Characterizing Atacama B-mode Search Detectors with a Half-Wave Plate

The Atacama B-Mode Search (ABS) instrument is a cryogenic ($\sim$10 K) crossed-Dragone telescope located at an elevation of 5190 m in the Atacama Desert in Chile that observed for three seasons between February 2012 and October 2014. ABS observed the Cosmic Microwave Background (CMB) at large angular scales ($40<\ell<500$) to limit the B-mode polarization spectrum around the primordial B-mode peak from inflationary gravity waves at $\ell \sim100$. The ABS focal plane consists of 480 transition-edge sensor (TES) bolometers. They are coupled to orthogonal polarizations from a planar ortho-mode transducer (OMT) and observe at 145 GHz. ABS employs an ambient-temperature, rapidly rotating half-wave plate (HWP) to mitigate systematic effects and move the signal band away from atmospheric $1/f$ noise, allowing for the recovery of large angular scales. We discuss how the signal at the second harmonic of the HWP rotation frequency can be used for data selection and for monitoring the detector responsivities.Comment: 7 pages, 3 figures, conference proceedings submitted to the Journal of Low Temperature Detector

Recovery of Large Angular Scale CMB Polarization for Instruments Employing Variable-delay Polarization Modulators

Variable-delay Polarization Modulators (VPMs) are currently being implemented in experiments designed to measure the polarization of the cosmic microwave background on large angular scales because of their capability for providing rapid, front-end polarization modulation and control over systematic errors. Despite the advantages provided by the VPM, it is important to identify and mitigate any time-varying effects that leak into the synchronously modulated component of the signal. In this paper, the effect of emission from a $300$ K VPM on the system performance is considered and addressed. Though instrument design can greatly reduce the influence of modulated VPM emission, some residual modulated signal is expected. VPM emission is treated in the presence of rotational misalignments and temperature variation. Simulations of time-ordered data are used to evaluate the effect of these residual errors on the power spectrum. The analysis and modeling in this paper guides experimentalists on the critical aspects of observations using VPMs as front-end modulators. By implementing the characterizations and controls as described, front-end VPM modulation can be very powerful for mitigating $1/f$ noise in large angular scale polarimetric surveys. None of the systematic errors studied fundamentally limit the detection and characterization of B-modes on large scales for a tensor-to-scalar ratio of $r=0.01$. Indeed, $r<0.01$ is achievable with commensurately improved characterizations and controls.Comment: 13 pages, 13 figures, 1 table, matches published versio

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Week 48 outcomes from the BRAAVE 2020 study: a randomised switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in African American adults with HIV

Background: Black Americans are disproportionately impacted by HIV. The BRAAVE 2020 study, evaluated the safety and efficacy of switching to the guidelines- recommended single- tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) in Black adults through week (W) 48. Method: Adults with HIV self- identifying as Black or African American and virologically suppressed on 2 NRTIs plus a 3rd agent were randomised (2:1) to switch to open- label B/F/TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was allowed except failure on an INSTI. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except K65R/E/N, ≥3 thymidine analog mutations or T69- insertions. Primary INSTI- resistance was excluded. SBR participants switched to B/F/TAF at W24. Efficacy was assessed at W24 (Primary endpoint, noninferiority margin 6%) and at W48 as the proportion with HIV- 1 RNA ≥50 c/mL by FDA Snapshot and by changes in CD4 count. Safety was assessed by adverse events (AE) and lab results. Results: 495 were randomised and treated (B/F/TAF n = 330, SBR n = 165): 32% cis women, 2% transgender women, median age 49 years (range 18– 79) and 10% had pre- existing M184V/I mutation. At W24, 1% (2/328) on B/F/TAF vs 2% (3/165) on SBR had HIV- 1 RNA ≥50 c/mL (difference - 1.2%; 95% CI - 4.8% to 0.9%) demonstrating non-inferiority of B/F/TAF; 2 with pre- existing primary INSTI resistance were excluded from analysis. 163 assigned to SBR completed W24 and switched to B/F/TAF (SBR to B/F/TAF). At W48 1% (3/328) originally randomised to B/F/TAF and 0 SBR to B/F/TAF had HIV- 1 RNA ≥50 c/mL. Baseline NRTI resistance did not affect the efficacy of B/F/TAF. No treatment emergent resistance was detected. Median (IQR) weight increased 0.9 kg (- 1.5, 4.1) and 0.6 kg (- 1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. Study drug- related AEs occurred in 10% of participants while on B/F/TAF; most were grade 1. Conclusion: Switching to B/F/TAF was highly effective for Black adults regardless of baseline regimen or pre- existing NRTI resistance and was associated with few treatment re-lated AEs or discontinuations

Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

The Atacama Cosmology Telescope: A Measurement of the 600< ell <8000 Cosmic Microwave Background Power Spectrum at 148 GHz

We present a measurement of the angular power spectrum of the cosmic microwave background (CMB) radiation observed at 148 GHz. The measurement uses maps with 1.4' angular resolution made with data from the Atacama Cosmology Telescope (ACT). The observations cover 228 square degrees of the southern sky, in a 4.2-degree-wide strip centered on declination 53 degrees South. The CMB at arcminute angular scales is particularly sensitive to the Silk damping scale, to the Sunyaev-Zel'dovich (SZ) effect from galaxy clusters, and to emission by radio sources and dusty galaxies. After masking the 108 brightest point sources in our maps, we estimate the power spectrum between 600 < \ell < 8000 using the adaptive multi-taper method to minimize spectral leakage and maximize use of the full data set. Our absolute calibration is based on observations of Uranus. To verify the calibration and test the fidelity of our map at large angular scales, we cross-correlate the ACT map to the WMAP map and recover the WMAP power spectrum from 250 < ell < 1150. The power beyond the Silk damping tail of the CMB is consistent with models of the emission from point sources. We quantify the contribution of SZ clusters to the power spectrum by fitting to a model normalized at sigma8 = 0.8. We constrain the model's amplitude ASZ < 1.63 (95% CL). If interpreted as a measurement of sigma8, this implies sigma8^SZ < 0.86 (95% CL) given our SZ model. A fit of ACT and WMAP five-year data jointly to a 6-parameter LCDM model plus terms for point sources and the SZ effect is consistent with these results.Comment: 15 pages, 8 figures. Accepted for publication in Ap

Detection of the Power Spectrum of Cosmic Microwave Background Lensing by the Atacama Cosmology Telescope

We report the first detection of the gravitational lensing of the cosmic microwave background through a measurement of the four-point correlation function in the temperature maps made by the Atacama Cosmology Telescope. We verify our detection by calculating the levels of potential contaminants and performing a number of null tests. The resulting convergence power spectrum at 2-degree angular scales measures the amplitude of matter density fluctuations on comoving length scales of around 100 Mpc at redshifts around 0.5 to 3. The measured amplitude of the signal agrees with Lambda Cold Dark Matter cosmology predictions. Since the amplitude of the convergence power spectrum scales as the square of the amplitude of the density fluctuations, the 4-sigma detection of the lensing signal measures the amplitude of density fluctuations to 12%.Comment: 4 pages, 4 figures, replaced title and author list with version accepted by Physical Review Letters. Likelihood code can be downloaded from http://bccp.lbl.gov/~sudeep/ACTLensLike.htm

Functional Analysis of the Two Brassica AP3 Genes Involved in Apetalous and Stamen Carpelloid Phenotypes

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B. napus were investigated and two types of AP3 genes, B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share high similarity in amino acid sequences except for 8 residues difference located at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI-derived motifs. Meanwhile, B.AP3.a specified petal and stamen development, whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the apetalous mutation, however, the loss-of-function in all four AP3 was related to the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3 gene probably relates to petal formation