedication to science, his compassionate character, and wonderful sense of humor were exemplary. We, who were his friends and colleagues, will mourn his passing deeply.

The first catalog of active galactic nuclei detected by the FERMI large area telescope

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2010-04-29

Here, we present the first catalog of active galactic nuclei (AGNs) detected by the Large Area Telescope (LAT), corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes 671 γ-ray sources located at high Galactic latitudes (|b|>10°) that are detected with a test statistic greater than 25 and associated statistically with AGNs. Some LAT sources are associated with multiple AGNs, and consequently, the catalog includes 709 AGNs, comprising 300 BL Lacertae objects, 296 flat-spectrum radio quasars, 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazarsmore » based on their spectral energy distributions as archival radio, optical, and X-ray data permit. In addition to the formal 1LAC sample, we provide AGN associations for 51 low-latitude LAT sources and AGN "affiliations" (unquantified counterpart candidates) for 104 high-latitude LAT sources without AGN associations. The overlap of the 1LAC with existing γ-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties—such as γ-ray fluxes and photon power-law spectral indices, redshifts, γ-ray luminosities, variability, and archival radio luminosities—and their correlations are presented and discussed for the different blazar classes. Lastly, we compare the 1LAC results with predictions regarding the γ-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequence.« less

Fermi Large Area Telescope Observation Of A Gamma-Ray Source At The Position Of Eta Carinae

DOE PAGES

Abdo, A. A,

2010-10-13

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope detected a γ-ray source that is spatially consistent with the location of Eta Carinae. This source has been persistently bright since the beginning of the LAT survey observations (from 2008 August to 2009 July, the time interval considered here). The γ-ray signal is detected significantly throughout the LAT energy band (i.e., up to ~100 GeV). The 0.1-100 GeV energy spectrum is well represented by a combination of a cutoff power-law model (<10 GeV) and a hard power-law component (>10 GeV). The total flux (>100 MeV) is 3.7 +0.3more » –0.1 × 10 –7 photons s –1 cm –2, with additional systematic uncertainties of 10%, and consistent with the average flux measured by AGILE. The light curve obtained by Fermi is consistent with steady emission. Our observations do not confirm the presence of a γ-ray flare in 2008 October, as reported by Tavani et al., although we cannot exclude that a flare lasting only a few hours escaped detection by the Fermi LAT. We also do not find any evidence for γ-ray variability that correlates with the large X-ray variability of Eta Carinae observed during 2008 December and 2009 January. We are thus not able to establish an unambiguous identification of the LAT source with Eta Carinae.« less

Ammonia Reduces Intracellular Asymmetric Dimethylarginine in Cultured Astrocytes Stimulating Its y⁺LAT2 Carrier-Mediated Loss.

PubMed

Milewski, Krzysztof; Bogacińska-Karaś, Małgorzata; Fręśko, Inez; Hilgier, Wojciech; Jaźwiec, Radosław; Albrecht, Jan; Zielińska, Magdalena

2017-11-02

Previously we had shown that ammonia stimulates nitric oxide (NO) synthesis in astrocytes by increasing the uptake of the precursor amino acid, arginine via the heteromeric arginine/glutamine transporter y⁺LAT2. Ammonia also increases the concentration in the brain of the endogenous inhibitor of nitric oxide synthases (NOS), asymmetric dimethylarginine (ADMA), but distribution of ADMA surplus between the intraastrocytic and extracellular compartments of the brain has not been studied. Here we tested the hypothesis that ammonia modulates the distribution of ADMA and its analog symmetric dimethylarginine (SDMA) between the two compartments of the brain by competition with arginine for the y⁺LAT2 transporter. In extension of the hypothesis we analyzed the ADMA/Arg interaction in endothelial cells forming the blood-brain barrier. We measured by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) technique the concentration of arginine, ADMA and SDMA in cultured cortical astrocytes and in a rat brain endothelial cell line (RBE-4) treated with ammonia and the effect of silencing the expression of a gene coding y⁺LAT2. We also tested the expression of ADMA metabolism enzymes: protein arginine methyltransferase (PRMT) and dimethylarginine dimethyl aminohydrolase (DDAH) and arginine uptake to astrocytes. Treatment for 48 h with 5 mM ammonia led to an almost 50% reduction of ADMA and SDMA concentration in both cell types, and the effect in astrocytes was substantially attenuated by silencing of the Slc7a6 gene. Moreover, the y⁺LAT2-dependent component of ammonia-evoked arginine uptake in astrocytes was reduced in the presence of ADMA in the medium. Our results suggest that increased ADMA efflux mediated by upregulated y⁺LAT2 may be a mechanism by which ammonia interferes with intra-astrocytic (and possibly intra-endothelial cell) ADMA content and subsequently, NO synthesis in both cell types.

SUZAKU X-RAY FOLLOW-UP OBSERVATIONS OF SEVEN UNASSOCIATED FERMI-LAT GAMMA-RAY SOURCES AT HIGH GALACTIC LATITUDES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Y.; Kataoka, J.; Nakamori, T.

2012-03-01

We report on our second-year campaign of X-ray follow-up observations of unidentified Fermi Large Area Telescope (LAT) {gamma}-ray sources at high Galactic latitudes (|b| > 10 Degree-Sign ) using the X-ray Imaging Spectrometer on board the Suzaku X-ray Observatory. In this second year of the project, seven new targets were selected from the First Fermi-LAT Catalog, and studied with 20-40 ks effective Suzaku exposures. We detected an X-ray point source coincident with the position of the recently discovered millisecond pulsar (MSP) PSR J2302+4442 within the 95% confidence error circle of 1FGL J2302.8+4443. The X-ray spectrum of the detected counterpart wasmore » well fit by a blackbody model with temperature of kT {approx_equal} 0.3 keV, consistent with an origin of the observed X-ray photons from the surface of a rotating magnetized neutron star. For four other targets that were also recently identified with a normal pulsar (1FGL J0106.7+4853) and MSPs (1FGL J1312.6+0048, J1902.0-5110, and J2043.2+1709), only upper limits in the 0.5-10 keV band were obtained at the flux levels of {approx_equal} 10{sup -14} erg cm{sup -2} s{sup -1}. A weak X-ray source was found in the field of 1FGL J1739.4+8717, but its association with the variable {gamma}-ray emitter could not be confirmed with the available Suzaku data alone. For the remaining Fermi-LAT object 1FGL J1743.8-7620 no X-ray source was detected within the LAT 95% error ellipse. We briefly discuss the general properties of the observed high Galactic-latitude Fermi-LAT objects by comparing their multiwavelength properties with those of known blazars and MSPs.« less

Elimination of human T cell leukemia virus type-1-infected cells by neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies against human t cell leukemia virus type-1 envelope gp46.

PubMed

Tanaka, Yuetsu; Takahashi, Yoshiaki; Tanaka, Reiko; Kodama, Akira; Fujii, Hideki; Hasegawa, Atsuhiko; Kannagi, Mari; Ansari, Aftab A; Saito, Mineki

2014-06-01

Human T cell leukemia virus type-1 (HTLV-1) is prevalent worldwide with foci of high prevalence. However, to date no effective vaccine or drug against HTLV-1 infection has been developed. In efforts to define the role of antibodies in the control of HTLV-1 infection, we capitalized on the use of our previously defined anti-gp46 neutralizing monoclonal antibody (mAb) (clone LAT-27) and high titers of human anti-HTLV-1 IgG purified from HAM/TSP patients (HAM-IgG). LAT-27 and HAM-IgG completely blocked syncytium formation and T cell immortalization mediated by HTLV-1 in vitro. The addition of these antibodies to cultures of CD8(+) T cell-depleted peripheral blood mononuclear cells (PBMCs) from HAM/TSP patients at the initiation of culture not only decreased the numbers of Tax-expressing cells and the production of HTLV-1 p24 but also inhibited the spontaneous immortalization of T cells. Coculture of in vitro-HTLV-1-immortalized T cell lines with autologous PBMCs in the presence of LAT-27 or HAM-IgG, but not an F(ab')2 fragment of LAT-27 or nonneutralizing anti-gp46 mAbs, resulted in depletion of HTLV-1-infected cells. A 24-h (51)Cr release assay showed the presence of significant antibody-dependent cellular cytotoxicity (ADCC) activity in LAT-27 and HAM-IgG, but not F(ab')2 of LAT-27, resulting in the depletion of HTLV-1-infected T cells by autologous PBMCs. The depletion of natural killer (NK) cells from the effector PBMCs reduced this ADCC activity. Altogether, the present data demonstrate that the neutralizing and ADCC-inducing activities of anti-HTLV-1 antibodies are capable of reducing infection and eliminating HTLV-1-infected cells in the presence of autologous PBMCs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hektor, Andi; Marzola, Luca; Institute of Physics, University of Tartu,Ravila 14c, 50411 Tartu

Motivated by the recent indications for a 750 GeV resonance in the di-photon final state at the LHC, in this work we analyse the compatibility of the excess with the broad photon excess detected at the Galactic Centre. Intriguingly, by analysing the parameter space of an effective models where a 750 GeV pseudoscalar particles mediates the interaction between the Standard Model and a scalar dark sector, we prove the compatibility of the two signals. We show, however, that the LHC mono-jet searches and the Fermi LAT measurements strongly limit the viable parameter space. We comment on the possible impact ofmore » cosmic antiproton flux measurement by the AMS-02 experiment.« less

Constraining Gamma-Ray Pulsar Gap Models with a Simulated Pulsar Population

NASA Technical Reports Server (NTRS)

Pierbattista, Marco; Grenier, I. A.; Harding, A. K.; Gonthier, P. L.

2012-01-01

With the large sample of young gamma-ray pulsars discovered by the Fermi Large Area Telescope (LAT), population synthesis has become a powerful tool for comparing their collective properties with model predictions. We synthesised a pulsar population based on a radio emission model and four gamma-ray gap models (Polar Cap, Slot Gap, Outer Gap, and One Pole Caustic). Applying gamma-ray and radio visibility criteria, we normalise the simulation to the number of detected radio pulsars by a select group of ten radio surveys. The luminosity and the wide beams from the outer gaps can easily account for the number of Fermi detections in 2 years of observations. The wide slot-gap beam requires an increase by a factor of 10 of the predicted luminosity to produce a reasonable number of gamma-ray pulsars. Such large increases in the luminosity may be accommodated by implementing offset polar caps. The narrow polar-cap beams contribute at most only a handful of LAT pulsars. Using standard distributions in birth location and pulsar spin-down power (E), we skew the initial magnetic field and period distributions in a an attempt to account for the high E Fermi pulsars. While we compromise the agreement between simulated and detected distributions of radio pulsars, the simulations fail to reproduce the LAT findings: all models under-predict the number of LAT pulsars with high E , and they cannot explain the high probability of detecting both the radio and gamma-ray beams at high E. The beaming factor remains close to 1.0 over 4 decades in E evolution for the slot gap whereas it significantly decreases with increasing age for the outer gaps. The evolution of the enhanced slot-gap luminosity with E is compatible with the large dispersion of gamma-ray luminosity seen in the LAT data. The stronger evolution predicted for the outer gap, which is linked to the polar cap heating by the return current, is apparently not supported by the LAT data. The LAT sample of gamma-ray pulsars therefore provides a fresh perspective on the early evolution of the luminosity and beam width of the gamma-ray emission from young pulsars, calling for thin and more luminous gaps.

77 FR 30512 - Native American Career and Technical Education Program; Final Waivers and Extension of Project...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... DEPARTMENT OF EDUCATION Native American Career and Technical Education Program; Final Waivers and... American Career and Technical Education Program Catalog of Federal Domestic Assistance (CFDA) Number: 84.101A. SUMMARY: For 60-month projects funded in fiscal year (FY) 2007 under the Native American Career...

Fermi LAT detection of increased gamma-ray activity from blazar S5 0716+71

NASA Astrophysics Data System (ADS)

Buson, S.

2014-04-01

The Large Area Telescope (LAT), one of two instruments on-board the Fermi Gamma-ray Space Telescope, has observed an increase in gamma-ray activity from a source positionally coincident with the BL Lac object S5 0716+71 (also known as 2FGL J0721.9+7120, Nolan et al. ...

75 FR 48550 - Amendment of Class E Airspace; Pine Mountain, GA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... Airport, GA (Lat. 32[deg]50'26'' N., long. 84[deg]52'57'' W.) Pine Mountain NDB, GA (Lat. 32[deg]50'34'' N...-0498; Airspace Docket No. 10-ASO-26] Amendment of Class E Airspace; Pine Mountain, GA AGENCY: Federal... Pine Mountain, GA, to accommodate the Standard Instrument Approach Procedures (SIAPs) developed for...

Forest restoration in the Nordic countries

Treesearch

Palle Madsen; Ása Arad•ttir; Emile Gardiner; Pelle Gemmel; Kåre Lund Høie; Magnus Löf; John A. Stanturf; Peter Tigerstedt; Hardi Tullus; Sauli Valkonen; Veiko Uri

2000-01-01

The Nordic countries include Iceland, Norway, Sweden, Finland, and Denmark, which range from lat. 54° in southern Denmark to lat. 72° at North Cape, Norway. This region is dominated by the boreal coniferous vegetational zone.Denmark and southern Sweden are, however, located in the deciduous (nemoral) forest zone, whereas the interior part of Iceland and the high...

50 CFR Table 1c to Part 660... - Sablefish North of 36° N. lat. Allocations, 2013

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Sablefish North of 36° N. lat. Allocations, 2013 1c Table 1c to Part 660, Subpart C Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OFF...

75 FR 61611 - Modification of Class E Airspace; San Clemente, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... [Modified] San Clemente Island NALF (Fredrick Sherman Field), CA (Lat. 33[deg]01'22'' N., long. 118[deg]35'19'' W.) San Clemente Island TACAN (Lat. 33[deg]01'37'' N., long. 118[deg]34'46'' W.) That airspace... San Clemente, CA. Decommissioning of the San Clemente Island Non-Directional Radio Beacon (NDB) at San...

76 FR 56099 - Amendment of Class E Airspace; Orangeburg, SC

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... Group, Eastern Service Center, Federal Aviation Administration, P.O. Box 20636, Atlanta, Georgia 30320... the airspace descriptor from ``ASO GA E5 Orangeburg, SC [Amended]'' to ``ASO SC E5 Orangeburg, SC... Airport, SC, remove ``lat. 33[deg]27[min]39[sec] N., long. 80[deg]51[min]32[sec] W.'' and insert ``lat. 33...

Sweetgum Dormancy Release: Effects of Chilling, Photoperiod, and Genotype

Treesearch

Robert E. Farmer

1968-01-01

In L., 1200 to 1600 hours of chilling (3 D C) resulted in rapid resumption of growth under greenhouse forcing conditions. Long photoperiods were effective substitutes for chilling. Plants from southern Alabama (Lat. 31°) had a lower chilling requirement than those from western Tennessee (Lat. 36°). Growth rate of plants under...

14 CFR 93.176 - Description of area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... base of the overlaying Phoenix Class B airspace bounded by a line beginning at: Lat. 33°23′56″ N; Long...) South section lower includes airspace extending from 2,100 feet MSL to the base of the overlaying Phoenix Class B airspace, excluding the Luke Class D airspace area bounded by a line beginning at: Lat. 33...

Studies of EGRET sources with a novel image restoration technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tajima, Hiroyasu; Cohen-Tanugi, Johann; Kamae, Tuneyoshi

2007-07-12

We have developed an image restoration technique based on the Richardson-Lucy algorithm optimized for GLAST-LAT image analysis. Our algorithm is original since it utilizes the PSF (point spread function) that is calculated for each event. This is critical for EGRET and GLAST-LAT image analysis since the PSF depends on the energy and angle of incident gamma-rays and varies by more than one order of magnitude. EGRET and GLAST-LAT image analysis also faces Poisson noise due to low photon statistics. Our technique incorporates wavelet filtering to minimize noise effects. We present studies of EGRET sources using this novel image restoration techniquemore » for possible identification of extended gamma-ray sources.« less

Detection of 16 gamma-ray pulsars through blind frequency searches using the Fermi LAT.

PubMed

Abdo, A A; Ackermann, M; Ajello, M; Anderson, B; Atwood, W B; Axelsson, M; Baldini, L; Ballet, J; Barbiellini, G; Baring, M G; Bastieri, D; Baughman, B M; Bechtol, K; Bellazzini, R; Berenji, B; Bignami, G F; Blandford, R D; Bloom, E D; Bonamente, E; Borgland, A W; Bregeon, J; Brez, A; Brigida, M; Bruel, P; Burnett, T H; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Cecchi, C; Celik, O; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Conrad, J; Cutini, S; Dermer, C D; de Angelis, A; de Luca, A; de Palma, F; Digel, S W; Dormody, M; do Couto e Silva, E; Drell, P S; Dubois, R; Dumora, D; Farnier, C; Favuzzi, C; Fegan, S J; Fukazawa, Y; Funk, S; Fusco, P; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giommi, P; Giordano, F; Glanzman, T; Godfrey, G; Grenier, I A; Grondin, M-H; Grove, J E; Guillemot, L; Guiriec, S; Gwon, C; Hanabata, Y; Harding, A K; Hayashida, M; Hays, E; Hughes, R E; Jóhannesson, G; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, T; Katagiri, H; Kataoka, J; Kawai, N; Kerr, M; Knödlseder, J; Kocian, M L; Kuss, M; Lande, J; Latronico, L; Lemoine-Goumard, M; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Madejski, G M; Makeev, A; Marelli, M; Mazziotta, M N; McConville, W; McEnery, J E; Meurer, C; Michelson, P F; Mitthumsiri, W; Mizuno, T; Monte, C; Monzani, M E; Morselli, A; Moskalenko, I V; Murgia, S; Nolan, P L; Norris, J P; Nuss, E; Ohsugi, T; Omodei, N; Orlando, E; Ormes, J F; Paneque, D; Parent, D; Pelassa, V; Pepe, M; Pesce-Rollins, M; Pierbattista, M; Piron, F; Porter, T A; Primack, J R; Rainò, S; Rando, R; Ray, P S; Razzano, M; Rea, N; Reimer, A; Reimer, O; Reposeur, T; Ritz, S; Rochester, L S; Rodriguez, A Y; Romani, R W; Ryde, F; Sadrozinski, H F-W; Sanchez, D; Sander, A; Saz Parkinson, P M; Scargle, J D; Sgrò, C; Siskind, E J; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Starck, J-L; Strickman, M S; Suson, D J; Tajima, H; Takahashi, H; Takahashi, T; Tanaka, T; Thayer, J G; Thompson, D J; Tibaldo, L; Tibolla, O; Torres, D F; Tosti, G; Tramacere, A; Uchiyama, Y; Usher, T L; Van Etten, A; Vasileiou, V; Vilchez, N; Vitale, V; Waite, A P; Wang, P; Watters, K; Winer, B L; Wolff, M T; Wood, K S; Ylinen, T; Ziegler, M

2009-08-14

Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations. We report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Direct detection of gamma-ray pulsars enables studies of emission mechanisms, population statistics, and the energetics of pulsar wind nebulae and supernova remnants.

48 CFR 1852.235-73 - Final Scientific and Technical Reports.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Final Scientific and Technical Reports. 1852.235-73 Section 1852.235-73 Federal Acquisition Regulations System NATIONAL..., including recommendations and conclusions based on the experience and results obtained. The final report...

Coosa River Storage Annex, Talladega, Alabama Environmental Investigation, Final Management and Resources Utilization Plan

DTIC Science & Technology

1991-02-01

to adequately assess the health and environmental risks associated with the closure and transfer of the Annex forI other use; and 3) identification of...1990); Draft Final Technical Plan, Draft Final Sampling Design Plan and Draft Final Health and Safety Plan, USATHAMA, June 1990. 2.1.2 Draft Final...Final Technical Plan, Sampling Design Plan and Health and Safety Plan) supplied by USATHAMA. The estimate may be revised, with USATHAMA approval, as

Fermi Large Area Telescope Observations Of Misaligned Active Galactic Nuclei

DOE PAGES

Abdo, A. A.

2010-08-13

Analysis is presented for 15 months of data taken with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope for 11 non-blazar active galactic nuclei (AGNs), including seven FRI radio galaxies and four FRII radio sources consisting of two FRII radio galaxies and two steep spectrum radio quasars. The broad line FRI radio galaxy 3C 120 is reported here as a γ-ray source for the first time. The analysis is based on directional associations of LAT sources with radio sources in the 3CR, 3CRR, and MS4 (collectively referred to as 3C-MS) catalogs. Seven of the eleven LAT sourcesmore » associated with 3C-MS radio sources have spectral indices larger than 2.3 and, except for the FRI radio galaxy NGC 1275 that shows possible spectral curvature, are well described by a power law. No evidence for time variability is found for any sources other than NGC 1275. The γ-ray luminosities of FRI radio galaxies are significantly smaller than those of the BL Lac objects detected by the LAT, whereas the γ-ray luminosities of the FRII sources are quite similar to those of FSRQs, which could reflect different beaming factors for the γ-ray emission. A core dominance (CD) study of the 3CRR sample indicates that sources closer to the jet axis are preferentially detected with the Fermi LAT, insofar as the γ-ray-detected misaligned AGNs have larger CD at a given average radio flux. The results are discussed in view of the AGN unification scenario.« less

Fermi Large Area Telescope Observations of Misaligned Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Abdo, A. A.; Ackermann, M.; Ajello, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Borgland, A. W.; Bouvier, A.; Brandt, T. J.; Bregeon, J.; Brez, A.; Brigida, M.; Bruel, P.; Buehler, R.; Burnett, T. H.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Cannon, A.; Caraveo, P. A.; Carrigan, S.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Çelik, Ö.; Celotti, A.; Charles, E.; Chekhtman, A.; Chen, A. W.; Cheung, C. C.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Colafrancesco, S.; Conrad, J.; Davis, D. S.; Dermer, C. D.; de Angelis, A.; de Palma, F.; Silva, E. do Couto e.; Drell, P. S.; Dubois, R.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Fortin, P.; Frailis, M.; Fukazawa, Y.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grandi, P.; Grenier, I. A.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Hadasch, D.; Hayashida, M.; Hays, E.; Horan, D.; Hughes, R. E.; Jackson, M. S.; Jóhannesson, G.; Johnson, A. S.; Johnson, W. N.; Kamae, T.; Katagiri, H.; Kataoka, J.; Knödlseder, J.; Kuss, M.; Lande, J.; Latronico, L.; Lee, S.-H.; Lemoine-Goumard, M.; Llena Garde, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Makeev, A.; Malaguti, G.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Michelson, P. F.; Migliori, G.; Mitthumsiri, W.; Mizuno, T.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Naumann-Godo, M.; Nestoras, I.; Nolan, P. L.; Norris, J. P.; Nuss, E.; Ohsugi, T.; Okumura, A.; Omodei, N.; Orlando, E.; Ormes, J. F.; Paneque, D.; Panetta, J. H.; Parent, D.; Pelassa, V.; Pepe, M.; Persic, M.; Pesce-Rollins, M.; Piron, F.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Reyes, L. C.; Roth, M.; Sadrozinski, H. F.-W.; Sanchez, D.; Sander, A.; Scargle, J. D.; Sgrò, C.; Siskind, E. J.; Smith, P. D.; Spandre, G.; Spinelli, P.; Stawarz, Ł.; Stecker, F. W.; Strickman, M. S.; Suson, D. J.; Takahashi, H.; Tanaka, T.; Thayer, J. B.; Thayer, J. G.; Thompson, D. J.; Tibaldo, L.; Torres, D. F.; Torresi, E.; Tosti, G.; Tramacere, A.; Uchiyama, Y.; Usher, T. L.; Vandenbroucke, J.; Vasileiou, V.; Vilchez, N.; Villata, M.; Vitale, V.; Waite, A. P.; Wang, P.; Winer, B. L.; Wood, K. S.; Yang, Z.; Ylinen, T.; Ziegler, M.

2010-09-01

Analysis is presented for 15 months of data taken with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope for 11 non-blazar active galactic nuclei (AGNs), including seven FRI radio galaxies and four FRII radio sources consisting of two FRII radio galaxies and two steep spectrum radio quasars. The broad line FRI radio galaxy 3C 120 is reported here as a γ-ray source for the first time. The analysis is based on directional associations of LAT sources with radio sources in the 3CR, 3CRR, and MS4 (collectively referred to as 3C-MS) catalogs. Seven of the eleven LAT sources associated with 3C-MS radio sources have spectral indices larger than 2.3 and, except for the FRI radio galaxy NGC 1275 that shows possible spectral curvature, are well described by a power law. No evidence for time variability is found for any sources other than NGC 1275. The γ-ray luminosities of FRI radio galaxies are significantly smaller than those of the BL Lac objects detected by the LAT, whereas the γ-ray luminosities of the FRII sources are quite similar to those of FSRQs, which could reflect different beaming factors for the γ-ray emission. A core dominance (CD) study of the 3CRR sample indicates that sources closer to the jet axis are preferentially detected with the Fermi LAT, insofar as the γ-ray-detected misaligned AGNs have larger CD at a given average radio flux. The results are discussed in view of the AGN unification scenario.

77 FR 21506 - Proposed Amendment of Class E Airspace; Augusta, GA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... in the Augusta, GA area. This proposal will be subject to an environmental analysis in accordance... Augusta Regional At Bush Field Airport, GA (Lat. 33[deg]22'12'' N., long. 81[deg]57'52'' W.) Emory NDB...'22'' W.) Burke County Airport, GA (Lat. 32[deg]02'29'' N., long. 82[deg]00'10'' W.) Millen Airport...

78 FR 52114 - Proposed Amendment of Class E Airspace; Macon, GA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-22

..., GA (Lat. 32[deg]41'34'' N., long. 83[deg]38'57'' W.) Macon Downtown Airport (Lat. 32[deg]49'18'' N...-0552; Airspace Docket No. 13-ASO-14] Proposed Amendment of Class E Airspace; Macon, GA AGENCY: Federal... proposes to amend Class E Airspace at Macon, GA, as the Bay Creek NDB has been decommissioned and airspace...

50 CFR Table 2c to Part 660... - Sablefish North of 36° N. lat. Allocations, 2014 and Beyond

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Sablefish North of 36° N. lat. Allocations, 2014 and Beyond 2c Table 2c to Part 660, Subpart C Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED...

78 FR 41336 - Proposed Establishment of Class E Airspace; Wasatch, UT

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-10

... lat. 39[deg]03'55'' N., long. 110[deg]37'49'' W.; to lat. 38[deg]28'51'' N., long. 110[deg]38'05'' W... Flight Rules (IFR) aircraft under control of Salt Lake City Air Route Traffic Control Center (ARTCC). The... considered before taking action on the proposed rule. The proposal contained in this action may be changed in...

50 CFR 660.50 - Pacific Coast treaty Indian fisheries.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... This allocation is, for each year, 10 percent of the Monterey through Vancouver area (North of 36° N... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Pacific Coast treaty Indian fisheries. 660... of the FMA between 47°40.10′ N. lat. (Destruction Island) and 46°53.30′ N. lat. (Point Chehalis) and...

75 FR 50947 - Proposed Amendment of Class E Airspace; Kokomo, IN

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... Logansport/Cass County Airport and Peru Municipal Airport also would be made in accordance with the FAA's...'32'' W.) Peru, Grissom Air Reserve Base, IN (Lat. 40[deg]38'53'' N., long. 86[deg]09'08'' W.) Grissom..., Logansport/Cass County Airport, IN (Lat. 40[deg]42'41'' N., long. 86[deg]22'22'' W.) Peru, Peru Municipal...

50 CFR 635.69 - Vessel monitoring systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... gear on board; (2) Whenever a vessel issued a directed shark LAP, is away from port with bottom longline gear on board, is located between 33°00′ N. lat. and 36°30′ N. lat., and the mid-Atlantic shark closed area is closed as specified in § 635.21(d)(1); or (3) Whenever a vessel, issued a directed shark...

50 CFR 635.69 - Vessel monitoring systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Whenever a vessel issued a directed shark LAP, has bottom longline gear on board, is located between 33°00′ N. lat. and 36°30′ N. lat., and the mid-Atlantic shark closed area is closed as specified in § 635.21(d)(1); or (3) Whenever a vessel issued a directed shark LAP has gillnet gear on board from...

78 FR 16399 - Amendment of Class E Airspace; Unalakleet, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

..., AK (Lat. 63[deg]53'19'' N., long. 160[deg]47'57'' W.) That airspace within a 4.2-mile radius of.... * * * * * AAL AK E5 Unalakleet, AK [Modified] Unalakleet Airport, AK (Lat. 63[deg]53'19'' N., long. 160[deg]47...; Airspace Docket No. 12-AAL-3] Amendment of Class E Airspace; Unalakleet, AK AGENCY: Federal Aviation...

FLaapLUC: A pipeline for the generation of prompt alerts on transient Fermi-LAT γ-ray sources

NASA Astrophysics Data System (ADS)

Lenain, J.-P.

2018-01-01

The large majority of high energy sources detected with Fermi-LAT are blazars, which are known to be very variable sources. High cadence long-term monitoring simultaneously at different wavelengths being prohibitive, the study of their transient activities can help shedding light on our understanding of these objects. The early detection of such potentially fast transient events is the key for triggering follow-up observations at other wavelengths. A Python tool, FLaapLUC, built on top of the Science Tools provided by the Fermi Science Support Center and the Fermi-LAT collaboration, has been developed using a simple aperture photometry approach. This tool can effectively detect relative flux variations in a set of predefined sources and alert potential users. Such alerts can then be used to trigger target of opportunity observations with other facilities. It is shown that FLaapLUC is an efficient tool to reveal transient events in Fermi-LAT data, providing quick results which can be used to promptly organise follow-up observations. Results from this simple aperture photometry method are also compared to full likelihood analyses. The FLaapLUC package is made available on GitHub and is open to contributions by the community.

The Canada-France Ecliptic Plane Survey (CFEPS)—High-latitude Component

NASA Astrophysics Data System (ADS)

Petit, J.-M.; Kavelaars, J. J.; Gladman, B. J.; Jones, R. L.; Parker, J. Wm.; Bieryla, A.; Van Laerhoven, C.; Pike, R. E.; Nicholson, P.; Ashby, M. L. N.; Lawler, S. M.

2017-05-01

The High Ecliptic Latitude (HiLat) extension of the Canada-France Ecliptic Plane Survey (CFEPS), conducted from 2006 June to 2009 July, discovered a set of Trans-Neptunian objects (TNOs) that we report here. The HiLat component was designed to address one of the shortcomings of ecliptic surveys (like CFEPS), their low sensitivity to high-inclination objects. We searched 701 deg2 of sky ranging from 12° to 85° ecliptic latitude and discovered 24 TNOs, with inclinations between 15° and 104°. This survey places a very strong constraint on the inclination distribution of the hot component of the classical Kuiper Belt, ruling out any possibility of a large intrinsic fraction of highly inclined orbits. Using the parameterization of Brown, the HiLat sample combined with CFEPS imposes a width 14° ≤ σ ≤ 15.°5, with a best match for σ = 14.°5. HiLat discovered the first retrograde TNO, 2008 KV42, with an almost polar orbit with inclination 104°, and (418993) = 2009 MS9, a scattering object with perihelion in the region of Saturn’s influence, with a ˜ 400 au and I = 68°.

VizieR Online Data Catalog: Observation of first Fermi-LAT sources at Parkes (Camilo+, 2015)

NASA Astrophysics Data System (ADS)

Camilo, F.; Kerr, M.; Ray, P. S.; Ransom, S. M.; Sarkissian, J.; Cromartie, H. T.; Johnston, S.; Reynolds, J. E.; Wolff, M. T.; Freire, P. C. C.; Bhattacharyya, B.; Ferrara, E. C.; Keith, M.; Michelson, P. F.; Parkinson, P. M. S.; Wood, K. S.

2017-10-01

Keith et al. (2011MNRAS.414.1292K) used a digital filterbank at Parkes to search 11 unidentified sources from the first Fermi-LAT catalog (1FGL; Abdo et al. 2010, J/ApJS/188/405). Two MSPs and one slow pulsar were discovered in single observations of each target at a central frequency of 1.4 GHz. Subsequently, one of these MSPs was found to be associated with the corresponding LAT source. At nearly the same time, in late 2009, we used an analog filterbank at Parkes to search 14 unidentified 1FGL sources (Kerr et al. 2012ApJ...748L...2K). The single observations of these targets resulted in the detection of six MSPs, five of them discoveries. However, confirmation of some of these MSPs was not easy: the search observations lasted for 1-2 hr each, but some of the pulsars were not detected in equivalent initial confirmation attempts, owing to the effects of interstellar scintillation. These and other selection effects (see Section 2.2 for details) led us to search some promising unidentified LAT sources repeatedly. (1 data file).

De-novo NAD+ synthesis regulates SIRT1-FOXO1 apoptotic pathway in response to NQO1 substrates in lung cancer cells

PubMed Central

Cheng, Xuefang; Li, Qingran; Liu, Fang; Ye, Hui; Zhao, Min; Wang, Hong; Wang, Guangji; Hao, Haiping

2016-01-01

Tryptophan metabolism is essential in diverse kinds of tumors via regulating tumor immunology. However, the direct role of tryptophan metabolism and its signaling pathway in cancer cells remain largely elusive. Here, we establish a mechanistic link from L-type amino acid transporter 1 (LAT1) mediated transport of tryptophan and the subsequent de-novo NAD+ synthesis to SIRT1-FOXO1 regulated apoptotic signaling in A549 cells in response to NQO1 activation. In response to NQO1 activation, SIRT1 is repressed leading to the increased cellular accumulation of acetylated FOXO1 that transcriptionally activates apoptotic signaling. Decreased uptake of tryptophan due to the downregulation of LAT1 coordinates with PARP-1 hyperactivation to induce rapid depletion of NAD+ pool. Particularly, the LAT1-NAD+-SIRT1 signaling is activated in tumor tissues of patients with non-small cell lung cancer. Because NQO1 activation is characterized with oxidative challenge induced DNA damage, these results suggest that LAT1 and de-novo NAD+ synthesis in NSCLC cells may play essential roles in sensing excessive oxidative stress. PMID:27566573

AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2.

PubMed

Philippe, Chloé; Pinson, Benoît; Dompierre, Jim; Pantesco, Véronique; Viollet, Benoît; Daignan-Fornier, Bertrand; Moenner, Michel

2018-06-01

AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz. This transcriptional signature, together with the observation of increased levels in phosphorylation of Lats1 and Yap1 proteins, suggested that the Hippo signaling pathway was activated by AICAR. This effect was observed in both fibroblasts and epithelial cells. Knockdown of Lats1/2 prevented the cytoplasmic delocalization of Yap1/Taz proteins in response to AICAR and conferred a higher resistance to the drug. These results indicate that activation of the most downstream steps of the Hippo cascade participates to the antiproliferative effects of AICAR. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Einstein@Home Gamma-ray Pulsar Survey. II. Source Selection, Spectral Analysis, and Multiwavelength Follow-up

NASA Astrophysics Data System (ADS)

Wu, J.; Clark, C. J.; Pletsch, H. J.; Guillemot, L.; Johnson, T. J.; Torne, P.; Champion, D. J.; Deneva, J.; Ray, P. S.; Salvetti, D.; Kramer, M.; Aulbert, C.; Beer, C.; Bhattacharyya, B.; Bock, O.; Camilo, F.; Cognard, I.; Cuéllar, A.; Eggenstein, H. B.; Fehrmann, H.; Ferrara, E. C.; Kerr, M.; Machenschalk, B.; Ransom, S. M.; Sanpa-Arsa, S.; Wood, K.

2018-02-01

We report on the analysis of 13 gamma-ray pulsars discovered in the Einstein@Home blind search survey using Fermi Large Area Telescope (LAT) Pass 8 data. The 13 new gamma-ray pulsars were discovered by searching 118 unassociated LAT sources from the third LAT source catalog (3FGL), selected using the Gaussian Mixture Model machine-learning algorithm on the basis of their gamma-ray emission properties being suggestive of pulsar magnetospheric emission. The new gamma-ray pulsars have pulse profiles and spectral properties similar to those of previously detected young gamma-ray pulsars. Follow-up radio observations have revealed faint radio pulsations from two of the newly discovered pulsars and enabled us to derive upper limits on the radio emission from the others, demonstrating that they are likely radio-quiet gamma-ray pulsars. We also present results from modeling the gamma-ray pulse profiles and radio profiles, if available, using different geometric emission models of pulsars. The high discovery rate of this survey, despite the increasing difficulty of blind pulsar searches in gamma rays, suggests that new systematic surveys such as presented in this article should be continued when new LAT source catalogs become available.

Diffuse Cosmic Rays Shining in the Galactic Center: A Novel Interpretation of H.E.S.S. and Fermi-LAT γ-Ray Data.

PubMed

Gaggero, D; Grasso, D; Marinelli, A; Taoso, M; Urbano, A

2017-07-21

We present a novel interpretation of the γ-ray diffuse emission measured by Fermi-LAT and H.E.S.S. in the Galactic center (GC) region and the Galactic ridge (GR). In the first part we perform a data-driven analysis based on PASS8 Fermi-LAT data: We extend down to a few GeV the spectra measured by H.E.S.S. and infer the primary cosmic-ray (CR) radial distribution between 0.1 and 3 TeV. In the second part we adopt a CR transport model based on a position-dependent diffusion coefficient. Such behavior reproduces the radial dependence of the CR spectral index recently inferred from the Fermi-LAT observations. We find that the bulk of the GR emission can be naturally explained by the interaction of the diffuse steady-state Galactic CR sea with the gas present in the central molecular zone. Although we confirm the presence of a residual radial-dependent emission associated with a central source, the relevance of the large-scale diffuse component prevents to claim a solid evidence of GC pevatrons.

Spectral properties of bright Fermi-detected blazars in the gamma-ray band

DOE PAGES

Abdo, A. A.

2010-01-28

We investigated the gamma-ray energy spectra of bright blazars of the LAT Bright AGN Sample (LBAS) using Fermi-LAT data. Spectral properties (hardness, curvature, and variability) established using a data set accumulated over 6 months of operation are presented and discussed for different blazar classes and subclasses: flat spectrum radio quasars (FSRQs), low-synchrotron peaked BLLacs (LSP-BLLacs), intermediate-synchrotron peaked BLLacs (ISP-BLLacs), and high-synchrotron peaked BLLacs (HSP-BLLacs). Furthermore, the distribution of photon index (Γ, obtained from a power-law fit above 100 MeV) is found to correlate strongly with blazar subclass. The change in spectral index from that averaged over the 6 months observingmore » period is < 0.2-0.3 when the flux varies by about an order of magnitude, with a tendency toward harder spectra when the flux is brighter for FSRQs and LSP-BLLacs. A strong departure from a single power-law spectrum appears to be a common feature for FSRQs. Finally, we present this feature for some high-luminosity LSP-BLLacs, and a small number of ISP-BLLacs. It is absent in all LBAS HSP-BLLacs. For 3C 454.3 and AO 0235+164, the two brightest FSRQ source and LSP-BLLac source, respectively, a broken power law (BPL) gives the most acceptable of power law, BPL, and curved forms. The consequences of these findings are discussed.« less

Prospects for GRB science with the Fermi Large Area Telescope

DOE PAGES

Band, D. L.; Axelsson, M.; Baldini, L.; ...

2009-08-04

The Large Area Telescope (LAT) instrument on the Fermi mission will reveal the rich spectral and temporal gamma-ray burst (GRB) phenomena in the >100 MeV band. The synergy with Fermi's Gamma-ray Burst Monitor detectors will link these observations to those in the well explored 10-1000 keV range; the addition of the >100 MeV band observations will resolve theoretical uncertainties about burst emission in both the prompt and afterglow phases. Trigger algorithms will be applied to the LAT data both onboard the spacecraft and on the ground. Furthermore, the sensitivity of these triggers will differ because of the available computing resourcesmore » onboard and on the ground. Here we present the LAT's burst detection methodologies and the instrument's GRB capabilities.« less

77 FR 50589 - Agreements and Memoranda of Understanding Between the Food and Drug Administration and Other...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

...: Final rule. SUMMARY: This final rule makes technical changes that will update a requirement that many of the written agreements and memoranda of understanding (MOUs) between the Food and Drug Administration.... This final rule, accordingly, eliminates it. We are making these technical changes to conserve Agency...

77 FR 30514 - Native Hawaiian Career and Technical Education Program; Final Waiver and Extension of Project Period

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... DEPARTMENT OF EDUCATION Native Hawaiian Career and Technical Education Program; Final Waiver and.... ACTION: Notice. Overview Information Final Waiver and Extension of Project Period for the Native Hawaiian.... SUMMARY: For 36-month projects funded in fiscal year (FY) 2009 under the Native Hawaiian Career and...

Growth of embryo and gene expression of nutrient transporters in the small intestine of the domestic pigeon (Columba livia).

PubMed

Chen, Ming-xia; Li, Xiang-guang; Yang, Jun-xian; Gao, Chun-qi; Wang, Bin; Wang, Xiu-qi; Yan, Hui-chao

2015-06-01

The objective of this study was to investigate the relationship between gene expression of nutrient (amino acid, peptide, sodium and proton) transporters in the small intestine and embryonic growth in domestic pigeons (Columba livia). One hundred and twenty-five fertilized eggs were randomly assigned into five groups and were incubated under optimal conditions (temperature of 38.1 °C and relative humidity of 55%). Twenty embryos/birds from each group were sacrificed by cervical dislocation on embryonic day (E) 9, 11, 13, 15 and day of hatch (DOH). The eggs, embryos (without yolk sac), and organs (head, brain, heart, liver, lungs, kidney, gizzard, small intestine, legs, and thorax) were dissected, cleaned, and weighed. Small intestine samples were collected for RNA isolation. The mRNA abundance of intestinal nutrient transporters was evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). We classified these ten organs into four types according to the changes in relative weight during embryonic development. In addition, the gene expression of nutrient transporters was differentially regulated by embryonic day. The mRNA abundances of b(0,+)AT, EAAT3, y(+)LAT2, PepT1, LAT4, NHE2, and NHE3 increased linearly with age, whereas mRNA abundances of CAT1, CAT2, LAT1, EAAT2, SNAT1, and SNAT2 were increased to higher levels on E9 or E11 and then decreased to lower levels until DOH. The results of correlation analysis showed that the gene expressions of b(0,+)AT, EAAT3, PepT1, LAT4, NHE2, NHE3, and y(+)LAT2 had positive correlations with body weight (0.71

Imaging melphalan therapy response in preclinical extramedullary myeloma with 18F-FDOPA and 18F-FDG PET.

PubMed

Hathi, Deep; DeLassus, Elizabeth; Achilefu, Samuel; McConathy, Jonathan; Shokeen, Monica

2018-04-26

Multiple myeloma (MM) is a debilitating neoplasm of terminally differentiated plasma B-cells that has resulted in over 13,000 deaths in 2017 alone. Combination therapies involving melphalan, a small molecule DNA alkylating agent, are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Here, we evaluated the use of 18 F-FDOPA, a clinically available positron emission tomography (PET) radiotracer with specificity to the L-type amino acid transporter-1 (LAT1), which also mediates melphalan uptake, for imaging melphalan therapy response in a preclinical immunocompetent model of MM. Methods: C57Bl/KaLwRij mice were implanted subcutaneously with unilateral murine 5TGM1-GFP tumors, and divided into three independent groups: untreated, treated beginning week 2, and treated beginning week 3 post tumor implantation. The untreated and week 2 therapy cohorts were imaged with preclinical magnetic resonance imaging (MRI) and dynamic 18 F-FDG and 18 F-FDOPA-PET/computed tomography (PET/CT) at week 4 on separate, contiguous days, while the week 3 therapy cohort was longitudinally imaged weekly for 2 weeks. Metabolic tumor volume, lesion avidity, maximum standard uptake value, and total uptake metrics were calculated for both tracers. Immunohistochemistry was performed on representative tissue from all groups for LAT1 and glucose transporter-1 (GLUT1) expression. Results: Melphalan therapy induced a statistically significant reduction in lesion avidity and uptake metrics for both 18 F-FDG and 18 F-FDOPA. There was no visible effect on GLUT1 expression, but LAT1 density was increased in the week 2 therapy cohort. Longitudinal imaging of the week 3 group showed variable changes in 18 F-FDG and 18 F-FDOPA uptake, with increase in 18 F-FDOPA lesion avidity in the 2nd week relative to baseline. LAT1 and GLUT1 surface density in the untreated tumor and week 3 treatment group were qualitatively similar. Conclusion: 18 F-FDOPA-PET/CT served as a complementary method to 18 F-FDG-PET/CT in imaging melphalan therapy response in extramedullary preclinical MM. 18 F-FDOPA uptake was linked to LAT1 expression and melphalan response, with longitudinal imaging suggesting stabilization of LAT1 levels and melphalan tumor cytotoxicity. Future work will explore additional MM cell lines with heterogeneous LAT1 expression and response to melphalan therapy.  . Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

VizieR Online Data Catalog: Fermi LAT second source catalog (2FGL) (Nolan+, 2012)

NASA Astrophysics Data System (ADS)

Nolan, P. L.; Abdo, A. A.; Ackermann, M.; Ajello, M.; Allafort, A.; Antolini, E.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Belfiore, A.; Bellazzini, R.; Berenji, B.; Bignami, G. F.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Bonnell, J.; Borgland, A. W.; Bottacini, E.; Bouvier, A.; Brandt, T. J.; Bregeon, J.; Brigida, M.; Bruel, P.; Buehler, R.; Burnett, T. H.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Campana, R.; Canadas, B.; Cannon, A.; Caraveo, P. A.; Casandjian, J. M.; Cavazzuti, E.; Ceccanti, M.; Cecchi, C.; Celik, O.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Chipaux, R.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Cominsky, L. R.; Conrad, J.; Corbet, R.; Cutini, S.; D'Ammando, F.; Davis, D. S.; de Angelis, A.; Decesar, M. E.; Deklotz, M.; de Luca A.; den Hartog, P. R.; de Palma, F.; Dermer, C. D.; Digel, S. W.; Do Couto, E. Silva E.; Drell, P. S.; Drlica-Wagner, A.; Dubois, R.; Dumora, D.; Enoto, T.; Escande, L.; Fabiani, D.; Falletti, L.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Focke, W. B.; Fortin, P.; Frailis, M.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giebels, B.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Gustafsson, M.; Hadasch, D.; Hanabata, Y.; Harding, A. K.; Hayashida, M.; Hays, E.; Hill, A. B.; Horan, D.; Hou, X.; Hughes, R. E.; Iafrate, G.; Itoh, R.; Johannesson, G.; Johnson, R. P.; Johnson, T. E.; Johnson, A. S.; Johnson, T. J.; Kamae, T.; Katagiri, H.; Kataoka, J.; Katsuta, J.; Kawai, N.; Kerr, M.; Knodlseder, J.; Kocevski, D.; Kuss, M.; Lande, J.; Landriu, D.; Latronico, L.; Lemoine-Goumard, M.; Lionetto, A. M.; Llena Garde, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Madejski, G. M.; Marelli, M.; Massaro, E.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Mehault, J.; Michelson, P. F.; Minuti, M.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Mongelli, M.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Nakamori, T.; Naumann-God, O. M.; Norris, J. P.; Nuss, E.; Nymark, T.; Ohno, M.; Ohsugi, T.; Okumura, A.; Omodei, N.; Orlando, E.; Ormes, J. F.; Ozaki, M.; Paneque, D.; Panetta, J. H.; Parent, D.; Perkins, J. S.; Pesce-Rollins, M.; Pierbattista, M.; Pinchera, M.; Piron, F.; Pivato, G.; Porter, T. A.; Racusin, J. L.; Raino, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Reposeur, T.; Ritz, S.; Rochester, L. S.; Romani, R. W.; Roth, M.; Rousseau, R.; Ryde, F.; Sadrozinski, H. F.-W.; Salvetti, D.; Sanchez, D. A.; Saz Parkinson, P. M.; Sbarra, C.; Scargle, J. D.; Schalk, T. L.; Sgro, C.; Shaw, M. S.; Shrader, C.; Siskind, E. J.; Smith, D. A.; Spandre, G.; Spinelli, P.; Stephens, T. E.; Strickman, M. S.; Suson, D. J.; Tajima, H.; Takahashi, H.; Takahashi, T.; Tanaka, T.; Thayer, J. G.; Thayer, J. B.; Thompson, D. J.; Tibaldo, L.; Tibolla, O.; Tinebra, F.; Tinivella, M.; Torres, D. F.; Tosti, G.; Troja, E.; Uchiyama, Y.; Vandenbroucke, J.; van Etten, A.; van Klaveren, B.; Vasileiou, V.; Vianello, G.; Vitale, V.; Waite, A. P.; Wallace, E.; Wang, P.; Werner, M.; Winer, B. L.; Wood, D. L.; Wood, K. S.; Wood, M.; Yang, Z.; Zimmer, S.

2012-06-01

This paper presents a catalog of high-energy γ-ray sources detected, in the 100MeV-100GeV energy range, in the first two years of the Fermi Gamma-ray Space Telescope mission by the Large Area Telescope (LAT), during the period 2008 August 4 (15:43 UTC)-2010 August 1 (01:17 UTC). (4 data files).

High Energy Astrophysics with the Fermi Large Area Telescope

NASA Technical Reports Server (NTRS)

Hays, Elizabeth

2009-01-01

This slide presentation reviews some of the findings of the Large Area Telescope (LAT) aboard the Fermi Observatory. It includes information about the LAT, and the Gamma-Ray Burst Monitor (GBM), detection of the quiet sun and the moon in gamma rays, Pulsars observed by the observatory, Globular Star Clusters, Active Galactic Nucleus, and Gamma-Ray Bursts, with specific information about GRB 080916C.

75 FR 8285 - Establishment of Class D Airspace, Modification of Class E Airspace; Columbus, GA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... Army Airfield, Columbus, GA, would be removed from the Class E2 and E5 airspace description, and would... [NEW] Columbus Metropolitan Airport, GA (Lat. 32[deg]30[min]59[sec] N., long. 84[deg]56[min]20[sec] W... Columbus, GA [Amended] Columbus Metropolitan Airport, GA (Lat. 32[deg]30[min]59[sec] N., long. 84[deg]56...

78 FR 72001 - Amendment of Class D and E Airspace, and Establishment of Class E Airspace; Salisbury, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

...'' W.) That airspace extending upward from the surface to and including 2,500 feet MSL [[Page 72002...] Salisbury-Ocean City Wicomico Regional Airport, MD (Lat. 38[deg]20'25'' N., long. 75[deg]30'34'' W.) That... (Lat. 38[deg]20'25'' N., long. 75[deg]30'34'' W.) That airspace extending upward from the surface...

Historical evidence of the Spanish introduction of date palm (Phoenix dactylifera L., Arecaceae) into the Americas

USDA-ARS?s Scientific Manuscript database

America’s date palm (Phoenix dactylifera L.) groves can be found from 36o N Lat. (USA) to 21o S Lat. (Chile) and from 63o W Long. (Venezuela) to 117o W Long. (USA), at elevations from sea level 2000 m (Colombia). However, successful production of ripe dates is possible only in the arid regions of Pe...

Date palm (Phoenix dactylifera)dispersal to the Americas: Historical evidence of the Spanish introduction

USDA-ARS?s Scientific Manuscript database

Date palm (Phoenix dactylifera) groves are found in the Americas from the south-west USA (36°N lat.) to Chile (21°S lat.) and eastward to the Caribbean Islands; from Venezuela, 63°W long. to 117°W long. (USA) and at elevations from 0-2,000 m. However, successful production of ripe dates is possible ...

33 CFR 67.50-25 - Eighth Coast Guard District.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 27°00′ N., longitude 97°17′.5 W., thence to; (xxxii) A point at latitude 26°04′.1 N., longitude 97°08... Lat. 29°45′.6 N., Long. 93°13′.7 W., thence to; (xxxii) A point at Lat. 29°45′.6 N., Long. 93°17′.3 W...

50 CFR 635.69 - Vessel monitoring systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... operator of a commercial vessel, permitted to fish for Atlantic HMS under § 635.4 and that fishes with a... directed shark LAP, is away from port with bottom longline gear on board, is located between 33°00′ N. lat. and 36°30′ N. lat., and the mid-Atlantic shark closed area is closed as specified in § 635.21(d)(1...

50 CFR 635.69 - Vessel monitoring systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... operator of a commercial vessel, permitted to fish for Atlantic HMS under § 635.4 and that fishes with a... directed shark LAP, is away from port with bottom longline gear on board, is located between 33°00′ N. lat. and 36°30′ N. lat., and the mid-Atlantic shark closed area is closed as specified in § 635.21(d)(1...

FERMI LARGE AREA TELESCOPE VIEW OF THE CORE OF THE RADIO GALAXY CENTAURUS A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdo, A. A.; Ackermann, M.; Ajello, M.

2010-08-20

We present {gamma}-ray observations with the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope of the nearby radio galaxy Centaurus A (Cen A). The previous EGRET detection is confirmed, and the localization is improved using data from the first 10 months of Fermi science operation. In previous work, we presented the detection of the lobes by the LAT; in this work, we concentrate on the {gamma}-ray core of Cen A. Flux levels as seen by the LAT are not significantly different from that found by EGRET, nor is the extremely soft LAT spectrum ({Gamma} = 2.67 {+-}more » 0.10{sub stat} {+-} 0.08{sub sys} where the photon flux is {Phi} {proportional_to} E {sup -{Gamma}}). The LAT core spectrum, extrapolated to higher energies, is marginally consistent with the non-simultaneous HESS spectrum of the source. The LAT observations are complemented by simultaneous observations from Suzaku, the Swift Burst Alert Telescope and X-ray Telescope, and radio observations with the Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry program, along with a variety of non-simultaneous archival data from a variety of instruments and wavelengths to produce a spectral energy distribution (SED). We fit this broadband data set with a single-zone synchrotron/synchrotron self-Compton model, which describes the radio through GeV emission well, but fails to account for the non-simultaneous higher energy TeV emission observed by HESS from 2004 to 2008. The fit requires a low Doppler factor, in contrast to BL Lac objects which generally require larger values to fit their broadband SEDs. This indicates that the {gamma}-ray emission originates from a slower region than that from BL Lac objects, consistent with previous modeling results from Cen A. This slower region could be a slower moving layer around a fast spine, or a slower region farther out from the black hole in a decelerating flow. The fit parameters are also consistent with Cen A being able to accelerate ultra-high energy cosmic-rays, as hinted at by results from the Auger observatory.« less

Fermi Large Area Telescope View of the Core of the Radio Galaxy Centaurus A

NASA Astrophysics Data System (ADS)

Abdo, A. A.; Ackermann, M.; Ajello, M.; Atwood, W. B.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Baughman, B. M.; Bechtol, K.; Bellazzini, R.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Borgland, A. W.; Bouvier, A.; Brandt, T. J.; Bregeon, J.; Brez, A.; Brigida, M.; Bruel, P.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Cannon, A.; Caraveo, P. A.; Carrigan, S.; Casandjian, J. M.; Cavazzuti, E.; Cecchi, C.; Çelik, Ö.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Colafrancesco, S.; Cominsky, L. R.; Conrad, J.; Costamante, L.; Davis, D. S.; Dermer, C. D.; de Angelis, A.; de Palma, F.; Silva, E. do Couto e.; Drell, P. S.; Dubois, R.; Dumora, D.; Falcone, A.; Farnier, C.; Favuzzi, C.; Fegan, S. J.; Finke, J.; Focke, W. B.; Fortin, P.; Frailis, M.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Georganopoulos, M.; Germani, S.; Giebels, B.; Giglietto, N.; Giommi, P.; Giordano, F.; Giroletti, M.; Glanzman, T.; Godfrey, G.; Grandi, P.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Hadasch, D.; Harding, A. K.; Hase, Hayo; Hayashida, M.; Hays, E.; Horan, D.; Hughes, R. E.; Itoh, R.; Jackson, M. S.; Jóhannesson, G.; Johnson, A. S.; Johnson, T. J.; Johnson, W. N.; Kadler, M.; Kamae, T.; Katagiri, H.; Kataoka, J.; Kawai, N.; Kishishita, T.; Knödlseder, J.; Kuss, M.; Lande, J.; Latronico, L.; Lee, S.-H.; Lemoine-Goumard, M.; Llena Garde, M.; Longo, F.; Loparco, F.; Lott, B.; Lovellette, M. N.; Lubrano, P.; Makeev, A.; Mazziotta, M. N.; McConville, W.; McEnery, J. E.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Moiseev, A. A.; Monte, C.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Müller, C.; Nakamori, T.; Naumann-Godo, M.; Nolan, P. L.; Norris, J. P.; Nuss, E.; Ohno, M.; Ohsugi, T.; Ojha, R.; Okumura, A.; Omodei, N.; Orlando, E.; Ormes, J. F.; Ozaki, M.; Pagani, C.; Paneque, D.; Panetta, J. H.; Parent, D.; Pelassa, V.; Pepe, M.; Pesce-Rollins, M.; Piron, F.; Plötz, C.; Porter, T. A.; Rainò, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Reposeur, T.; Ripken, J.; Ritz, S.; Rodriguez, A. Y.; Roth, M.; Ryde, F.; Sadrozinski, H. F.-W.; Sanchez, D.; Sander, A.; Scargle, J. D.; Sgrò, C.; Siskind, E. J.; Smith, P. D.; Spandre, G.; Spinelli, P.; Starck, J.-L.; Stawarz, L.; Strickman, M. S.; Suson, D. J.; Tajima, H.; Takahashi, H.; Takahashi, T.; Tanaka, T.; Thayer, J. B.; Thayer, J. G.; Thompson, D. J.; Tibaldo, L.; Torres, D. F.; Tosti, G.; Tramacere, A.; Uchiyama, Y.; Usher, T. L.; Vandenbroucke, J.; Vasileiou, V.; Vilchez, N.; Vitale, V.; Waite, A. P.; Wang, P.; Winer, B. L.; Wood, K. S.; Yang, Z.; Ylinen, T.; Ziegler, M.

2010-08-01

We present γ-ray observations with the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope of the nearby radio galaxy Centaurus A (Cen A). The previous EGRET detection is confirmed, and the localization is improved using data from the first 10 months of Fermi science operation. In previous work, we presented the detection of the lobes by the LAT; in this work, we concentrate on the γ-ray core of Cen A. Flux levels as seen by the LAT are not significantly different from that found by EGRET, nor is the extremely soft LAT spectrum (Γ = 2.67 ± 0.10stat ± 0.08sys where the photon flux is Φ vprop E -Γ). The LAT core spectrum, extrapolated to higher energies, is marginally consistent with the non-simultaneous HESS spectrum of the source. The LAT observations are complemented by simultaneous observations from Suzaku, the Swift Burst Alert Telescope and X-ray Telescope, and radio observations with the Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry program, along with a variety of non-simultaneous archival data from a variety of instruments and wavelengths to produce a spectral energy distribution (SED). We fit this broadband data set with a single-zone synchrotron/synchrotron self-Compton model, which describes the radio through GeV emission well, but fails to account for the non-simultaneous higher energy TeV emission observed by HESS from 2004 to 2008. The fit requires a low Doppler factor, in contrast to BL Lac objects which generally require larger values to fit their broadband SEDs. This indicates that the γ-ray emission originates from a slower region than that from BL Lac objects, consistent with previous modeling results from Cen A. This slower region could be a slower moving layer around a fast spine, or a slower region farther out from the black hole in a decelerating flow. The fit parameters are also consistent with Cen A being able to accelerate ultra-high energy cosmic-rays, as hinted at by results from the Auger observatory.

Legal assessment tool (LAT): an interactive tool to address privacy and data protection issues for data sharing.

PubMed

Kuchinke, Wolfgang; Krauth, Christian; Bergmann, René; Karakoyun, Töresin; Woollard, Astrid; Schluender, Irene; Braasch, Benjamin; Eckert, Martin; Ohmann, Christian

2016-07-07

In an unprecedented rate data in the life sciences is generated and stored in many different databases. An ever increasing part of this data is human health data and therefore falls under data protected by legal regulations. As part of the BioMedBridges project, which created infrastructures that connect more than 10 ESFRI research infrastructures (RI), the legal and ethical prerequisites of data sharing were examined employing a novel and pragmatic approach. We employed concepts from computer science to create legal requirement clusters that enable legal interoperability between databases for the areas of data protection, data security, Intellectual Property (IP) and security of biosample data. We analysed and extracted access rules and constraints from all data providers (databases) involved in the building of data bridges covering many of Europe's most important databases. These requirement clusters were applied to five usage scenarios representing the data flow in different data bridges: Image bridge, Phenotype data bridge, Personalised medicine data bridge, Structural data bridge, and Biosample data bridge. A matrix was built to relate the important concepts from data protection regulations (e.g. pseudonymisation, identifyability, access control, consent management) with the results of the requirement clusters. An interactive user interface for querying the matrix for requirements necessary for compliant data sharing was created. To guide researchers without the need for legal expert knowledge through legal requirements, an interactive tool, the Legal Assessment Tool (LAT), was developed. LAT provides researchers interactively with a selection process to characterise the involved types of data and databases and provides suitable requirements and recommendations for concrete data access and sharing situations. The results provided by LAT are based on an analysis of the data access and sharing conditions for different kinds of data of major databases in Europe. Data sharing for research purposes must be opened for human health data and LAT is one of the means to achieve this aim. In summary, LAT provides requirements in an interactive way for compliant data access and sharing with appropriate safeguards, restrictions and responsibilities by introducing a culture of responsibility and data governance when dealing with human data.

Runx1t1 (Runt-Related Transcription Factor 1; Translocated to, 1) Epigenetically Regulates the Proliferation and Nitric Oxide Production of Microglia

PubMed Central

Baby, Nimmi; Li, Yali; Ling, Eng-Ang; Lu, Jia; Dheen, S. Thameem

2014-01-01

Background Microglia, the resident immune cells of the brain, undergo rapid proliferation and produce several proinflammatory molecules and nitric oxide (NO) when activated in neuropathological conditions. Runx1t1 (Runt-related transcription factor 1, translocated to 1) has been implicated in recruiting histone deacetylases (HDACs) for transcriptional repression, thereby regulating cell proliferation. In the present study, Runx1t1 expression was shown to localize in amoeboid microglial cells of the postnatal rat brain, being hardly detectable in ramified microglia of the adult brain. Moreover, a marked expression of Runx1t1was induced and translocated to nuclei in activated microglia in vitro and in vivo. In view of these findings, it was hypothesized that Runx1t1 regulates microglial functions during development and in neuropathological conditions. Methods and Findings siRNA-mediated knockdown of Runx1t1 significantly decreased the expression level of cell cycle-related gene, cyclin-dependent kinase 4 (Cdk4) and proliferation index in activated BV2 microglia. It was also shown that HDAC inhibitor (HDACi) treatment mimics the effects of Runx1t1 knockdown on microglial proliferation, confirming that microglial proliferation is associated with Runx1t1 expression and HDACs activity. Further, Runx1t1 and HDACs were shown to promote neurotoxic effect of microglia by repressing expression of LAT2, L-aminoacid transporter-2 (cationic amino acid transporter, y+ system), which normally inhibits NO production. This was confirmed by chromatin immunoprecipitation (ChIP) assay, which revealed that Runx1t1 binds to the promoter region of LAT2 and this binding increased upon microglial activation. However, the enhanced binding of Runx1t1 to the LAT2 promoter could not repress the LAT2 expression when the BV2 microglia cells were treated with HDACi, indicating that Runx1t1 requires HDACs to transcriptionally repress the expression of LAT2. Conclusion/Interpretation In conclusion, it is suggested that Runx1t1 controls proliferation and the neurotoxic effect of microglia by epigenetically regulating Cdk4 and LAT2 via its interaction with HDACs. PMID:24586690

FERMI Large Area Telescope View of the 1 Core of the Radio Galaxy Centaurus A

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2010-07-29

We present γ-ray observations with the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope of the nearby radio galaxy Centaurus A (Cen A). The previous EGRET detection is confirmed, and the localization is improved using data from the first 10 months of Fermi science operation. In previous work, we presented the detection of the lobes by the LAT; in this work, we concentrate on the γ-ray core of Cen A. Flux levels as seen by the LAT are not significantly different from that found by EGRET, nor is the extremely soft LAT spectrum (Γ = 2.67 ±more » 0.10 stat ± 0.08 sys where the photon flux is Φ ∝ E –Γ). The LAT core spectrum, extrapolated to higher energies, is marginally consistent with the non-simultaneous HESS spectrum of the source. The LAT observations are complemented by simultaneous observations from Suzaku, the Swift Burst Alert Telescope and X-ray Telescope, and radio observations with the Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry program, along with a variety of non-simultaneous archival data from a variety of instruments and wavelengths to produce a spectral energy distribution (SED). Here, we fit this broadband data set with a single-zone synchrotron/synchrotron self-Compton model, which describes the radio through GeV emission well, but fails to account for the non-simultaneous higher energy TeV emission observed by HESS from 2004 to 2008. The fit requires a low Doppler factor, in contrast to BL Lac objects which generally require larger values to fit their broadband SEDs. This indicates that the γ-ray emission originates from a slower region than that from BL Lac objects, consistent with previous modeling results from Cen A. This slower region could be a slower moving layer around a fast spine, or a slower region farther out from the black hole in a decelerating flow. The fit parameters are also consistent with Cen A being able to accelerate ultra-high energy cosmic-rays, as hinted at by results from the Auger observatory.« less

2005 v4.3 Technical Support Document

EPA Pesticide Factsheets

Emissions Modeling for the Final Mercury and Air Toxics Standards Technical Support Document describes how updated 2005 NEI, version 2 emissions were processed for air quality modeling in support of the final Mercury and Air Toxics Standards (MATS).

The Center for Space Telemetering and Telecommunications Systems

NASA Technical Reports Server (NTRS)

Horan, S.; DeLeon, P.; Borah, D.; Lyman, R.

2003-01-01

This report comprises the final technical report for the research grant 'Center for Space Telemetering and Telecommunications Systems' sponsored by the National Aeronautics and Space Administration's Goddard Space Flight Center. The grant activities are broken down into the following technology areas: (1) Space Protocol Testing; (2) Autonomous Reconfiguration of Ground Station Receivers; (3) Satellite Cluster Communications; and (4) Bandwidth Efficient Modulation. The grant activity produced a number of technical reports and papers that were communicated to NASA as they were generated. This final report contains the final summary papers or final technical report conclusions for each of the project areas. Additionally, the grant supported students who made progress towards their degrees while working on the research.

HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation.

PubMed

Abraham, Libin; Bankhead, Peter; Pan, Xiaoyu; Engel, Ulrike; Fackler, Oliver T

2012-08-15

Signal initiation by engagement of the TCR triggers actin rearrangements, receptor clustering, and dynamic organization of signaling complexes to elicit and sustain downstream signaling. Nef, a pathogenicity factor of HIV, disrupts early TCR signaling in target T cells. To define the mechanism underlying this Nef-mediated signal disruption, we employed quantitative single-cell microscopy following surface-mediated TCR stimulation that allows for dynamic visualization of distinct signaling complexes as microclusters (MCs). Despite marked inhibition of actin remodeling and cell spreading, the induction of MCs containing TCR-CD3 or ZAP70 was not affected significantly by Nef. However, Nef potently inhibited the subsequent formation of MCs positive for the signaling adaptor Src homology-2 domain-containing leukocyte protein of 76 kDa (SLP-76) to reduce MC density in Nef-expressing and HIV-1-infected T cells. Further analyses suggested that Nef prevents formation of SLP-76 MCs at the level of the upstream adaptor protein, linker of activated T cells (LAT), that couples ZAP70 to SLP-76. Nef did not disrupt pre-existing MCs positive for LAT. However, the presence of the viral protein prevented de novo recruitment of active LAT into MCs due to retargeting of LAT to an intracellular compartment. These modulations in MC formation and composition depended on Nef's ability to simultaneously disrupt both actin remodeling and subcellular localization of TCR-proximal machinery. Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs.

Constraining the High-Energy Emission from Gamma-Ray Bursts with Fermi

NASA Technical Reports Server (NTRS)

Gehrels, Neil; Harding, A. K.; Hays, E.; Racusin, J. L.; Sonbas, E.; Stamatikos, M.; Guirec, S.

2012-01-01

We examine 288 GRBs detected by the Fermi Gamma-ray Space Telescope's Gamma-ray Burst Monitor (GBM) that fell within the field-of-view of Fermi's Large Area Telescope (LAT) during the first 2.5 years of observations, which showed no evidence for emission above 100 MeV. We report the photon flux upper limits in the 0.1-10 GeV range during the prompt emission phase as well as for fixed 30 s and 100 s integrations starting from the trigger time for each burst. We compare these limits with the fluxes that would be expected from extrapolations of spectral fits presented in the first GBM spectral catalog and infer that roughly half of the GBM-detected bursts either require spectral breaks between the GBM and LAT energy bands or have intrinsically steeper spectra above the peak of the nuF(sub v) spectra (E(sub pk)). In order to distinguish between these two scenarios, we perform joint GBM and LAT spectral fits to the 30 brightest GBM-detected bursts and find that a majority of these bursts are indeed softer above E(sub pk) than would be inferred from fitting the GBM data alone. Approximately 20% of this spectroscopic subsample show statistically significant evidence for a cut-off in their high-energy spectra, which if assumed to be due to gamma gamma attenuation, places limits on the maximum Lorentz factor associated with the relativistic outflow producing this emission. All of these latter bursts have maximum Lorentz factor estimates that are well below the minimum Lorentz factors calculated for LAT-detected GRBs, revealing a wide distribution in the bulk Lorentz factor of GRB outflows and indicating that LAT-detected bursts may represent the high end of this distribution.

Fermi-LAT upper limits on gamma-ray emission from colliding wind binaries

DOE PAGES

Werner, Michael; Reimer, O.; Reimer, A.; ...

2013-07-09

Here, colliding wind binaries (CWBs) are thought to give rise to a plethora of physical processes including acceleration and interaction of relativistic particles. Observation of synchrotron radiation in the radio band confirms there is a relativistic electron population in CWBs. Accordingly, CWBs have been suspected sources of high-energy γ-ray emission since the COS-B era. Theoretical models exist that characterize the underlying physical processes leading to particle acceleration and quantitatively predict the non-thermal energy emission observable at Earth. Furthermore, we strive to find evidence of γ-ray emission from a sample of seven CWB systems: WR 11, WR 70, WR 125, WRmore » 137, WR 140, WR 146, and WR 147. Theoretical modelling identified these systems as the most favourable candidates for emitting γ-rays. We make a comparison with existing γ-ray flux predictions and investigate possible constraints. We used 24 months of data from the Large Area Telescope (LAT) on-board the Fermi Gamma Ray Space Telescope to perform a dedicated likelihood analysis of CWBs in the LAT energy range. As a result, we find no evidence of γ-ray emission from any of the studied CWB systems and determine corresponding flux upper limits. For some CWBs the interplay of orbital and stellar parameters renders the Fermi-LAT data not sensitive enough to constrain the parameter space of the emission models. In the cases of WR140 and WR147, the Fermi -LAT upper limits appear to rule out some model predictions entirely and constrain theoretical models over a significant parameter space. A comparison of our findings to the CWB η Car is made.« less

Constraining the high-energy emission from gamma-ray bursts with Fermi

DOE PAGES

Ackermann, M.; Ajello, M.; Baldini, L.; ...

2012-07-17

Here, we examine 288 gamma-ray bursts (GRBs) detected by the Fermi Gamma-ray Space Telescope's Gamma-ray Burst Monitor (GBM) that fell within the field of view of Fermi's Large Area Telescope (LAT) during the first 2.5 years of observations, which showed no evidence for emission above 100 MeV. We report the photon flux upper limits in the 0.1-10 GeV range during the prompt emission phase as well as for fixed 30 s and 100 s integrations starting from the trigger time for each burst. We also compare these limits with the fluxes that would be expected from extrapolations of spectral fitsmore » presented in the first GBM spectral catalog and infer that roughly half of the GBM-detected bursts either require spectral breaks between the GBM and LAT energy bands or have intrinsically steeper spectra above the peak of the νF ν spectra (E pk). In order to distinguish between these two scenarios, we perform joint GBM and LAT spectral fits to the 30 brightest GBM-detected bursts and find that a majority of these bursts are indeed softer above E pk than would be inferred from fitting the GBM data alone. Approximately 20% of this spectroscopic subsample show statistically significant evidence for a cutoff in their high-energy spectra, which if assumed to be due to γγ attenuation, places limits on the maximum Lorentz factor associated with the relativistic outflow producing this emission. Furthermore, all of these latter bursts have maximum Lorentz factor estimates that are well below the minimum Lorentz factors calculated for LAT-detected GRBs, revealing a wide distribution in the bulk Lorentz factor of GRB outflows and indicating that LAT-detected bursts may represent the high end of this distribution.« less

Detergent-Induced Stabilization and Improved 3D Map of the Human Heteromeric Amino Acid Transporter 4F2hc-LAT2

PubMed Central

Harder, Daniel; Stauffer, Mirko; Jeckelmann, Jean-Marc; Brühlmann, Béla; Rosell, Albert; Ilgü, Hüseyin; Kovar, Karin; Palacín, Manuel; Fotiadis, Dimitrios

2014-01-01

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level. PMID:25299125

Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.

PubMed

Meury, Marcel; Costa, Meritxell; Harder, Daniel; Stauffer, Mirko; Jeckelmann, Jean-Marc; Brühlmann, Béla; Rosell, Albert; Ilgü, Hüseyin; Kovar, Karin; Palacín, Manuel; Fotiadis, Dimitrios

2014-01-01

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level.

Fermi/LAT observations of lobe-dominant radio galaxy 3C 207 and possible radiation region of γ-rays

NASA Astrophysics Data System (ADS)

Guo, Sheng-Chu; Zhang, Hai-Ming; Zhang, Jin; Liang, En-Wei

2018-06-01

3C 207 is a lobe-dominant radio galaxy with a one sided jet and bright knots, spanning a kpc-Mpc scale, which have been resolved in the radio, optical and X-ray bands. This target was confirmed as a γ-ray emitter with Fermi/LAT, but it is uncertain whether the γ-ray emission region is the core or knots due to the low spatial resolution of Fermi/LAT. We present an analysis of its Fermi/LAT data acquired during the past 9 years. Different from the radio and optical emission from the core, it is found that the γ-ray emission is steady without detection of flux variation at over a 2σ confidence level. This likely implies that the γ-ray emission is from its knots. We collect the radio, optical and X-ray data of knot-A, the closest knot from the core at 1.4″, and compile its spectral energy distribution (SED). Although the single-zone synchrotron+SSC+IC/CMB model that assumes knot-A is at rest can reproduce the SED in the radio-optical-X-ray band, the predicted γ-ray flux is lower than the LAT observations and the derived magnetic field strength deviates from the equipartition condition by 3 orders of magnitude. Assuming that knot-A is moving relativistically, its SED from radio to γ-ray bands would be represented well with the single-zone synchrotron+SSC+IC/CMB model under the equipartition condition. These results likely suggest that the γ-ray emission may be from knot-A via the IC/CMB process and the knot should have relativistical motion. The jet power derived from our model parameters is also roughly consistent with the kinetic power estimated with radio data.

FERMI Observations of GRB 090902B: A Distinct Spectral Component in the Prompt and Delayed Emission

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-11-03

Here, we report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. This was one of the brightest GRBs to have been observed by the LAT, which detected several hundred photons during the prompt phase. With a redshift of z = 1.822, this burst is among the most luminous detected by Fermi. Time-resolved spectral analysis reveals a significant power-law component in the LAT data that is distinct from the usual Band model emission that is seen in the sub-MeV energy range.more » This power-law component appears to extrapolate from the GeV range to the lowest energies and is more intense than the Band component, both below ~50 keV and above 100 MeV. The Band component undergoes substantial spectral evolution over the entire course of the burst, while the photon index of the power-law component remains constant for most of the prompt phase, then hardens significantly toward the end. After the prompt phase, power-law emission persists in the LAT data as late as 1 ks post-trigger, with its flux declining as t –1.5. The LAT detected a photon with the highest energy so far measured from a GRB, 33.4 +2.7 –3.5 GeV. This event arrived 82 s after the GBM trigger and ~50 s after the prompt phase emission had ended in the GBM band. In conclusion, we discuss the implications of these results for models of GRB emission and for constraints on models of the extragalactic background light.« less

Fermi Large Area Telescope detection of two very-high-energy ( E > 100 GeV) γ-ray photons from the z = 1.1 blazar PKS 0426–380

DOE PAGES

Tanaka, Y. T.; Cheung, C. C.; Inoue, Y.; ...

2013-10-18

Here, we report the Fermi Large Area Telescope (LAT) detection of two very-high-energy (VHE, E > 100 GeV) γ-ray photons from the directional vicinity of the distant (redshift, z = 1.1) blazar PKS 0426–380. The null hypothesis that both the 134 and 122 GeV photons originate from unrelated sources can be rejected at the 5.5σ confidence level. We therefore claim that at least one of the two VHE photons is securely associated with PKS 0426–380, making it the most distant VHE emitter known to date. The results are in agreement with recent Fermi-LAT constraints on the extragalactic background light (EBL)more » intensity, which imply a z sime 1 horizon for sime 100 GeV photons. The LAT detection of the two VHE γ-rays coincided roughly with flaring states of the source, although we did not find an exact correspondence between the VHE photon arrival times and the flux maxima at lower γ-ray energies. Modeling the γ-ray continuum of PKS 0426–380 with daily bins revealed a significant spectral hardening around the time of the first VHE event detection (LAT photon index Γ sime 1.4) but on the other hand no pronounced spectral changes near the detection time of the second one. This combination implies a rather complex variability pattern of the source in γ-rays during the flaring epochs. An additional flat component is possibly present above several tens of GeV in the EBL-corrected Fermi-LAT spectrum accumulated over the ~8 month high state.« less

Constraining the High-energy Emission from Gamma-Ray Bursts with Fermi

NASA Astrophysics Data System (ADS)

Fermi Large Area Telescope Team; Ackermann, M.; Ajello, M.; Baldini, L.; Barbiellini, G.; Baring, M. G.; Bechtol, K.; Bellazzini, R.; Blandford, R. D.; Bloom, E. D.; Bonamente, E.; Borgland, A. W.; Bottacini, E.; Bouvier, A.; Brigida, M.; Buehler, R.; Buson, S.; Caliandro, G. A.; Cameron, R. A.; Cecchi, C.; Charles, E.; Chekhtman, A.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Cutini, S.; D'Ammando, F.; de Palma, F.; Dermer, C. D.; Silva, E. do Couto e.; Drell, P. S.; Drlica-Wagner, A.; Favuzzi, C.; Fukazawa, Y.; Fusco, P.; Gargano, F.; Gasparrini, D.; Gehrels, N.; Germani, S.; Giglietto, N.; Giordano, F.; Giroletti, M.; Glanzman, T.; Granot, J.; Grenier, I. A.; Grove, J. E.; Hadasch, D.; Hanabata, Y.; Harding, A. K.; Hays, E.; Horan, D.; Jóhannesson, G.; Kataoka, J.; Knödlseder, J.; Kocevski, D.; Kuss, M.; Lande, J.; Longo, F.; Loparco, F.; Lovellette, M. N.; Lubrano, P.; Mazziotta, M. N.; McEnery, J.; McGlynn, S.; Michelson, P. F.; Mitthumsiri, W.; Monzani, M. E.; Moretti, E.; Morselli, A.; Moskalenko, I. V.; Murgia, S.; Naumann-Godo, M.; Norris, J. P.; Nuss, E.; Nymark, T.; Ohsugi, T.; Okumura, A.; Omodei, N.; Orlando, E.; Panetta, J. H.; Parent, D.; Pelassa, V.; Pesce-Rollins, M.; Piron, F.; Pivato, G.; Racusin, J. L.; Rainò, S.; Rando, R.; Razzaque, S.; Reimer, A.; Reimer, O.; Ritz, S.; Ryde, F.; Sgrò, C.; Siskind, E. J.; Sonbas, E.; Spandre, G.; Spinelli, P.; Stamatikos, M.; Stawarz, Łukasz; Suson, D. J.; Takahashi, H.; Tanaka, T.; Thayer, J. G.; Thayer, J. B.; Tibaldo, L.; Tinivella, M.; Tosti, G.; Uehara, T.; Vandenbroucke, J.; Vasileiou, V.; Vianello, G.; Vitale, V.; Waite, A. P.; Fermi Gamma-ray Burst Monitor Team; Connaughton, V.; Briggs, M. S.; Guirec, S.; Goldstein, A.; Burgess, J. M.; Bhat, P. N.; Bissaldi, E.; Camero-Arranz, A.; Fishman, J.; Fitzpatrick, G.; Foley, S.; Gruber, D.; Jenke, P.; Kippen, R. M.; Kouveliotou, C.; McBreen, S.; Meegan, C.; Paciesas, W. S.; Preece, R.; Rau, A.; Tierney, D.; van der Horst, A. J.; von Kienlin, A.; Wilson-Hodge, C.; Xiong, S.

2012-08-01

We examine 288 gamma-ray bursts (GRBs) detected by the Fermi Gamma-ray Space Telescope's Gamma-ray Burst Monitor (GBM) that fell within the field of view of Fermi's Large Area Telescope (LAT) during the first 2.5 years of observations, which showed no evidence for emission above 100 MeV. We report the photon flux upper limits in the 0.1-10 GeV range during the prompt emission phase as well as for fixed 30 s and 100 s integrations starting from the trigger time for each burst. We compare these limits with the fluxes that would be expected from extrapolations of spectral fits presented in the first GBM spectral catalog and infer that roughly half of the GBM-detected bursts either require spectral breaks between the GBM and LAT energy bands or have intrinsically steeper spectra above the peak of the νF ν spectra (E pk). In order to distinguish between these two scenarios, we perform joint GBM and LAT spectral fits to the 30 brightest GBM-detected bursts and find that a majority of these bursts are indeed softer above E pk than would be inferred from fitting the GBM data alone. Approximately 20% of this spectroscopic subsample show statistically significant evidence for a cutoff in their high-energy spectra, which if assumed to be due to γγ attenuation, places limits on the maximum Lorentz factor associated with the relativistic outflow producing this emission. All of these latter bursts have maximum Lorentz factor estimates that are well below the minimum Lorentz factors calculated for LAT-detected GRBs, revealing a wide distribution in the bulk Lorentz factor of GRB outflows and indicating that LAT-detected bursts may represent the high end of this distribution.

Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

PubMed Central

Jones, Clinton

2013-01-01

α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts. PMID:25278776

Promotion of the Equal Access of Girls and Women to Technical and Vocational Education. Studies on Technical and Vocational Education 7.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

This monograph includes the final report of the International Expert Meeting on the Promotion of Equal Access of Girls and Women to Technical and Vocational Education (TVE) held in Seoul, Republic of Korea, and country discussion papers. The final report is composed of an introduction that proposes that many Member States require special measures…

Air Quality Modeling Technical Support Document for the Final Cross State Air Pollution Rule Update

EPA Pesticide Factsheets

In this technical support document (TSD) we describe the air quality modeling performed to support the final Cross State Air Pollution Rule for the 2008 ozone National Ambient Air Quality Standards (NAAQS).

Decline and decadence in Iraq and Syria after the age of Avicenna? 'Abd al-Latīf al-Baghdādī (1162-1231) between myth and history.

PubMed

Joosse, N Peter; Pormann, Peter E

2010-01-01

'Abd al-Latīf al-Baghdādī's (d. 1231) work Book of the Two Pieces of Advice (Kitāb al Nasīhatayn) challenges the idea that Islamic medicine declined after the twelfth century AD. Moreover, it offers some interesting insights into the social history of medicine. 'Abd al-Latīf advocated using the framework of Greek medical epistemology to criticize the rationalist physicians of his day; he argued that female and itinerant practitioners, relying on experience, were superior to some rationalists. He lambasted contemporaneous medical education because it put too much faith in a restricted number of textbooks such as the Canon by Ibn Sīnā (Avicenna, d. 1037) or imperfect abridgments.

Fermi-LAT View of Bright Flaring Gamma-Ray Blazars

NASA Astrophysics Data System (ADS)

Bastieri, D.; Ciprini, S.; Gasparrini, D.

2011-06-01

The Fermi LAT provides a continuous and uniform monitoring of the Universe in the gamma-ray band. During the first year many gamma-ray blazar flares, some unidentified transients and emission by the Sun while in a quiet state were promptly detected. This is mainly due to the design of the mission, featuring a detector, the LAT with a wide field of view, and to the operation of the spacecraft itself, that can cover every region of the sky every 3 hours. Nevertheless, the scientific exploitation of this monitoring is more fruitful when early information about transients reaches a broader community. In this respect, the indefatigable activity of flare advocates, who worked on weekly shifts to validate the results and quickly broadcast information about flares and new detections, was the key to most scientific results.

Studies on the seasonal variation of atmospheric electricity parameters at a tropical station in Kolkata, India

NASA Astrophysics Data System (ADS)

De, S. S.; Paul, Suman; Barui, S.; Pal, Pinaki; Bandyopadhyay, B.; Kala, D.; Ghosh, A.

2013-12-01

The paper deals with the analyses of the atmospheric vertical potential gradient (PG) from the ground for 90 fair weather days during 2006-2009 measured at Kolkata (Lat: 22.56°N). The variations of PG have been studied extensively to investigate their values during monsoon and winter seasons. Higher values of PG at Kolkata are observed due to higher abundance of pollutant particles. The observed PG are compared with the results of Potsdam station (Lat: 52°N) and Johannesburg station (Lat: 26°S), with 9 years data and 2 years data respectively. The correlations studies are carried out among PG, PDC (Point Discharge Current) as well as negative and positive carrier conductivities. The corresponding correlation coefficients are obtained as 0.93, -0.842 and -0.844.

7 CFR 614.7 - Preliminary technical determinations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Preliminary technical determinations. 614.7 Section... Preliminary technical determinations. (a) A preliminary technical determination becomes final 30 days after... purpose of gathering additional information and discussing the facts relating to the preliminary technical...

LatMix 2011 and 2012 Dispersion Analysis

DTIC Science & Technology

2015-09-30

work included the airborne lidar operations as well as a substantial part of the field operations and analysis. A primary objective of our LatMix... lidar ) surveys of evolving dye experiments as a tool for studying submesoscale lateral dispersion. 2 Numerous papers by our group relating to the...drifter / lidar effort, however, there are additional aspects of the data and analysis that are beyond the scope of these already-in-progress

76 FR 47060 - Amendment of Class D and Class E Airspace; Columbus Lawson AAF, GA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... Lawson AAF, GA [Amended] Columbus Lawson AAF, GA (Lat. 32[deg]19'55'' N., long 84[deg]59'14'' W.) That... * * * * * ASO GA E2 Columbus Lawson AAF, GA [Amended] Columbus Lawson AAF, GA (Lat. 32[deg]19'55'' N., long. 84...-0012; Airspace Docket No. 10-ASO-44] Amendment of Class D and Class E Airspace; Columbus Lawson AAF, GA...

78 FR 52109 - Proposed Amendment of Class D and E Airspace, and Establishment of Class E Airspace; Salisbury, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-22

...]30'34'' W.) That airspace extending upward from the surface within 2.5 miles each side of a 133[deg...-Ocean City Wicomico Regional Airport, MD (Lat. 38[deg]20'25'' N., long. 75[deg]30'34'' W.) That airspace... (Lat. 38[deg]20'25'' N., long. 75[deg]30'34'' W.) That airspace extending upward from the surface...

The Canada–France Ecliptic Plane Survey (CFEPS)—High-latitude Component

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petit, J-M.; Kavelaars, J. J.; Gladman, B. J.

The High Ecliptic Latitude (HiLat) extension of the Canada–France Ecliptic Plane Survey (CFEPS), conducted from 2006 June to 2009 July, discovered a set of Trans-Neptunian objects (TNOs) that we report here. The HiLat component was designed to address one of the shortcomings of ecliptic surveys (like CFEPS), their low sensitivity to high-inclination objects. We searched 701 deg{sup 2} of sky ranging from 12° to 85° ecliptic latitude and discovered 24 TNOs, with inclinations between 15° and 104°. This survey places a very strong constraint on the inclination distribution of the hot component of the classical Kuiper Belt, ruling out any possibilitymore » of a large intrinsic fraction of highly inclined orbits. Using the parameterization of Brown, the HiLat sample combined with CFEPS imposes a width 14° ≤  σ  ≤ 15.°5, with a best match for σ  = 14.°5. HiLat discovered the first retrograde TNO, 2008 KV{sub 42}, with an almost polar orbit with inclination 104°, and (418993) = 2009 MS{sub 9}, a scattering object with perihelion in the region of Saturn’s influence, with a  ∼ 400 au and i  = 68°.« less

Five Years of the Fermi LAT Flare Advocate

NASA Astrophysics Data System (ADS)

Carpenter, Bryce; Ojha, R.; Gasparrini, D.; Ciprini, S.; Fermi LAT Collaboration; Fermi LAT Flare Advocates

2014-01-01

Since the launch of the Fermi satellite, the Fermi Large Area Telescope (LAT) team has run a program that provides a daily review of the the gamma-ray sky as soon as Fermi LAT data becomes available. The Flare Advocate/Gamma-ray Sky Watcher (FA-GSW) program allows a rapid analysis of the Automatic Science Processing (ASP) products and triggers dedicated followup analyses by several LAT science groups such as those studying Galactic transients, extragalactic sources and new gamma-ray sources. Significant gamma-ray detections also trigger rapid communications to the entire astrophysical community via astronomical telegrams and gamma-ray coordination network notices. The FA-GSW program plays a key role in maximizing the science return from Fermi by increasing the rate of multi-frequency observations of sources in an active gamma-ray state. In the past ~5 years blazar flaring activity of varying strength and duty cycles, gravitationally lensed blazars, flares from Galactic sources (like Nova Delphini and the Crab Nebula), unidentified transients near and off the Galactic plane, and emission from the quiet and flaring Sun, represent the range of detections made. Flare Advocates have published about 250 Astronomical Telegrams and they publish a weekly blog. Timely, extensive multi-frequency campaigns have been organized to follow-up on these phenomena leading to some of Fermi’s most interesting results.

Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells.

PubMed

Shim, Eun Kyung; Jung, Seung Hee; Lee, Jong Ran

2011-03-01

Previously, we identified p85, a subunit of PI3K, as one of the molecules that interacts with the N-terminal region of Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76). We also demonstrated that tyrosine phosphorylation either at the 113 and/or 128 position is sufficient for the association of SLP-76 with the Src homology 2 domain near the N terminus of p85. The present study further examines the role of the association of these two molecules on the activation of PI3K signaling cascade. Experiments were done to determine the role of SLP-76, either wild-type, tyrosine mutants, or membrane-targeted forms of various SLP-76 constructs, on the membrane localization and phosphorylation of Akt, which is an event downstream of PI3K activation. Reconstitution studies with these various SLP-76 constructs in a Jurkat variant cell line that lacks SLP-76 or linker for activation of T cells (LAT) show that the activation of PI3K pathway following TCR ligation requires both SLP-76 and LAT adaptor proteins. The results suggest that SLP-76 associates with p85 after T cell activation and that LAT recruits this complex to the membrane, leading to Akt activation.

Development of a blocking latex agglutination test for the detection of antibodies to chicken anemia virus.

PubMed

Trinh, Dai Quang; Ogawa, Haruko; Bui, Vuong Nghia; Nguyen, Tham Thi Hong; Gronsang, Dulyatad; Baatartsogt, Tugsbaatar; Kizito, Mugimba Kahoza; AboElkhair, Mohammed; Yamaguchi, Shigeo; Nguyen, Viet Khong; Imai, Kunitoshi

2015-09-01

A blocking latex agglutination test (b-LAT) developed in this study was evaluated for the detection of antibodies against chicken anemia virus (CAV) in chickens. Polystyrene latex beads were coupled with a neutralizing monoclonal antibody (mAb) to CAV (mAb-beads). When mAb-beads were mixed with antigens prepared from the lysate of MDCC-MSB1 cells infected with CAV, agglutination occurred. A short pre-incubation of CAV antigens with CAV-specific antiserum inhibited the agglutination of mAb-beads. The test results were obtained within 5min. The specificity of b-LAT was evaluated using sera from specific pathogen-free chickens and sera containing antibodies to avian influenza virus, Newcastle disease virus, infectious bursal disease virus, and Marek's disease virus; nonspecific agglutination and cross-reactivity with antibodies to unrelated viruses were not observed. The examination of 94 serum samples collected from commercial breeder chickens of various ages (17-63 weeks) revealed good agreement (93.6%, Kappa value=0.82) between b-LAT and a virus neutralization test, known to be most sensitive and specific in the detection of antibodies to CAV. These results indicate that b-LAT, a simple and rapid test, is a useful and reliable tool in CAV serology. Copyright © 2015 Elsevier B.V. All rights reserved.

Disruption of the actin cytoskeleton results in the promotion of gravitropism in inflorescence stems and hypocotyls of Arabidopsis

NASA Technical Reports Server (NTRS)

Yamamoto, Kazuyoshi; Kiss, John Z.

2002-01-01

The actin cytoskeleton is hypothesized to play a major role in gravity perception and transduction mechanisms in roots of plants. To determine whether actin microfilaments (MFs) are involved in these processes in stem-like organs, we studied gravitropism in Arabidopsis inflorescence stems and hypocotyls. Localization studies using Alexa Fluor-phalloidin in conjugation with confocal microscopy demonstrated a longitudinally and transversely oriented actin MF network in endodermal cells of stems and hypocotyls. Latrunculin B (Lat-B) treatment of hypocotyls caused depolymerization of actin MFs in endodermal cells and a significant reduction of hypocotyl growth rates. Actin MFs in Lat-B-treated inflorescence stems also were disrupted, but growth rates were not affected. Despite disruption of the actin cytoskeleton in these two organs, Lat-B-treated stems and hypocotyls exhibited a promotion of gravitropic curvature in response to reorientation. In contrast, Lat-B reduced gravitropic curvature in roots but also reduced the growth rate. Thus, in contrast to prevailing hypotheses, our results suggest that actin MFs are not a necessary component of gravitropism in inflorescence stems and hypocotyls. Furthermore, this is the first study to demonstrate a prominent actin MF network in endodermal cells in the putative gravity-perceiving cells in stems.

Effect of mitral regurgitation on cerebrovascular accidents in patients with atrial fibrillation and left atrial thrombus.

PubMed

Nair, Chandra K; Aronow, Wilbert S; Shen, Xuedong; Anand, Kishlay; Holmberg, Mark J; Esterbrooks, Dennis J

2009-11-01

The effect of mitral regurgitation (MR) on the incidence of new cerebrovascular accidents (CVA) and mortality in patients with atrial fibrillation (AF) and left atrial thrombus (LAT) is unknown. To investigate the effect of MR in patients with AF and LAT on new CVA and mortality. Eighty nine consecutive patients, mean age 71 years, with AF and LAT documented by transesophageal echocardiography were investigated to determine the prevalence and severity of MR and the association of the severity of MR with new cerebrovascular accidents (CVA) and mortality at 34-mo follow-up. Of 89 patients, 1 + MR was present in 23 patients (26%), 2 + MR in 44 patients (50%), 3 + MR in 17 patients (19%), and 4 + MR in 3 patients (4%). Mean follow-up was 34 +/- 28 mo. The Cox proportional hazards model showed that the severity of increased MR did not significantly increase new CVA or mortality at 34-mo follow-up. The only variable predictive of mortality was left ventricular ejection fraction (LVEF), and with every unit increase in LVEF, the risk decreased by 3%. MR occurred in 87 of 89 patients (98%) with AF and LAT. There was no association between the severity of MR and the incidence of CVA or mortality.

Investigating source confusion in PMN J1603-4904

NASA Astrophysics Data System (ADS)

Krauß, F.; Kreter, M.; Müller, C.; Markowitz, A.; Böck, M.; Burnett, T.; Dauser, T.; Kadler, M.; Kreikenbohm, A.; Ojha, R.; Wilms, J.

2018-02-01

PMN J1603-4904 is a likely member of the rare class of γ-ray emitting young radio galaxies. Only one other source, PKS 1718-649, has been confirmed so far. These objects, which may transition into larger radio galaxies, are a stepping stone to understanding AGN evolution. It is not completely clear how these young galaxies, seen edge-on, can produce high-energy γ rays. PMN J1603-4904 has been detected by TANAMI Very Long Baseline Interferometry (VLBI) observations and has been followed-up with multiwavelength observations. A Fermi Gamma-ray Space Telescope Large Area Telescope (Fermi-LAT) γ-ray source has been associated with this young galaxy in the LAT catalogs. We have obtained Chandra observations of the source to consider the possibility of source confusion due to the relatively large positional uncertainty of Fermi-LAT. The goal was to investigate the possibility of other X-ray bright sources in the vicinity of PMN J1603-4904 that could be counterparts to the γ-ray emission. With Chandra/ACIS, we find no other sources in the uncertainty ellipse of Fermi-LAT data, which includes an improved localization analysis of eight years of data. We further study the X-ray fluxes and spectra. We conclude that PMN J1603-4904 is indeed the second confirmed γ-ray bright young radio galaxy.

Searches for correlation between UHECR events and high-energy gamma-ray Fermi-LAT data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Álvarez, Ezequiel; Cuoco, Alessandro; Mirabal, Nestor

The astrophysical sources responsible for ultra high-energy cosmic rays (UHECRs) continue to be one of the most intriguing mysteries in astrophysics. We present a comprehensive search for correlations between high-energy (∼> 1 GeV) gamma-ray events from the Fermi Large Area Telescope (LAT) and UHECRs (∼> 60 EeV) detected by the Telescope Array and the Pierre Auger Observatory. We perform two separate searches. First, we conduct a standard cross-correlation analysis between the arrival directions of 148 UHECRs and 360 gamma-ray sources in the Second Catalog of Hard Fermi-LAT sources (2FHL). Second, we search for a possible correlation between UHECR directions andmore » unresolved Fermi -LAT gamma-ray emission. For the latter, we use three different methods: a stacking technique with both a model-dependent and model-independent background estimate, and a cross-correlation function analysis. We also test for statistically significant excesses in gamma rays from signal regions centered on Cen A and the Telescope Array hotspot. No significant correlation is found in any of the analyses performed, except a weak (∼< 2σ) hint of signal with the correlation function method on scales ∼ 1°. Upper limits on the flux of possible power-law gamma-ray sources of UHECRs are derived.« less

Searches for correlation between UHECR events and high-energy gamma-ray Fermi-LAT data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Álvarez, Ezequiel; Cuoco, Alessandro; Mirabal, Nestor

The astrophysical sources responsible for ultra high-energy cosmic rays (UHECRs) continue to be one of the most intriguing mysteries in astrophysics. Here, we present a comprehensive search for correlations between high-energy (≳ 1 GeV) gamma-ray events from the Fermi Large Area Telescope (LAT) and UHECRs (≳ 60 EeV) detected by the Telescope Array and the Pierre Auger Observatory. We perform two separate searches. First, we conduct a standard cross-correlation analysis between the arrival directions of 148 UHECRs and 360 gamma-ray sources in the Second Catalog of Hard Fermi-LAT sources (2FHL). Second, we search for a possible correlation between UHECR directionsmore » and unresolved Fermi-LAT gamma-ray emission. For the latter, we use three different methods: a stacking technique with both a model-dependent and model-independent background estimate, and a cross-correlation function analysis. We also test for statistically significant excesses in gamma rays from signal regions centered on Cen A and the Telescope Array hotspot. There was no significant correlation is found in any of the analyses performed, except a weak (≲ 2σ) hint of signal with the correlation function method on scales ~ 1°. Upper limits on the flux of possible power-law gamma-ray sources of UHECRs are derived.« less

Searches for correlation between UHECR events and high-energy gamma-ray Fermi-LAT data

DOE PAGES

Álvarez, Ezequiel; Cuoco, Alessandro; Mirabal, Nestor; ...

2016-12-13

The astrophysical sources responsible for ultra high-energy cosmic rays (UHECRs) continue to be one of the most intriguing mysteries in astrophysics. Here, we present a comprehensive search for correlations between high-energy (≳ 1 GeV) gamma-ray events from the Fermi Large Area Telescope (LAT) and UHECRs (≳ 60 EeV) detected by the Telescope Array and the Pierre Auger Observatory. We perform two separate searches. First, we conduct a standard cross-correlation analysis between the arrival directions of 148 UHECRs and 360 gamma-ray sources in the Second Catalog of Hard Fermi-LAT sources (2FHL). Second, we search for a possible correlation between UHECR directionsmore » and unresolved Fermi-LAT gamma-ray emission. For the latter, we use three different methods: a stacking technique with both a model-dependent and model-independent background estimate, and a cross-correlation function analysis. We also test for statistically significant excesses in gamma rays from signal regions centered on Cen A and the Telescope Array hotspot. There was no significant correlation is found in any of the analyses performed, except a weak (≲ 2σ) hint of signal with the correlation function method on scales ~ 1°. Upper limits on the flux of possible power-law gamma-ray sources of UHECRs are derived.« less

Disruption of the Actin Cytoskeleton Results in the Promotion of Gravitropism in Inflorescence Stems and Hypocotyls of Arabidopsis1

PubMed Central

Yamamoto, Kazuyoshi; Kiss, John Z.

2002-01-01

The actin cytoskeleton is hypothesized to play a major role in gravity perception and transduction mechanisms in roots of plants. To determine whether actin microfilaments (MFs) are involved in these processes in stem-like organs, we studied gravitropism in Arabidopsis inflorescence stems and hypocotyls. Localization studies using Alexa Fluor-phalloidin in conjugation with confocal microscopy demonstrated a longitudinally and transversely oriented actin MF network in endodermal cells of stems and hypocotyls. Latrunculin B (Lat-B) treatment of hypocotyls caused depolymerization of actin MFs in endodermal cells and a significant reduction of hypocotyl growth rates. Actin MFs in Lat-B-treated inflorescence stems also were disrupted, but growth rates were not affected. Despite disruption of the actin cytoskeleton in these two organs, Lat-B-treated stems and hypocotyls exhibited a promotion of gravitropic curvature in response to reorientation. In contrast, Lat-B reduced gravitropic curvature in roots but also reduced the growth rate. Thus, in contrast to prevailing hypotheses, our results suggest that actin MFs are not a necessary component of gravitropism in inflorescence stems and hypocotyls. Furthermore, this is the first study to demonstrate a prominent actin MF network in endodermal cells in the putative gravity-perceiving cells in stems. PMID:11842170

Discovery of GeV emission from the Circinus galaxy with the Fermi Large Area Telescope [Discovery of GeV emission from the Circinus galaxy with the Fermi-LAT

DOE PAGES

Hayashida, Masaaki; Stawarz, Łukasz; Cheung, Chi C.; ...

2013-12-03

We report the discovery of γ-ray emission from the Circinus galaxy using the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. Circinus is a nearby (~4 Mpc) starburst with a heavily obscured Seyfert-type active nucleus, bipolar radio lobes perpendicular to the spiral disk, and kpc-scale jet-like structures. Our analysis of 0.1-100 GeV events collected during 4 yr of LAT observations reveals a significant (≃ 7.3σ) excess above the background. We find no indications of variability or spatial extension beyond the LAT point-spread function. A power-law model used to describe the 0.1-100 GeV γ-ray spectrum yields a fluxmore » of (18.8 ± 5.8) × 10 –9 photon cm –2 s –1 and photon index 2.19 ± 0.12, corresponding to an isotropic γ-ray luminosity of 3 × 10 40 erg s –1. This observed γ-ray luminosity exceeds the luminosity expected from cosmic-ray interactions in the interstellar medium and inverse Compton radiation from the radio lobes. Furthermore, the origin of the GeV excess requires further investigation.« less

Latin America: A Development Pole for Phenomics

PubMed Central

Camargo, Anyela V.; Lobos, Gustavo A.

2016-01-01

Latin America and the Caribbean (LAC) has long been associated with the production and export of a diverse range of agricultural commodities. Due to its strategic geographic location, which encompasses a wide range of climates, it is possible to produce almost any crop. The climate diversity in LAC is a major factor in its agricultural potential but this also means climate change represents a real threat to the region. Therefore, LAC farming must prepare and quickly adapt to an environment that is likely to feature long periods of drought, excessive rainfall and extreme temperatures. With the aim of moving toward a more resilient agriculture, LAC scientists have created the Latin American Plant Phenomics Network (LatPPN) which focuses on LAC's economically important crops. LatPPN's key strategies to achieve its main goal are: (1) training of LAC members on plant phenomics and phenotyping, (2) establish international and multidisciplinary collaborations, (3) develop standards for data exchange and research protocols, (4) share equipment and infrastructure, (5) disseminate data and research results, (6) identify funding opportunities and (7) develop strategies to guarantee LatPPN's relevance and sustainability across time. Despite the challenges ahead, LatPPN represents a big step forward toward the consolidation of a common mind-set in the field of plant phenotyping and phenomics in LAC. PMID:27999577

Seven-year Collection of Well-monitored Fermi-LAT Gamma-Ray Burst Afterglows

NASA Astrophysics Data System (ADS)

Panaitescu, A.

2017-03-01

We present the light curves and spectra of 24 afterglows that have been monitored by Fermi-LAT at 0.1-100 GeV over more than a decade. All light curves (except 130427) are consistent with a single power law starting from their peaks, which occur in most cases before the burst end. The light curves display a brightness-decay rate correlation, with all but one (130427) of the bright afterglows decaying faster than the dimmer afterglows. We attribute this dichotomy to the quick deposition of relativistic ejecta energy in the external shock for the brighter/faster-decaying afterglows and to an extended energy injection in the afterglow shock for the dimmer/slower-decaying light curves. The spectra of six afterglows (090328, 100414, 110721, 110731, 130427, 140619B) indicate the existence of a harder component above a spectral dip or ankle at energies of 0.3-3 GeV, offering evidence for inverse-Compton emission at higher energies and suggesting that the harder power-law spectra of five other LAT afterglows (130327B, 131231, 150523, 150627, 160509) could also be inverse-Compton, while the remaining, softer LAT afterglows should be synchrotron emission. Marginal evidence for a spectral break and softening at higher energies is found for two afterglows (090902B and 090926).

Latin America: A Development Pole for Phenomics.

PubMed

Camargo, Anyela V; Lobos, Gustavo A

2016-01-01

Latin America and the Caribbean (LAC) has long been associated with the production and export of a diverse range of agricultural commodities. Due to its strategic geographic location, which encompasses a wide range of climates, it is possible to produce almost any crop. The climate diversity in LAC is a major factor in its agricultural potential but this also means climate change represents a real threat to the region. Therefore, LAC farming must prepare and quickly adapt to an environment that is likely to feature long periods of drought, excessive rainfall and extreme temperatures. With the aim of moving toward a more resilient agriculture, LAC scientists have created the Latin American Plant Phenomics Network (LatPPN) which focuses on LAC's economically important crops. LatPPN's key strategies to achieve its main goal are: (1) training of LAC members on plant phenomics and phenotyping, (2) establish international and multidisciplinary collaborations, (3) develop standards for data exchange and research protocols, (4) share equipment and infrastructure, (5) disseminate data and research results, (6) identify funding opportunities and (7) develop strategies to guarantee LatPPN's relevance and sustainability across time. Despite the challenges ahead, LatPPN represents a big step forward toward the consolidation of a common mind-set in the field of plant phenotyping and phenomics in LAC.

Programs of Study as a State Policy Mandate: A Longitudinal Study of the South Carolina Personal Pathways to Success Initiative. Final Technical Report: Major Findings and Implications

ERIC Educational Resources Information Center

Hammond, Cathy; Drew, Sam F.; Withington, Cairen; Griffith, Cathy; Swiger, Caroline M.; Mobley, Catherine; Sharp, Julia L.; Stringfield, Samuel C.; Stipanovic, Natalie; Daugherty, Lindsay

2013-01-01

This is the final technical report from the National Research Center for Career and Technical Education's (NRCCTE's) five-year longitudinal study of South Carolina's Personal Pathway to Success initiative, which was authorized by the state's Education and Economic Development Act (EEDA) in 2005. NRCCTE-affiliated researchers at the National…

Direct Final Rule: Nonroad Diesel Technical Amendments and Tier 3 Technical Relief Provision

EPA Pesticide Factsheets

Rule making certain technical corrections to the rules establishing emission standards for nonroad diesel engines and amending those rules to provide manufacturers with a production technical relief provision for Tier 3 equipment.

A Multi-frequency analysis of dark matter annihilation interpretations of recent anti-particle and γ-ray excesses in cosmic structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beck, G.; Colafrancesco, S., E-mail: geoff.m.beck@gmail.com, E-mail: sergio.colafrancesco@wits.ac.za

2016-05-01

The Fermi-LAT observation of a γ-ray excess from the galactic-centre, as well as the PAMELA, AMS, and AMS-2 anti-particle excesses, and the recent indications of a Fermi-LAT γ-ray excess in the Reticulum II dwarf galaxy have all been variously put forward as possible indirect signatures of supersymmetric neutralino dark matter. These are of particular interest as the neutralino annihilation models which fit these observations must have observable consequences across the frequency spectrum, from radio to γ-ray emission. Moreover, since dark matter is expected to be a major constituent of cosmic structure, these multi-frequency consequences should be common to such structuresmore » across the mass spectrum, from dwarf galaxies to galaxy clusters. Thus, in this work we make predictions for the multi-frequency spectra of three well-known sources dominated by dark matter on cluster, galaxy and dwarf galaxy scales, e.g. the Coma cluster, the galaxy M81, and the Draco dwarf galaxy, using models favoured by dark matter interpretations of the aforementioned observations. We pay special attention to the consequences for these models when their cross-sections are renormalised to reproduce the recent γ-ray excess observed in the Reticulum II dwarf galaxy, as well as using cross-sections from the Fermi-LAT dwarf galaxy limits, which throw a dark matter interpretation of this excess into doubt. We find that the multi-frequency data of Coma and Draco are in conflict with the dark matter interpretation of the AMS, PAMELA and Fermi positron excess. Additionally, models derived from Fermi-LAT galactic centre observations, and AMS-2 re-analysis, present similar but less extensive conflicts. Using the sensitivity projections for the Square Kilometre Array, the Cherenkov Telescope Array, as well as the ASTROGAM and ASTRO-H satellites, we determine the detection prospects for a subset of neutralino models that remain consistent with Planck cosmological constraints. Although the SKA has the greatest sensitivity to dark matter models, we demonstrate that ASTRO-H is well positioned to probe the inverse-Compton scattering emissions from neutralino annihilation and identify characteristics of the spectra which contain information about the neutralino mass and annihilation channel. This means that, given environments with favourable X-ray backgrounds, multi-frequency observation with the next generation of experiments will allow for unprecedented sensitivity to the neutralino parameter space as well as offsetting the individual weaknesses of each observation mode. Finally we show that all of the studied models can be better tested with the SKA phase 1.« less

Latrunculin B and substratum stiffness regulate corneal fibroblast to myofibroblast transformation.

PubMed

Thomasy, Sara M; Raghunathan, Vijay Krishna; Miyagi, Hidetaka; Evashenk, Alexander T; Sermeno, Jasmyne C; Tripp, Geneva K; Morgan, Joshua T; Murphy, Christopher J

2018-05-01

The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h. Cells were treated with 0.4 μM Lat-B or DMSO for 30 min every 24 h for 72 h. RNA was collected from cells and expression of alpha-smooth muscle actin (α-SMA), keratocan, and ALDH1A1 determined using qPCR; immunocytochemistry was used to assess α-SMA protein expression. A rabbit phototherapeutic keratectomy (PTK) model was used to assess the impact of 0.1% Lat-B (n = 3) or 25% DMSO (vehicle control, n = 3) on corneal wound healing by assessment of epithelial wound size with fluorescein stain and semi-quantitative stromal haze scoring by an observer masked to treatment group as well as Fourier-domain optical coherence tomography (FD-OCT) at set time points. Statistical analysis was completed using one-way or two-way analysis of variance. Treatment with Lat-B versus DMSO resulted in significantly less αSMA mRNA (P ≤ 0.007) for RCF cells grown on 22 and 71 kPa substrates as well as TCP without or with TGFβ1, and significantly decreased α-SMA protein expression in RCFs cultured on the intermediate (22 kPa) stiffness in the absence (P = 0.028) or presence (P = 0.018) of TGFβ1. Treatment with Lat-B versus DMSO but did not significantly alter expression of keratocan or ALDH1A1 mRNA in RCFs (P > 0.05) in the absence or presence of TGFβ1, but RCFs grown on stiff hydrogels (71 kPa) had significantly more keratocan mRNA expression versus the 22 kPa hydrogel or TCP (P < 0.001) without TGFβ1. Administration of topical Lat-B BID was well tolerated by rabbits post-PTK but did not significantly alter epithelial wound closure, stromal haze score, stromal haze thickness as measured by FD-OCT in comparison to DMSO-treated rabbits. When corneal stromal cells are cultured on substrates possessing biologically relevant substratum stiffnesses, Lat-B modulates mRNA and protein expression of α-SMA and thus modulates myofibroblast transformation. At a dose and dose-frequency that reduced IOP in human glaucoma patients, Lat-B treatment did not substantially impact corneal epithelial or stromal wound healing in a rabbit PTK model. While a significant impact on wound healing was observed at the concentration and dose frequency reported here was not found, encouraging in vitro data support further investigations of topically applied Lat-B to determine if this compound can reduce stromal fibrosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dangers Files Data: January-February 1979

DTIC Science & Technology

1979-05-01

National Salvation. (NYT) (LAT); 01/08/79 *** 0086 *** 001 010 290 365 394 002 002 002 005 003 003 POLAND-USSR RELATIONS: The Polish leadership has...Militant Islamic clergymen in Iran express fears that leftist extremists may seize the leadership of +he struggle to oust the Shah. In recent weeks...disavowed +he religious leadership of the struggle. (LAT); 01/11/79 *** 0072 *** 003 010 630 000 000 001 002 008 008 008 008 IRAN INTERNAL DISSENSION

JPRS Report. Science & Technology: China.

DTIC Science & Technology

1989-03-17

From Simple Colliding-Pulse Mode- Locking Dye Laser With Double Coated Stack Mirrors [Wang Qingyue, et al.; GUANGXUE XUEBAO, No 11, Nov 88] 82...86 Influence of Stimulated Raman Process on Fundamental Solitons in Fibers [Qu Linjie, et al.; GUANGXUE XUEBAO, No 11, Nov 88] 87 650 nm...synapses are the same regarding the relationship of he and hi to N. Each component of the vector lat represents the delay time lat of each synapse as it

The Synergy between the LAT and GBM in GLAST's Study of Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Band, David L.

2007-01-01

Using semi-analytic calculations I characterize the gamma-ray bursts to which GLAST's LAT and GBM detectors will be sensitive. The thresholds of both instruments are at approximately the same vfv proportional to E(sup 2)N(E) values, i.e., the thresholds can be connected by an E(sup -2) spectrum. Therefore simultaneous detections by both instruments will be biased towards spectral components flatter than E(sup -2).

50 CFR Table 3 (south) to Part 660... - Non-Trawl Rockfish Conservation Areas and Trip Limits for Open Access Gears South of 40°10′ N. Lat.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Non-Trawl Rockfish Conservation Areas and Trip Limits for Open Access Gears South of 40°10ⲠN. Lat. 3 Table 3 (South) to Part 660, Subpart F Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION...

50 CFR Table 3 (north) to Part 660... - Non-Trawl Rockfish Conservation Areas and Trip Limits for Open Access Gears North of 40°10′ N. Lat.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Non-Trawl Rockfish Conservation Areas and Trip Limits for Open Access Gears North of 40°10ⲠN. Lat. 3 Table 3 (North) to Part 660, Subpart F Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION...

Enhanced high-energy gamma-ray emission from the microquasar Cygnus X-3 detected by Fermi/LAT

NASA Astrophysics Data System (ADS)

Loh, Alan; Corbel, Stephane

2017-02-01

Following the recent decrease of the hard X-ray emission from the high-mass X-ray binary Cygnus X-3 as seen by the Swift/Burst Alert Telescope (https://swift.gsfc.nasa.gov/results/transients/CygX-3/), the Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed significant gamma-ray emission originating from the microquasar.

Fermi-LAT Observations of Continued Gamma-ray Activity from Nova ASASSN-16ma

NASA Astrophysics Data System (ADS)

Li, Kwan-Lok; Chomiuk, Laura; Strader, Jay; Cheung, C. C.; Jean, P.; Shore, S. N.; Fermi Large Area Telescope Collaboration

2016-11-01

Following the report of a sudden gamma-ray onset detection of nova ASASSN-16ma coincident with the optical peak of 5.5 mag on November 8 (ATel #9736), ASASSN-16ma was observed to slowly decrease in gamma-rays but has remained bright enough to be detectable with Fermi-LAT over the last 9 days (test statistic, TS > 10 per day, except for November 17 with TS=5).

Femtosecond laser-induced size reduction and emission quantum yield enhancement of colloidal silicon nanocrystals: Effect of laser ablation time.

PubMed

Zhang, Yingxiong; Wu, Wenshun; Hao, Huilian; Shen, Wenzhong

2018-06-19

Colloidal silicon (Si) nanocrystals (NCs) with different sizes were successfully prepared by femtosecond laser ablation under different laser ablation time (LAT). The mean size decreases from 4.23 to 1.42 nm with increasing LAT from 30 to 120 min. In combination with structural characterization, temperature-dependent photoluminescence (PL), time-resolved PL, and PL excitation spectra, we attribute room temperature blue emissions peaked at 405 and 430 nm to the radiative recombination of electron-hole pairs via the oxygen deficient centers related to Si-C-H2 and Si-O-Si bonds of colloidal Si NCs prepared in 1-octene, respectively. In particular, the measured PL quantum yield of colloidal Si NCs has been enhanced significantly from 23.6% to 55.8% with prolonging LAT from 30 to 120 min. © 2018 IOP Publishing Ltd.

Discovery of Very High Energy Gamma-Ray Emission from Rbs 0723 with the Magic Telescopes

NASA Astrophysics Data System (ADS)

Mirzoyan, Razmik

2014-01-01

The MAGIC collaboration reports the discovery of very high energy (VHE; E>100 GeV) gamma-ray emission from RBS 0723 (RA: 08:47:12.9 DEC: +11:33:50, J2000.0) RBS 0723 is a BL Lac object at redshift z=0.198. The source has been detected by Fermi-LAT, in the Second Fermi-LAT source Catalogue (2FGL; Nolan et al. 2012) with F(>1 GeV) = (5.3+-1.2)e-10 cm^-2 s^-1 and with photon index 1.48+-0.16. It also belongs to the first Fermi-LAT catalog of >10 GeV sources (1FHL; Ackermann et al, 2013), showing a hard (photon index = 1.4 +- 0.4) and bright (photon flux = 9.6e-11 ph cm^-2 s^-1) emission above 10 GeV, and identified as a good candidate for VHE detection.

The GLAST Burst Monitor

NASA Technical Reports Server (NTRS)

Meegan, Charles A.

2004-01-01

The Gamma Ray Large Area Space Telescope (GLAST) observatory, scheduled for launch in 2007, comprises the Large Area Telescope (LAT) and the GLAST Burst Monitor (GBM). spectral changes that are known to occur within GRBs. between the NASA Marshall Space Flight Center, the University of Alabama in Huntsville, and the Max Planck Institute for Extraterrestrial Physics. It consists of an array of NaI and BGO scintillation detectors operating in the 10 kev to 25 MeV range. The field of view includes the entire unocculted sky when the observatory is pointing close to the zenith. The GBM will enhance LAT observations of GRBs by extending the spectral coverage into the range of current GRB databases, and will provide a trigger for reorienting the spacecraft to observe delayed emission from bursts outside the LAT field of view. GBM is expected to trigger on about 200 bursts per year, and will provide on-board locations of strong bursts accurate to better than 10 degrees.

MODELING THE EARLY AFTERGLOW IN THE SHORT AND HARD GRB 090510

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraija, N.; Lee, W. H.; Veres, P.

2016-11-01

The bright, short, and hard GRB 090510 was detected by all instruments aboard the Fermi and Swift satellites. The multiwavelength observations of this burst presented similar features to the Fermi -LAT-detected gamma-ray bursts. In the framework of the external shock model of early afterglow, a leptonic scenario that evolves in a homogeneous medium is proposed to revisit GRB 090510 and explain the multiwavelength light curve observations presented in this burst. These observations are consistent with the evolution of a jet before and after the jet break. The long-lasting LAT, X-ray, and optical fluxes are explained in the synchrotron emission frommore » the adiabatic forward shock. Synchrotron self-Compton emission from the reverse shock is consistent with the bright LAT peak provided that the progenitor environment is entrained with strong magnetic fields. It could provide compelling evidence of magnetic field amplification in the neutron star merger.« less

Searching for γ-ray emission from Reticulum II by Fermi-LAT

NASA Astrophysics Data System (ADS)

Zhao, Yi; Bi, Xiao-Jun; Yin, Peng-Fei; Zhang, Xinmin

2018-02-01

Recently, many new dwarf spheroidal satellites (dSphs) have been discovered by the Dark Energy Survey (DES). These dSphs are ideal candidates for probing for gamma-ray emissions from dark matter (DM) annihilation. However, no significant signature has been found by the Fermi-LAT dSph observations. In this work, we reanalyze the Fermi-LAT Pass 8 data from the direction of Reticulum II, where a slight excess has been reported by some previous studies. We treat Reticulum II (DES J0335.6-5403) as a spatially extended source, and find that no significant gamma-ray signature is observed. Based on this result, we set upper-limits on the DM annihilation cross section. Supported by National Natural Science Foundation of China (11121092, 11033005, 11375202, 11475191, 11475189), the CAS pilot B program (XDB23020000) and the National Key Program for Research and Development (2016YFA0400200)

Modeling and Maximum Likelihood Fitting of Gamma-Ray and Radio Light Curves of Millisecond Pulsars Detected with Fermi

NASA Technical Reports Server (NTRS)

Johnson, T. J.; Harding, A. K.; Venter, C.

2012-01-01

Pulsed gamma rays have been detected with the Fermi Large Area Telescope (LAT) from more than 20 millisecond pulsars (MSPs), some of which were discovered in radio observations of bright, unassociated LAT sources. We have fit the radio and gamma-ray light curves of 19 LAT-detected MSPs in the context of geometric, outermagnetospheric emission models assuming the retarded vacuum dipole magnetic field using a Markov chain Monte Carlo maximum likelihood technique. We find that, in many cases, the models are able to reproduce the observed light curves well and provide constraints on the viewing geometries that are in agreement with those from radio polarization measurements. Additionally, for some MSPs we constrain the altitudes of both the gamma-ray and radio emission regions. The best-fit magnetic inclination angles are found to cover a broader range than those of non-recycled gamma-ray pulsars.

Leptonic v.s. Hadronic Origin of the Gamma-ray Emission of the Fermi bubbles: Updates from Fermi-LAT and Forecast for Future Gamma-ray Telescopes

NASA Astrophysics Data System (ADS)

Su, Meng

2014-06-01

Data from the Fermi-LAT revealed two large gamma-ray bubbles, extending 50 degrees above and below the Galactic center, with a width of about 40 degrees in longitude. Such structure has been confirmed with multi-wavelength observations. With the most up to date Fermi-LAT data analysis, I will show that the Fermi bubbles have a spectral cutoff at both low energy < 1 GeV and high energy > 150 GeV. Detailed analysis of the spectral features will help us to distinguish the leptonic origin from hadronic origin of the gamma-ray emission from the bubbles. I will also describe what we expect to learn about the bubbles from future gamma-ray telescopes after Fermi, with an emphasis on Dark Matter Particle Explorer and Pair Production Gamma-ray Unit.

Modeling the Early Afterglow in the Short and Hard GRB 090510

NASA Astrophysics Data System (ADS)

Fraija, N.; Lee, W. H.; Veres, P.; Barniol Duran, R.

2016-11-01

The bright, short, and hard GRB 090510 was detected by all instruments aboard the Fermi and Swift satellites. The multiwavelength observations of this burst presented similar features to the Fermi-LAT-detected gamma-ray bursts. In the framework of the external shock model of early afterglow, a leptonic scenario that evolves in a homogeneous medium is proposed to revisit GRB 090510 and explain the multiwavelength light curve observations presented in this burst. These observations are consistent with the evolution of a jet before and after the jet break. The long-lasting LAT, X-ray, and optical fluxes are explained in the synchrotron emission from the adiabatic forward shock. Synchrotron self-Compton emission from the reverse shock is consistent with the bright LAT peak provided that the progenitor environment is entrained with strong magnetic fields. It could provide compelling evidence of magnetic field amplification in the neutron star merger.

Search For Dark Matter Satellites Using Fermi-Lat

DOE PAGES

Ackermann, M.

2012-02-23

Numerical simulations based on the ΛCDM model of cosmology predict a large number of as yet unobserved Galactic dark matter satellites. We report the results of a Large Area Telescope (LAT) search for these satellites via the γ-ray emission expected from the annihilation of weakly interacting massive particle (WIMP) dark matter. Some dark matter satellites are expected to have hard γ-ray spectra, finite angular extents, and a lack of counterparts at other wavelengths. We sought to identify LAT sources with these characteristics, focusing on γ-ray spectra consistent with WIMP annihilation through themore » $$b \\bar{b}$$ channel. We found no viable dark matter satellite candidates using one year of data, and we present a framework for interpreting this result in the context of numerical simulations to constrain the velocity-averaged annihilation cross section for a conventional 100 GeV WIMP annihilating through the $$b \\bar{b}$$ channel.« less

Search for Dark Matter Satellites Using the Fermi-Lat

NASA Technical Reports Server (NTRS)

Ackermann, M.; Albert, A.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bechtol, K.; Bellazzini, R.; Blandford, R. D.; Bloom, E. D.;

Gamma-Ray "Raindrops" from Flaring Blazar

NASA Image and Video Library

2017-12-08

This visualization shows gamma rays detected during 3C 279's big flare by the LAT instrument on NASA's Fermi satellite. Gamma rays are represented as expanding circles reminiscent of raindrops on water. The flare is an abrupt shower of "rain" that trails off toward the end of the movie. Both the maximum size of the circle and its color represent the energy of the gamma ray, with white lowest and magenta highest. In a second version of the visualization, a background map shows how the LAT detects 3C 279 and other sources by accumulating high-energy photons over time (brighter squares reflect higher numbers of gamma rays). The movie starts on June 14 and ends June 17. The area shown is a region of the sky five degrees on a side and centered on the position of 3C 279. Read more: go.nasa.gov/1TqximF Credits: NASA/DOE/Fermi LAT Collaboration

Growth of embryo and gene expression of nutrient transporters in the small intestine of the domestic pigeon (Columba livia)*

PubMed Central

Chen, Ming-xia; Li, Xiang-guang; Yang, Jun-xian; Gao, Chun-qi; Wang, Bin; Wang, Xiu-qi; Yan, Hui-chao

2015-01-01

The objective of this study was to investigate the relationship between gene expression of nutrient (amino acid, peptide, sodium and proton) transporters in the small intestine and embryonic growth in domestic pigeons (Columba livia). One hundred and twenty-five fertilized eggs were randomly assigned into five groups and were incubated under optimal conditions (temperature of 38.1 °C and relative humidity of 55%). Twenty embryos/birds from each group were sacrificed by cervical dislocation on embryonic day (E) 9, 11, 13, 15 and day of hatch (DOH). The eggs, embryos (without yolk sac), and organs (head, brain, heart, liver, lungs, kidney, gizzard, small intestine, legs, and thorax) were dissected, cleaned, and weighed. Small intestine samples were collected for RNA isolation. The mRNA abundance of intestinal nutrient transporters was evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). We classified these ten organs into four types according to the changes in relative weight during embryonic development. In addition, the gene expression of nutrient transporters was differentially regulated by embryonic day. The mRNA abundances of b0,+AT, EAAT3, y+LAT2, PepT1, LAT4, NHE2, and NHE3 increased linearly with age, whereas mRNA abundances of CAT1, CAT2, LAT1, EAAT2, SNAT1, and SNAT2 were increased to higher levels on E9 or E11 and then decreased to lower levels until DOH. The results of correlation analysis showed that the gene expressions of b0,+AT, EAAT3, PepT1, LAT4, NHE2, NHE3, and y+LAT2 had positive correlations with body weight (0.71

Arizona Deafblind Project, 1995-1999. Final Report.

ERIC Educational Resources Information Center

Arizona State School for the Deaf and Blind, Tucson.

This final report describes accomplishments of the four-year federally funded Arizona Deafblind Project which attempted to: (1) identify all deafblind children in Arizona; (2) deliver technical assistance to families; (3) deliver technical assistance to service providers; and (4) enhance community oversight, coordination, and collaboration with…

Minimal spanning tree algorithm for γ-ray source detection in sparse photon images: cluster parameters and selection strategies

DOE PAGES

Campana, R.; Bernieri, E.; Massaro, E.; ...

2013-05-22

We present that the minimal spanning tree (MST) algorithm is a graph-theoretical cluster-finding method. We previously applied it to γ-ray bidimensional images, showing that it is quite sensitive in finding faint sources. Possible sources are associated with the regions where the photon arrival directions clusterize. MST selects clusters starting from a particular “tree” connecting all the point of the image and performing a cut based on the angular distance between photons, with a number of events higher than a given threshold. In this paper, we show how a further filtering, based on some parameters linked to the cluster properties, canmore » be applied to reduce spurious detections. We find that the most efficient parameter for this secondary selection is the magnitudeM of a cluster, defined as the product of its number of events by its clustering degree. We test the sensitivity of the method by means of simulated and real Fermi-Large Area Telescope (LAT) fields. Our results show that √M is strongly correlated with other statistical significance parameters, derived from a wavelet based algorithm and maximum likelihood (ML) analysis, and that it can be used as a good estimator of statistical significance of MST detections. Finally, we apply the method to a 2-year LAT image at energies higher than 3 GeV, and we show the presence of new clusters, likely associated with BL Lac objects.« less

Fermi LAT Observation of Diffuse Gamma Rays Produced Through Interactions Between Local Interstellar Matter and High-Energy Cosmic Rays

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2009-09-08

Observations by the Large Area Telescope (LAT) on the Fermi mission of diffuse γ-rays in a mid-latitude region in the third quadrant (Galactic longitude l from 200° to 260° and latitude |b| from 22° to 60°) are reported in this paper. The region contains no known large molecular cloud and most of the atomic hydrogen is within 1 kpc of the solar system. The contributions of γ-ray point sources and inverse Compton scattering are estimated and subtracted. The residual γ-ray intensity exhibits a linear correlation with the atomic gas column density in energy from 100 MeV to 10 GeV. Themore » measured integrated γ-ray emissivity is (1.63 ± 0.05) × 10 –26 photons s –1sr –1 H-atom –1 and (0.66 ± 0.02) × 10 –26 photons s –1sr –1 H-atom –1 above 100 MeV and above 300 MeV, respectively, with an additional systematic error of ~10%. The differential emissivity from 100 MeV to 10 GeV agrees with calculations based on cosmic ray spectra consistent with those directly measured, at the 10% level. Finally, the results obtained indicate that cosmic ray nuclei spectra within 1 kpc from the solar system in regions studied are close to the local interstellar spectra inferred from direct measurements at the Earth within ~10%.« less

A cross-correlation study of the Fermi-LAT γ-ray diffuse extragalactic signal

DOE PAGES

Xia, Jun -Qing; Cuoco, Alessandro; Branchini, Enzo; ...

2011-09-12

In this work, starting from 21 months of data from the Fermi Large Area Telescope (LAT), we derive maps of the residual isotropic γ-ray emission, a relevant fraction of which is expected to be contributed by the extragalactic diffuse γ-ray background (EGB). We search for the auto-correlation signals in the above γ-ray maps and for the cross-correlation signal with the angular distribution of different classes of objects that trace the large-scale structure of the Universe. We compute the angular two-point auto-correlation function of the residual Fermi-LAT maps at energies E > 1 GeV, E > 3 GeV and E >more » 30 GeV well above the Galactic plane and find no significant correlation signal. This is, indeed, what is expected if the EGB were contributed by BL Lacertae (BLLacs), Flat Spectrum Radio Quasars (FSRQs) or star-forming galaxies, since, in this case, the predicted signal is very weak. Then, we search for the Integrated Sachs–Wolfe (ISW) signature by cross-correlating the Fermi-LAT maps with the 7-year Wilkinson Microwave Anisotropy Probe ( WMAP7) cosmic microwave background map. We find a cross-correlation consistent with zero, even though the expected signal is larger than that of the EGB auto-correlation. Lastly, in an attempt to constrain the nature of the γ-ray background, we cross-correlate the Fermi-LAT maps with the angular distributions of objects that may contribute to the EGB: quasi-stellar objects (QSOs) in the Sloan Digital Sky Survey Data Release 6 (SDSS-DR6) catalogue, NRAO VLA Sky Survey (NVSS) galaxies, Two Micron All Sky Survey (2MASS) galaxies and Luminous Red Galaxies (LRGs) in the SDSS catalogue. The cross-correlation is always consistent with zero, in agreement with theoretical expectations, but we find (with low statistical significance) some interesting features that may indicate that some specific classes of objects contribute to the EGB. A χ 2 analysis confirms that the correlation properties of the 21-month data do not provide strong constraints of the EGB origin. However, the results suggest that the situation will significantly improve with the 5- and 10-yr Fermi-LAT data. In future, the EGB analysis will then allow placing significant constraints on the nature of the EGB and might provide, in addition, a detection of the ISW signal.« less

7th International Fermi Symposium

NASA Astrophysics Data System (ADS)

2017-10-01

The two Fermi instruments have been surveying the high-energy sky since August 2008. The Large Area Telescope (LAT) has discovered more than three thousand gamma-ray sources and many new source classes, bringing the importance of gamma-ray astrophysics to an ever-broadening community. The LAT catalog includes supernova remnants, pulsar wind nebulae, pulsars, binary systems, novae, several classes of active galaxies, starburst galaxies, normal galaxies, and a large number of unidentified sources. Continuous monitoring of the high-energy gamma-ray sky has uncovered numerous outbursts from a wide range of transients. Fermi LAT's study of diffuse gamma-ray emission in our Galaxy revealed giant bubbles, as well as an excess of gamma-rays from the Galactic center region, both observations have become exciting puzzles for the astrophysics community. The direct measurement of a harder-than- expected cosmic-ray electron spectrum may imply the presence of nearby cosmic-ray accelerators. LAT data have provided stringent constraints on new phenomena such as supersymmetric dark-matter annihilations as well as tests of fundamental physics. The full reprocessing of the entire mission dataset with Pass 8 includes improved event reconstruction, a wider energy range, better energy measurements, and significantly increased effective area, all them boosting the discovery potential and the ability to do precision observations with LAT. The Gamma-ray Burst Monitor (GBM) continues to be a prolific detector of gamma-ray transients: magnetars, solar flares, terrestrial gamma-ray flashes and gamma-ray bursts at keV to MeV energies, complementing the higher energy LAT observations of those sources in addition to providing valuable science return in their own right. All gamma-ray data are made immediately available at the Fermi Science Support Center (http://fermi.gsfc.nasa.gov/ssc). These publicly available data and Fermi analysis tools have enabled a large number of important studies. We especially encourage guest investigators worldwide to participate in this symposium to share results and to learn about upcoming opportunities. This meeting will focus on the new scientific investigations and results enabled by Fermi, the mission and instrument characteristics, future opportunities, coordinated observations and analysis techniques. In particular, we also encourage discussion of future prospects/science with Fermi in preparation for the upcoming NASA senior review. Details on the 7th International Fermi Symposium can be found here: https://events.mpe.mpg.de/Fermi2017

Joint Common Architecture Demonstration (JCA Demo) Final Report

DTIC Science & Technology

2016-07-28

approach for implementing open systems [16], formerly known as the Modular Open Systems Approach (MOSA). OSA is a business and technical strategy to... TECHNICAL REPORT RDMR-AD-16-01 JOINT COMMON ARCHITECTURE DEMONSTRATION (JCA DEMO) FINAL REPORT Scott A. Wigginton... Modular Avionics .......................................................................... 5 E. Model-Based Engineering

Inferring the Presence of Reverse Proxies Through Timing Analysis

DTIC Science & Technology

2015-06-01

16 Figure 3.2 The three different instances of timing measurement configurations 17 Figure 3.3 Permutation of a web request iteration...Their data showed that they could detect at least 6 bits of entropy between unlike devices and that it was enough to determine that they are in fact...depending on the permutation being executed so that every iteration was conducted under the same distance 15 City   Lat   Long   City   Lat   Long

50 CFR Appendix B to Part 622 - Gulf Areas

Code of Federal Regulations, 2012 CFR

2012-10-01

... Restricted Area Point No. and reference location 1 North lat. West long. 1Seaward limit of Florida's waters...—Offshore 26°26.0′ 82°59.0′ 4West of Egmont Key 27°30.0′ 83°21.5′ 5Off Anclote Keys—Offshore 28°10.0′ 83°45... Point No. and reference location 1 North lat. West long. 1Seaward limit of Florida's waters northeast of...

50 CFR Appendix B to Part 622 - Gulf Areas

Code of Federal Regulations, 2010 CFR

2010-10-01

... Restricted Area Point No. and reference location 1 North lat. West long. 1Seaward limit of Florida's waters...—Offshore 26°26.0′ 82°59.0′ 4West of Egmont Key 27°30.0′ 83°21.5′ 5Off Anclote Keys—Offshore 28°10.0′ 83°45... Point No. and reference location 1 North lat. West long. 1Seaward limit of Florida's waters northeast of...

50 CFR Appendix B to Part 622 - Gulf Areas

Code of Federal Regulations, 2011 CFR

2011-10-01

... Restricted Area Point No. and reference location 1 North lat. West long. 1Seaward limit of Florida's waters...—Offshore 26°26.0′ 82°59.0′ 4West of Egmont Key 27°30.0′ 83°21.5′ 5Off Anclote Keys—Offshore 28°10.0′ 83°45... Point No. and reference location 1 North lat. West long. 1Seaward limit of Florida's waters northeast of...

50 CFR Table 5 (south) to Part 660... - 2009-2010 Trip Limits for Open Access Gears South of 40°10′ N. Lat.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2009-2010 Trip Limits for Open Access Gears South of 40°10ⲠN. Lat. 5 Table 5 (South) to Part 660, Subpart G Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OFF WEST COAST STATES Pt....

50 CFR Table 5 (north) to Part 660... - 2009-2010 Trip Limits for Open Access Gears North of 40°10′ N. Lat.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2009-2010 Trip Limits for Open Access Gears North of 40°10ⲠN. Lat. 5 Table 5 (North) to Part 660, Subpart G Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OFF WEST COAST STATES Pt....

Joint Collaborative Technology Experiment (JCTE)

DTIC Science & Technology

2010-12-01

Rm = Earth meridian radius Rn = Earth normal radius Compute: α = ψ + β Lat ldg = Lat ant – (r * cos ( α )) / Rm Lon ldg = Lon ant – (r...Watt selectable Comm-Payload Hardware mounted to 24-in x 7-in x 0.25-in (Length x Width x Thick) Aluminum (AL) plate Designed for dual carriage...was installed into a 24-in long by 7.5-in inner diameter fiberglass tube. This integration included modifying two 7.5-in diameter aluminum endplates

The role of latex agglutination test for the etiological diagnosis of pleural effusion in children and adolescents.

PubMed

Camargos, Paulo; Fonseca, Ana Cristina; Amantéa, Sérgio; Oliveira, Elizabeth; Benfica, Maria das Graças; Chamone, Chequer

2017-05-01

The etiological diagnosis of pleural effusion is a difficult task because the diagnostic tools can only establish a definitive etiological diagnosis in at most 76% of cases. To verify the diagnostic accuracy of the latex agglutination test (LAT) for the etiological diagnosis of pleural effusions caused by Streptococcus pneumoniae and Haemophilus influenzae type b. After thoracocentesis, paired fresh samples of pleural fluid from 418 children and adolescents were included in this investigation. They were tested blindly and simultaneously through counterimmunoelectrophoresis (CIE) and LAT for both bacteria. Sensitivity, specificity, predictive values and likelihood ratios (LR) were calculated taking CIE as a reference standard. The sensitivity and specificity of LAT was 100% (95% confidence interval, 94.4%-100%) and 83.3% (95% confidence interval, 79.0%-87.0%), respectively, whereas the positive (calculated from Bayes' theorem) and negative predictive values were, respectively, lower than 1% and 100% (95% confidence interval, 98.8%-100%). Positive and negative LR were 6.0 (95% confidence interval, 4.7-7.6) and zero, respectively. Our results suggest that LAT is a useful tool for the etiological diagnosis of pleural effusion. It is a reliable, rapid, simple to perform and shows an excellent yield in our studied population, helping to prescribe appropriate antibiotics for this clinical condition. © 2015 John Wiley & Sons Ltd.

FERMI large area telescope observations of the vela-x pulsar wind nebula

DOE PAGES

Abdo, A. A.; Ackermann, M.; Ajello, M.; ...

2010-03-18

Here, we report on gamma-ray observations in the off-pulse window of the Vela pulsar PSR B0833–45 using 11 months of survey data from the Fermi Large Area Telescope (LAT). This pulsar is located in the 8° diameter Vela supernova remnant, which contains several regions of non-thermal emission detected in the radio, X-ray, and gamma-ray bands. The gamma-ray emission detected by the LAT lies within one of these regions, the 2° × 3° area south of the pulsar known as Vela-X. The LAT flux is significantly spatially extended with a best-fit radius of 0°more » $$_.$$88 ± 0°$$_.$$12 for an assumed radially symmetric uniform disk. The 200 MeV to 20 GeV LAT spectrum of this source is well described by a power law with a spectral index of 2.41 ± 0.09 ± 0.15 and integral flux above 100 MeV of (4.73 ± 0.63 ± 1.32) × 10 –7 cm –2 s –1. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Detailed morphological and spectral analyses give strong constraints on the energetics and magnetic field of the pulsar wind nebula system and favor a scenario with two distinct electron populations.« less

Latin American Network of students in Atmospheric Sciences and Meteorology

NASA Astrophysics Data System (ADS)

Cuellar-Ramirez, P.

2017-12-01

The Latin American Network of Students in Atmospheric Sciences and Meteorology (RedLAtM) is a civil nonprofit organization, organized by students from Mexico and some Latin- American countries. As a growing organization, providing human resources in the field of meteorology at regional level, the RedLAtM seeks to be a Latin American organization who helps the development of education and research in Atmospheric Sciences and Meteorology in order to engage and promote the integration of young people towards a common and imminent future: Facing the still unstudied various weather and climate events occurring in Latin America. The RedLAtM emerges from the analysis and observation/realization of a limited connection between Latin American countries around research in Atmospheric Sciences and Meteorology. The importance of its creation is based in cooperation, linking, research and development in Latin America and Mexico, in other words, to join efforts and stablish a regional scientific integration who leads to technological progress in the area of Atmospheric Sciences and Meteorology. As ultimate goal the RedLAtM pursuit to develop climatic and meteorological services for those countries unable to have their own programs, as well as projects linked with the governments of Latin American countries and private companies for the improvement of prevention strategies, research and decision making. All this conducing to enhance the quality of life of its inhabitants facing problems such as poverty and inequality.

Multiple-wavelength Variability and Quasi-periodic Oscillation of PMN J0948+0022

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jin; Zhang, Hai-Ming; Zhu, Yong-Kai

We present a comprehensive analysis of multiple-wavelength observational data of the first GeV-selected narrow-line Seyfert 1 galaxy PMN J0948+0022. We derive its light curves in the γ -ray and X-ray bands from the data observed with Fermi /LAT and Swift /XRT, and generate the optical and radio light curves by collecting the data from the literature. These light curves show significant flux variations. With the LAT data we show that this source is analogous to typical flat spectrum radio quasars in the L {sub γ} –Γ {sub γ} plane, where L {sub γ} and Γ {sub γ} are the luminositymore » and spectral index in the LAT energy band. The γ -ray flux is correlated with the V-band flux with a lag of ∼44 days, and a moderate quasi-periodic oscillation (QPO) with a periodicity of ∼490 days observed in the LAT light curve. A similar QPO signature is also found in the V-band light curve. The γ -ray flux is not correlated with the radio flux in 15 GHz, and no similar QPO signature is found at a confidence level of 95%. Possible mechanisms of the QPO are discussed. We propose that gravitational-wave observations in the future may clarify the current plausible models for the QPO.« less

Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function

PubMed Central

May, Rebecca M.; Okumura, Mariko; Hsu, Chin-Jung; Bassiri, Hamid; Yang, Enjun; Rak, Gregory; Mace, Emily M.; Philip, Naomi H.; Zhang, Weiguo; Baumgart, Tobias; Orange, Jordan S.; Nichols, Kim E.

2013-01-01

Signaling pathways leading to natural killer (NK)–cell effector function are complex and incompletely understood. Here, we investigated the proximal signaling pathways downstream of the immunotyrosine-based activation motif (ITAM) bearing activating receptors. We found that the adaptor molecule SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is recruited to microclusters at the plasma membrane in activated NK cells and that this is required for initiation of downstream signaling and multiple NK-cell effector functions in vitro and in vivo. Surprisingly, we found that 2 types of proximal signaling complexes involving SLP-76 were formed. In addition to the canonical membrane complex formed between SLP-76 and linker for activation of T cells (LAT) family members, a novel LAT family–independent SLP-76–dependent signaling pathway was identified. The LAT family–independent pathway involved the SH2 domain of SLP-76 and adhesion and degranulation-promoting adaptor protein (ADAP). Both the LAT family–dependent and ADAP-dependent pathway contributed to interferon-gamma production and cytotoxicity; however, they were not essential for other SLP-76–dependent events, including phosphorylation of AKT and extracellular signal–related kinase and cellular proliferation. These results demonstrate that NK cells possess an unexpected bifurcation of proximal ITAM-mediated signaling, each involving SLP-76 and contributing to optimal NK-cell function. PMID:23407547

Actin-binding and cell proliferation activities of angiomotin family members are regulated by Hippo pathway-mediated phosphorylation.

PubMed

Chan, Siew Wee; Lim, Chun Jye; Guo, Fusheng; Tan, Ivan; Leung, Thomas; Hong, Wanjin

2013-12-27

Whether the Hippo pathway has downstream targets other than YAP and TAZ is unknown. In this report, we have identified angiomotin (Amot) family members as novel substrates of Hippo core kinases. The N-terminal regions of Amot proteins contain a conserved HXRXXS consensus site for LATS1/2-mediated phosphorylation. Phospho-specific antibodies showed that Hippo core kinases could mediate phosphorylation of endogenous as well as exogenous Amot family members. Knockdown of LATS1 and LATS2 endogenously reduced the phosphorylation of Amots detected by the phospho-specific antibodies. Mutation of the serine to alanine within this HXRXXS site in Amot and AmotL2 established that this site was essential for Hippo core kinase-mediated phosphorylation. Wild-type and non-phosphorylated Amot (Amot-S175A) were targeted to actin filaments, whereas phospho-mimic Amot (Amot-S175D) failed to be localized with actin. Overexpression of LATS2 caused dissociation of Amot from actin but not Amot-S175A. Mapping of the actin-binding site of Amot showed that serine 175 of Amot was important for the actin-binding activity. Amot-S175A promoted, whereas Amot and Amot-S175D inhibited, cell proliferation. These results collectively suggest that the Hippo pathway negatively regulates the actin-binding activity of Amot family members through direct phosphorylation.

Assessing risk of navigational hazard from sea-level-related datum in the South West of Java Sea, Indonesia

NASA Astrophysics Data System (ADS)

Poerbandono

2017-07-01

This paper assesses the presence of navigational hazards due to underestimation of charted depths originated from an establishment of a sea-level-related reference plane, i.e. datum. The study domain is situated in one of Indonesia's densest marine traffic, SW Java Sea, Indonesia. The assessment is based on the comparison of the authorized Chart Datum (CD), being uniformly located at 0.6 m below Mean Sea Level (MSL), and a spatially varying Lowest Astronomical Tide (LAT) generated for the purpose of this research. Hazards are considered here as the deviation of LAT from CD and quantified as the ratio of LAT -CD deviation with respect to the allowable Total Vertical Uncertainty (TVU), i.e. the international standard for accuracy of depth information on nautical charts. Underestimation of charted depth is expected for the case that LAT falls below CD. Such a risk magnifies with decreasing depths, as well as the increasing volume of traffic and draught of the vessel. It is found that most of the domain is in the interior of risk-free zone from using uniform CD. As much as 0.08 and 0.19 parts of the area are in zones where the uncertainty of CD contributes respectively to 50% and 30% of Total Vertical Uncertainty. These are zones where the hazard of navigation is expected to increase due to underestimated lowest tidal level.

HESS J1640-465 and HESS J1641-463: Two Intriguing TeV Sources in Light of New Fermi-LAT Observations

NASA Astrophysics Data System (ADS)

Lemoine-Goumard, M.; Grondin, M.-H.; Acero, F.; Ballet, J.; Laffon, H.; Reposeur, T.

2014-10-01

We report on γ-ray analysis of the region containing the bright TeV source HESS J1640-465 and the close-by TeV source HESS J1641-463 using 64 months of observations with the Fermi Large Area Telescope (LAT). Previously only one GeV source was reported in this region and was associated with HESS J1640-465. With an increased data set and the improved sensitivity afforded by the reprocessed data (P7REP) of the LAT, we now report the detection, morphological study, and spectral analysis of two distinct sources above 100 MeV. The softest emission in this region comes from the TeV source HESS J1641-463 which is well fitted with a power law of index Γ = 2.47 ± 0.05 ± 0.06 and presents no significant γ-ray signal above 10 GeV, which contrasts with its hard spectrum at TeV energies. The Fermi-LAT spectrum of the second TeV source, HESS J1640-465 is well described by a power-law shape of index Γ = 1.99 ± 0.04 ± 0.07 that links up naturally with the spectral data points obtained by the High Energy Stereoscopic System (H.E.S.S.). These new results provide new constraints concerning the identification of these two puzzling γ-ray sources.

Regulation of Nitrate Transport in Citrus Rootstocks Depending on Nitrogen Availability

PubMed Central

Cerezo, Miguel; Camañes, Gemma; Flors, Víctor; Primo-Millo, Eduardo

2007-01-01

Previously, we reported that in Citrus plants, nitrate influx through the plasmalemma of roots cells follows a biphasic pattern, suggesting the existence of at least two different uptake systems, a high and low affinity transport system (HATS and LATS, respectively). Here, we describe a novel inducible high affinity transport system (iHATS). This new nitrate transport system has a high capacity to uptake nitrate in two different Citrus rootstocks (Cleopatra mandarin and Troyer citrange). The iHATS was saturable, showing higher affinity than constitutive high affinity transport system (cHATS) to the substrate NO3−. The Vmax for this saturable component iHATS was higher than cHATS, reaching similar values in both rootstocks. Additionally, we studied the regulation of root NO3− uptake mediated by both HATS (iHATS and cHATS) and LATS. In both rootstocks, cHATS is constitutive and independent of N-status. Concerning the regulation of iHATS, this system is upregulated by NO3− and down-regulated by the N status and by NO3− itself when plants are exposed to it for a longer period of time. LATS in Cleopatra mandarin and Troyer citrange rootstocks is repressed by the N-status. The use of various metabolic uncouplers or inhibitors indicated that NO3− net uptake mediated by iHATS and LATS was an active transport system in both rootstocks. PMID:19516998

Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS

DOE PAGES

Huang, William Y. C.; Yan, Qingrong; Lin, Wan-Chen; ...

2016-07-01

The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kineticsmore » and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. In conclusion, the generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.« less

The Sensitivity of Atlantic Meridional Overturning Circulation to Dynamical Framework in an Ocean General Circulation Model

NASA Astrophysics Data System (ADS)

Li, X.; Yu, Y.

2016-12-01

The horizontal coordinate systems commonly used in most global ocean models are the sphere latitude-longitude grid and displaced poles such as tripolar grid. The effect of the horizontal coordinate system on Atlantic Meridional Overturning Circulation (AMOC) is evaluated using an oceanic general circulation model (OGCM). Two experiments are conducted with the model using latitude-longitude grid (Lat_1) and tripolar grid (Tri). Results show that Tri simulates a stronger NADW than Lat_1, as more saline water masses enter into the GIN Seas in Tri. Two reasons can be attributed to the stronger NADW. One is the removal of zonal filter in Tri, which leads to an increasing of zonal gradient of temperature and salinity, thus strengthens the north geostrophic flow. In turn, it decreases the positive subsurface temperature and salinity biases in the subtropical regions. The other may be associated with topography at the North Pole, because the realistic topography is applied in tripolar grid and the longitude-latitude grid employs an artificial island around the North Pole. In order to evaluate the effect of filter on AMOC, three enhanced filter experiments are carried out. Compared to Lat_1, enhanced filter can also increase the NADW, for more saline water is suppressed to go north and accumulated in the Labrador Sea, especially in the experiment with enhanced filter on salinity (Lat_2_S).

Limits on dark matter annihilation signals from the Fermi LAT 4-year measurement of the isotropic gamma-ray background

DOE PAGES

Ackermann, M.

2015-09-02

We search for evidence of dark matter (DM) annihilation in the isotropic gamma-ray background (IGRB) measured with 50 months of Fermi Large Area Telescope (LAT) observations. An improved theoretical description of the cosmological DM annihilation signal, based on two complementary techniques and assuming generic weakly interacting massive particle (WIMP) properties, renders more precise predictions compared to previous work. More specifically, we estimate the cosmologically-induced gamma-ray intensity to have an uncertainty of a factor ~ 20 in canonical setups. We consistently include both the Galactic and extragalactic signals under the same theoretical framework, and study the impact of the former onmore » the IGRB spectrum derivation. We find no evidence for a DM signal and we set limits on the DM-induced isotropic gamma-ray signal. Our limits are competitive for DM particle masses up to tens of TeV and, indeed, are the strongest limits derived from Fermi LAT data at TeV energies. This is possible thanks to the new Fermi LAT IGRB measurement, which now extends up to an energy of 820 GeV. As a result, we quantify uncertainties in detail and show the potential this type of search offers for testing the WIMP paradigm with a complementary and truly cosmological probe of DM particle signals.« less

Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS

PubMed Central

Huang, William Y. C.; Yan, Qingrong; Lin, Wan-Chen; Chung, Jean K.; Hansen, Scott D.; Christensen, Sune M.; Tu, Hsiung-Lin; Kuriyan, John; Groves, Jay T.

2016-01-01

The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes. PMID:27370798

Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS.

PubMed

Huang, William Y C; Yan, Qingrong; Lin, Wan-Chen; Chung, Jean K; Hansen, Scott D; Christensen, Sune M; Tu, Hsiung-Lin; Kuriyan, John; Groves, Jay T

2016-07-19

The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.

Limits on dark matter annihilation signals from the Fermi LAT 4-year measurement of the isotropic gamma-ray background

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collaboration: Fermi LAT Collaboration

2015-09-01

We search for evidence of dark matter (DM) annihilation in the isotropic gamma-ray background (IGRB) measured with 50 months of Fermi Large Area Telescope (LAT) observations. An improved theoretical description of the cosmological DM annihilation signal, based on two complementary techniques and assuming generic weakly interacting massive particle (WIMP) properties, renders more precise predictions compared to previous work. More specifically, we estimate the cosmologically-induced gamma-ray intensity to have an uncertainty of a factor ∼ 20 in canonical setups. We consistently include both the Galactic and extragalactic signals under the same theoretical framework, and study the impact of the former on themore » IGRB spectrum derivation. We find no evidence for a DM signal and we set limits on the DM-induced isotropic gamma-ray signal. Our limits are competitive for DM particle masses up to tens of TeV and, indeed, are the strongest limits derived from Fermi LAT data at TeV energies. This is possible thanks to the new Fermi LAT IGRB measurement, which now extends up to an energy of 820 GeV. We quantify uncertainties in detail and show the potential this type of search offers for testing the WIMP paradigm with a complementary and truly cosmological probe of DM particle signals.« less

Pre-launch estimates for GLAST sensitivity to dark matter annihilation signals

DOE PAGES

Baltz, E. A.; Berenji, B.; Bertone, G.; ...

2008-07-17

Here, we investigate the sensitivity of the Gamma-ray Large Area Space Telescope (GLAST) to indirectly detect weakly interacting massive particles (WIMPs) through the γ-ray signal that their pair annihilation produces. WIMPs are among the favorite candidates to explain the compelling evidence that about 80% of the mass in the Universe is non-baryonic dark matter (DM). They are serendipitously motivated by various extensions of the standard model of particle physics such as Supersymmetry and Universal Extra Dimensions (UED). With its unprecedented sensitivity and its very large energy range (20 MeV to more than 300 GeV) the main instrument on board themore » GLAST satellite, the Large Area Telescope (LAT), will open a new window of discovery. As our estimates show, the LAT will be able to detect an indirect DM signature for a large class of WIMP models given a cuspy profile for the DM distribution. Using the current state of the art Monte Carlo and event reconstruction software developed within the LAT collaboration, we present preliminary sensitivity studies for several possible sources inside and outside the Galaxy. Lastly, we also discuss the potential of the LAT to detect UED via the electron/positron channel. Diffuse background modeling and other background issues that will be important in setting limits or seeing a signal are presented.« less

The Hippo Pathway: Immunity and Cancer.

PubMed

Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

2018-03-28

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

76 FR 80226 - Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... final rule, effective upon publication. Generally, the Administrative Procedure Act (APA) requires a.... Additionally, the APA requires that a final rule must have a delayed effective date of 30 days from the date of... delayed effective date requirement under the APA. 5 U.S.C. 553(d)(3). Again the technical change conforms...