Study to establish cost predictions for the production of Redox chemicals

The chromium and iron chloride chemicals are significant first costs for NASA Redox energy storage systems. This study was performed to determine the lowest cost at which chromium and iron chlorides could be obtained for a complex of redox energy storage systems. In addition, since the solutions gradually become intermixed during the course of operation of Redox units, it was an objective to evaluate schemes for regeneration of the operating solutions. Three processes were evaluated for the production of chromium and iron chlorides. As a basis for the preliminary plant design and economic evaluation, it was assumed that the plant would produce about 25,000 tons of contained chromium as CrCl3 and an equivalent molar quantity of FeCl2. Preliminary plant designs, including materials and energy balances and sizing of major equipment, were prepared, and capital and operating costs were estimated

Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis

In membranous nephropathy autoantibodies target podocytes of the kidney filter resulting in injury. Here the authors show that the ensuing proteostatic disturbances and proteinuria relate to aberrant interactions of non-functional UCH-L1 enzyme with the proteasome, curtailing its capacity.Little is known about the mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment. In membranous nephropathy (MN), autoantibodies target podocytes of the glomerular filter resulting in proteinuria. Converging biochemical, structural, mouse pathomechanistic, and clinical information we report that the deubiquitinase Ubiquitin C-terminal hydrolase L1 (UCH-L1) is induced by oxidative stress in podocytes and is directly involved in proteasome substrate accumulation. Mechanistically, this toxic gain-of-function is mediated by non-functional UCH-L1, which interacts with and thereby impairs proteasomes. In experimental MN, UCH-L1 becomes non-functional and MN patients with poor outcome exhibit autoantibodies with preferential reactivity to non-functional UCH-L1. Podocyte-specific deletion of UCH-L1 protects from experimental MN, whereas overexpression of non-functional UCH-L1 impairs podocyte proteostasis and drives injury in mice. In conclusion, the UPS is pathomechanistically linked to podocyte disease by aberrant proteasomal interactions of non-functional UCH-L1.Bio-organic Synthesi

Comparative Transmissibility of SARS-CoV-2 Variants Delta and Alpha in New England, USA

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant quickly rose to dominance in mid-2021, displacing other variants, including Alpha. Studies using data from the United Kingdom and India estimated that Delta was 40-80% more transmissible than Alpha, allowing Delta to become the globally dominant variant. However, it was unclear if the ostensible difference in relative transmissibility was due mostly to innate properties of Delta\u27s infectiousness or differences in the study populations. To investigate, we formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont). Finally, using RT-PCR data, we estimated that Delta infections generate on average ∼6 times more viral RNA copies per mL than Alpha infections. Overall, our evidence indicates that Delta\u27s enhanced transmissibility could be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on the underlying immunity and behavior of distinct populations

Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.

The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England in the United States. We compare logistic growth rates during each variant\u27s respective emergence period, finding that Delta emerged 1.37-2.63 times faster than Alpha (range across states). We compute variant-specific effective reproductive numbers, estimating that Delta is 63%-167% more transmissible than Alpha (range across states). Finally, we estimate that Delta infections generate on average 6.2 (95% CI 3.1-10.9) times more viral RNA copies per milliliter than Alpha infections during their respective emergence. Overall, our evidence suggests that Delta\u27s enhanced transmissibility can be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on underlying population attributes and sequencing data availability

Mutations affecting disulphide bonds contribute to a fairly common prevalence of F13B gene defects: results of a genetic study in 14 families with factor XIII B deficiency

Severe factor XIII (FXIII) deficiency is a rare autosomal recessive coagulation disorder affecting one in two million individuals. The aim of the present study was to screen for and analyse F13B gene defects in the German population. A total of 150 patients presenting with suspected FXIII deficiency and one patient with severe (homozygous) FXIII deficiency were screened for mutations in F13A and F13B genes. Twenty-five individuals presented with detectable heterozygous mutations, 12 of them in the F13A gene and 13 of them in the F13B gene. We report on the genotype-phenotype correlations of the individuals showing defects in the F13B gene. Direct sequencing revealed 12 unique mutations including seven missense mutations (Cys5Arg, Ile81Asn, Leu116Phe, Val217Ile, Cys316Phe, Val401Glu, Pro428Ser), two splice site mutations (IVS2-1G>C, IVS3-1G>C), two insertions (c.1155_1158dupACTT, c.1959insT) and one in-frame deletion (c.471-473delATT). Two of the missense mutations (Cys5Arg, Cys316Phe) eliminated disulphide bonds (Cys5-Cys56, Cys316-Cys358). Another three missense mutations, (Leu116Phe, Val401Glu, Pro428Ser) were located proximal to other cysteine disulphide bonds, therefore indicating that the region in and around these disulphide bonds is prone to functionally relevant mutations in the FXIII-B subunit. The present study reports on a fairly common prevalence of F13B gene defects in the German population. The regions in and around the cysteine disulphide bonds in the FXIII-B protein may be regions prone to frequent mutations

Novel biomarkers of a peripheral blood interferon signature associated with drug-naïve early arthritis patients distinguish persistent from self-limiting disease course

We profiled gene expression signatures to distinguish rheumatoid arthritis (RA) from non-inflammatory arthralgia (NIA), self-limiting arthritis (SLA), and undifferentiated arthritis (UA) as compared to healthy controls as novel potential biomarkers for therapeutic responsiveness. Global gene expression profiles of PBMCs from 43 drug-naïve patients presenting with joint symptoms were evaluated and differentially expressed genes identified by comparative analysis with 24 healthy volunteers. Patients were assessed at presentation with follow up at 6 and 12 months. Gene ontology and network pathway analysis were performed using DAVID Bioinformatics Resources v6.7. Gene expression profiles were also determined after disease-modifying anti-rheumatic drug (DMARD) treatment in the inflammatory arthritis groups (i.e. RA and UA) and confirmed by qRT-PCR. Receiver operating characteristic (ROC) curves analysis and Area Under the Curve (AUC) estimation were performed to assess the diagnostic value of candidate gene expression signatures. A type I interferon (IFN) gene signature distinguished DMARD-naïve patients who will subsequently develop persistent inflammatory arthritis (i.e. RA and UA) from those with NIA. In patients with RA, the IFN signature is characterised by up-regulation of SIGLEC1 (p = 0.00597) and MS4A4A (p = 0.00000904). We also identified, EPHB2 (p = 0.000542) and PDZK1IP1 (p = 0.0206) with RA-specific gene expression profiles and elevated expression of the ST6GALNAC1 (p = 0.0023) gene in UA. ROC and AUC risk score analysis suggested that MSA4A (AUC: 0.894, 0.644, 0.720), PDZK1IP1 (AUC: 0.785, 0.806, 0.977), and EPHB2 (AUC: 0.794, 0.723, 0.620) at 0, 6, and 12 months follow-up can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. In patients with early inflammatory arthritis, ST6GALNAC1 is a potential biomarker for UA as compared with healthy controls whereas EPHB2, MS4A4A, and particularly PDZK1IP1 may discriminate RA patients. SIGLEC1 may also be a useful marker of disease activity in UA