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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 5. |
- Hsieh, Yu-Hsin, et al.
(författare)
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Collaborative Home-Visit Program for Young Children With Motor Delays in Rural Taiwan : A Pilot Randomized Controlled Trial
- 2020
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Ingår i: Physical Therapy. - : Oxford University Press (OUP). - 0031-9023 .- 1538-6724. ; 100:6, s. 979-994
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Tidskriftsartikel (refereegranskat)abstract
- Background. Caregiver engagement and collaborative team early childhood intervention (ECI) services are international trends; however, relevant evidence of collaborative home-visiting ECI in rural areas is as yet undetermined.Objective. The study aimed to investigate the effectiveness of a collaborative ECI program in a rural area of Taiwan.Design. The study was a pilot randomized control led trial.Methods. Children aged 6 to 33 months experiencing motor delays and their caregivers were enrolled in Taitung, Taiwan. Using stratified randomization, 24 participants were allocated to either experimental or control groups, and both received 5 home visits within 3 months. The experimental group received ECI services based on the International Classification of Functioning, Disability and Health framework and family-centered approaches. The control group received regular home visits by local social workers. Child outcomes included Pediatric Evaluation of Disability Inventory Chinese Version and Peabody Developmental Motor Scale, 2nd edition. Family outcomes included the Disability-Adapted Infant–Toddler version of Home Observation for Measurement, and Chinese versions of the Knowledge of Infant Development Inventory and Parental Stress Index-Short Form. A tester blinded to the study conducted assessments at baseline, postintervention, and 3-month follow-up. Two-way mixed analysis of variance was used with α = .05 (2-tailed).Results. The experimental group improved scores on the Disability-Adapted Infant–Toddler version of Home Observation for Measurement significantly more than the control group with an effect size of 0.64 at follow-up. In other outcomes, both groups showed no significant differences. The follow-up rate was 69%, and adherence to the ECI program was acceptable.Limitations. A limitation of the study was the heterogeneity of the sample.Conclusions. This pilot study revealed possible effectiveness in implementing collaborative ECI programs based on family-centered approaches and the International Classification of Functioning, Disability and Health in rural areas. Larger field studies are needed to confirm our findings.
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| 6. |
- Abdulla, Parosh, Professor, 1961-, et al.
(författare)
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Efficient Handling of String-Number Conversion
- 2020
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Ingår i: PLDI 2020. - New York, NY, USA : ACM. - 9781450376136 ; , s. 943-957
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Konferensbidrag (refereegranskat)abstract
- String-number conversion is an important class of constraints needed for the symbolic execution of string-manipulating programs. In particular solving string constraints with string-number conversion is necessary for the analysis of scripting languages such as JavaScript and Python, where string-number conversion is a part of the definition of the core semantics of these languages. However, solving this type of constraint is very challenging for the state-of-the-art solvers. We propose in this paper an approach that can efficiently support both string-number conversion and other common types of string constraints. Experimental results show that it significantly outperforms other state-of-the-art tools on benchmarks that involves string-number conversion.
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| 7. |
- Fang, Hsin-Yu, et al.
(författare)
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Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:4, s. 844-859
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia exists in many diseased tissues, including arthritic joints, atherosclerotic plaques, and malignant tumors. Macrophages accumulate in these sites and up-regulate hypoxia-inducible transcription factors (HIFs) 1 and 2 in response to the hypoxia present. Here we show that the gene expression profile in primary human and murine macrophages changes markedly when they are exposed to hypoxia for 18 hours. For example, they were seen to up-regulate the cell surface receptors, CXCR4 and GLUT1, and the potent, tumor-promoting cytokines, vascular endothelial growth factor A, interleukin (IL)-1 beta and IL-8, adrenomedullin, CXCR4, and angiopoietin-2. Hypoxia also stimulated their expression and/or phosphorylation of various proteins in the nuclear factor-kappa B (NF-kappa B) signaling pathway. We then used both genetic and pharmacologic methods to manipulate the levels of HIFs-1 alpha and 2 alpha or NF-kappa B in primary macrophages to elucidate their role in the hypoxic induction of many of these key genes. These studies showed that both HIF-1 and -2, but not NF-kappa B, are important transcriptional effectors regulating the responses of macrophages to such a period of hypoxia. Further studies using experimental mouse models are now warranted to investigate the role of such macrophage responses in the progression of various diseased tissues, such as malignant tumors. (Blood. 2009; 114: 844-859)
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| 8. |
- Muthana, Munitta, et al.
(författare)
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Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors
- 2011
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 71:5, s. 1805-1815
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Tidskriftsartikel (refereegranskat)abstract
- New therapies are required to target hypoxic areas of tumors as these sites are highly resistant to conventional cancer therapies. Monocytes continuously extravasate from the bloodstream into tumors where they differentiate into macrophages and accumulate in hypoxic areas, thereby opening up the possibility of using these cells as vehicles to deliver gene therapy to these otherwise inaccessible sites. We describe a new cell-based method that selectively targets an oncolytic adenovirus to hypoxic areas of prostate tumors. In this approach, macrophages were cotransduced with a hypoxia-regulated E1A/B construct and an E1A-dependent oncolytic adenovirus, whose proliferation is restricted to prostate tumor cells using prostate-specific promoter elements from the TARP, PSA, and PMSA genes. When such cotransduced cells reach an area of extreme hypoxia, the E1A/B proteins are expressed, thereby activating replication of the adenovirus. The virus is subsequently released by the host macrophage and infects neighboring tumor cells. Following systemic injection into mice bearing subcutaneous or orthotopic prostate tumors, cotransduced macrophages migrated into hypoxic tumor areas, upregulated E1A protein, and released multiple copies of adenovirus. The virus then infected neighboring cells but only proliferated and was cytotoxic in prostate tumor cells, resulting in the marked inhibition of tumor growth and reduction of pulmonary metastases. This novel delivery system employs 3 levels of tumor specificity: the natural "homing" of macrophages to hypoxic tumor areas, hypoxia-induced proliferation of the therapeutic adenovirus in host macrophages, and targeted replication of oncolytic virus in prostate tumor cells.
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| 9. |
- Piponiot, Camille, et al.
(författare)
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Distribution of biomass dynamics in relation to tree size in forests across the world
- 2022
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 234, s. 1664-1677
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Tidskriftsartikel (refereegranskat)abstract
- Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4–52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1–10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.
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