695 research outputs found

    The challenge of forecasting high streamflows 1–3 months in advance with lagged climate indices in southeast Australia

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    Skilful forecasts of high streamflows a month or more in advance are likely to be of considerable benefit to emergency services and the broader community. This is particularly true for mesoscale catchments (< 2000 km<sup>2</sup>) with little or no seasonal snowmelt, where real-time warning systems are only able to give short notice of impending floods. In this study, we generate forecasts of high streamflows for the coming 1-month and coming 3-month periods using large-scale ocean–atmosphere climate indices and catchment wetness as predictors. Forecasts are generated with a combination of Bayesian joint probability modelling and Bayesian model averaging. High streamflows are defined as maximum single-day streamflows and maximum 5-day streamflows that occur during each 1-month or 3-month forecast period. Skill is clearly evident in the 1-month forecasts of high streamflows. Surprisingly, in several catchments positive skill is also evident in forecasts of large threshold events (exceedance probabilities of 25%) over the next month. Little skill is evident in forecasts of high streamflows for the 3-month period. We show that including lagged climate indices as predictors adds little skill to the forecasts, and thus catchment wetness is by far the most important predictor. Accordingly, we recommend that forecasts may be improved by using accurate estimates of catchment wetness

    Monitoring Replication Protein A (RPA) Dynamics in Homologous Recombination Through Site-specific Incorporation of Non-canonical Amino Acids

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    An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance

    PCR Based Genotyping of Lulu Cattle of Nepal for A1, A2 Type Beta-caseins

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    Lulu is an indigenous breed of cattle (Bos taurus) found in high altitude regions of western Nepal. Population of Lulu cattle has been declining due to introgression with other exotic breeds to increase milk productivity. Here we aimed at finding potential approach for conserving Lulu cattle and its assets by studying the milk contents and investigating which variant of beta-casein protein is present in this breed. Beta caseins are an abundant protein in cow milk with A1 and A2 being the most common genetic variants of this protein. Consumption of A1 type of milk has numerous health-related complications whereas A2 type of milk has numerous human health promoting factors. We used restriction fragment length polymorphism (RFLP) for determining the A1 and A2 variant of beta casein in Lulu cattle. For performing DNA extraction, we collected (n = 18) blood samples of Lulu from Mustang and (n=17) Nepal Agriculture research council farm. The amplified fragments in 3% agarose at 251bp and 213bp respectively confirmed the presence of both A1 and A2 gene in Lulu; however, A2 was of greater abundance. Our study indicated that Lulu has A2 variant of beta-casein predominantly. The gene frequency of A1A1 is 0, A1A2 is 0.06 and A2A2 is 0.94. We further found that the allele frequency of A1 and A2 is 0.03 and 0.97 respectively. We designed special primer for sequencing CSN2 genes since A2 type beta casein gene was predominantly seen on Lulu. The sequencing result further supports our RFLP result as most of our samples have “C” nucleotide SNP in amplified CSN2 gene sequence. The Chi-square value of the current study is 0.04 which supports Hardy-Weinberg equilibrium inferring that Lulu cattle are still in the pure state, where there is no genetic introgression with the exotic breed for the sake of improvement of productivity

    Human rights violations among sexual and gender minorities in Kathmandu, Nepal: a qualitative investigation

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    BACKGROUND: Nepal has experienced sporadic reports of human rights violations among sexual and gender minorities. Our objective was to identify a range of human rights that are enshrined in international law and/or are commonly reported by sexual and gender minority participants in Kathmandu, to be nonprotected or violated. METHODS: In September 2009 three focus group discussions were conducted by trained interviewers among a convenience sample of sexual and gender minority participants in Kathmandu Nepal. The modified Delphi technique was utilized to elicit and rank participant-generated definitions of human rights and their subsequent violations. Data was analyzed independently and cross checked by another investigator. RESULTS: Participants (n = 29) reported experiencing a range of human rights violations at home, work, educational, health care settings and in public places. Lack of adequate legal protection, physical and mental abuse and torture were commonly reported. Access to adequate legal protection and improvements in the family and healthcare environment were ranked as the most important priority areas. CONCLUSIONS: Sexual and gender minorities in Nepal experienced a range of human rights violations. Future efforts should enroll a larger and more systematic sample of participants to determine frequency, timing, and/or intensity of exposure to rights violations, and estimate the population-based impact of these rights violations on specific health outcome

    Evaluation of Plan Quality and Treatment Efficiency for Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy

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    Purpose/objectives: To evaluate the plan quality and treatment delivery efficiency of single‐isocenter/two‐lesions volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Materials/methods: Eight consecutive patients with two peripherally located early stage nonsmall‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal noncoplanar VMAT SBRT treatment in our institution. A single‐isocenter was placed between the two lesions. Doses were 54 or 50 Gy in 3 and 5 fractions respectively. Patients were treated every other day. Plans were calculated in Eclipse with AcurosXB algorithm and normalized to at least 95% of the planning target volume (PTV) receiving 100% of the prescribed dose. For comparison, two‐isocenter plans (isocenter placed centrally in each target) were retrospectively created. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were calculated. The normal lung V5, V10, V20, mean lung dose (MLD) and other organs at risk (OARs) doses were evaluated. Total number of monitor units (MUs), beam‐on time, and patient‐specific quality assurance (QA) results were recorded. Results: The mean isocenter to tumor distance was 6.7 ± 2.3 cm. The mean combined PTV was 44.0 ± 23.4 cc. There was no clinically significant difference in CI, HI, GD, GI, D2cm, and V20 including most of the OARs between single‐isocenter and two‐isocenter lung SBRT plans, evaluated per RTOG guidelines. However, for single‐isocenter plans as the distance between the lesions increased, the V5, V10, and MLD increased, marginally. The total number of MUs and beam‐on time was reduced by a factor of 1.5 for a single‐isocenter plan compared to a two‐isocenter plan. The single‐isocenter/two‐lesions VMAT lung SBRT QA plans demonstrated an accurate dose delivery of 98.1 ± 3.2% for clinical gamma passing rate of 3%/3 mm. Conclusion: The SBRT treatment of two peripherally located lung lesions with a centrally placed single‐isocenter was dosimetrically equivalent to two‐isocenter plans. Faster treatment delivery for single‐isocenter treatment can improve patient compliance and reduce the amount of intrafraction motion errors for well‐suited patients

    Evidence That the P\u3csub\u3ei\u3c/sub\u3e Release Event Is the Rate-Limiting Step in the Nitrogenase Catalytic Cycle

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    Nitrogenase reduction of dinitrogen (N2) to ammonia (NH3) involves a sequence of events that occur upon the transient association of the reduced Fe protein containing two ATP molecules with the MoFe protein that includes electron transfer, ATP hydrolysis, Pi release, and dissociation of the oxidized, ADP-containing Fe protein from the reduced MoFe protein. Numerous kinetic studies using the nonphysiological electron donor dithionite have suggested that the rate-limiting step in this reaction cycle is the dissociation of the Fe protein from the MoFe protein. Here, we have established the rate constants for each of the key steps in the catalytic cycle using the physiological reductant flavodoxin protein in its hydroquinone state. The findings indicate that with this reductant, the rate-limiting step in the reaction cycle is not protein–protein dissociation or reduction of the oxidized Fe protein, but rather events associated with the Pi release step. Further, it is demonstrated that (i) Fe protein transfers only one electron to MoFe protein in each Fe protein cycle coupled with hydrolysis of two ATP molecules, (ii) the oxidized Fe protein is not reduced when bound to MoFe protein, and (iii) the Fe protein interacts with flavodoxin using the same binding interface that is used with the MoFe protein. These findings allow a revision of the rate-limiting step in the nitrogenase Fe protein cycle

    ALMA observations of dust polarization and molecular line emission from the Class 0 protostellar source Serpens SMM1

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    We present high angular resolution dust polarization and molecular line observations carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) toward the Class 0 protostar Serpens SMM1. By complementing these observations with new polarization observations from the Submillimeter Array (SMA) and archival data from the Combined Array for Research in Millimeter-wave Astronomy (CARMA) and the James Clerk Maxwell Telescopes (JCMT), we can compare the magnetic field orientations at different spatial scales. We find major changes in the magnetic field orientation between large (~0.1 pc) scales -- where the magnetic field is oriented E-W, perpendicular to the major axis of the dusty filament where SMM1 is embedded -- and the intermediate and small scales probed by CARMA (~1000 AU resolution), the SMA (~350 AU resolution), and ALMA (~140 AU resolution). The ALMA maps reveal that the redshifted lobe of the bipolar outflow is shaping the magnetic field in SMM1 on the southeast side of the source; however, on the northwestern side and elsewhere in the source, low velocity shocks may be causing the observed chaotic magnetic field pattern. High-spatial-resolution continuum and spectral-line observations also reveal a tight (~130 AU) protobinary system in SMM1-b, the eastern component of which is launching an extremely high-velocity, one-sided jet visible in both CO(2-1) and SiO(5-4); however, that jet does not appear to be shaping the magnetic field. These observations show that with the sensitivity and resolution of ALMA, we can now begin to understand the role that feedback (e.g., from protostellar outflows) plays in shaping the magnetic field in very young, star-forming sources like SMM1.Comment: 15 pages, 6 figures, 4 tables, 1 appendix. Accepted for publication in the Astrophysical Journal. Materials accessible in the online version of the (open-access) ApJ article include the FITS files used to make the ALMA image in Figure 1(d), and a full, machine-readable version of Table
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