The Evolving Activity of the Dynamically Young Comet C/2009 P1 (Garradd)

We used the UltraViolet-Optical Telescope on board Swift to observe the dynamically young comet C/2009 P1 (Garradd) from a heliocentric distance of 3.5 AU pre-perihelion until 4.0 AU outbound. At 3.5 AU pre-perihelion, comet Garradd had one of the highest dust-to-gas ratios ever observed, matched only by comet Hale-Bopp. The evolving morphology of the dust in its coma suggests an outburst that ended around 2.2 AU pre-perihelion. Comparing slit-based measurements and observations acquired with larger fields of view indicated that between 3 AU and 2 AU pre-perihelion a significant extended source started producing water in the coma. We demonstrate that this source, which could be due to icy grains, disappeared quickly around perihelion. Water production by the nucleus may be attributed to a constantly active source of at least 75 km$^2$, estimated to be more than 20 percent of the surface. Based on our measurements, the comet lost $4x10^{11}$ kg of ice and dust during this apparition, corresponding to at most a few meters of its surface.Even though this was likely not Garradd's first passage through the inner solar system, the activity of the comet was complex and changed significantly during the time it was observed

Increased risk for other cancers in individuals with Ewing sarcoma and their relatives.

BackgroundThere are few reports of the association of other cancers with Ewing sarcoma in patients and their relatives. We use a resource combining statewide genealogy and cancer reporting to provide unbiased risks.MethodsUsing a combined genealogy of 2.3 million Utah individuals and the Utah Cancer Registry (UCR), relative risks (RRs) for cancers of other sites were estimated in 143 Ewing sarcoma patients using a Cox proportional hazards model with matched controls; however, risks in relatives were estimated using internal cohort-specific cancer rates in first-, second-, and third-degree relatives.ResultsCancers of three sites (breast, brain, complex genotype/karyotype sarcoma) were observed in excess in Ewing sarcoma patients. No Ewing sarcoma patients were identified among first-, second-, or third-degree relatives of Ewing sarcoma patients. Significantly increased risk for brain, lung/bronchus, female genital, and prostate cancer was observed in first-degree relatives. Significantly increased risks were observed in second-degree relatives for breast cancer, nonmelanoma eye cancer, malignant peripheral nerve sheath cancer, non-Hodgkin lymphoma, and translocation sarcomas. Significantly increased risks for stomach cancer, prostate cancer, and acute lymphocytic leukemia were observed in third-degree relatives.ConclusionsThis analysis of risk for cancer among Ewing sarcoma patients and their relatives indicates evidence for some increased cancer predisposition in this population which can be used to individualize consideration of potential treatment of patients and screening of patients and relatives

Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner.

BackgroundRewriting of the epigenome has risen as a promising alternative to gene editing for precision medicine. In nature, epigenetic silencing can result in complete attenuation of target gene expression over multiple mitotic divisions. However, persistent repression has been difficult to achieve in a predictable manner using targeted systems.ResultsHere, we report that persistent epigenetic memory required both a DNA methyltransferase (DNMT3A-dCas9) and a histone methyltransferase (Ezh2-dCas9 or KRAB-dCas9). We demonstrate that the histone methyltransferase requirement can be locus specific. Co-targeting Ezh2-dCas9, but not KRAB-dCas9, with DNMT3A-dCas9 and DNMT3L induced long-term HER2 repression over at least 50 days (approximately 57 cell divisions) and triggered an epigenetic switch to a heterochromatic environment. An increase in H3K27 trimethylation and DNA methylation was stably maintained and accompanied by a sustained loss of H3K27 acetylation. Interestingly, substitution of Ezh2-dCas9 with KRAB-dCas9 enabled long-term repression at some target genes (e.g., SNURF) but not at HER2, at which H3K9me3 and DNA methylation were transiently acquired and subsequently lost. Off-target DNA hypermethylation occurred at many individual CpG sites but rarely at multiple CpGs in a single promoter, consistent with no detectable effect on transcription at the off-target loci tested. Conversely, robust hypermethylation was observed at HER2. We further demonstrated that Ezh2-dCas9 required full-length DNMT3L for maximal activity and that co-targeting DNMT3L was sufficient for persistent repression by Ezh2-dCas9 or KRAB-dCas9.ConclusionsThese data demonstrate that targeting different combinations of histone and DNA methyltransferases is required to achieve maximal repression at different loci. Fine-tuning of targeting tools is a necessity to engineer epigenetic memory at any given locus in any given cell type

Spitzer Space Telescope Observations of the Nucleus of Comet 103P/Hartley 2

We have used the Spitzer Space Telescope InfraRed Spectrograph (IRS) 22-μm peakup array to observe thermal emission from the nucleus and trail of comet 103P/Hartley 2, the target of NASA’s Deep Impact Extended Investigation (DIXI). The comet was observed on UT 2008 August 12 and 13, while 5.5 AU from the Sun. We obtained two 200 frame sets of photometric imaging over a 2.7 hr period. To within the errors of the measurement, we find no detection of any temporal variation between the two images. The comet showed extended emission beyond a point source in the form of a faint trail directed along the comet’s antivelocity vector. After modeling and removing the trail emission, a NEATM model for the nuclear emission with beaming parameter of 0.95 ± 0.20 indicates a small effective radius for the nucleus of 0.57 ± 0.08 km and low geometric albedo 0.028 ± 0.009 (1σ). With this nucleus size and a water production rate of 3 × 10^(28) molecules s^(-1) at perihelion, we estimate that ~100% of the surface area is actively emitting volatile material at perihelion. Reports of emission activity out to ~5 AU support our finding of a highly active nuclear surface. Compared to Deep Impact’s first target, comet 9P/Tempel 1, Hartley 2’s nucleus is one-fifth as wide (and about one-hundredth the mass) while producing a similar amount of outgassing at perihelion with about 13 times the active surface fraction. Unlike Tempel 1, comet Hartley 2 should be highly susceptible to jet driven spin-up torques, and so could be rotating at a much higher frequency. Since the amplitude of nongravitational forces are surprisingly similar for both comets, close to the ensemble average for ecliptic comets, we conclude that comet Hartley 2 must have a much more isotropic pattern of time-averaged outgassing from its nuclear surface. Barring a catastrophic breakup or major fragmentation event, the comet should be able to survive up to another 100 apparitions (~700 yr) at its current rate of mass loss

Preventing Perinatal Transmission of HIV Costs and Effectiveness of a Recommended Intervention

In the United States, nearly all new human immunodeficiency virus (HIV) infections in children are acquired through perinatal (mother-to-infant) transmission. Each year, approximately 7000 infants are born to HIV-infected women in the United States.1 Without intervention, an estimated 15-30% of these infants would become infected.2 In 1994, results of the AIDS Clinical Trial Group (ACTG) Protocol 076 showed that treatment of infected pregnant women and their infants with zidovudine (ZDV) reduced the rate of perinatal HIV transmission from 25% to 8%.3,4 Following these findings, the Public Health Service (PHS) issued recommendations for ZDV therapy to prevent perinatal HIV transmission5 and for HIV counseling and voluntary testing of pregnant women.

Nuclear Sizes and the Isotope Shift

Darwin-Foldy nuclear-size corrections in electronic atoms and nuclear radii are discussed from the nuclear-physics perspective. Interpretation of precise isotope-shift measurements is formalism dependent, and care must be exercised in interpreting these results and those obtained from relativistic electron scattering from nuclei. We strongly advocate that the entire nuclear-charge operator be used in calculating nuclear-size corrections in atoms, rather than relegating portions of it to the non-radiative recoil corrections. A preliminary examination of the intrinsic deuteron radius obtained from isotope-shift measurements suggests the presence of small meson-exchange currents (exotic binding contributions of relativistic order) in the nuclear charge operator, which contribute approximately 1/2%.Comment: 17 pages, latex, 1 figure -- Submitted to Phys. Rev. A -- epsfig.sty require

Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis

Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations.We developed the Progression and Transmission of HIV/AIDS model, a health state transition model that tracks index patients and their infected partners from HIV infection to death. We used program characteristics for each setting to compare the incremental cost per quality-adjusted life year gained from early versus late diagnosis and treatment. We ran the model for 10,000 index patients for each setting, examining alternative scenarios, excluding and including transmission to partners, and assuming HAART was initiated at a CD4 count of either 350 or 500 cells/µL. Screening in STD clinics and EDs was cost-effective compared with diagnosing inpatients, even when including only the benefits to the index patients. Screening patients in STD clinics, who have less-advanced disease, was cost-effective compared with ED screening when treatment with HAART was initiated at a CD4 count of 500 cells/µL. When the benefits of reduced transmission to partners from early diagnosis were included, screening in settings with less-advanced disease stages was cost-saving compared with screening later in the course of infection. The study was limited by a small number of observations on CD4 count at diagnosis and by including transmission only to first generation partners of the index patients.HIV prevention efforts can be advanced by screening in settings where patients present with less-advanced stages of HIV infection and by initiating treatment with HAART earlier in the course of infection

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos’s along-track orbital velocity component of 2.70 ± 0.10 mm s−1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m−3, we find that the expected value of the momentum enhancement factor, β, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m−3, β=3.61+0.19−0.25(1σ). These β values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos

Limits on Gravitational-Wave Emission from Selected Pulsars Using LIGO Data

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10^(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10^(-5) for the four closest pulsars