95 research outputs found

    Modeling streamlines and mass transport in circulating flow

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    State-of-the-art of hydraulic and water quality modeling in streams and rivers does not include the role of large, slowly circulating regions in dilution and transport of effluents discharged in such water bodies. Examples of circulating regions include meander, blocked arms of the stream, and flow behind engineering structures such as jetties, wing dams, and bridge piers as well as flow within small marinas and fleeting areas. Numerical schemes have been developed to simulate streamline patterns and mass transport within a circulating region approximated by a square cavity on the side of a channel. The circulating flow is assumed two-dimensional (depth averaged) and is generated and maintained by a known main flow at the open boundary. Results are given for characteristic Reynolds numbers ranging from 500 to 30,000. The equation governing the mixing and transport of a finite quantity of conservative tracer instantaneously introduced at any location in the flow field has been numerically solved. The numerical scheme is based on the finite element approximation of the governing differential equation and uses the method of weighted residuals. The flow geometry is represented by triangular elements, and a linear basis function is used in the interpolation scheme. The unsteady term is approximated by finite differencing in full-forward time steps. Dispersion coefficient has been represented as a first-order tensor, the components of which are functions of the dispersion coefficients along and normal to the streamlines. Results are given for scalar and vectorized dispersion coefficients as well as a range of computation time steps.U.S. Department of the InteriorU.S. Geological SurveyOpe

    Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970-2019: A systematic analysis for the Global Burden of Disease Study 2019

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    Background: Meeting the contraceptive needs of women of reproductive age is beneficial for the health of women and children, and the economic and social empowerment of women. Higher rates of contraceptive coverage have been linked to the availability of a more diverse range of contraceptive methods. We present estimates of the contraceptive prevalence rate (CPR), modern contraceptive prevalence rate (mCPR), demand satisfied, and the method of contraception used for both partnered and unpartnered women for 5-year age groups in 204 countries and territories between 1970 and 2019.Methods: We used 1162 population-based surveys capturing contraceptive use among women between 1970 and 2019, in which women of reproductive age (15-49 years) self-reported their, or their partner\u27s, current use of contraception for family planning purposes. Spatiotemporal Gaussian process regression was used to generate estimates of the CPR, mCPR, demand satisfied, and method mix by age and marital status. We assessed how age-specific mCPR and demand satisfied changed with the Socio-demographic Index (SDI), a measure of social and economic development, using the meta-regression Bayesian, regularised, trimmed method from the Global Burden of Diseases, Injuries, and Risk Factors Study.Findings: In 2019, 162·9 million (95% uncertainty interval [UI] 155·6-170·2) women had unmet need for contraception, of whom 29·3% (27·9-30·6) resided in sub-Saharan Africa and 27·2% (24·4-30·3) resided in south Asia. Women aged 15-19 years (64·8% [62·9-66·7]) and 20-24 years (71·9% [68·9-74·2]) had the lowest rates of demand satisfied, with 43·2 million (95% UI 39·3-48·0) women aged 15-24 years with unmet need in 2019. The mCPR and demand satisfied among women aged 15-19 years were substantially lower than among women aged 20-49 years at SDI values below 60 (on a 0-100 scale), but began to equalise as SDI increased above 60. Between 1970 and 2019, the global mCPR increased by 20·1 percentage points (95% UI 18·7-21·6). During this time, traditional methods declined as a proportion of all contraceptive methods, whereas the use of implants, injections, female sterilisation, and condoms increased. Method mix differs substantially depending on age and geography, with the share of female sterilisation increasing with age and comprising more than 50% of methods in use in south Asia. In 28 countries, one method was used by more than 50% of users in 2019.Interpretation: The dominance of one contraceptive method in some locations raises the question of whether family planning policies should aim to expand method mix or invest in making existing methods more accessible. Lower rates of demand satisfied among women aged 15-24 years are also concerning because unintended pregnancies before age 25 years can forestall or eliminate education and employment opportunities that lead to social and economic empowerment. Policy makers should strive to tailor family planning programmes to the preferences of the groups with the most need, while maintaining the programmes used by existing users.Funding: Bill & Melinda Gates Foundation

    Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma

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    Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor development in vivo on xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the ''fuzzy'' interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs

    Continuous Symmetry Breaking in a Two-dimensional Rydberg Array

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    Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions. The nature of the underlying symmetry being broken determines many of the qualitative properties of the phase; this is illustrated by the case of discrete versus continuous symmetry breaking. Indeed, in contrast to the discrete case, the breaking of a continuous symmetry leads to the emergence of gapless Goldstone modes controlling, for instance, the thermodynamic stability of the ordered phase. Here, we realize a two-dimensional dipolar XY model -- which exhibits a continuous spin-rotational symmetry -- utilizing a programmable Rydberg quantum simulator. We demonstrate the adiabatic preparation of correlated low-temperature states of both the XY ferromagnet and the XY antiferromagnet. In the ferromagnetic case, we characterize the presence of long-range XY order, a feature prohibited in the absence of long-range dipolar interaction. Our exploration of the many-body physics of XY interactions complements recent works utilizing the Rydberg-blockade mechanism to realize Ising-type interactions exhibiting discrete spin rotation symmetry.Comment: 18 pages, 3 figures in main text, 9 figures in supplemental method

    Face Mis-ID: An Interactive Pedagogical Tool Demonstrating Disparate Accuracy Rates in Facial Recognition

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    This paper reports on the making of an interactive demo to illustrate algorithmic bias in facial recognition. Facial recognition technology has been demonstrated to be more likely to misidentify women and minoritized people. This risk, among others, has elevated facial recognition into policy discussions across the country, where many jurisdictions have already passed bans on its use. Whereas scholarship on the disparate impacts of algorithmic systems is growing, general public awareness of this set of problems is limited in part by the illegibility of machine learning systems to non-specialists. Inspired by discussions with community organizers advocating for tech fairness issues, we created the Face Mis-ID Demo to reveal the algorithmic functions behind facial recognition technology and to demonstrate its risks to policymakers and members of the community. In this paper, we share the design process behind this interactive demo, its form and function, and the design decisions that honed its accessibility, toward its use for improving legibility of algorithmic systems and awareness of the sources of their disparate impacts

    Role of the ubiquitin-binding domain of Polη in Rad18-independent translesion DNA synthesis in human cell extracts

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    In eukaryotic cells, the Rad6/Rad18-dependent monoubiquitination of the proliferating cell nuclear antigen (PCNA) plays an essential role in the switching between replication and translesion DNA synthesis (TLS). The DNA polymerase Polη binds to PCNA via a consensus C-terminal PCNA-interacting protein (PIP) motif. It also specifically interacts with monoubiquitinated PCNA thanks to a recently identified ubiquitin-binding domain (UBZ). To investigate whether the TLS activity of Polη is always coupled to PCNA monoubiquitination, we monitor the ability of cell-free extracts to perform DNA synthesis across different types of lesions. We observe that a cis-syn cyclobutane thymine dimer (TT-CPD), but not a N-2-acetylaminofluorene-guanine (G-AAF) adduct, is efficiently bypassed in extracts from Rad18-deficient cells, thus demonstrating the existence of a Polη-dependent and Rad18-independent TLS pathway. In addition, by complementing Polη-deficient cells with PIP and UBZ mutants, we show that each of these domains contributes to Polη activity. The finding that the bypass of a CPD lesion in vitro does not require Ub-PCNA but nevertheless depends on the UBZ domain of Polη, reveals that this domain may play a novel role in the TLS process that is not related to the monoubiquitination status of PCNA

    Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study

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    Background: The effect of mode of infant feeding on adiposity deposition is not fully understood. Objective: The objective was to test the hypothesis that differences in total and regional adipose tissue content and intrahepatocellular lipid (IHCL) arise in early infancy between breast- and formula-fed infants and to describe longitudinal changes. Design: This prospective longitudinal cohort study was performed in 2 hospitals in the United Kingdom. Healthy, full-term, appropriate weight-for-gestational age infants were recruited; adipose tissue volume and distribution were directly quantified by using whole-body magnetic resonance imaging; IHCL was assessed by in vivo proton magnetic resonance spectroscopy. Measurements were performed after birth (median age: 13 d) and at 6–12 wk of age. Method of infant feeding was recorded prospectively by using maternally completed feeding diaries. Breastfed was defined as >80% of feeds consisting of breast milk at both points; formula-fed was defined as >80% of feeds consisting of formula milk at both points. Results: Longitudinal results were obtained from 70 infants (36 breastfed, 9 mixed-fed, and 25 formula-fed). No differences were found in total or regional adipose tissue or IHCL between breastfed and formula-fed infants. In pooled analyses including all feeding groups, IHCL and total adipose tissue approximately doubled between birth and 6–12 wk: IHCL after birth (median: 0.949; IQR: 0.521–1.711) and at 6–12 wk (1.828; 1.376–2.697; P < 0.001) and total adipose tissue after birth (0.749 L; 0.620–0.928 L) and at 6–12 wk (1.547 L; 1.332–1.790 L; P < 0.001). Increasing adiposity was characterized by greater relative increases in subcutaneous than in internal adipose tissue depots. Conclusions: No differences were detectable in adipose tissue or IHCL accretion between breastfed and formula-fed infants up to 2 mo. The substantial increase in IHCL seen over this period in both breastfed and formula-fed infants is a novel observation, which suggests that hepatic storage of lipids may be physiologic up to 2 mo. This trial was registered at www.clinicaltrials.gov as NCT02033005

    An Action-Oriented AI Policy Toolkit for Technology Audits by Community Advocates and Activists

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    Motivated by the extensive documented disparate harms of artificial intelligence (AI), many recent practitioner-facing reflective tools have been created to promote responsible AI development. However, the use of such tools internally by technology development firms addresses responsible AI as an issue of closed-door compliance rather than a matter of public concern. Recent advocate and activist efforts intervene in AI as a public policy problem, inciting a growing number of cities to pass bans or other ordinances on AI and surveillance technologies. In support of this broader ecology of political actors, we present a set of reflective tools intended to increase public participation in technology advocacy for AI policy action. To this end, the Algorithmic Equity Toolkit (the AEKit) provides a practical policy-facing definition of AI, a flowchart for assessing technologies against that definition, a worksheet for decomposing AI systems into constituent parts, and a list of probing questions that can be posed to vendors, policy-makers, or government agencies. The AEKit carries an action-orientation towards political encounters between community groups in the public and their representatives, opening up the work of AI reflection and remediation to multiple points of intervention. Unlike current reflective tools available to practitioners, our toolkit carries with it a politics of community participation and activism

    Evidence for a Rad18-Independent Frameshift Mutagenesis Pathway in Human Cell-Free Extracts

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    Bypass of replication blocks by specialized DNA polymerases is crucial for cell survival but may promote mutagenesis and genome instability. To gain insight into mutagenic sub-pathways that coexist in mammalian cells, we examined N-2-acetylaminofluorene (AAF)-induced frameshift mutagenesis by means of SV40-based shuttle vectors containing a single adduct. We found that in mammalian cells, as previously observed in E. coli, modification of the third guanine of two target sequences, 5'-GGG-3' (3G) and 5'-GGCGCC-3' (NarI site), induces –1 and –2 frameshift mutations, respectively. Using an in vitro assay for translesion synthesis, we investigated the biochemical control of these events. We showed that Pol eta, but neither Pol iota nor Pol zeta, plays a major role in the frameshift bypass of the AAF adduct located in the 3G sequence. By complementing PCNA-depleted extracts with either a wild-type or a non-ubiquitinatable form of PCNA, we found that this Pol eta-mediated pathway requires Rad18 and ubiquitination of PCNA. In contrast, when the AAF adduct is located within the NarI site, TLS is only partially dependent upon Pol eta and Rad18, unravelling the existence of alternative pathways that concurrently bypass this lesion
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