Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Constraints on Primordial Gravitational Waves Using Planck, WMAP, and New BICEP2/Keck Observations through the 2015 Season.

We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at 220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.

Improved Constraints on Cosmology and Foregrounds from BICEP2 and Keck Array Cosmic Microwave Background Data with Inclusion of 95 GHz Band.

We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross-spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed ΛCDM is detected at modest significance in the 95×150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23×95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23×353. We take the likelihood of all the spectra for a multicomponent model including lensed ΛCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.

Detection of B-mode polarization at degree angular scales by BICEP2.

We report results from the BICEP2 experiment, a cosmic microwave background (CMB) polarimeter specifically designed to search for the signal of inflationary gravitational waves in the B-mode power spectrum around ℓ∼80. The telescope comprised a 26 cm aperture all-cold refracting optical system equipped with a focal plane of 512 antenna coupled transition edge sensor 150 GHz bolometers each with temperature sensitivity of ≈300 µK(CMB)√s. BICEP2 observed from the South Pole for three seasons from 2010 to 2012. A low-foreground region of sky with an effective area of 380 square deg was observed to a depth of 87 nK deg in Stokes Q and U. In this paper we describe the observations, data reduction, maps, simulations, and results. We find an excess of B-mode power over the base lensed-ΛCDM expectation in the range 30 < ℓ < 150, inconsistent with the null hypothesis at a significance of >5σ. Through jackknife tests and simulations based on detailed calibration measurements we show that systematic contamination is much smaller than the observed excess. Cross correlating against WMAP 23 GHz maps we find that Galactic synchrotron makes a negligible contribution to the observed signal. We also examine a number of available models of polarized dust emission and find that at their default parameter values they predict power ∼(5-10)× smaller than the observed excess signal (with no significant cross-correlation with our maps). However, these models are not sufficiently constrained by external public data to exclude the possibility of dust emission bright enough to explain the entire excess signal. Cross correlating BICEP2 against 100 GHz maps from the BICEP1 experiment, the excess signal is confirmed with 3σ significance and its spectral index is found to be consistent with that of the CMB, disfavoring dust at 1.7σ. The observed B-mode power spectrum is well fit by a lensed-ΛCDM+tensor theoretical model with tensor-to-scalar ratio r = 0.20_(-0.05)(+0.07), with r = 0 disfavored at 7.0σ. Accounting for the contribution of foreground, dust will shift this value downward by an amount which will be better constrained with upcoming data sets.

Thymic selection of cytotoxic T cells independent of CD8 alpha-Lck association.

The CD8 alpha cytoplasmic domain associates with p56lck, a nonreceptor protein-tyrosine kinase. The biological relevance of CD8 alpha-Lck association in T cell development was tested with transgenic mice generated to express a CD8 alpha molecule with two amino acid substitutions in its cytoplasmic domain, which abolishes the association of CD8 alpha with Lck. The CD8 alpha mutant was analyzed in a CD8-/- background and in the context of the transgenic 2C T cell receptor. The development and function of CD8+ T cells in these mice were apparently normal. Thus, CD8 alpha-Lck association is not necessary for positive selection, negative selection, or CD8-dependent cytotoxic function.

Sulfide resorption during crustal ascent and degassing of oceanic plateau basalts.

Mantle plume-related magmas typically have higher chalcophile and siderophile element (CSE) contents than mid-ocean ridge basalts (MORB). These differences are often attributed to sulfide-under-saturation of plume-related melts. However, because of eruption-related degassing of sulfur (S) and the compositional, pressure, temperature and redox effects on S-solubility, understanding the magmatic behavior of S is challenging. Using CSE data for oceanic plateau basalts (OPB), which rarely degas S, we show that many OPB are sulfide-saturated. Differences in the timing of sulfide-saturation between individual OPB suites can be explained by pressure effects on sulfur solubility associated with ascent through over-thickened crust. Importantly, where S-degassing does occur, OPB have higher CSE contents than S-undegassed melts at similar stages of differentiation. This can be explained by resorption of earlier-formed sulfides, which might play an important role in enriching degassed melts in sulfide-compatible CSE and potentially contributes to anomalous enrichments of CSE in the crust.

Relaxation and imagery techniques without sedation during right ventricular endomyocardial biopsy in pediatric heart transplant patients.

Routine endomyocardial biopsies after heart transplantation can be performed in pediatric patients with the right internal jugular venous approach. To minimize hospital time, limit disruption of daily activities, and eliminate the need for sedation, biopsies in patients older than 7 years of age were done with relaxation and imagery techniques. No complications occurred with this method, and all patients tolerated the procedure well.

Murine monoclonal CD3 antibody (OKT3)-based early rejection prophylaxis in pediatric heart transplantation.

The purpose of this study was to review our experience with the use of OKT3 (a murine monoclonal CD3 antibody) used as immune prophylaxis for pediatric heart transplant recipients. Orthotopic heart transplantation was performed in 18 pediatric patients, 8 girls and 10 boys, ranging in age from 17 days to 17 years. OKT3 therapy was initiated intraoperatively at a dose of approximately 0.2 mg/kg and was administered at a dose of approximately 0.1 to 0.2 mg/kg/day for a period of 11.5 +/- 2.5 days. Daily average OKT3 levels were 1132 +/- 469 ng/ml. Side effects that occurred during OKT3 therapy were fever (59%), diarrhea (24%), headaches (24%), vomiting (18%), encephalopathy (12%), pulmonary edema (6%), and rash (6%). Infections occurred in 24% of patients, all within 6 months of transplantation. In the first year after transplantation, patients experienced 3.4 +/- 2.4 episodes of mild rejection and 1.0 +/- 0.8 episodes of moderate rejection. No patient experienced severe rejection. Five of the surviving 14 patients (36%) have been weaned from chronic steroid therapy, and 42% are being maintained on alternate-day prednisone at a dose of 0.06 +/- 0.02 mg/kg/day. Coronary artery disease developed in three patients; two of whom died. Actuarial survival was 83% at 1 year and 73% at 2 years. This report shows that OKT3 prophylaxis in pediatric heart transplantation can be used with acceptable short-term adverse side effects and overall survival.

Methotrexate therapy in pediatric heart transplantation as treatment of recurrent mild to moderate acute cellular rejection.

We have used adjunctive therapy with methotrexate as treatment of recurrent mild-to-moderate acute cellular rejection and in an attempt to reduce rejection frequency and corticosteroid dosage. The purpose of this study was to review our experience with this treatment strategy. Eight patients, 13.1 +/- 1.1 years of age (mean +/- standard error of the mean) at the time of transplantation, were given methotrexate in addition to their standard triple therapy immunosuppression. Methotrexate was started at 6.2 +/- 2 months after transplantation after an average of 3.1 +/- 0.4 rejection episodes. Patients were given methotrexate weekly for 8 weeks at 2.5 or 5 mg orally every 12 hours for three doses (0.23 +/- 0.02 mg/kg/week). The time to resolution of rejection was 17.9 +/- 4 days after initiating methotrexate therapy. The number of rejections per month decreased significantly from the 2 months before methotrexate therapy (1.49 +/- 0.1) when compared with both the 2 months during methotrexate therapy (0.50 +/- 0.1) and the 2 months after methotrexate therapy was completed (0.44 +/- 0.3) (p < 0.005). Furthermore, when comparing total rejection frequency since transplantation and before methotrexate therapy to a follow-up period of 21.8 +/- 5 months after completion of methotrexate therapy, the rejection frequency was significantly less (0.81 +/- 0.2 versus 0.10 +/- 0.06 rejections/month) (p < 0.01). Prednisone dosage was also significantly less when comparing the time before methotrexate therapy to immediately after completion of methotrexate therapy (0.23 +/- 0.04 versus 0.15 +/- 0.03 mg/kg/day) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Epoetin alfa therapy in infants awaiting heart transplantation.

OBJECTIVE: To determine the safety and efficacy of epoetin alfa therapy in infants awaiting heart transplantation to minimize the need for blood transfusions. DESIGN: Prospective case series analysis. SETTING: Pediatric tertiary care center. PATIENTS: Eleven term infants (4 to 54 days old) awaiting heart transplantation. INTERVENTION: Infants received 16 courses of daily epoetin therapy and four subsequent courses of alternate-day epoetin therapy. RESULTS: Daily epoetin therapy was instituted at 23.6 +/- 4.5 days of age, and the duration of treatment was 13.8 +/- 3.9 days (mean +/- SEM). During daily epoetin therapy, the hematocrit increased from 0.42 +/- 0.015 to 0.50 +/- 0.019 (P < .001), and the reticulocyte count increased from 58 +/- 9 x 10(-3) to 105 +/- 16 X 10(-3) (P < .05). There were no significant changes in leukocyte count (13.4 +/- 1.0 X 10(9)/L vs 15.1 +/- 0.9 X 10(9)/L), platelet count (402 +/- 43 X 10(9)/L vs 387 +/- 39 X 10(9)/L), or creatinine (53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL] vs 53 +/- 9 mumol/L [0.6 +/- 0.1 mg/dL]) (not significant). Four patients received blood transfusions during daily epoetin therapy, but the amount of blood administered to patients was significantly less (0.9 +/- 0.5 mL/kg per day) than the phlebotomy losses (1.8 +/- 0.4 mL/kg per day) (P < .01). During alternate-day epoetin therapy, the hematocrit decreased from 0.53 +/- 0.014 to 0.43 +/- 0.019 (P < .05). CONCLUSIONS: Daily epoetin therapy appears to be effective in maintaining stable hematocrit in infants awaiting heart transplantation, who generally require multiple transfusions secondary to iatrogenic blood losses.

Etiology and outcome of outpatient fevers in pediatric heart transplant patients.

We reviewed 74 outpatient febrile episodes in 22 pediatric heart transplant patients in order to determine etiologies, rates of serious and nonserious illness, and factors predictive of serious disease. Twenty-two febrile episodes (30%) resulted in hospital admission. Only three variables were predictive of serious illness: longer duration of fever, shorter time since transplant, and lower febrile episode number. We conclude that at least 70% of outpatient febrile episodes are nonserious and can be managed safely in an outpatient setting. The duration of fever may be predictive of serious disease but is not useful at initial presentation.

A reduced organic carbon component in martian basalts.

The source and nature of carbon on Mars have been a subject of intense speculation. We report the results of confocal Raman imaging spectroscopy on 11 martian meteorites, spanning about 4.2 billion years of martian history. Ten of the meteorites contain abiotic macromolecular carbon (MMC) phases detected in association with small oxide grains included within high-temperature minerals. Polycyclic aromatic hydrocarbons were detected along with MMC phases in Dar al Gani 476. The association of organic carbon within magmatic minerals indicates that martian magmas favored precipitation of reduced carbon species during crystallization. The ubiquitous distribution of abiotic organic carbon in martian igneous rocks is important for understanding the martian carbon cycle and has implications for future missions to detect possible past martian life.

Comet 81P/Wild 2 under a microscope.

The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.

Efficacy of 100 consecutive right ventricular endomyocardial biopsies in pediatric patients using the right internal jugular venous approach.

Indications for endomyocardial biopsy (EMB) in pediatric patients include cardiomyopathy and postheart transplant rejection surveillance. There have been few reports of the use of the internal jugular venous approach for right ventricular EMB in pediatric patients. In this study, we report our experience with 100 consecutive EMBs in pediatric patients using this approach. Indications for EMB were cardiomyopathy of unknown etiology in four patients, adriamycin cardiomyopathy in three patients, postheart transplant rejection surveillance in five patients, right ventricular outflow tract tumors in one patient, and sustained ventricular tachycardia in one patient. Histologic diagnoses of biopsy specimens included interstitial fibrosis, vasculopathy, hypertrophy, anthracycline cardiotoxicity, and various degrees of allograft rejection. All EMBs were performed successfully and without complications. We conclude that right ventricular EMB using the right internal jugular venous approach can be performed safely and successfully in pediatric patients as young as 2 months of age and repeatedly in patients as young as 8 years old.

Nerve growth factor induces the expression of certain cytokine genes and bcl-2 in mast cells. Potential role in survival promotion.

Nerve growth factor (NGF) promotes mast cell survival in vitro (Horigome, K., Bullock, E. D., and Johnson, E. M., Jr. (1994) J. Biol. Chem. 269, 2695-2702). NGF survival promotion is cell density-dependent, and conditioned medium experiments have shown that NGF increases the production of an autocrine mast cell survival activity. Cytokines are potential candidates for autocrine survival factors. In rat peritoneal mast cells (RPMC), NGF caused an increase in the messenger RNAs for interleukin (IL)-3, IL-4, IL-10, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor. This induction was NGF dose-dependent, was blocked by NGF-neutralizing antibodies, and was not observed in the non-mast peritoneal cell population. The immunosuppressive agent, cyclosporin A, blocked both cytokine induction and NGF-activated survival promotion but not survival promotion activated by IL-3 or stem cell factor, suggesting that NGF enhanced RPMC survival by increasing cytokine production. We also examine the effects of NGF on the expression levels of some members of the bcl-2 family and the interleukin-1beta-converting enzyme-like cysteine protease families. NGF markedly increased bcl-2 expression but had little or no effect on the other genes studied. The induction of bcl-2 mRNA by NGF was not blocked by cyclosporin A. These data suggest that induced cytokine gene expression but not increased expression of bcl-2 mediates NGF-survival promotion in RPMC.

Dipeptide frequencies in proteins and the CpG deficiency in vertebrate DNA.

Analysis of vertebrate protein sequences totalling 4040 residues shows that amino acids with a high proportion of codons ending in C occur with significantly reduced frequency before amino acids whose codons start with G. This effect is not shown by "control" bacterial protein sequences. The consequent implication of shortage of XXC. GXX codon pairs in vertebrate messenger RNA is discussed in relation to the extreme rarity of the base doublet CpG in vertebrate DNA.