Data Analysis for Precision 21 cm Cosmology Liu, Adrian; Shaw, J. Richard
Publications of the Astronomical Society of the Pacific,
06/2020, Letnik:
132, Številka:
1012
Journal Article
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The redshifted 21 cm line is an emerging tool in cosmology, in principle permitting three-dimensional surveys of our universe that reach unprecedentedly large volumes, previously inaccessible length ...scales, and hitherto unexplored epochs of our cosmic timeline. Large radio telescopes have been constructed for this purpose, and in recent years there has been considerable progress in transforming 21 cm cosmology from a field of considerable theoretical promise to one of observational reality. Increasingly, practitioners in the field are coming to the realization that the success of observational 21 cm cosmology will hinge on software algorithms and analysis pipelines just as much as it does on careful hardware design and telescope construction. This review provides a pedagogical introduction to state-of-the-art ideas in 21 cm data analysis, covering a wide variety of steps in a typical analysis pipeline, from calibration to foreground subtraction to map making to power spectrum estimation to parameter estimation.
The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. ...Studies of the type I 'interferome' have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved 'core' of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response.
Summary Most patients requiring midface reconstruction have had ablative surgery for malignant disease, and most require postoperative radiotherapy. This type of facial reconstruction attracts ...controversy, not only because of the many reconstructive options, but also because dental and facial prostheses can be very successful in selected cases. This Personal View is based on a new classification of the midface defect, which emphasises the increasing complexity of the problem. Low defects not involving the orbital adnexae can often be successfully treated with dental obturators. For the more extensive maxillary defects, there is consensus that a free flap is required. Composite flaps of bone and muscle harvested from the iliac crest with internal oblique or the scapula tip with latissimus dorsi can more reliably support the orbit and cheek than soft-tissue free flaps and non-vascularised grafts, and also enable an implant-borne dental or orbital prosthesis. Nasomaxillary defects usually require bone to augment the loss of the nasal bones, but orbitomaxillary cases can be managed more simply with local or soft-tissue free flaps. We review the current options and our own experience over the past 15 years in an attempt to rationalise the management of these defects.
The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions ...(FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis.
Death by suicide is one of the great challenges in public health. Suicide is a tragedy that affects not only the deceased individual but also everybody to whom that individual was connected. Yet, ...despite the link between death by suicide and social integration being long recognized and many efforts to reduce suicide rates in recent decades,1 the age-adjusted rate of suicide in the United States increased from 10.5 per 100 000 in 1999 to 13.9 in 2019.2 Before the pandemic, suicide was the 10th leading cause of death in terms of all-age mortality; in comparison, ageadjusted rates for the top three causes of death are 161.5 per 100 000 for heart disease, 146.2 for cancer, and 49.3 for unintentional injuries. Suicide is even more important among those younger than 65 years, ranking as the fifth leading cause of death.2 The US suicide rate is not atypical, with the suicide rate for other high-income countries being 13.7 per 100 0003 Thus, identifying how to best target interventions to address suicide is a global priority.In this issue of AJPH, Olfson et al. (p. 1774) describe who dies alone and how. The strongest associations between living alone and risk of suicide are for those with the most advantaged social positions, as indicated by education, income, and ethnicity. Looking at the results in additional detail provides more information. Among adults living with others, suicide rates decline with increasing income and education levels. Conversely, there is little evidence of any differences in suicide rates by income or education among people living alone, a finding that cannot be explained by chance.
Amyotrophic lateral sclerosis (ALS) is a devastating disease caused by degeneration of motor neurons. As with all major neurodegenerative disorders, development of disease-modifying therapies has ...proven challenging for multiple reasons. Nevertheless, ALS is one of the few neurodegenerative diseases for which disease-modifying therapies are approved. Significant discoveries and advances have been made in ALS preclinical models, genetics, pathology, biomarkers, imaging and clinical readouts over the last 10-15 years. At the same time, novel therapeutic paradigms are being applied in areas of high unmet medical need, including neurodegenerative disorders. These developments have evolved our knowledge base, allowing identification of targeted candidate therapies for ALS with diverse mechanisms of action. In this Review, we discuss how this advanced knowledge, aligned with new approaches, can enable effective translation of therapeutic agents from preclinical studies through to clinical benefit for patients with ALS. We anticipate that this approach in ALS will also positively impact the field of drug discovery for neurodegenerative disorders more broadly.
Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence ...of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups (‘no COVID-19’, ‘COVID-19 in last 12 weeks’, ‘COVID-19 > 12 weeks ago’), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the ‘COVID-19 in last 12 weeks’ and ‘no COVID-19’ groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the ‘COVID-19 > 12 weeks ago’ and ‘no COVID-19’ groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.
In this paper, we describe the spherical harmonic transit telescope through the use of a novel formalism for the analysis of transit radio telescopes. This all-sky approach bypasses the curved-sky ...complications of traditional interferometry and so is particularly well-suited to the analysis of wide-field radio interferometers. It enables compact and computationally efficient representations of the data and its statistics, which allow new ways of approaching important problems like map-making and foreground removal. In particular, we show how it enables the use of the Karhunen-Loeve transform as a highly effective foreground filter, suppressing realistic foreground residuals for our fiducial example by at least a factor 20 below the 21 cm signal, even in highly contaminated regions of the sky. This is despite the presence of the mode-mixing inherent in real-world instruments with frequency-dependent beams. We show, using Fisher forecasting, that foreground cleaning has little effect on power spectrum constraints compared to hypothetical foreground-free measurements. Beyond providing a natural real-world data analysis framework for 21 cm telescopes now under construction and future experiments, this formalism allows accurate power spectrum forecasts to be made that include the interplay of design constraints and realistic experimental systematics with 21st century 21 cm science.
Abstract
We present a detection of 21 cm emission from large-scale structure (LSS) between redshift 0.78 and 1.43 made with the Canadian Hydrogen Intensity Mapping Experiment. Radio observations ...acquired over 102 nights are used to construct maps that are foreground filtered and stacked on the angular and spectral locations of luminous red galaxies (LRGs), emission-line galaxies (ELGs), and quasars (QSOs) from the eBOSS clustering catalogs. We find decisive evidence for a detection when stacking on all three tracers of LSS, with the logarithm of the Bayes factor equal to 18.9 (LRG), 10.8 (ELG), and 56.3 (QSO). An alternative frequentist interpretation, based on the likelihood ratio test, yields a detection significance of 7.1
σ
(LRG), 5.7
σ
(ELG), and 11.1
σ
(QSO). These are the first 21 cm intensity mapping measurements made with an interferometer. We constrain the effective clustering amplitude of neutral hydrogen (H
i
), defined as
H
I
≡
10
3
Ω
H
I
b
H
I
+
〈
f
μ
2
〉
, where Ω
H
i
is the cosmic abundance of H
i
,
b
H
i
is the linear bias of H
i
, and 〈
f
μ
2
〉 = 0.552 encodes the effect of redshift-space distortions at linear order. We find
H
I
=
1.51
−
0.97
+
3.60
for LRGs (
z
= 0.84),
H
I
=
6.76
−
3.79
+
9.04
for ELGs (
z
= 0.96), and
H
I
=
1.68
−
0.67
+
1.10
for QSOs (
z
= 1.20), with constraints limited by modeling uncertainties at nonlinear scales. We are also sensitive to bias in the spectroscopic redshifts of each tracer, and we find a nonzero bias Δ
v
= − 66 ± 20 km s
−1
for the QSOs. We split the QSO catalog into three redshift bins and have a decisive detection in each, with the upper bin at
z
= 1.30 producing the highest-redshift 21 cm intensity mapping measurement thus far.
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