Localness of energy cascade in hydrodynamic turbulence, II. Sharp spectral filter

We investigate the scale-locality of subgrid-scale (SGS) energy flux and inter-band energy transfers defined by the sharp spectral filter. We show by rigorous bounds, physical arguments and numerical simulations that the spectral SGS flux is dominated by local triadic interactions in an extended turbulent inertial-range. Inter-band energy transfers are also shown to be dominated by local triads if the spectral bands have constant width on a logarithmic scale. We disprove in particular an alternative picture of ``local transfer by nonlocal triads,'' with the advecting wavenumber mode at the energy peak. Although such triads have the largest transfer rates of all {\it individual} wavenumber triads, we show rigorously that, due to their restricted number, they make an asymptotically negligible contribution to energy flux and log-banded energy transfers at high wavenumbers in the inertial-range. We show that it is only the aggregate effect of a geometrically increasing number of local wavenumber triads which can sustain an energy cascade to small scales. Furthermore, non-local triads are argued to contribute even less to the space-average energy flux than is implied by our rigorous bounds, because of additional cancellations from scale-decorrelation effects. We can thus recover the -4/3 scaling of nonlocal contributions to spectral energy flux predicted by Kraichnan's ALHDIA and TFM closures. We support our results with numerical data from a $512^3$ pseudospectral simulation of isotropic turbulence with phase-shift dealiasing. We conclude that the sharp spectral filter has a firm theoretical basis for use in large-eddy simulation (LES) modeling of turbulent flows.Comment: 42 pages, 9 figure

Mutator Suppression and Escape from Replication Error–Induced Extinction in Yeast

Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10−3 inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

The Fermentation of Propylene Glycol by Members of the Escherichia-Aerobacter-Intermediate Groups

The possibility has been suggested of differentiating the "in-termediates " from Escherichia and Aerobacter by the use of propylene glycol (Dozois et al., 1936). It was observed, in the limited number of cultures'studied, that Escherichia and Aero-bacter formed acid from propylene glycol, while the "intermedi-ates " did not. In order to determine whether the utilization of this glycol might serve as a convenient additional taxonomic characteristic of this group, extensive observations were deemed advisable. Therefore, the propylene-glycol broth medium was used, in the study of a number of stock cultures, and in the routine examination of strains isolated from water, milk, crabmeat, oys-ters and feces. In an attempt to differentiate between the various strains of the "intermediates " observations on the fermentation of propy-lene glycol, ethylene glycol, adonitol and inositol were made. Those coli-form microorganisms which were found to be methyl-red positive and Voges-Proskauer negative, and which also grew in citrate broth (Koser's) were classed as members of the "inter-mediate " group. METHODS AND MATERIALS One per cent of the specific sugar alcohol was added to sugar-free broth of a pH of 7.0. The indicator used was chlorpheno

The Performance and Fouling Control of Submerged Hollow Fiber (HF) Systems: A Review

The submerged membrane filtration concept is well-established for low-pressure microfiltration (MF) and ultrafiltration (UF) applications in the water industry, and has become a mainstream technology for surface-water treatment, pretreatment prior to reverse osmosis (RO), and membrane bioreactors (MBRs). Compared to submerged flat sheet (FS) membranes, submerged hollow fiber (HF) membranes are more common due to their advantages of higher packing density, the ability to induce movement by mechanisms such as bubbling, and the feasibility of backwashing. In view of the importance of submerged HF processes, this review aims to provide a comprehensive landscape of the current state-of-the-art systems, to serve as a guide for further improvements in submerged HF membranes and their applications. The topics covered include recent developments in submerged hollow fiber membrane systems, the challenges and developments in fouling-control methods, and treatment protocols for membrane permeability recovery. The highlighted research opportunities include optimizing the various means to manipulate the hydrodynamics for fouling mitigation, developing online monitoring devices, and extending the submerged HF concept beyond filtration.MOE (Min. of Education, S’pore)Published versio

Bulk phase resource ratio alters carbon steel corrosion rates and endogenously produced extracellular electron transfer mediators in a sulfate-reducing biofilm.

Desulfovibrio alaskensis G20 biofilms were cultivated on 316 steel, 1018 steel, or borosilicate glass under steady-state conditions in electron-acceptor limiting (EAL) and electron-donor limiting (EDL) conditions with lactate and sulfate in a defined medium. Increased corrosion was observed on 1018 steel under EDL conditions compared to 316 steel, and biofilms on 1018 carbon steel under the EDL condition had at least twofold higher corrosion rates compared to the EAL condition. Protecting the 1018 metal coupon from biofilm colonization significantly reduced corrosion, suggesting that the corrosion mechanism was enhanced through attachment between the material and the biofilm. Metabolomic mass spectrometry analyses demonstrated an increase in a flavin-like molecule under the 1018 EDL condition and sulfonates under the 1018 EAL condition. These data indicate the importance of S-cycling under the EAL condition, and that the EDL is associated with increased biocorrosion via indirect extracellular electron transfer mediated by endogenously produced flavin-like molecules