327 research outputs found
Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity
<p>Abstract</p> <p>Background</p> <p>Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.</p> <p>Methods</p> <p>We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.</p> <p>Results</p> <p>The 50% effective inhibitory concentration (IC<sub>50</sub>) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.</p> <p>Conclusions</p> <p>To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.</p
The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies
Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity
The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys
We present new quasars discovered in the vicinity of the Andromeda and
Triangulum galaxies with the LAMOST during the 2010 and 2011 observational
seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m
telescope, XSTPS optical, and WISE near infrared photometric data. We present
509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along
the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new
quasars discovered in an area of ~100 sq. deg that covers the central region
and the southeastern halo of M31 in the 2010 commissioning datasets. These 526
new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to
3.2. They represent a significant increase of the number of identified quasars
in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in
this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0
respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars
provide an invaluable collection with which to probe the kinematics and
chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars
are now known with locations within 2.5 deg of M31, of which 73 are newly
discovered. Tens of quasars are now known to be located behind the Giant
Stellar Stream, and hundreds behind the extended halo and its associated
substructures of M31. The much enlarged sample of known quasars in the vicinity
of M31 and M33 can potentially be utilized to construct a perfect astrometric
reference frame to measure the minute PMs of M31 and M33, along with the PMs of
substructures associated with the Local Group of galaxies. Those PMs are some
of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte
An IoT-based smart mosquito trap system embedded with real-time mosquito image processing by neural networks for mosquito surveillance
An essential aspect of controlling and preventing mosquito-borne diseases is to reduce mosquitoes that carry viruses. We designed a smart mosquito trap system to reduce the density of mosquito vectors and the spread of mosquito-borne diseases. This smart trap uses computer vision technology and deep learning networks to identify features of live Aedes aegypti and Culex quinquefasciatus in real-time. A unique mechanical design based on the rotation concept is also proposed and implemented to capture specific living mosquitoes into the corresponding chambers successfully. Moreover, this system is equipped with sensors to detect environmental data, such as CO2 concentration, temperature, and humidity. We successfully demonstrated the implementation of such a tool and paired it with a reliable capture mechanism for live mosquitos without destroying important morphological features. The neural network achieved 91.57% accuracy with test set images. When the trap prototype was applied in a tent, the accuracy rate in distinguishing live Ae. aegypti was 92%, with a capture rate reaching 44%. When the prototype was placed into a BG trap to produce a smart mosquito trap, it achieved a 97% recognition rate and a 67% catch rate when placed in the tent. In a simulated living room, the recognition and capture rates were 90% and 49%, respectively. This smart trap correctly differentiated between Cx. quinquefasciatus and Ae. aegypti mosquitoes, and may also help control mosquito-borne diseases and predict their possible outbreak
Measurements of the observed cross sections for exclusive light hadrons containing at , 3.650 and 3.6648 GeV
By analyzing the data sets of 17.3, 6.5 and 1.0 pb taken,
respectively, at , 3.650 and 3.6648 GeV with the BES-II
detector at the BEPC collider, we measure the observed cross sections for
, , ,
and at the three energy
points. Based on these cross sections we set the upper limits on the observed
cross sections and the branching fractions for decay into these
final states at 90% C.L..Comment: 7 pages, 2 figure
Partial wave analysis of J/\psi \to \gamma \phi \phi
Using events collected in the BESII detector, the
radiative decay is
studied. The invariant mass distribution exhibits a near-threshold
enhancement that peaks around 2.24 GeV/.
A partial wave analysis shows that the structure is dominated by a
state () with a mass of
GeV/ and a width of GeV/. The
product branching fraction is: .Comment: 11 pages, 4 figures. corrected proof for journa
Direct Measurements of Absolute Branching Fractions for D0 and D+ Inclusive Semimuonic Decays
By analyzing about 33 data sample collected at and around 3.773
GeV with the BES-II detector at the BEPC collider, we directly measure the
branching fractions for the neutral and charged inclusive semimuonic decays
to be and , and determine the ratio of the two branching
fractions to be
Measurements of the observed cross sections for exclusive light hadron production in e^+e^- annihilation at \sqrt{s}= 3.773 and 3.650 GeV
By analyzing the data sets of 17.3 pb taken at GeV
and 6.5 pb taken at GeV with the BESII detector at the
BEPC collider, we have measured the observed cross sections for 12 exclusive
light hadron final states produced in annihilation at the two energy
points. We have also set the upper limits on the observed cross sections and
the branching fractions for decay to these final states at 90%
C.L.Comment: 8 pages, 5 figur
Search for the Rare Decays J/Psi --> Ds- e+ nu_e, J/Psi --> D- e+ nu_e, and J/Psi --> D0bar e+ e-
We report on a search for the decays J/Psi --> Ds- e+ nu_e + c.c., J/Psi -->
D- e+ nu_e + c.c., and J/Psi --> D0bar e+ e- + c.c. in a sample of 5.8 * 10^7
J/Psi events collected with the BESII detector at the BEPC. No excess of signal
above background is observed, and 90% confidence level upper limits on the
branching fractions are set: B(J/Psi --> Ds- e+ nu_e + c.c.)<4.8*10^-5, B(J/Psi
--> D- e+ nu_e + c.c.) D0bar e+ e- + c.c.)<1.1*10^-5Comment: 10 pages, 4 figure
A study of charged kappa in
Based on events collected by BESII, the decay
is studied. In the invariant mass
spectrum recoiling against the charged , the charged
particle is found as a low mass enhancement. If a Breit-Wigner function of
constant width is used to parameterize the kappa, its pole locates at MeV/. Also in this channel,
the decay is observed for the first time.
Its branching ratio is .Comment: 14 pages, 4 figure
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