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.

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.

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.

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.

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.

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.

Antigen-driven differentiation of naive Ig-transgenic B cells in vitro.

We have established a culture system in which naive B cells bearing a transgenic, chicken OVA (cOVA)-specific Ig differentiate to plasma cells in vitro after interaction with cOVA plus cOVA-specific helper T cells. B cell-enriched populations from Ig-transgenic mice, but not from nontransgenic mice, proliferated after presenting nanomolar concentrations of cross-linked cOVA to DO11.10 (cOVA plus IAd-specific) T cells. After 6 to 9 days of culture with Ag and specific T cells, the B cells acquired a plasma cell phenotype and secreted the transgene-derived Ig at high levels. Engagement of B cell surface Ig was not essential for primary B cell differentiation. Differentiating B cells enlarged, clustered, and acquired two plasma cell markers, Syndecan and CD43. B cell CD45 isoform expression changed: the B220 isoform was lost in a T cell-dependent manner, whereas the CD45RB isoform was gained in a T-independent manner. Although unstimulated B cells survived less than 72 h in vitro, those in Ag-stimulated cultures showed reduced early death, a surge of proliferation at 3 to 5 days, and increased death late in the culture. Using a large population of naive B cells of defined antigenic specificity permits us to study a primary immune response to an Ag, rather than to less physiologic polyclonal stimuli. Because all steps of differentiation occurred in vitro, they are easily accessible for study. This coculture system provides an opportunity to observe Ag-specific T cell-B cell collaboration.

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.

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)

Effects of nerve growth factor on rat peritoneal mast cells. Survival promotion and immediate-early gene induction.

Purified rat peritoneal mast cells in vitro die over a period of 2-6 days in conventional serum-containing medium. As mast cells die, they become pyknotic and undergo DNA fragmentation suggestive of an apoptotic process. Treatment of in vitro mast cells with nerve growth factor (NGF) greatly retards and reduces the death of mast cells (EC50 approximately 1 nM), with no effect on mast cell proliferation. Other neurotrophins have no such effect. NGF also induces the immediate early genes c-fos and NGFI-A with a similar dose dependence. In contrast to the secretagogue activity of NGF, neither the survival-promoting effect nor immediate early gene induction requires lysophosphatidylserine. The ability of NGF to promote mast cell survival is cell density-dependent and appears to be primarily because of induction of the synthesis and/or secretion of an autocrine survival factor by stimulated mast cells. These results suggest that the previously observed effects of NGF on mast cell numbers in vivo may in part be because of enhanced survival and that NGF may be an important mediator of mast cell function in normal and pathological states.

The first pediatric Japanese case to undergo heart transplantation in the Utah Cardiac Transplant Program in the United States.

A seven-year-old girl underwent heart transplantation because of progressive congestive heart failure resulting from familial dilated cardiomyopathy. Her parents were second cousins to each other and her brother had died of dilated cardiomyopathy. Her symptoms of congestive heart failure began four months before the transplantation and became gradually worse. Left ventricular ejection fraction was 10 to 20% echocardiographically, and mitral and tricuspid valve regurgitation were present. Her condition of NYHA IV was not improved by treatment with dobutamine infusion and isosorbide dinitrate. She was transported to the Primary Children's Medical Center in Utah, USA, on July 22, 1991 in critical condition to undergo heart transplantation. Despite treatment with amrinone and additional catecholamines, she became semicomatose due to ischemic liver injury on July 24, 1991. A donor became available on July 25, 1991, and the transplantation was performed. Cardiac ischemic time was 97 min. Although she had transient OKT3 monoclonal antibody-related encephalopathy on her fifth postoperative day, she recovered normally. She had moderate rejection on the 20th postoperative day and mild rejection on the 79th and 149th postoperative days. She has had no significant infectious diseases. The baseline examination performed three months after heart transplantation revealed no abnormal findings on her coronary arteriogram. She returned to Japan and has been attending elementary school. The annual examination of her transplanted heart showed neither stenosis nor occlusion in her coronary angiogram. She has been receiving cyclosporine, azathioprine, and a low dose of prednisone as an immunosuppressive regimen. If she does not exhibit rejection, the use of steroids will be decreased or discontinued.

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.

Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation.

Nerve growth factor causes mediator release from rat peritoneal mass cells in the presence of lysophosphatidylserine. We have investigated the neurotrophin and receptor specificity involved in this response. Nerve growth factor produced a dose-dependent release of [14C]serotonin in the presence of lysophosphatidylserine with an EC50 of approximately 1 nM. Incubation with brain-derived neurotrophic factor and neurotrophin-3 did not produce a response. Northern blot analysis with probes for low affinity nerve growth factor receptor (p75), trkA, trkB, and trkC demonstrated a detectable signal for trkA only. Western blots of trkA immunoprecipitates from mast cell culture lysates, probed with anti-phosphotyrosine antibodies, demonstrated expression of functional TrkA protein. To determine whether p75, trkB, or trkC mRNA was present in amounts below the limit of detection for Northern analysis, a sensitive reverse transcriptase polymerase chain reaction protocol was used; again rat peritoneal mast cells demonstrated only trkA. The predominant form of trkA message expressed in rat peritoneal mast cells was smaller than the neuronal form. An 18-nucleotide exon (coding for 6 amino acids in the extracellular domain) in the neuronal message was not found in the predominant mast cell trkA message. PC12 cells, a rat pheochromocytoma cell line, and dissociated rat sympathetic neurons showed both trkA and p75, but not trkB or trkC. Anterior pituitary expressed both trkB and trkC, but not trkA. To confirm the lack of expression of p75 on mast cells, 125I-nerve growth factor was chemically cross-linked to mast cells or PC12 cells and then immunoprecipitated with a monoclonal antibody specific for p75, 192-IgG; no p75 was detected. Thus, mediator release from rat peritoneal mast cells by nerve growth factor was specific and not a general property of neurotrophins, and the response was modulated through the trkA proto-oncogene. To our knowledge, this is the first description of a bone marrow-derived cell type that expresses trkA at both the mRNA and protein levels. These data provide further evidence that p75 is not necessary for nerve growth factor signal transduction.