ABSTRACT The 1.69 ms spin period of PSR J1227−4853 was recently discovered in radio observations of the low-mass X-ray binary XSS J12270−4859 following the announcement of a possible transition to a ...rotation-powered millisecond pulsar state, inferred from decreases in optical, X-ray, and gamma-ray flux from the source. We report the detection of significant (5 ) gamma-ray pulsations after the transition, at the known spin period, using ∼1 year of data from the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. The gamma-ray light curve of PSR J1227−4853 can be fit by one broad peak, which occurs at nearly the same phase as the main peak in the 1.4 GHz radio profile. The partial alignment of light-curve peaks in different wavebands suggests that at least some of the radio emission may originate at high altitude in the pulsar magnetosphere, in extended regions co-located with the gamma-ray emission site. We folded the LAT data at the orbital period, both pre- and post-transition, but find no evidence for significant modulation of the gamma-ray flux. Analysis of the gamma-ray flux over the mission suggests an approximate transition time of 2012 November 30. Continued study of the pulsed emission and monitoring of PSR J1227−4853, and other known redback systems, for subsequent flux changes will increase our knowledge of the pulsar emission mechanism and transitioning systems.
Extensive interindividual variation in response to chemotherapy is a major stumbling block in achieving desirable efficacy in the treatment of cancers, including multiple myeloma (MM). In this study, ...our goal was to develop a gene expression signature that predicts response specific to proteasome inhibitor (PI) treatment in MM. Using a well-characterized panel of human myeloma cell lines (HMCLs) representing the biological and genetic heterogeneity of MM, we created an in vitro chemosensitivity profile in response to treatment with the four PIs bortezomib, carfilzomib, ixazomib and oprozomib as single agents. Gene expression profiling was performed using next-generation high-throughput RNA-sequencing. Applying machine learning-based computational approaches including the supervised ensemble learning methods Random forest and Random survival forest, we identified a 42-gene expression signature that could not only distinguish good and poor PI response in the HMCL panel, but could also be successfully applied to four different clinical data sets on MM patients undergoing PI-based chemotherapy to distinguish between extraordinary (good and poor) outcomes. Our results demonstrate the use of in vitro modeling and machine learning-based approaches to establish predictive biomarkers of response and resistance to drugs that may serve to better direct myeloma patient treatment options.
We present the first catalog of active galactic nuclei (AGN) detected by the LAT, corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes ...671 gamma-ray sources located at high Galactic latitudes (|b| > 10 deg) that are detected with a test statistic (TS) 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 (BL Lacs), 296 flat-spectrum radio quasars (FSRQs), 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazars based on their spectral energy distributions (SEDs) as archival radio, optical, and X-ray data permit. In addition to the format 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 gamma-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties--such as gamma-ray fluxes and photon power law spectral indices, redshifts, gamma-ray luminosities, variability, and archival radio luminosities--and their correlations are presented and discussed for the different blazar classes. We compare the 1LAC results with predictions regarding the gamma-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequence.
A major issue in any multidiscipline collaborative project is how to best share and simultaneously exploit different types of expertise, without duplicating efforts or inadvertently causing conflicts ...or loss of efficiency through misunderstanding of individual or shared goals. Moderators are knowledge based systems designed to support collaborative teams by raising awareness of potential problems or conflicts. However, the functioning of a Moderator is limited by the knowledge it has about the team members. Knowledge acquisition, learning and updating of knowledge are the major challenges for a Moderator's implementation. To address these challenges a Knowledge discOvery And daTa minINg inteGrated (KOATING) framework is presented for Moderators to enable them to continuously learn from the operational databases of the company and semi-automatically update their knowledge about team members. This enables the reuse of discovered knowledge from operational databases within collaborative projects. The integration of knowledge discovery in database (KDD) techniques into the existing Knowledge Acquisition Module of a moderator enables hidden data dependencies and relationships to be utilised to facilitate the moderation process. The architecture for the Universal Knowledge Moderator (UKM) shows how Moderators can be extended to incorporate a learning element which enables them to provide better support for virtual enterprises. Unified Modelling Language diagrams were used to specify the ways to design and develop the proposed system. The functioning of a UKM is presented using an illustrative example.
We report on the observation of the bright, long gamma-ray burst, GRB 090926A, by the Gamma-ray Burst Monitor and Large Area Telescope (LAT) instruments on board the Fermi Gamma-ray Space Telescope. ...GRB 090926A shares several features with other bright LAT bursts. In particular, it clearly shows a short spike in the light curve that is present in all detectors that see the burst, and this in turn suggests that there is a common region of emission across the entire Fermi energy range. In addition, while a separate high-energy power-law component has already been observed in other gamma-ray bursts, here we report for the first time the detection with good significance of a high-energy spectral break (or cutoff) in this power-law component around 1.4 GeV in the time-integrated spectrum. If the spectral break is caused by opacity to electron-positron pair production within the source, then this observation allows us to compute the bulk Lorentz factor for the outflow, rather than a lower limit.
Downstream purification of a model recombinant protein (human myelin basic protein) from milk of transgenic cows is described. The recombinant protein was expressed as a His tagged fusion protein in ...the milk of transgenic cows and was found associated with the casein micellar phase. While difficulties in obtaining good recoveries were found when employing conventional micelle disruption procedures, direct capture using the cation exchanger SP Sepharose Big Beads™ was found successful in the extraction of the recombinant protein. Early breakthrough suggested a slow release of the recombinant protein from the micelles and dictated micelle disruption in order to obtain good yields. A new approach for deconstruction of the calcium core of the casein micelles, employing the interaction between the micellar calcium and the active sites of the cation exchanger resin was developed. Milk samples were loaded to the column in aliquots with a column washing step after each aliquot. This sequential loading approach successfully liberated the recombinant protein from the micelles and was found superior to the conventional sample loading approach. It increased the recovery by more than 25%, reduced fouling due to milk components and improved the column hydrodynamic properties as compared to the conventional sample loading approach. Hardware and software modifications to the chromatography system were necessary in order to keep the whole process automated. A second purification step using a Ni
2+ affinity column was used to isolate the recombinant protein at purity more than 90% and a recovery percentage of 78%.
We present observations of the young supernova remnant (SNR) RX J1713.7--3946 with the Fermi Large Area Telescope (LAT). We clearly detect a source positionally coincident with the SNR. The source is ...extended with a best-fit extension of 055 ? 004 matching the size of the non-thermal X-ray and TeV gamma-ray emission from the remnant. The positional coincidence and the matching extended emission allow us to identify the LAT source with SNR RX J1713.7--3946. The spectrum of the source can be described by a very hard power law with a photon index of Delta *G = 1.5 ? 0.1 that coincides in normalization with the steeper H.E.S.S.-detected gamma-ray spectrum at higher energies. The broadband gamma-ray emission is consistent with a leptonic origin as the dominant mechanism for the gamma-ray emission.
We study the rotational distortions of the vacuum dipole magnetic field in the context of geometric models of the radio emission from pulsars. We find that at low altitudes the rotation deflects the ...local direction of the magnetic field by at most an angle of the order of r super(2) sub(n), where r sub(n) = r/R sub(lc), r is the radial distance, and R sub(lc) is the light cylinder radius. To the lowest (i.e., second) order in r sub(n), this distortion is symmetric with respect to the plane containing the dipole axis and the rotation axis (, k) plane. The lowest order distortion that is asymmetric with respect to the (, k) plane is third-order in r sub(n). These results confirm the common assumption that the rotational sweepback has negligible effect on the position angle (P.A.) curve. We show, however, that the influence of the sweepback on the outer boundary of the open field line region (open volume) is a much larger effect, of the order of r super(1) sub(n) super(/2). The open volume is shifted backward with respect to the rotation direction by an angle d sub(ov) 6 0.2 sin ar super(1) sub(n) super(/2), where a is the dipole inclination with respect to the rotation axis. The associated phase shift of the pulse profile phi sub(ov) 6 0.2r super(1) sub(n) super(/2) can easily exceed the shift caused by combined effects of aberration and propagation time delays (-2r sub(n)). This strongly affects the misalignment of the center of the P.A. curve and the center of the pulse profile, thereby modifying the delay-radius relation. Contrary to intuition, the effect of sweepback dominates over other effects when emission occurs at low altitudes. For r sub(n) 3 x 10 super(-3) the shift becomes negative; i.e., the center of the P.A. curve precedes the profile center. With the sweepback effect included, the modified delay-radius relation predicts larger emission radii and is in much better agreement with the other methods of determining r sub(n).
The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the ...target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment.
Our primary objectives were to determine: the relative virulence of porcine circovirus (PCV) 2a and PCV2b, if heterologous infection induces severe illness, and the relative concentration of PCV2a ...and PCV2b in tissues of heterologously infected pigs. In experiment 1, 18 germ-free piglets served as controls or were infected with PCV2a or PCV2b. Half were immune stimulated with keyhole limpet hemocyanin (KLH) emulsified in incomplete Freund's adjuvant (2aKLH, 2bKLH). No piglets demonstrated severe illness. Lesion severity did not differ, but PCV2 capsid staining was more intense in 2a- than 2b-infected pigs (
P
<
.05). In experiment 2, 20 germ-free piglets were dual inoculated 7 days apart with PCV2a and PCV2b (2a2b, 2b2a), PCV2b twice (2b2b), or PCV2a (2a2a) twice. Five of 9 heterologous-infected pigs developed severe illness. All heterologously infected pigs demonstrated ascites or edema, and 8/9 developed thymic atrophy. By contrast, 1 of 5 2b2b-infected pigs developed bronchopneumonia and pleural effusion. No 2a2a-infected pig developed illness. Gross lesions were more severe in heterologously infected pigs than in 2b2b pigs (
P
<
.05), and were more severe in 2b2b than 2a2a pigs (
P
<
.05). PCV2 capsid staining intensity did not differ by group. In heterologously infected pigs, higher levels of PCV2 DNA reflective of the first inoculum compared to the second were found in mesenteric lymph node (
P
=
.04), spleen (
P
=
.004) and liver (
P
=
.04). These results indicate that dual heterologous PCV2a/2b inoculation 7 days apart may induce severe clinical illness, but PCV2a and PCV2b when administered singularly or in combination with KLH appear to be of equivalent virulence.
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