150 research outputs found
Anion-Channel Blockers Inhibit S-Type Anion Channels and Abscisic Acid Responses in Guard Cells
Robust Online Hamiltonian Learning
In this work we combine two distinct machine learning methodologies,
sequential Monte Carlo and Bayesian experimental design, and apply them to the
problem of inferring the dynamical parameters of a quantum system. We design
the algorithm with practicality in mind by including parameters that control
trade-offs between the requirements on computational and experimental
resources. The algorithm can be implemented online (during experimental data
collection), avoiding the need for storage and post-processing. Most
importantly, our algorithm is capable of learning Hamiltonian parameters even
when the parameters change from experiment-to-experiment, and also when
additional noise processes are present and unknown. The algorithm also
numerically estimates the Cramer-Rao lower bound, certifying its own
performance.Comment: 24 pages, 12 figures; to appear in New Journal of Physic
Human induced pluripotent stem cell engineering establishes a humanized mouse platform for pediatric low-grade glioma modeling
A major obstacle to identifying improved treatments for pediatric low-grade brain tumors (gliomas) is the inability to reproducibly generate human xenografts. To surmount this barrier, we leveraged human induced pluripotent stem cell (hiPSC) engineering to generate low-grade gliomas (LGGs) harboring the two most common pediatric pilocytic astrocytoma-associated molecular alterations, NF1 loss and KIAA1549:BRAF fusion. Herein, we identified that hiPSC-derived neuroglial progenitor populations (neural progenitors, glial restricted progenitors and oligodendrocyte progenitors), but not terminally differentiated astrocytes, give rise to tumors retaining LGG histologic features for at least 6 months in vivo. Additionally, we demonstrated that hiPSC-LGG xenograft formation requires the absence of CD4 T cell-mediated induction of astrocytic Cxcl10 expression. Genetic Cxcl10 ablation is both necessary and sufficient for human LGG xenograft development, which additionally enables the successful long-term growth of patient-derived pediatric LGGs in vivo. Lastly, MEK inhibitor (PD0325901) treatment increased hiPSC-LGG cell apoptosis and reduced proliferation both in vitro and in vivo. Collectively, this study establishes a tractable experimental humanized platform to elucidate the pathogenesis of and potential therapeutic opportunities for childhood brain tumors
SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters
The recent emergence of B.1.1.529, the Omicron varian
Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device
Copy Number Variations (CNVs) of regions of the human genome have been associated with multiple diseases. We present an algorithm which is mathematically sound and computationally efficient to accurately analyze CNV in a DNA sample utilizing a nanofluidic device, known as the digital array. This numerical algorithm is utilized to compute copy number variation and the associated statistical confidence interval and is based on results from probability theory and statistics. We also provide formulas which can be used as close approximations
Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity
Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms
Evaluation of an Unsuccessful Brook Trout Electrofishing Removal Project in a Small Rocky Mountain Stream.
In the western United States, exotic brook trout Salvelinus fontinalis frequently have a deleterious effect on native salmonids, and biologists often attempt to remove brook trout from streams by means of electrofishing. Although the success of such projects typically is low, few studies have assessed the underlying mechanisms of failure, especially in terms of compensatory responses. A multiagency watershed advisory group (WAG) conducted a 3-year removal project to reduce brook trout and enhance native salmonids in 7.8 km of a southwestern Idaho stream. We evaluated the costs and success of their project in suppressing brook trout and looked for brook trout compensatory responses, such as decreased natural mortality, increased growth, increased fecundity at length, and earlier maturation. The total number of brook trout removed was 1,401 in 1998, 1,241 in 1999, and 890 in 2000; removal constituted an estimated 88% of the total number of brook trout in the stream in 1999 and 79% in 2000. Although abundance of age-1 and older brook trout declined slightly during and after the removals, abundance of age-0 brook trout increased 789% in the entire stream 2 years after the removals ceased. Total annual survival rate for age-2 and older brook trout did not decrease during the removals, and the removals failed to produce an increase in the abundance of native redband trout Oncorhynchus mykiss gairdneri. Lack of a meaningful decline and unchanged total mortality for older brook trout during the removals suggest that a compensatory response occurred in the brook trout population via reduced natural mortality, which offset the removal of large numbers of brook trout. Although we applaud WAG personnel for their goal of enhancing native salmonids by suppressing brook trout via electrofishing removal, we conclude that their efforts were unsuccessful and suggest that similar future projects elsewhere over such large stream lengths would be costly, quixotic enterprises
Evaluating vital rate contributions to greater sage-grouse population dynamics to inform conservation
Species conservation efforts often use short‐term studies that fail to identify the vital rates that contribute most to population growth. Although the greater sage‐grouse (Centrocercus urophasianus; sage‐grouse) is a candidate for protection under the U.S. Endangered Species Act, and is sometimes referred to as an umbrella species in the sagebrush (Artemisia spp.) biome of western North America, the failure of proposed management strategies to focus on key vital rates that may contribute most to achieving population stability remains problematic for sustainable conservation. To address this dilemma, we performed both prospective and retrospective perturbation analyses of a life cycle model based on a 12‐yr study that encompassed nearly all sage‐grouse vital rates. To validate our population models, we compared estimates of annual finite population growth rates (λ) from our female‐based life cycle models to those attained from male‐based lek counts. Post‐fledging (i.e., after second year, second year, and juvenile) female survival parameters contributed most to past variation in λ during our study and had the greatest potential to change λ in the future, indicating these vital rates as important determinants of sage‐grouse population dynamics. In addition, annual estimates of λ from female‐based life cycle models and male‐based lek data were similar, providing the most rigorous evidence to date that lek counts of males can serve as a valid index of sage‐grouse population change. Our comparison of fixed and mixed statistical models for evaluating temporal variation in nest survival and initiation suggest that conservation planners use caution when evaluating short‐term nesting studies and using associated fixed‐effect results to develop conservation objectives. In addition, our findings indicated that greater attention should be paid to those factors affecting sage‐grouse post‐fledging females. Our approach demonstrates the need for more long‐term studies of species vital rates across the life cycle. Such studies should address the decoupling of sampling variation from underlying process (co)variation in vital rates, identification of how such variation drives population dynamics, and how decision makers can use this information to re‐direct conservation efforts to address the most limiting points in the life cycle for a given population.Peer reviewedNatural Resource Ecology and Managemen
Narrativa de aula de uma professora sobre a investigação estatística
Este texto analisa a narrativa de aula de uma professora que ensina Matemática nos anos iniciais do Ensino Fundamental e que participa de um grupo que desenvolve uma pesquisa colaborativa, no âmbito do Projeto Observatório da Educação, com o objetivo de investigar os letramentos matemáticos escolares e as práticas de formação docente. Em sua narrativa, a professora descreve o processo de investigação estatística desenvolvido com uma turma de 1º ano. A análise traz indícios de aprendizagens docente, relativos ao letramento estatístico das crianças - em particular, no que se refere ao desenvolvimento da linguagem gráfica - , e revela a apropriação de práticas de letramento pela professora
Experimental and analytical studies on the response of 1/4-scale models of freestanding laboratory equipment subjected to strong earthquake shaking
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