Advanced power sources for space missions

Approaches to satisfying the power requirements of space-based Strategic Defense Initiative (SDI) missions are studied. The power requirements for non-SDI military space missions and for civil space missions of the National Aeronautics and Space Administration (NASA) are also considered. The more demanding SDI power requirements appear to encompass many, if not all, of the power requirements for those missions. Study results indicate that practical fulfillment of SDI requirements will necessitate substantial advances in the state of the art of power technology. SDI goals include the capability to operate space-based beam weapons, sometimes referred to as directed-energy weapons. Such weapons pose unprecedented power requirements, both during preparation for battle and during battle conditions. The power regimes for these two sets of applications are referred to as alert mode and burst mode, respectively. Alert-mode power requirements are presently stated to range from about 100 kW to a few megawatts for cumulative durations of about a year or more. Burst-mode power requirements are roughly estimated to range from tens to hundreds of megawatts for durations of a few hundred to a few thousand seconds. There are two likely energy sources, chemical and nuclear, for powering SDI directed-energy weapons during the alert and burst modes. The choice between chemical and nuclear space power systems depends in large part on the total duration during which power must be provided. Complete study findings, conclusions, and eight recommendations are reported

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells

X-inactivation, the molecular mechanism enabling dosage compensation in mammals, is tightly controlled during mouse early embryogenesis. In the morula, X-inactivation is imprinted with exclusive silencing of the paternally inherited X-chromosome. In contrast, in the post-implantation epiblast, X-inactivation affects randomly either the paternal or the maternal X-chromosome. The transition from imprinted to random X-inactivation takes place in the inner cell mass (ICM) of the blastocyst from which embryonic stem (ES) cells are derived. The trigger of X-inactivation, Xist, is specifically downregulated in the pluripotent cells of the ICM, thereby ensuring the reactivation of the inactive paternal X-chromosome and the transient presence of two active X-chromosomes. Moreover, Tsix, a critical cis-repressor of Xist, is upregulated in the ICM and in ES cells where it imposes a particular chromatin state at the Xist promoter that ensures the establishment of random X-inactivation upon differentiation. Recently, we have shown that key transcription factors supporting pluripotency directly repress Xist and activate Tsix and thus couple Xist/Tsix control to pluripotency. In this manuscript, we report that Rnf12, a third X-linked gene critical for the regulation of X-inactivation, is under the control of Nanog, Oct4 and Sox2, the three factors lying at the heart of the pluripotency network. We conclude that in mouse ES cells the pluripotency-associated machinery exerts an exhaustive control of X-inactivation by taking over the regulation of all three major regulators of X-inactivation: Xist, Tsix, and Rnf12

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Low-dose CT for lung cancer screening in a high-risk population (SUMMIT): a prospective, longitudinal cohort study

Background: Low-dose CT screening reduces lung cancer mortality. In advance of planned national lung cancer screening programmes, research is needed to inform policies regarding implementation. We aimed to assess the implementation of low-dose CT for lung cancer screening in a high-risk population and to validate a multicancer early detection blood test.// Methods: In this prospective, longitudinal cohort study, individuals aged 55–77 years recorded as current smokers in their primary care records at any point within the past 20 years were identified from 329 primary care practices in London (UK) and invited for a lung health check via postal letter. Individuals meeting the 2013 United States Preventive Services Taskforce criteria (current or former smokers within the past 15 years with at least 30 pack-year smoking histories) or having a Prostate, Lung, Colorectal and Ovarian 2012 model 6-year risk of 1·3% or greater, and not currently receiving treatment for an active cancer (except adjuvant hormonal therapy), were eligible for the study. These individuals underwent lung cancer screening via non-contrast, thin collimation low-dose CT. In this analysis, we report the results of the baseline round of low-dose CT screening. Key primary endpoints were those associated with examining the performance of a lung cancer screening service. Outcome measures were analysed on a per-participant level using descriptive frequencies. The study was registered with ClinicalTrials.gov, NCT03934866.// Findings: Between April 8, 2019, and May 14, 2021, 12 773 participants were recruited and analysed. 7353 (57·6%) of 12 773 participants were male and 5420 (42·4%) were female, and 10 665 (83·5%) participants were White. 261 (2·0%) of 12 773 participants were diagnosed with lung cancer (including 163 [1·3%] participants with screen-detected lung cancer and 98 [0·8%] with delayed screen-detected lung cancer [ie, after a 3-month or 6-month nodule follow-up CT]) and 276 (2·2%) participants were diagnosed with any intrathoracic malignancy after a positive baseline screen. 207 (79·3%) of 261 individuals with prevalent screen-detected lung cancer were diagnosed at stage I or II and surgical resection was the primary treatment modality in 201 (77·0%) of 261 individuals. Including cases where multiple resections were done in the same participant (eg, for synchronous primaries), 28 (11·6%) of 241 surgical resections were benign, and there was one (0·4%) death within 90 days of surgery. At 12 months, the episode sensitivity of our low-dose CT screening protocol for detecting lung cancer was 97·0% (95% CI 95·0–99·1; 261 of 269 participants). The specificity was 95·2% (94·8–95·6; 11 905 of 12 504 participants), with a false-positive rate of 4·8% (4·4–5·2).// Interpretation: Large-scale lung cancer screening is effective and can be delivered efficiently to an ethnically and socioeconomically diverse population. Funding GRAIL

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies