31 research outputs found
Fermi Large Area Telescope View of the Core of the Radio Galaxy Centaurus A
We present gamma-ray observations with the LAT on board the Fermi Gamma-Ray
Telescope of the nearby radio galaxy Centaurus~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
(\G=2.67\pm0.10_{stat}\pm0.08_{sys} where the photon flux is \Phi\propto
E^{-\G}). 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 (TANAMI) 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 2004-2008. The fit requires a
low Doppler factor, in contrast to BL Lacs which generally require larger
values to fit their broadband SEDs. This indicates the \g-ray emission
originates from a slower region than that from BL Lacs, 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.Comment: Accepted by ApJ. 32 pages, 5 figures, 2 tables. J. Finke and Y.
Fukazawa corresponding author
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Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks
无线传感器网络,作为全球未来十大技术之一,集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术,可实时感知、采集、处理、传输网络分布区域内的各种信息数据,在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议,并针对大规模的无线传感器网络设计了一种树状路由协议,它根据节点地址信息来形成路由,从而简化了复杂繁冗的路由表查找和维护,节省了不必要的开销,提高了路由效率,实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR(AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位:工学硕士院系专业:信息科学与技术学院通信工程系_通信与信息系统学号:2332007115216
Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade
AMPK (AMP-activated protein kinase) is activated allosterically by AMP and by phosphorylation of Thr(172) within the catalytic α subunit. Here we show that mutations in the regulatory γ subunit reduce allosteric activation of the kinase by AMP. In addition to its allosteric effect, AMP significantly reduces the dephosphorylation of Thr(172) by PP (protein phosphatase)2Cα. Moreover, a mutation in the γ subunit almost completely abolishes the inhibitory effect of AMP on dephosphorylation. We were unable to detect any effect of AMP on Thr(172) phosphorylation by either LKB1 or CaMKKβ (Ca(2+)/calmodulin-dependent protein kinase kinase β) using recombinant preparations of the proteins. However, using partially purified AMPK from rat liver, there was an apparent AMP-stimulation of Thr(172) phosphorylation by LKB1, but this was blocked by the addition of NaF, a PP inhibitor. Western blotting of partially purified rat liver AMPK and LKB1 revealed the presence of PP2Cα in the preparations. We suggest that previous studies reporting that AMP promotes phosphorylation of Thr(172) were misinterpreted. A plausible explanation for this effect of AMP is inhibition of dephosphorylation by PP2Cα, present in the preparations of the kinases used in the earlier studies. Taken together, our results demonstrate that AMP activates AMPK via two mechanisms: by direct allosteric activation and by protecting Thr(172) from dephosphorylation. On the basis of our new findings, we propose a simple model for the regulation of AMPK in mammalian cells by LKB1 and CaMKKβ. This model accounts for activation of AMPK by two distinct signals: a Ca(2+)-dependent pathway, mediated by CaMKKβ and an AMP-dependent pathway, mediated by LKB1
Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA<sub>2</sub>)
Lp-PLA<sub>2</sub> has been explored as a target for a number of
inflammation associated diseases, including cardiovascular disease
and dementia. This article describes the discovery of a new fragment
derived chemotype that interacts with the active site of Lp-PLA<sub>2</sub>. The starting fragment hit was discovered through an X-ray
fragment screen and showed no activity in the bioassay (IC<sub>50</sub> > 1 mM). The fragment hit was optimized using a variety of structure-based
drug design techniques, including virtual screening, fragment merging,
and improvement of shape complementarity. A novel series of Lp-PLA<sub>2</sub> inhibitors was generated with low lipophilicity and a promising
pharmacokinetic profile
How Health Professionals Conceptualize and Represent Placebo Treatment in Clinical Trials and How Their Patients Understand It: Impact on Validity of Informed Consent
Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA<sub>2</sub>) Discovered through X‑ray Fragment Screening
Elevated levels of
human lipoprotein-associated phospholipase A2
(Lp-PLA<sub>2</sub>) are associated with cardiovascular disease and
dementia. A fragment screen was conducted against Lp-PLA<sub>2</sub> in order to identify novel inhibitors. Multiple fragment hits were
observed in different regions of the active site, including some hits
that bound in a pocket created by movement of a protein side chain
(approximately 13 Å from the catalytic residue Ser273). Using
structure guided design, we optimized a fragment that bound in this
pocket to generate a novel low nanomolar chemotype, which did not
interact with the catalytic residues
Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA<sub>2</sub>) Discovered through X‑ray Fragment Screening
Elevated levels of
human lipoprotein-associated phospholipase A2
(Lp-PLA<sub>2</sub>) are associated with cardiovascular disease and
dementia. A fragment screen was conducted against Lp-PLA<sub>2</sub> in order to identify novel inhibitors. Multiple fragment hits were
observed in different regions of the active site, including some hits
that bound in a pocket created by movement of a protein side chain
(approximately 13 Å from the catalytic residue Ser273). Using
structure guided design, we optimized a fragment that bound in this
pocket to generate a novel low nanomolar chemotype, which did not
interact with the catalytic residues