Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?

Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly

Shear flow of angular grains: acoustic effects and non-monotonic rate dependence of volume

Naturally-occurring granular materials often consist of angular particles whose shape and frictional characteristics may have important implications on macroscopic flow rheology. In this paper, we provide a theoretical account for the peculiar phenomenon of auto-acoustic compaction -- non-monotonic variation of shear band volume with shear rate in angular particles -- recently observed in experiments. Our approach is based on the notion that the volume of a granular material is determined by an effective-disorder temperature known as the compactivity. Noise sources in a driven granular material couple its various degrees of freedom and the environment, causing the flow of entropy between them. The grain-scale dynamics is described by the shear-transformation-zone (STZ) theory of granular flow, which accounts for irreversible plastic deformation in terms of localized flow defects whose density is governed by the state of configurational disorder. To model the effects of grain shape and frictional characteristics, we propose an Ising-like internal variable to account for nearest-neighbor grain interlocking and geometric frustration, and interpret the effect of friction as an acoustic noise strength. We show quantitative agreement between experimental measurements and theoretical predictions, and propose additional experiments that provide stringent tests on the new theoretical elements.Comment: 12 pages, 3 figure

Saudi SCD patients’ symptoms and quality of life relative to the number of ED visits

Background Individuals living with sickle cell disease (SCD) have significantly increased emergency department (ED) use compared to the general population. In Saudi Arabia, health care is free for all individuals and therefore has no bearing on increased ED visits. However, little is known about the relationship between quality of life (QoL) and frequency of acute care utilization in this patient population. Methods A cross-sectional study was conducted on 366 patients with SCD who attended the outpatient department at King Fahad Hospital, Hofuf, Saudi Arabia. Data were collected through self-administered surveys, which included: demographics, SCD-related ED visits, clinical issues, and QoL levels. We assessed the ED use by asking for the number of SCD-related ED visits within a 6-month period. Results The self-report survey of ED visits was completed by 308 SCD patients. The median number of SCD-related ED visits within a 6-month time period (IQR) was four (2-7 visits). According to the unadjusted negative binomial model, the rate of SCD-related ED visits increased by (46, 39.3, 40, and 53.5 %) for patients with fever, skin redness with itching, swelling, and blood transfusion, respectively. Poor QoL tends to increase the rate of SCD-related ED visits. Well education and poor general health positively influenced the rate of SCD-related ED visits. Well education tends to increase the rate of SCD-related ED visits by 50.2 %. The rate of SCD-related ED visits decreased by 1.4 % for every point increase in general health. Conclusion Saudi patients with sickle cell disease reported a wide range of SCD-related ED visits. It was estimated that six of 10 SCD patients had at least three ED visits within a 6-month period. Well education and poor general health resulted in an increase in the rate of SCD-related ED visits

Single Pion production from Nuclei

We have studied charged current one pion production induced by $\nu_\mu(\bar\nu_\mu)$ from some nuclei. The calculations have been done for the incoherent pion production processes from these nuclear targets in the $\Delta$ dominance model and take into account the effect of Pauli blocking, Fermi motion and renormalization of $\Delta$ properties in the nuclear medium. The effect of final state interactions of pions has also been taken into account. The numerical results have been compared with the recent results from the MiniBooNE experiment for the charged current 1$\pi$ production, and also with some of the older experiments in Freon and Freon-Propane from CERN.Comment: 5 pages, 5 figures, 5th International Workshop on Neutrino-Nucleus Interactions in the few GeV region(NuInt07), Batavia, Illinois, 30May-3June, 200

Stick-slip instabilities in sheared granular flow: the role of friction and acoustic vibrations

We propose a theory of shear flow in dense granular materials. A key ingredient of the theory is an effective temperature that determines how the material responds to external driving forces such as shear stresses and vibrations. We show that, within our model, friction between grains produces stick-slip behavior at intermediate shear rates, even if the material is rate-strengthening at larger rates. In addition, externally generated acoustic vibrations alter the stick-slip amplitude, or suppress stick-slip altogether, depending on the pressure and shear rate. We construct a phase diagram that indicates the parameter regimes for which stick-slip occurs in the presence and absence of acoustic vibrations of a fixed amplitude and frequency. These results connect the microscopic physics to macroscopic dynamics, and thus produce useful information about a variety of granular phenomena including rupture and slip along earthquake faults, the remote triggering of instabilities, and the control of friction in material processing.Comment: 12 pages, 8 figure