Search

Objectives Low-grade serous ovarian carcinomas (LGSOC) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30–60% of LGSOC. A phase II study of the MEK inhibitor selumetinib showed promising response rate of 15% in LGSOC and binimetinib, a potent MEK1/2 inhibitor, has demonstrated activity across multiple cancers. Methods MILO (MEK-Inhibitor in Low-grade Serous Ovarian Cancer)/ENGOT-ov11 was an open-label, 2:1-randomized study of binimetinib (45-mg BID) vs PCC in LGSOC. Eligible patients had recurrent or persistent measurable LGSOC following ≥1 prior platinum-based chemotherapy, ≤3 prior chemotherapy lines, and no prior MEK-or BRAF-inhibitor. The primary endpoint was progression-free survival (PFS) by blinded central review; additional assessments: overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety.(NCT01849874). Results 303 patients were randomized (201 binimetinib,102 PCC). Median PFS was 9.1 months (95% CI:7.3,11.3) for binimetinib and 10.6 months (95% CI:9.2,14.5) for PCC (HR:1.21(0.79,1.86);closed early for futility). Secondary efficacy endpoints were similar in the two groups: ORR 16%(complete/partial responses[CR/PRs]=32) vs 13%(CR/PRs=13); median DOR 8.1 (range:0.3–12.0+ months) vs 6.7 (0.3–9.7+ months); and median OS 25.3 vs 20.8 months, for binimetinib and PCC, respectively. Safety results were consistent with known safety profile of binimetinib; most common ≥grade 3 events were blood CK increased(20%) and hypertension(20%). Post-hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Conclusions Although MILO did not meet its primary endpoint, binimetinib showed activity in LGSOC across the efficacy endpoints evaluated. Chemotherapy responses were higher than predicted. Further evaluation is warranted.

We report the identification of a bright hard X-ray source dominating the M31 bulge above 25 keV from a simultaneous NuSTAR-Swift observation. We find that this source is the counterpart to Swift J0042.6+4112, which was previously detected in the Swift BAT All-sky Hard X-ray Survey. This Swift BAT source had been suggested to be the combined emission from a number of point sources; our new observations have identified a single X-ray source from 0.5 to 50 keV as the counterpart for the first time. In the 0.5-10 keV band, the source had been classified as an X-ray binary candidate in various Chandra and XMM studies; however, since it was not clearly associated with Swift J0042.6+4112, the previous E < 10 keV observations did not generate much attention. This source has a spectrum with a soft X-ray excess (kT~ 0.2 keV) plus a hard spectrum with a power law of Gamma ~ 1 and a cutoff around 15-20 keV, typical of the spectral characteristics of accreting pulsars. Unfortunately, any potential pulsation was undetected in the NuSTAR data, possibly due to insufficient photon statistics. The existing deep HST images exclude high-mass (>3 Msun) donors at the location of this source. The best interpretation for the nature of this source is an X-ray pulsar with an intermediate-mass (, 10 pages, 6 figures, accepted for publication in ApJ

Behavioral observations of lactating Steller sea lions (Eumetopias jubatus) and their offspring were recorded at four haulout sites in Alaska to determine (1) whether sea lions wean during winter while they are 7 to 9 mo old and (2) whether sea lions using sites in the Gulf of Alaska (the declining endangered population) made longer foraging trips than sea lions in southeast Alaska (where the population appeared larger and healthier). Longer foraging trips are commonly thought to be an indicator of nutritional stress. Eight sets of behavioral observations were made using focal and scan-sampling techniques at haulouts from 1995 to 1998 during three seasons (winter, spring, and summer). Counter to expectations, we found no significant differences between haulout populations in the time that lactating Steller sea lions spent at sea or on shore. This suggests that lactating sea lions did not have more difficulty capturing prey from winter through summer in the area of decline compared to where sea lion numbers increased. Lactating Steller sea lions in both regions did make longer foraging trips in winter than they did in spring and summer. These changes in foraging patterns among seasons were consistent among all years and sites. The proportion of time that immature Steller sea lions suckled declined through the spring to early summer, suggesting that sea lions began supplementing their milk diet with solid food in the spring. We did not observe any sea lions weaning during winter; rather, most appeared to wean at the start of the breeding season when they were 1 or 2 y old. Sea lions observed in southeast Alaska during the late 1990s while population growth was slowing suggest that most males weaned at 2 y and that about 50% of females weaned at 1 y and the remainder at 2 y.

Iron supply is thought to regulate primary production in high nitrate, low chlorophyll (HNLC) regions of the sea in both the past and the present. A critical aspect of this relationship is acquisition of iron (Fe) by phytoplankton, which occurs through a complex series of extracellular reactions that are influenced by Fe chemistry and speciation. During the first in situ mesoscale Fe-enrichment experiment in the Southern Ocean (Southern Ocean iron release experiment [SOIREE]), we monitored the uptake of Fe by three size classes of plankton and their ensuing physiological response to the Fe enrichment. Rates of Fe uptake from both inorganic Fe (Fe') and organic Fe complexes (FeL) were initially fast, indicative of Fe-limitation. After Fe enrichment phytoplankton down-regulated Fe uptake and optimized physiological performance, but by day 12 they had greatly increased their capacity to acquire Fe from FeL. The increase in Fe uptake from FeL coincided with a sixfold decrease in Fe' that followed the production of Fe-binding organic ligands. Phytoplankton were able to use organically bound Fe at rates sufficient to maintain net growth for more than 42 d. Adaptation to such shifts in Fe chemistry may contribute to bloom longevity in these polar HNLC waters.

Most information scientists appear to agree that the discipline absorbs, within its boundaries, all or part of certain other subject areas. Certain scholars, including Borko, Garrison, Rayward, James G. Williams and Martha E. Williams, have published, separately, what each of them considers those disciplines to be. My research, for which I present preliminary results in this paper, will. . .

For fifty years information scientists have argued that information science, or IS, in an interdisciplinary subject area, a claim I appraise here. I am mapping a representative sample of citations from IS article literature, from the period of 1973 to 1998, against the Dewey Decimal and Library of Congress classification schemes; thus far, through Dewey, I have de facto charted the 1970s, 1980s and early-1990s.

The Ultraviolet/Optical Telescope (UVOT) is one of three instruments onboard the Swift observatory. The photometric calibration has been published, and this paper follows up with details on other aspects of the calibration including a measurement of the point spread function with an assessment of the orbital variation and the effect on photometry. A correction for large scale variations in sensitivity over the field of view is described, as well as a model of the coincidence loss which is used to assess the coincidence correction in extended regions. We have provided a correction for the detector distortion and measured the resulting internal astrometric accuracy of the UVOT, also giving the absolute accuracy with respect to the International Celestial Reference System. We have compiled statistics on the background count rates, and discuss the sources of the background, including instrumental scattered light. In each case we describe any impact on UVOT measurements, whether any correction is applied in the standard pipeline data processing or whether further steps are recommended., Comment: Accepted for publication in MNRAS. 15 pages, 21 figures, 4 tables

In brief Shin splints, or more precisely, medial tibial stress syndrome (MTSS), are painful and troublesome. Despite treatment or activity modification, they often recur. Distinguishing MTSS, the most common running overuse injury, from other overuse injuries can help focus treatment, which starts conservatively. Recommending activity modification, ice massage, NSAIDs, and stretching is a good first step. Patients who don't respond to treatment may need additional diagnostic workup and more restrictive activity guidelines.

A Synechococcus sp. strain PCC 7002 Fe bioreporter was constructed containing the isiAB promoter fused to the Vibrio harveyi luxAB genes. Bioreporter luminescence was characterized with respect to the free ferric ion concentration in trace metal-buffered synthetic medium. The applicability of the Fe bioreporter to assess Fe availability in the natural environment was tested by using samples collected from the Baltic Sea and from the high-nutrient, low-chlorophyll subarctic Pacific Ocean. Parallel assessment of dissolved Fe and bioreporter response confirmed that direct chemical measurements of dissolved Fe should not be considered alone when assessing Fe availability to phytoplankton.

We present the photometric calibration of the Swift UltraViolet/Optical Telescope (UVOT) which includes: optimum photometric and background apertures, effective area curves, colour transformations, conversion factors for count rates to flux, and the photometric zero points (which are accurate to better than 4 per cent) for each of the seven UVOT broadband filters. The calibration was performed with observations of standard stars and standard star fields that represent a wide range of spectral star types. The calibration results include the position dependent uniformity, and instrument response over the 1600-8000A operational range. Because the UVOT is a photon counting instrument, we also discuss the effect of coincidence loss on the calibration results. We provide practical guidelines for using the calibration in UVOT data analysis. The results presented here supersede previous calibration results., Comment: Minor improvements after referees report. Accepted for publication in MNRAS

Although the link between long Gamma Ray Bursts (GRBs) and supernovae (SNe) has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know however how a GRB jet emerges from the star surface nor how a GRB progenitor explodes. Here we report on observations of the close GRB060218 and its connection to SN2006aj. In addition to the classical non-thermal emission, GRB060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/UV band as time passes. We interpret these features as arising from the break out of a shock driven by a mildly relativistic shell into the dense wind surrounding the progenitor. Our observations allow us for the first time to catch a SN in the act of exploding, to directly observe the shock break-out and to provide strong evidence that the GRB progenitor was a Wolf-Rayet star., Comment: 12 pages, 3 color figures (final version). Accepted for publication in Nature

We present Swift-UVOT data on the optical afterglow of the X-ray flash of 2005 April 6 (XRF 050406) from 88s to \sim 10^5s after the initial prompt gamma-ray emission. Our observations in the V, B and U bands are the earliest that have been taken of an XRF optical counterpart. Combining the early -time optical temporal and spectral properties with \gamma- and simultaneous X-ray data taken with the BAT and XRT telescopes on-board Swift, we are able to constrain possible origins of the XRF. The prompt emission had a FRED profile (fast-rise, exponential decay) with a duration of T_90 = 5.7\pm 0.2s, putting it at the short end of the long-burst duration distribution. The absence of photoelectric absorption red-ward of 4000 \AA in the UV/optical spectrum provides a firm upper limit of z\leq 3.1 on the redshift, thus excluding a high redshift as the sole reason for the soft spectrum. The optical light curve is consistent with a power-law decay with slope alpha = -0.75\pm 0.26 (F_{\nu}\propto t^{\alpha}), and a maximum occurring in the first 200s after the initial gamma-ray emission. The softness of the prompt emission is well described by an off-axis structured jet model, which is able to account for the early peak flux and shallow decay observed in the optical and X-ray bands., Comment: 14 pages, 4 figures, accepted for publication in ApJ; typos corrected and upper limits in table 1 changed from background subtracted count rate in extraction region to the error associated with this

An improved knowledge of iron biogeochemistry is needed to better understand key controls on the functioning of high-nitrate low-chlorophyll (HNLC) oceanic regions. Iron budgets for HNLC waters have been constructed using data from disparate sources ranging from laboratory algal cultures to ocean physics. In summer 2003 we conducted FeCycle, a 10-day mesoscale tracer release in HNLC waters SE of New Zealand, and measured concurrently all sources (with the exception of aerosol deposition) to, sinks of iron from, and rates of iron recycling within, the surface mixed layer. A pelagic iron budget (timescale of days) indicated that oceanic supply terms (lateral advection and vertical diffusion) were relatively small compared to the main sink (downward particulate export). Remote sensing and terrestrial monitoring reveal 13 dust or wildfire events in Australia, prior to and during FeCycle, one of which may have deposited iron at the study location. However, iron deposition rates cannot be derived from such observations, illustrating the difficulties in closing iron budgets without quantification of episodic atmospheric supply. Despite the threefold uncertainties reported for rates of aerosol deposition (Duce et al., 1991), published atmospheric iron supply for the New Zealand region is ∼50-fold (i.e., 7- to 150-fold) greater than the oceanic iron supply measured in our budget, and thus was comparable (i.e., a third to threefold) to our estimates of downward export of particulate iron. During FeCycle, the fluxes due to short term (hours) biological iron uptake and regeneration were indicative of rapid recycling and were tenfold greater than for new iron (i.e. estimated atmospheric and measured oceanic supply), giving an “fe” ratio (uptake of new iron/uptake of new + regenerated iron) of 0.17 (i.e., a range of 0.06 to 0.51 due to uncertainties on aerosol iron supply), and an “Fe” ratio (biogenic Fe export/uptake of new + regenerated iron) of 0.09 (i.e., 0.03 to 0.24).

Among the 57 monoclonal antibodies analyzed within the T-cell group of the Second International Swine CD Workshop, one mAb fell within cluster T14a that included the CD6 standard a38b2 (No. 175). The new mAb MIL8 (No. 082) and a38b2 both precipitated from activated T-cells a 150 kDa monomeric protein. Staining patterns on the various cell types were similar. There was no inhibition of binding of either mAb to peripheral blood T-cells with the opposite mAb. The new mAb, MIL8, reacts with a separate epitope on porcine wCD6.

We report the discovery of a low dimensional dynamical system in a 5.5 hr Hubble Space Telescope High Speed Photometer observation of a rapidly oscillating star. The topological description of the phase space orbits is given, as well as a dynamical model which describes the results. This model should motivate theorists of stellar pulsations to search for a three-dimensional system with the same topological structure to describe the mechanisms for pulsation. The equations are compatible with recently proposed nonlinear mode interaction models., Comment: 6 pages, LaTex, Figures available upon request to padi@lhea1.gsfc.nasa.gov

A power supply designed to operate a high-efficiency, ten-watt TWT used as the power amplifier in a communications satellite is described. The electrical environment in which the power supply must operate and the required functional outputs are defined. Emphasis is placed on efficiency and regulation of the high-voltage converter. Operation is outlined by use of a functional block diagram and description of the primary power-handling circuits. Command, monitoring, and fault control, while vital to the proper operation of the amplifier, are not topics of this paper. The high-voltage converter achieves primary regulation through pulse-width modulation. The basic relationships which control its design, and the base drive circuit used to modulate the pulse width are described. An energyrecovery system using a two-winding inductor is employed in conjunction with the buck-mode converter. The principal sources of dissipation in the supply, contained in the highvoltage converter, are described. Relationships governing the dissipative loss in each are developed, and solved by use of a computer program. The results are presented in terms of graphs showing the effect on overall loss of varying critical parameters. Control of ripple, both externally imposed and internally developed, is a primary consideration of the power supply design. Its accomplishment is described in terms of the primary regulator, supplemental regulation by means of a linear regulator, and filtering at both input and output. Results of the design effort are summarized by a presentation of operational characteristics, and a brief description of the packaging.

The Joint Global Ocean Flux Study (JGOFS) has completed a decade of intensive process and time-series studies on the regional and temporal dynamics of biogeochemical processes in five diverse ocean basins. Its field program also included a global survey of dissolved inorganic carbon (DIC) in the ocean, including estimates of the exchange of carbon dioxide (CO2) between the ocean and the atmosphere, in cooperation with the World Ocean Circulation Experiment (WOCE). This report describes the principal achievements of JGOFS in ocean observations, technology development and modelling. The study has produced a comprehensive and high-quality database of measurements of ocean biogeochemical properties. Data on temporal and spatial changes in primary production and CO2 exchange, the dynamics of of marine food webs, and the availability of micronutrients have yielded new insights into what governs ocean productivity, carbon cycling and export into the deep ocean, the set of processes collectively known as the "biological pump." With large-scale, high-quality data sets for the partial pressure of CO2 in surface waters as well for other DIC parameters in the ocean and trace gases in the atmosphere, reliable estimates, maps and simulations of air-sea gas flux, anthropogenic carbon and inorganic carbon export are now available. JGOFS scientists have also obtained new insights into the export flux of particulate and dissolved organic carbon (POC and DOG), the variations that occur in the ratio of elements in organic matter, and the utilization and remineralization of organic matter as it falls through the ocean interior to the sediments. JGOFS scientists have amassed long-term data on temporal variability in the exchange of CO2 between the ocean and atmosphere, ecosystem dynamics, and carbon export in the oligotrophic subtropical gyres. They have documented strong links between these variables and large-scale climate patterns such as the El Nino-Southern Oscillation (ENSO) or the North Atlantic Oscillation (NAO). An increase in the abundance of organisms that fix free nitrogen (N-2) and a shift in nutrient limitation from nitrogen to phosphorus in the subtropical North Pacific provide evidence of the effects of a decade of strong El Ninos on ecosystem structure and nutrient dynamics. High-quality data sets, including ocean-color observations from satellites, have helped modellers make great strides in their ability to simulate the biogeochemical and physical constraints on the ocean carbon cycle and to extend their results from the local to the regional and global scales. Ocean carbon-cycle models, when coupled to atmospheric and terrestrial models, will make it possible in the future to predict ways in which land and ocean ecosystems might respond to changes in climate.

Electron spin transient nutation (ESTN) experiments show that the spin multiplicity of the ground state of C603- in frozen solution is a doublet with S = 1/2. In purified samples, there is no evidence for excited states or other species with higher multiplicity. In the anions of C120On- (n = 2, 3, 4), where the CW EPR experiments have shown that a mixture of species is present, ESTN experiments confirm that a doublet with S = 1/2 is associated with the 3- anion and triplets with S = 1 are associated with the 2- and 4- anions. A weak nutation peak attributable to ms = -1/2 ↔ 1/2 transitions within a quartet state may arise from association of anions with spins of 1/2 and 1 in solute aggregates.

Fil:Solari, H.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.

We analyze the Swift XRT light curves and spectra of the gamma-ray bursts (GRBs) for which the redshift has been measured. The sample consists of seven GRBs. The soft X-ray light curves of all these GRBs are separated into at least two morphological classes: 1) those starting off with a very steep light curve decay and 2) those showing a rather mild initial decay. This initial decay is followed by a flattening and by a further steepening. During these transitions the soft X-ray spectrum of these GRBs remains constant within the observational errors (except for one case, GRB050319). For the first time we are able to exploit the early light curve of GRB afterglows in the comoving frame. Besides the temporal and spectral behavior we find that the energy of the afterglow emitted in the (rest frame) time interval 20-200 s and 1300-12600 s after the trigger correlates with the mean energy of the prompt emission, hinting at a close link between the two. Averaging over the bursts that have a rather well sampled light curve and starting immediately after the prompt phase, the energy emitted in the soft X-rays is about 3% of the energy emitted during the prompt phase, except for GRB050315, where the soft X-ray emission is as high as 14% of the prompt emission., Submitted to ApJ

A woman had clinically isolated renal failure caused by granulomatous sarcoid nephritis. At the onset of her illness, there were no historical, physical, or clinical features to suggest a definite causative diagnosis. After a renal biopsy specimen disclosed noncaseating epithelioid granulomas, a course of steroid therapy resulted in prompt disappearance of uremic symptoms and amelioration of her renal failure. Although leukopenia, delayed cellular immunity, and the response to steroids increased the suspicion that the patient had sarcoidosis, it was not until identical granulomas were obtained via mediastinal node biopsy that the diagnosis was confirmed. Sarcoidosis may occur as isolated renal failure. Renal biopsy is indicated to ensure early diagnosis and prompt treatment of this steroid-responsive lesions.

著者人数: 71名, Accepted: 2004-04-14, 資料番号: SA1003385000

Swift discovered the high redshift (z=6.29) GRB050904 with the Burst Alert Telescope (BAT) and began observing with its narrow field instruments 161 s after the burst onset. This gamma-ray burst is the most distant cosmic explosion ever observed. Because of its high redshift, the X-ray Telescope (XRT) and BAT simultaneous observations provide 4 orders of magnitude of spectral coverage (0.2-150 keV; 1.4-1090 keV in the source rest frame) at a very early source-frame time (22 s). GRB050904 was a long, multi-peaked, bright GRB with strong variability during its entire evolution. The light curve observed by the XRT is characterized by the presence of a long flaring activity lasting up to 1-2 hours after the burst onset in the burst rest frame, with no evidence of a smooth power-law decay following the prompt emission as seen in other GRBs. However, the BAT tail extrapolated to the XRT band joins the XRT early light curve and the overall behavior resembles that of a very long GRB prompt. The spectral energy distribution softens with time, with the photon index decreasing from -1.2 during the BAT observation to -1.9 at the end of the XRT observation. The dips of the late X-ray flares may be consistent with an underlying X-ray emission arising from the forward shock and with the properties of the optical afterglow reported by Tagliaferri et al. (2005b). We interpret the BAT and XRT data as a single continuous observation of the prompt emission from a very long GRB. The peculiarities observed in GRB050904 could be due to its origin within one of the first star-forming regions in the Universe; very low metallicities of the progenitor at these epochs may provide an explanation., Comment: 9 pages, 2 table, 6 figures, accepted for publication on A&A