Pion production in relativistic collisions of nuclear drops

In a continuation of the long-standing effort of the nuclear physics community to model atomic nuclei as droplets of a specialized nuclear fluid, we have developed a hydrodynamic model for simulating the collisions of heavy nuclei at relativistic speeds. Our model couples ideal relativistic hydrodynamics with a new Monte Carlo treatment of dynamic pion production and tracking. The collective flow for low-energy (200 MeV/N) collisions predicted by this model compares favorably with results from earlier hydrodynamic calculations which used quite different numerical techniques. Our pion predictions at these lower energies appear to differ, however, from the experimental data on pion multiplicities. In this case of ultra-relativistic (200 GeV/N) collisions, our hydrodynamic model has produced baryonic matter distributions which are in reasonable agreement with recent experimental data. These results may shed some light on the sensitivity of relativistic collision data to the nuclear equation of state. 20 refs., 12 figs

Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable

Readthrough of Premature Termination Codons in the Adenomatous Polyposis Coli Gene Restores Its Biological Activity in Human Cancer Cells

The APC tumor suppressor gene is frequently mutated in human colorectal cancer, with nonsense mutations accounting for 30% of all mutations in this gene. Reintroduction of the WT APC gene into cancer cells generally reduces tumorigenicity or induces apoptosis. In this study, we explored the possibility of using drugs to induce premature termination codon (PTC) readthrough (aminoglycosides, negamycin), as a means of reactivating endogenous APC. By quantifying the readthrough of 11 nonsense mutations in APC, we were able to identify those giving the highest levels of readthrough after treatment. For these mutations, we demonstrated that aminoglycoside or negamycin treatment led to a recovery of the biological activity of APC in cancer cell lines, and showed that the level of APC activity was proportional to the level of induced readthrough. These findings show that treatment with readthrough inducers should be considered as a potential strategy for treating cancers caused by nonsense mutations APC gene. They also provide a rational basis for identifying mutations responsive to readthrough inducers

Remdesivir for the Treatment of Covid-19 — Preliminary Report

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705. opens in new tab.

Activation of cGMP-Dependent Protein Kinase Stimulates Cardiac ATP-Sensitive Potassium Channels via a ROS/Calmodulin/CaMKII Signaling Cascade

) channels, an ion channel critical for stress adaptation in the heart; however, the underlying mechanism remains largely unknown. The present study was designed to address this issue. channels was confirmed in intact ventricular cardiomyocytes, which was ROS- and CaMKII-dependent. Kinetically, PKG appeared to stimulate these channels by destabilizing the longest closed state while stabilizing the long open state and facilitating opening transitions. channels and contribute to cardiac protection against ischemia-reperfusion injury

Relativistic Numerical Method for Close Neutron Star Binaries

We describe a numerical method for calculating the (3+1) dimensional general relativistic hydrodynamics of a coalescing neutron-star binary system. The relativistic field equations are solved at each time slice with a spatial 3-metric chosen to be conformally flat. Against this solution to the general relativistic field equations the hydrodynamic variables and gravitational radiation are allowed to respond. The gravitational radiation signal is derived via a multipole expansion of the metric perturbation to the hexadecapole order including both mass and current moments and a correction for the slow motion approximation. Using this expansion, the effect of gravitational radiation on the system evolution can also be recovered by introducing an acceleration term in the matter evolution.Comment: 15 pages, 5 figures. Figures available by anonymous ftp at ftp://cygnus.phys.nd.edu/pub/gr/gr-qc9601017

Exploring the relationship between chronic undernutrition and asymptomatic malaria in Ghanaian children

<p>Abstract</p> <p>Background</p> <p>A moderate association has been found between asymptomatic parasitaemia and undernutrition. However, additional investigation using the gold standard for asymptomatic parasitaemia confirmation, polymerase chain reaction (PCR), is needed to validate this association. Anthropometric measurements and blood samples from children less than five years of age in a rural Ghanaian community were used to determine if an association exists between chronic undernutrition and PCR-confirmed cases of asymptomatic malaria.</p> <p>Methods</p> <p>This was a descriptive cross-sectional study of 214 children less than five years of age from a community near Kumasi, Ghana. Blood samples and anthropometric measurements from these children were collected during physical examinations conducted in January 2007 by partners of the Barekuma Collaborative Community Development Programme.</p> <p>Results</p> <p>Findings from the logistic model predicting the odds of asymptomatic malaria indicate that children who experienced mild, moderate or severe stunting were not more likely to have asymptomatic malaria than children who were not stunted. Children experiencing anaemia had an increased likelihood (OR = 4.15; 95% CI: 1.92, 8.98) of asymptomatic malaria. Similarly, increased spleen size, which was measured by ultrasound, was also associated with asymptomatic malaria (OR = 2.17; 95% CI: 1.44, 3.28). Fast breathing, sex of the child, and age of the child were not significantly associated with the asymptomatic malaria.</p> <p>Conclusions</p> <p>No significant association between chronic undernutrition and presence of asymptomatic malaria was found. Children who experience anaemia and children who have splenomegaly are more likely to present asymptomatic malaria. Programmes aimed at addressing malaria should continue to include nutritional components, especially components that address anaemia.</p