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The BeyondPlanck and Cosmoglobe collaborations have implemented the first integrated Bayesian end-to-end analysis pipeline for CMB experiments. The primary long-term motivation for this work is to develop a common analysis platform that supports efficient global joint analysis of complementary radio, microwave, and sub-millimeter experiments. A strict prerequisite for this to succeed is broad participation from the CMB community, and two foundational aspects of the program are therefore reproducibility and Open Science. In this paper, we discuss our efforts toward this aim. We also discuss measures toward facilitating easy code and data distribution, community-based code documentation, user-friendly compilation procedures, etc. This work represents the first publicly released end-to-end CMB analysis pipeline that includes raw data, source code, parameter files, and documentation. We argue that such a complete pipeline release should be a requirement for all major future and publicly-funded CMB experiments, noting that a full public release significantly increases data longevity by ensuring that the data quality can be improved whenever better processing techniques, complementary datasets, or more computing power become available, and thereby also taxpayers' value for money; providing only raw data and final products is not sufficient to guarantee full reproducibility in the future.

We present constraints on the tensor-to-scalar ratio r using a combination of BICEP/Keck 2018 (BK18) and Planck PR4 data allowing us to fit for r consistently with the six parameters of the Λ CDM model. We discuss the sensitivity of constraints on r to uncertainties in the Λ CDM parameters as defined by the Planck data. In particular, we are able to derive a constraint on the reionization optical depth τ and thus propagate its uncertainty into the posterior distribution for r. While Planck sensitivity to r is slightly lower than the current ground-based measurements, the combination of Planck with BK18 and baryon-acoustic-oscillation data yields results consistent with r=0 and tightens the constraint to r, We gratefully acknowledge support from the CNRS/IN2P3 Computing Center for providing computing and data-processing resources needed for this work. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC0205CH11231. Part of the research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (Grant No. 80NM0018D0004). Planck is a project of the European Space Agency (ESA).

We constrain the spectral index of polarized synchrotron emission, $\beta_s$, by correlating the recently released 2.3 GHz S-Band Polarization All Sky Survey (S-PASS) data with the 23 GHz 9-year Wilkinson Microwave Anisotropy Probe (WMAP) sky maps. We subdivide the S-PASS field, which covers the southern ecliptic hemisphere, into 95 $15^{\circ}\times15^{\circ}$ regions and estimate the spectral index of polarized synchrotron emission within each region using a simple but robust T-T plot technique. Three different versions of the S-PASS data are considered, corresponding to: no correction for Faraday rotation; Faraday correction based on the rotation measure model presented by the S-PASS team; or Faraday correction based on a rotation measure model presented by Hutschenreuter and En{\ss}lin. We find that the correlation between S-PASS and WMAP is strongest when applying the S-PASS model. Adopting this correction model, we find that the mean spectral index of polarized synchrotron emission gradually steepens from $\beta_s\approx-2.8$ at low Galactic latitudes to $\beta_s\approx-3.3$ at high Galactic latitudes, in good agreement with previously published results. Finally, we consider two special cases defined by the BICEP2 and SPIDER fields and obtain mean estimates of $\beta_{BICEP2}=-3.22\pm0.06$ and $\beta_{SPIDER}=-3.21\pm0.03$, respectively. A comparison with a similar analysis performed in the 23-33 GHz range suggests a flattening of about $\Delta\beta_s \sim 0.1 \pm 0.2$ from low to higher frequencies, but with no statistical significance due to high uncertainties., Comment: 16 pages, 15 figures. Figure number 10 and 15 are new. Published in A&A

We present constraints on the tensor-to-scalar ratio r using Planck data. We use the latest release of Planck maps, processed with the NPIPE code, which produces calibrated frequency maps in temperature and polarisation for all Planck channels from 30 GHz to 857 GHz using the same pipeline. We computed constraints on r using the BB angular power spectrum, and we also discuss constraints coming from the TT spectrum. Given Planck’s noise level, the TT spectrum gives constraints on r that are cosmic-variance limited (with σr = 0.093), but we show that the marginalised posterior peaks towards negative values of r at about the 1.2σ level. We derived Planck constraints using the BB power spectrum at both large angular scales (the ‘reionisation bump’) and intermediate angular scales (the ‘recombination bump’) from ℓ = 2 to 150 and find a stronger constraint than that from TT, with σr = 0.069. The Planck BB spectrum shows no systematic bias and is compatible with zero, given both the statistical noise and the systematic uncertainties. The likelihood analysis using B modes yields the constraint r, Planck is a project of the European Space Agency (ESA) with instruments provided by two scientific consortia funded by ESA member states and led by Principal Investigators from France and Italy, telescope reflectors provided through a collaboration between ESA and a scientific consortium led and funded by Denmark, and additional contributions from NASA (USA). Some of the results in this paper have been derived using the HEALPix package. This research used resources of the National Energy Research Scientific Computing Center (NERSC), a U.S. Department of Energy Office of Science User Facility operated under Contract No. DE-AC02-05CH11231. We gratefully acknowledge support from the CNRS/IN2P3 Computing Center for providing computing and data-processing resources needed for this work.

We review and compare two different CMB dipole estimators discussed in the literature, and assess their performances through Monte Carlo simulations. The first method amounts to simple template regression with partial sky data, while the second method is an optimal Wiener filter (or Gibbs sampling) implementation. The main difference between the two methods is that the latter approach takes into account correlations with higher-order CMB temperature fluctuations that arise from non-orthogonal spherical harmonics on an incomplete sky, which for recent CMB data sets (such as Planck) is the dominant source of uncertainty. For an accepted sky fraction of 81% and an angular CMB power spectrum corresponding to the best-fit Planck 2018 $\Lambda$CDM model, we find that the uncertainty on the recovered dipole amplitude is about six times smaller for the Wiener filter approach than for the template approach, corresponding to 0.5 and 3$~\mu$K, respectively. Similar relative differences are found for the corresponding directional parameters and other sky fractions. We note that the Wiener filter algorithm is generally applicable to any dipole estimation problem on an incomplete sky, as long as a statistical and computationally tractable model is available for the unmasked higher-order fluctuations. The methodology described in this paper forms the numerical basis for the most recent determination of the CMB solar dipole from Planck, as summarized by arXiv:2007.04997., Comment: 8 pages, 10 figures, submitted to A&A

We study the propagation of cosmic rays generated by sources residing inside superbubbles. We show that the enhanced magnetic field in the bubble wall leads to an increase of the interior cosmic ray density. Because of the large matter density in the wall, the probability for cosmic ray interactions on gas peaks there. As a result, the walls of superbubbles located near young cosmic ray sources emit efficiently neutrinos. We apply this scenario to the Loop~I and Local Superbubble: These bubbles are sufficiently near such that cosmic rays from a young source as Vela interacting in the bubble wall can generate a substantial fraction of the observed astrophysical high-energy neutrino flux below $\sim$ few $\times 100$ TeV., Comment: 5 pages, 3 eps figures; v2: explanations and 2 figures added, to appear in ApJL

Previous reports state that there is absorption of bismuth through active peptic ulcers. It was therefore of interest to investigate the extent of absorption in patients at the ulcer and post-ulcer stages.Twenty H. pylori-positive patients with gastroscopically verified gastric or duodenal ulcers were randomly allocated to ingest 3000 mg bismuth subnitrate (BSN) (10 patients) or 480 mg colloidal bismuth subcitrate (CBS) (10 patients). Bismuth serum concentration in 12 samples drawn during the first 4 hours after drug intake was analyzed and the area under the curve (Bi-AUC) was calculated. Anti-H. pylori therapy with amoxicillin and lanzoprazole eradicated H. pylori in 10 patients and healed the ulcers in all patients 4 weeks after therapy ended, then the bismuth absorption test was repeated.There was no significant difference between ulcer- and post-ulcer Bi-AUC for patients receiving BSN or for patients receiving CBS. On a molar basis, CBS gave a 17.4-fold greater absorption of bismuth compared to BSN.The presence of an active ulcer does not significantly influence the absorption of bismuth from CBS or BSN.

The established renal epithelial cell line LLC-PK1 (proximal tubule) started to form multicellular spheroids within 24 h when grown in agar overlay culture. The spheroids, average diameter 100 to 350 microns, were free-floating with a butterfly-like structure due to the formation of several hollow microspheres. The microspheres were lined with polarized epithelial cells that had an abundance of microvilli protruding into the external medium and a well developed vacuolar apparatus, including coated pits, endocytotic vacuoles, and lysosomes. The microspheres were sealed between lumen and the surrounding medium by tight junctions and fluctuated in size due to fluid being transported in an apical-to-basal direction. Vasopressin was found to stimulate this transport, whereas the addition of ouabain or HgCl2 inhibited both spheroid growth and fluctuation in size with time. Biochemical assays of brush-border and lysosomal marker enzymes demonstrated an increase in enzyme activity during spheroid formation and growth. The most dramatic changes were observed for dipeptidyl peptidase IV (two- to threefold after 1 d and 53.5-fold after 15 d), reflecting the cellular polarization and brush-border formation during spheroid formation. When the typical lysosomal enzymes were compared, the activity of peptide bond splitting enzymes increased earlier than others. In conclusion, LLC-PK1 spheroids capable of forming microspheres represent an in vitro manifestation of specialized epithelial properties maintained in cell culture, thus providing a tool for studying renal physiologic mechanisms at a cellular level.

In a patient, at revisional Christiansen total hip arthroplasty, silver-impregnated bone cement was used as prophylaxis against deep infection. Five years later the patient developed serious neurological deficits, and the prosthesis was loose. The loose Christiansen prosthesis and the silver-impregnated bone cement were removed and a Charnley prosthesis inserted. Intra-operatively the concentration of silver in fluid drawn from the hip joint was assessed to be about 1000 times the normal serum reference value, and tissue samples from the acetabulum were densely impregnated with silver. During the following 2 years the serum concentration of silver decreased from more than 60 times to 20 times the normal; simultaneously the patient partially recovered from her grave muscle paralysis.

We have previously found reduced absorption of vitamin B12 in rats with choledochocolic fistulae. To investigate whether the reduction is caused by epithelial dysfunction or mucosal hypoplasia, choledochocolic fistulae were made in 11 rats, whereas 10 rats were sham-operated. The epithelial function was evaluated 9 days later by measuring the uptake of 57CoB12 and glucose in perfused intestinal segments and by determining the activities of 11 mucosal enzymes. Hypoplasia was investigated by performing morphometric measurements of the villus surface area and by measuring the weight, protein, and DNA in mucosal scrapings. The results suggest that choledochocolic fistulae in rats do not impair the epithelial function or cause mucosal hypoplasia. The urinary excretion of indican was increased in the fistula-operated rats, but further studies are needed to establish the significance of this observation.

The rat kidney cortex was found to contain two N-terminal exopeptidases of the tripeptidyl peptidase (TPP) class. Each required a free N-terminus to catalyze the release of collagen-related (Gly-Pro-X) "triplets." In accordance with their apparent pH optima, activities were routinely determined fluorimetrically at pH 4.0 (TPP 4) and at pH 7.0 (TPP 7) on Gly-Pro-Met-2-naphthylamide. The specific activity in both the homogenate and the classical subfractions was much greater at pH 7 than at pH 4. Subfractionation of the microsomal fraction by equilibrium banding in sucrose did not separate the TPP 4 and TPP 7 activities. The banding density (1.18 g/ml) and the distribution patterns for TPP 7 in the microsomal subfractions, and also in the subfractions of the small lysosomes in the mitochondrial-lysosomal (ML) fraction, demonstrate that TPP 7 is associated with smooth membranes. The TPP 4 and TPP 7 activities were clearly separated during subfractionation of the ML fraction. Rate sedimentation demonstrated that TPP 4 was present in the large, fast-sedimenting lysosomes (protein droplets) and in a heterogeneous broad band of smaller lysosomes. Equilibrium banding of the small lysosomes gave two distinct TPP 4-containing populations at densities 1.20 and 1.235 g/ml. Notably, dipeptidyl peptidase II (DPP II) gave identical banding densities and showed distributions very similar to TPP 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic extract (PE) reduced the uptake of rat intrinsic factor (IF)-bound 57CoB12 by perfused rat intestinal segments (p is less than 0.02) as well as by isolated rat intestinal brush borders (p is less than 0.01). The inhibition was concentration-dependent. Preincubation of the brush borders with PE recular weight of the 57CoB12-IF complex, as well as the uptake of the complex by isolated intestinal brush borders, was unchanged after prolonged preincubation with PE. PE also inhibited the uptake of glucose by perfused intestinal segments (p is less than 0.01), but the morphology and idsaccharidase activity (p is greater than 0.5) of the intestinaleptihelium was unaltered. The results indicate that the inhibition may be due to interaction between the intestinal epithelium and PE.

Determination of vitamin-B12-binding capacity and gel filtration of human pancreatic juice (HPJ) and rat pancreatic juice (RPJ) demonstrated a vitamin B12 binder different from gastric intrinsic factor (IF). The results also indicated the presence of the pancreatic B12 binding in human duodenal juice. The binder in RPJ had no significant effect on the uptake of 57CoB12 and 57CoB12 bound to rat IF by perfused rat intestinal segments (p greater than 0.5; p greater than 0.1). The binder in HPJ had no effect on the uptake of unbound 57CoB12 or 57CoB12 bound to human IF by guinea pig intestinal brush borders (p greater than 0.05; p greater than 0.1). The results indicate that the pancreatic vitamin B12 binder does not influence the intestinal uptake of vitamin B12.

The mean absorption of vitamin B12 (Schilling test) was 13.1 +/- 1.0 (% +/- S.E.M.) in 21 patients with chronic pancreatic insufficiency and 17.6 +/- 1.4 in 13 control patients (p less than 0.01). There was no correlation between pancreatic bicarbonate production after secretion stimulation and vitamin B12 absorption in the patient group (r = 0.117). Human duodenal juice reduced the uptake of 57CoB12-rat intrinsic factor (IF) by perfused rat small intestinal segments in vivo (p less than 0.01) as well as the uptake of 57CoB12-human IF by purified guinea-pig intestinal brush borders in vitro (p less than 0.01). The results confirm reduced absorption of vitamin B12 in chronic pancreatic insufficiency, but the mechanism remains uncertain.

To determine the mechanism by which pancreatic extract (PE) corrects the malabsorption of vitamin B12 in chronic pancreatic insufficiency (CPI), the following hypotheses were investigated: Firstly, PE might stimulate the absorption of vitamin B12 by changing the intestinal pH, secondly PE might stimulate the intestinal uptake of unbound vitamin B12, thirdly PE might abolish the inhibitory effect of vitamin B12 binders on the intestinal uptake of vitamin B12 bound to intrinsic factor (IF). PE had no effect on the pH in the small intestine and did not stimulate the uptake of unbound 57CoB12 by perfused rat intestinal segments. Preincubation of 57CoB12-IF with a non-IF B12-binder from human saliva (R-binder) reduced the uptake of 57CoB12 from 18.5 pg per cm intestine +/- 3.4 S.E.M. to 7.8 +/- 1.6 (p less than 0.02). PE abolished this inhibitory effect (p less than 0.05). The results indicate that PE corrects the malabsorption of vitamin B12 in CPI by an effect on non-IF B12- binders.

A simple, rapid and versatile technique for scintillation counting of double labelled fixed tissue is described. Furthermore, DNA determination can be performed on the same tissue digest.

We tested the radioassays for cyclic AMP and human gastrin, both involving separation on coated charcoal, for interaction with bile acids and detergents, and found a concentration-dependent interaction of taurocholic and glycocholic acid as well as of the surfactant Triton X-100 and sodium laurylsulfate in both assays. The interaction was detectable from concentrations of 0.5 mmol of bile acid per liter or 625 mg of detergent per liter, giving rise to falsely decreased gastrin values and falsely increased or decreased values for cyclic AMP. The interactions demonstrated may be a general effect on all radioassays that are based on the use of coated charcoal in the separation of free from bound ligands.

In order to evaluate the influence of cellular derangements on hepatic endocytosis, its pathways have to be elucidated. Ways are now described to separate different cell types concerned, and to follow the endocytosis of different labelled ligands by subcellular fractionation techniques employing sucrose, Nycodenz or Percoll density gradients. The fractions were analyzed for degraded (acidsoluble) and undegraded ligands and for relevant marker enzymes (more meaningful because of the use of purified cell types). Different cell types differed in the intracellular processing of the ligands. Endocytosis has been studied in cultures also. The steps seem to be: → small, then larger, endosomes → (degradation) lysosome progression.

Heavy and light microsomal fractions were subfractioned using high performance zonal rotors, and assayed for apoprotenin sensitive kallikrein-like amidolytic activity (pH 8.2). The activity profiles for the various substrates assayed show rather complex distribution pattern demonstrating kallikrein-like amidolytic activity in plasma membranes, basolateral membranes, rough endoplasmic reticulum and membranes derived from the Golgi complex.

Pancreatic extract (PE) contained small-molecular, thermo-stable as well as macro-molecular, thermo-labile factors capable of reducing the uptake of 57CoB12 bound to rat intrinsic factor by perfused rat intestinal segments (p less than 0.01 and p less than 0.01). Neither non-radioactive vitamin B12 nor non-pacreatic protein reduced the 57CoB12-uptake (p greater than 0.5 and p greater than 0.1) Crystalline trypsin and trypsinogen, but not chymotrypsin, also inhibited the uptake (p less than 0.05, p less than 0.02 and p greater than 0.05). The tryptic inhibition was abolished by soybean trypsin inhibitor (p greater than 0.05).

Human (D54Mg, GaMg) and rat (BT5C, BT4Cn) glioma cells cultured in a chemically defined medium showed reduced growth when compared to serum-supplemented medium. The BT5C cells changed from a flat epithelioid morphology to a more glia-like structure. The serum-free medium caused an aggregation of BT5C cells which spontaneously lost anchorage dependence and continued to grow in suspension as multicellular tumor spheroids. The BT4Cn and human cell lines did not show any change in morphology. Flow cytometric DNA measurements showed no change in ploidy for cells grown in serum-free medium. Cell cycle analysis revealed that the same proportion of cells were proliferating (S and G2M phase cells) in serum-free medium as compared to serum-supplemented medium. The reduced growth is probably due to increased cell cycle time.

Induction of acute Heyman nephritis in rats gave a significant increase in the urinary excretion of protein (p less than 0.001) and N-acetyl-beta-D-glucosaminidase (NAG; p less than 0.01) 14 days after injection of antibody. The isoelectric points (IP) of NAG were studied by chromatofocusing of the urine, serum and various lysosomal populations purified from kidney cortex homogenates of normal and nephritic rats. The chromatofocusing profiles for serum NAG (IP = 5.8) were totally different from the patterns found in normal and nephritic urines. The acidic IPs of NAG in normal urine (IP = 5.0) were changed into slightly more basic values in nephritic urine (IP = 5.15). Similar changes were also demonstrated in normal urine after acidification and prolonged incubation. The chromatofocusing profile obtained for NAG in the large, dense lysosomes was almost identical to the pattern observed in nephritic urine and demonstrated IPs for NAG in a slightly more basic pH area than observed for small and medium-sized lysosomes. The difference in IP in normal and nephritic urines may therefore be due to an increased autolytic degradation of NAG or excretion of the enzyme from different populations of lysosomes.

With a view to elucidating functional relationships among rat lysosomal populations from nephron regions, we induced acute nephritis immunologically, marked by heavy proteinuria and increased urinary activity of acid hydrolases. Acid hydrolases rose too in preparations of large lysosomes (protein droplets) derived from kidney proximal tubules and concerned in protein degradation. Isopycnic centrifugation of small lysosomes yielded a new population of lysosomes with a relatively high membrane content probably resulting from increased membrane turnover induced by the increase in protein uptake.

1. RNA polymerase activity of Escherichia coli extracts prepared from cells in exponential and stationary phases of growth, when measured in the presence and absence of external template, showed significant qualitative differences. 2. In both extracts, polymerase activity was higher when assayed with external template, suggesting the presence of a pool of enzyme not bound to cellular DNA. 3. In the crude extract, the fraction of enzyme bound to cellular DNA is higher during the exponential phase of growth. 4. A method is described for the purification of enzyme molecules not tightly bound to cellular DNA from exponential- and stationary-phase cultures. 5. Purified enzyme preparations showed differences in template requirement and subunit composition. 6. On phosphocellulose chromatography of stationary-phase enzyme, a major portion of polymerase activity eluted from the column with 0.25m-KCl. In the case of exponential-phase enzyme, polymerase activity eluted from a phosphocellulose column mainly with 0.35m-KCl. 7. Enzyme assays done with excess of bacteriophage T4 DNA showed a strong inhibition of stationary-phase enzyme by this template. The exponential-phase enzyme was only slightly inhibited by excess of bacteriophage T4 DNA.