It has been understood since 1897 that accelerating charges must emit electromagnetic radiation. Although first derived in 1904, cyclotron radiation from a single electron orbiting in a magnetic ...field has never been observed directly. We demonstrate single-electron detection in a novel radio-frequency spectrometer. The relativistic shift in the cyclotron frequency permits a precise electron energy measurement. Precise beta electron spectroscopy from gaseous radiation sources is a key technique in modern efforts to measure the neutrino mass via the tritium decay end point, and this work demonstrates a fundamentally new approach to precision beta spectroscopy for future neutrino mass experiments.
We present an apparatus for detection of cyclotron radiation yielding a frequency-based β± kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear β decays. The ...cyclotron frequency of the radiating β particles in a magnetic field is used to determine the β energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of β–’s from 6He and β+’s from 19Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for β spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic β’s in a waveguide. Furthermore, this work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision β-decay measurements.
Recent observations on cancer cell metabolism indicate increased serine synthesis from glucose as a marker of poor prognosis. We have predicted that a fraction of the synthesized serine is routed to ...a pathway for ATP production. The pathway is composed by reactions from serine synthesis, one-carbon (folate) metabolism and the glycine cleavage system (SOG pathway). Here we show that the SOG pathway is upregulated at the level of gene expression in a subset of human tumors and that its level of expression correlates with gene signatures of cell proliferation and Myc target activation. We have also estimated the SOG pathway metabolic flux in the NCI60 tumor-derived cell lines, using previously reported exchange fluxes and a personalized model of cell metabolism. We find that the estimated rates of reactions in the SOG pathway are highly correlated with the proliferation rates of these cell lines. We also observe that the SOG pathway contributes significantly to the energy requirements of biosynthesis, to the NADPH requirement for fatty acid synthesis and to the synthesis of purines. Finally, when the PC-3 prostate cancer cell line is treated with the antifolate methotrexate, we observe a decrease in the ATP levels, AMP kinase activation and a decrease in ribonucleotides and fatty acids synthesized from 1,2-(13)C2-D-glucose as the single tracer. Taken together our results indicate that the SOG pathway activity increases with the rate of cell proliferation and it contributes to the biosynthetic requirements of purines, ATP and NADPH of cancer cells.
Abstract Cyclotron radiation emission spectroscopy (CRES) is a modern technique for high-precision energy spectroscopy, in which the energy of a charged particle in a magnetic field is measured via ...the frequency of the emitted cyclotron radiation. The He6-CRES collaboration aims to use CRES to probe beyond the standard model physics at the TeV scale by performing high-resolution and low-background beta-decay spectroscopy of 6 He and 19 Ne . Having demonstrated the first observation of individual, high-energy (0.1–2.5 MeV) positrons and electrons via their cyclotron radiation, the experiment provides a novel window into the radiation of relativistic charged particles in a waveguide via the time-derivative (slope) of the cyclotron radiation frequency, d f c / d t . We show that analytic predictions for the total cyclotron radiation power emitted by a charged particle in circular and rectangular waveguides are approximately consistent with the Larmor formula, each scaling with the Lorentz factor of the underlying e ± as γ 4 . This hypothesis is corroborated with experimental CRES slope data.
The objectives of this study were to determine if residual feed intake (RFI) classification of beef heifers affected efficiency of forage utilization, body composition, feeding behavior, heart rate, ...and physical activity of pregnant females. Residual feed intake was measured in growing Bonsmara heifers for 2 yr (n=62 and 53/yr), and heifers with the lowest (n=12/yr) and highest (n=12/yr) RFI were retained for breeding. Of the 48 heifers identified as having divergent RFI, 19 second-parity and 23 first-parity females were used in the subsequent pregnant-female trial. Pregnant females were fed a chopped hay diet (ME=2.11 Mcal kg(-1) DM) in separate pens equipped with GrowSafe bunks to measure individual intake and feeding behavior. Body weights were measured at 7-d intervals and BCS and ultrasound measurements of 12th-rib fat depth, rump fat depth, and LM area obtained on d 0 and 77. Heart rate and physical activity were measured for 7 consecutive d. First-parity females had lower (P<0.05) initial BW, BW gain, and initial hip height and tended (P=0.07) to have lower DMI compared to second-parity females. Females with low RFI as heifers consumed 17% less (P<0.01) forage compared to females with high RFI as heifers but maintained the same BW, BW gain, and body composition. Likewise, RFI classification did not affect calving date. An interaction (P=0.04) between heifer RFI classification and parity was found for calf birth weight. Calves from first-parity low-RFI females were lighter at birth (P<0.01) than calves from high-RFI females, but RFI classification did not affect BW of calves born to second-parity females. Residual feed intake classification did not affect bunk visit frequency, but low-RFI females spent 26% less time (P<0.01) at the bunk compared to high-RFI females. First-parity females had more (P<0.05) daily step counts and greater lying-bout frequencies compared to second-parity females, but physical activity was not affected by RFI classification. Heart rates of females classified as low RFI were 7% lower (P=0.03) compared to high-RFI females. Heifer postweaning RFI but not G:F or residual gain were positively correlated with forage intake (r=0.38) and RFI (r=0.42) of pregnant females. Results indicate that heifers identified as having low postweaning RFI have greater efficiency of forage utilization as pregnant females, with minimal impacts on growth, body composition, calving date, and calf birth BW, compared to their high-RFI counterparts.
Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared ...zanubrutinib with bendamustine–rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL.
We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0–2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine–rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m2 of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m2 of body surface area on day 1 of cycles 2–6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment.
Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine–rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7–29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable NE to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 95% CI 0·28 to 0·63; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 11% of 240 patients in group A, 116 51% of 227 in group B, and 17 15% of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four 2% of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each 1% of 227 patients in group B).
Zanubrutinib significantly improved progression-free survival versus bendamustine–rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL.
BeiGene.
Poor-quality roughages are widely used as fiber sources in concentrate-based diets for ruminants. Because roughage quality is associated with the efficiency of energy use in forage-based diets, the ...objective of this study was to determine whether differing the roughage source in concentrate-based diets could change the energy requirements of growing lambs. Eighty-four 1/2 Dorper × 1/2 Santa Inês ram lambs (18.0 ± 3.3 kg BW) were individually penned and divided into 2 groups according to primary source of dietary roughage: low-quality roughage (LQR; sugarcane bagasse) or medium-quality roughage (MQR; coastcross hay). Diets were formulated to be isonitrogenous (2.6% N) and to meet 20% of physically effective NDF. After a 10-d ad libitum adaptation period, 7 lambs from each group were randomly selected and slaughtered (baseline). Twenty-one lambs in each diet group were fed ad libitum and slaughtered at 25, 35, or 45 kg BW. The remaining 28 lambs (14 from each diet group) were submitted to 1 of 2 levels of feed restriction: 70% or 50% of the ad libitum intake. Retentions of body fat, N, and energy were determined. Additionally, 6 ram lambs (44.3 ± 5.6 kg BW) were kept in metabolic cages and used in a 6 × 6 Latin square experiment designed to establish the ME content of the 2 diets at the 3 levels of DM intake. There was no effect of intake level on diet ME content, but it was greater in the diet with LQR than in the diet with MQR (3.18 vs. 2.94 Mcal/kg, respectively; P < 0.01). Lambs fed the diet with LQR had greater body fat (g/kg of empty BW) and energy concentrations (kcal/kg of empty BW) because of a larger visceral fat deposition (P < 0.05). Using a low-quality roughage as a primary source of forage in a concentrate-based diet for growing lambs did not change NEm and the efficiency of ME use for maintenance, which averaged 71.6 kcal/kg(0.75) of shrunk BW and 0.63, respectively. On the other hand, the greater nonfibrous carbohydrate content of the diet with LQR resulted in a 17% better efficiency of ME use for gain (P < 0.01), which was associated with a greater partial efficiency of energy retention as fat (P < 0.01). This increased nutritional efficiency, however, should be viewed with caution because it is related to visceral fat deposition, a nonedible tissue.
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