Laser phase noise effects on the dynamics of optomechanical resonators

We investigate theoretically the influence of laser phase noise on the cooling and heating of a generic cavity optomechanical system. We derive the back-action damping and heating rates and the mechanical frequency shift of the radiation pressure-driven oscillating mirror, and derive the minimum phonon occupation number for small laser linewidths. We find that in practice laser phase noise does not pose serious limitations to ground state cooling. We then consider the effects of laser phase noise in a parametric cavity driving scheme that minimizes the back-action heating of one of the quadratures of the mechanical oscillator motion. Laser linewidths narrow compared to the decay rate of the cavity field will not pose any problems in an experimental setting, but broader linewidths limit the practicality of this back-action evasion method.Comment: 9 pages, 7 figure

Establishment of invasive Black Carp (\u3ci\u3eMylopharyngodon piceus\u3c/i\u3e) in the Mississippi River basin: identifying sources and year classes contributing to recruitment

Black Carp (Mylopharyngodon piceus) was imported to the USA to control aquaculture pond snails. This species has escaped captivity and occurs in parts of the Mississippi River, several tributaries, and floodplain lakes, which is concerning due to potential competition with native fishes and predation on native mussels, many of which are imperiled. However, Black Carp captures have primarily been incidental by commercial fishers, and evidence of reproduction in the wild is limited. The objectives of this study were to assess relative abundance of aquaculture- origin and wild Black Carp using ploidy and otolith stable isotope analysis, identify spatial extent of natural reproduction using otolith microchemistry, assess age distributions of wild and aquaculturesource Black Carp to infer years in which natural reproduction occurred and timing of aquaculture escapement or introductions, and estimate size and age at maturation to assess whether recruitment to adulthood has occurred. Results revealed that Black Carp are established in parts of the Mississippi River basin based on findings that: (1) non-captive Black Carp primarily consist of fertile, naturally-reproduced fish, (2) reproduction has occurred in several rivers, (3) multiple year classes of wild fish are present, and (4) wild fish have recruited to adulthood. Multiple introductions or escapements of aquaculture-source fish into the wild, including both fertile and functionally sterile individuals, were also inferred. Individual growth appears to be rapid, although considerable variation was observed among fish. Additional study is suggested to refine understanding of where and when Black Carp reproduction is occurring in the Mississippi River basin

Long-Term PIT and T-Bar Anchor Tag Retention Rates in Adult Muskellunge

Mark-recapture studies require knowledge of tag retention rates specific to tag types, fish species and size, and study duration. We determined the probability of tag loss for passive integrated transponder (PIT) tags implanted into dorsal musculature, T-bar anchor tags attached to dorsal pterygiophores, and loss of both tags in relation to years post-tagging for double-marked adult muskellunge Esox masquinongy over a 10 year period. We also used PIT tags as a benchmark to assess the interactive effects of fish length at tagging, sex, and years post-tagging on T-bar anchor tag loss rates. Only five instances of PIT tag loss were identified; the calculated probability of a fish losing its PIT tag was consistently \u3c 1.0% for up to 10 years post-tagging. The probability of T-bar anchor tag loss by muskellunge was related to the number of years post-tagging and total length of fish at tagging. T-bar anchor tag loss rate one year after tagging was 6.5%. Individuals \u3c 750 mm total length at tagging had anchor tag loss rates \u3c 10% for up to 6 years after tagging. However, the proportion of fish losing T-bar anchor tags steadily increased with increasing years post-tagging (~30% after 6 years) for larger muskellunge. Fish gender did not influence probability of T-bar anchor tag loss. Our results indicate that T-bar anchor tags are best suited for short-term applications (≤ 1 year duration) involving adult muskellunge. We recommend use of PIT tags for longer-term tagging studies, particularly for muskellunge \u3e 750 mm total length

Dipolar quantum solids emerging in a Hubbard quantum simulator

In quantum mechanical many-body systems, long-range and anisotropic interactions promote rich spatial structure and can lead to quantum frustration, giving rise to a wealth of complex, strongly correlated quantum phases. Long-range interactions play an important role in nature; however, quantum simulations of lattice systems have largely not been able to realize such interactions. A wide range of efforts are underway to explore long-range interacting lattice systems using polar molecules, Rydberg atoms, optical cavities, and magnetic atoms. Here, we realize novel quantum phases in a strongly correlated lattice system with long-range dipolar interactions using ultracold magnetic erbium atoms. As we tune the dipolar interaction to be the dominant energy scale in our system, we observe quantum phase transitions from a superfluid into dipolar quantum solids, which we directly detect using quantum gas microscopy with accordion lattices. Controlling the interaction anisotropy by orienting the dipoles enables us to realize a variety of stripe ordered states. Furthermore, by transitioning non-adiabatically through the strongly correlated regime, we observe the emergence of a range of metastable stripe-ordered states. This work demonstrates that novel strongly correlated quantum phases can be realized using long-range dipolar interaction in optical lattices, opening the door to quantum simulations of a wide range of lattice models with long-range and anisotropic interactions

The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations in Staphylococcus aureus Dihydropteroate Synthase

Staphylococcal species are a leading cause of bacterial drug-resistant infections and associated mortality. One strategy to combat bacterial drug resistance is to revisit compromised targets, and to circumvent resistance mechanisms using structure-assisted drug discovery. The folate pathway is an ideal candidate for this approach. Antifolates target an essential metabolic pathway, and the necessary detailed structural information is now available for most enzymes in this pathway. Dihydropteroate synthase (DHPS) is the target of the sulfonamide class of drugs, and its well characterized mechanism facilitates detailed analyses of how drug resistance has evolved. Here, we surveyed clinical genetic sequencing data in S. aureus to distinguish natural amino acid variations in DHPS from those that are associated with sulfonamide resistance. Five mutations were identified, F17L, S18L, T51M, E208K, and KE257_dup. Their contribution to resistance and their cost to the catalytic properties of DHPS were evaluated using a combination of biochemical, biophysical and microbiological susceptibility studies. These studies show that F17L, S18L, and T51M directly lead to sulfonamide resistance while unexpectedly increasing susceptibility to trimethoprim, which targets the downstream enzyme dihydrofolate reductase. The secondary mutations E208K and KE257_dup restore trimethoprim susceptibility closer to wild-type levels while further increasing sulfonamide resistance. Structural studies reveal that these mutations appear to selectively disfavor the binding of the sulfonamides by sterically blocking an outer ring moiety that is not present in the substrate. This emphasizes that new inhibitors must be designed that strictly stay within the substrate volume in the context of the transition state

Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections

Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas

BACKGROUND: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial. OBJECTIVE: To compare the outcomes of observation versus intervention for low-grade dAVFs. METHODS: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up. RESULTS: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively. CONCLUSION: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs