Background Imaging of Cosmic Extragalactic Polarization (BICEP) is a bolometric polarimeter designed to measure the inflationary B-mode polarization of the cosmic microwave background (CMB) at degree ...angular scales. During three seasons of observing at the South Pole (2006 through 2008), BICEP mapped ~2% of the sky chosen to be uniquely clean of polarized foreground emission. Here, we present initial results derived from a subset of the data acquired during the first two years. We present maps of temperature, Stokes Q and U, E and B modes, and associated angular power spectra. We demonstrate that the polarization data are self-consistent by performing a series of jackknife tests. We study potential systematic errors in detail and show that they are sub-dominant to the statistical errors. We measure the E-mode angular power spectrum with high precision at 21 <= ell <= 335, detecting for the first time the peak expected at ell ~ 140. The measured E-mode spectrum is consistent with expectations from a ΛCDM model, and the B-mode spectrum is consistent with zero. The tensor-to-scalar ratio derived from the B-mode spectrum is r = 0.02+0.31 -0.26, or r < 0.72 at 95% confidence, the first meaningful constraint on the inflationary gravitational wave background to come directly from CMB B-mode polarization.
The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in ...both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin's lymphoma population, primarily consisting of patients with DLBCL.
Patients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells.
Thirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance.
AZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing.
Registered at ClinicalTrials.gov: NCT01563302 . First submitted 2/13/2012.
Next-generation sequencing technologies have greatly expanded our understanding of cancer genetics. Antisense technology is an attractive platform with the potential to translate these advances into ...improved cancer therapeutics, because antisense oligonucleotide (ASO) inhibitors can be designed on the basis of gene sequence information alone. Recent human clinical data have demonstrated the potent activity of systemically administered ASOs targeted to genes expressed in the liver. We describe the preclinical activity and initial clinical evaluation of a class of ASOs containing constrained ethyl modifications for targeting the gene encoding the transcription factor STAT3, a notoriously difficult protein to inhibit therapeutically. Systemic delivery of the unformulated ASO, AZD9150, decreased STAT3 expression in a broad range of preclinical cancer models and showed antitumor activity in lymphoma and lung cancer models. AZD9150 preclinical activity translated into single-agent antitumor activity in patients with highly treatment-refractory lymphoma and non-small cell lung cancer in a phase 1 dose-escalation study.
The Background Imaging of Cosmic Extragalactic Polarization (BICEP) experiment was designed specifically to search for the signature of inflationary gravitational waves in the polarization of the ...cosmic microwave background (CMB). Using a novel small-aperture refractor and 49 pairs of polarization-sensitive bolometers, BICEP has completed three years of successful observations at the South Pole beginning in 2006 February. To constrain the amplitude of the inflationary B-mode polarization, which is expected to be at least 7 orders of magnitude fainter than the 3 K CMB intensity, precise control of systematic effects is essential. This paper describes the characterization of potential systematic errors for the BICEP experiment, supplementing a companion paper on the initial cosmological results. Using the analysis pipelines for the experiment, we have simulated the impact of systematic errors on the B-mode polarization measurement. Guided by these simulations, we have established benchmarks for the characterization of critical instrumental properties including bolometer relative gains, beam mismatch, polarization orientation, telescope pointing, sidelobes, thermal stability, and timestream noise model. A comparison of the benchmarks with the measured values shows that we have characterized the instrument adequately to ensure that systematic errors do not limit BICEP's two-year results, and identifies which future refinements are likely necessary to probe inflationary B-mode polarization down to levels below a tensor-to-scalar ratio r = 0.1.
This book comprehensively reviews current pest management practices and explores novel integrated pest management strategies in Brassica oilseed crops. It is essential reading for pest management ...practitioners and researchers working on pest management in canola and other Brassica crops worldwide.Canola, mustard, camelina and crambe are the most important oilseed crops in the world. Canola is the second largest oilseed crop in the world providing 13% of the world's supply. Seeds of these species commonly contain 40% or more oil and produce meals with 35 to 40% protein. However, its production has declined significantly in recent years due to insect pest problems. The canola pest complexes are responsible for high insecticide applications on canola. Many growers rely on calendar-based spraying schedules for insecticide applications. The diamondback moth Plutella xylostella and flea beetles Phyllotreta spp. (P. cruciferae and P. striolata)cause serious damage to canola. In the Northern Great Plains, USA, for instance, P. xylostella is now recorded everywhere that canola is grown. Severe damage to canola plants can be caused by overwintering populations of flea beetles feeding on newly emerged seedlings. Cabbage seed pod weevil (Ceutorhynchus obstrictus), swede midge (Contarinia nasturtii), and tarnished plant bug (Lygus lineolaris) are also severe pests on canola. Minor pests include aphids (cabbage aphid, Brevicoryne brassicae and turnip aphid, Hyadaphis erysimi) and grasshopper, Melanoplus sanguinipes.This book:· is the only single compiled source of information on integrated management of canola and other Brassica oilseed pests· presents the biology and management of all the major and minor pests of Brassica oilseed crops· is an essential source of information for applied entomologists, crop protection researchers, extension agents and stakeholders
COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, ...business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia.
This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks.
We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.
Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India's speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak.
Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic.
We present the results of our photometric and spectroscopic follow-up of the intermediate-luminosity optical transient AT 2017jfs. At peak, the object reaches an absolute magnitude of Mg = −15.46 ± ...0.15 mag and a bolometric luminosity of 5.5 × 1041 erg s−1. Its light curve has the double-peak shape typical of luminous red novae (LRNe), with a narrow first peak bright in the blue bands, while the second peak is longer-lasting and more luminous in the red and near-infrared (NIR) bands. During the first peak, the spectrum shows a blue continuum with narrow emission lines of H and Fe II. During the second peak, the spectrum becomes cooler, resembling that of a K-type star, and the emission lines are replaced by a forest of narrow lines in absorption. About 5 months later, while the optical light curves are characterized by a fast linear decline, the NIR ones show a moderate rebrightening, observed until the transient disappears in solar conjunction. At these late epochs, the spectrum becomes reminiscent of that of M-type stars, with prominent molecular absorption bands. The late-time properties suggest the formation of some dust in the expanding common envelope or an IR echo from foreground pre-existing dust. We propose that the object is a common-envelope transient, possibly the outcome of a merging event in a massive binary, similar to NGC 4490−2011OT1.
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Since there has been a notable improvement in the performance of graphene-supported tin-based lithium ion battery anodes, they have become a viable alternative to state of the art graphite anodes. ...However, currently these anodes are produced by energy-demanding thermal processes and generate lithium chloride or other wastes. In this research, we demonstrate the formation of efficient and stable lithium ion battery anodes based on sodium stannate-coated reduced graphene oxide. Coating is performed at low temperatures and when a sodium peroxostannate precursor is used, the process can be carried out with zero waste discharge. Thermal treatment is required only for the solid material. The anode exhibited a charge capacity of 610 mA h g super(-1) after 140 cycles at 100 mA g super(-1). This is the first characterization of a sodium stannate-based anode for LIBs.
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