Base heating methodology improvements, volume 1

This document is the final report for NASA MSFC Contract NAS8-38141. The contracted effort had the broad objective of improving the launch vehicles ascent base heating methodology to improve and simplify the determination of that environment for Advanced Launch System (ALS) concepts. It was pursued as an Advanced Development Plan (ADP) for the Joint DoD/NASA ALS program office with project management assigned to NASA/MSFC. The original study was to be completed in 26 months beginning Sep. 1989. Because of several program changes and emphasis on evolving launch vehicle concepts, the period of performance was extended to the current completion date of Nov. 1992. A computer code incorporating the methodology improvements into a quick prediction tool was developed and is operational for basic configuration and propulsion concepts. The code and its users guide are also provided as part of the contract documentation. Background information describing the specific objectives, limitations, and goals of the contract is summarized. A brief chronology of the ALS/NLS program history is also presented to provide the reader with an overview of the many variables influencing the development of the code over the past three years

Utility of targeted gene sequencing to differentiate myeloid malignancies from other cytopenic conditions

The National Heart, Lung, and Blood Institute-funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best predict a diagnosis of myeloid malignancy and among those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a positive predictive value (PPV) of 0.84 and negative predictive value (NPV) of 0.8 with an area under the receiver operating characteristic curve (AUROC) of 0.85 when classifying patients as having myeloid vs no myeloid malignancy based on variant allele frequencies (VAFs) in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as having MDS vs non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard)

Classical and quantum communication without a shared reference frame

We show that communication without a shared reference frame is possible using entangled states. Both classical and quantum information can be communicated with perfect fidelity without a shared reference frame at a rate that asymptotically approaches one classical bit or one encoded qubit per transmitted qubit. We present an optical scheme to communicate classical bits without a shared reference frame using entangled photon pairs and linear optical Bell state measurements.Comment: 4 pages, published versio

Semi-automated assembly of high-quality diploid human reference genomes

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements