2,570 research outputs found
Lake Cycles and Sediments: Locality 80, Olduvai Gorge, Tanzania
Studies have shown that Bed I and Lower Bed II (1.92Ma- 1.76Ma) of Paleolake Olduvai at Locality 80 are primarily composed of the authigenic lacustrine clay minerals illite, smectite, and interlayered illite-smectite. X-ray fluorescence analysis and the sedimentation rates of Hay and Kyser (2001) were used to identify four apparent lake cycles beginning and ending with saline alkaline phases. Peaks in Al2O3/MgO ratios, and TiO2 and P2O5 abundances occur at approximately the same elevations within the stratigraphic section. Low values in these three parameters indicate saline alkaline conditions whereas high values represent fresh water conditions. Lake Cycles (LC) 1 and 4 completed in approximately 44,000 years and 42,000 years respectively, which is similar to the 41k.y. year cycle associated with Earth’s obliquity. Lake Cycles 2 and 3 span approximately 24,000 years and are similar to the 21k.y. precession cycle
Confirmatory Factor Analysis of the Pain Care Quality Surveys (Pain CQ © )
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/1/hesr12014-sup-0001-Author_matrix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/2/hesr12014.pd
Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis
BACKGROUND AND OBJECTIVES: In a phase 1 amyotrophic lateral sclerosis (ALS) study, autologous infusions of expanded regulatory T-lymphocytes (Tregs) combined with subcutaneous interleukin (IL)-2 were safe and well tolerated. Treg suppressive function increased and disease progression stabilized during the study. The present study was conducted to confirm the reliability of these results.
METHODS: Participants with ALS underwent leukapheresis, and their Tregs were isolated and expanded in a current Good Manufacturing Practice facility. Seven participants were randomly assigned in a 1:1 ratio to receive Treg infusions (1 × 10
RESULTS: The Treg/IL-2 treatments were safe and well tolerated, and Treg suppressive function was higher in the active group of the RCT. A meaningful evaluation of progression rates in the RCT between the placebo and active groups was not possible due to the limited number of enrolled participants aggravated by the COVID-19 pandemic. In the 24-week OLE, the Treg/IL-2 treatments were also safe and well tolerated in 8 participants who completed the escalating doses. Treg suppressive function and numbers were increased compared with baseline. Six of 8 participants changed by an average of -2.7 points per the ALS Functional Rating Scale-Revised, whereas the other 2 changed by an average of -10.5 points. Elevated levels of 2 markers of peripheral inflammation (IL-17C and IL-17F) and 2 markers of oxidative stress (oxidized low-density lipoprotein receptor 1 and oxidized LDL) were present in the 2 rapidly progressing participants but not in the slower progressing group.
DISCUSSION: Treg/IL-2 treatments were safe and well tolerated in the RCT and OLE with higher Treg suppressive function. During the OLE, 6 of 8 participants showed slow to no progression. The 2 of 8 rapid progressors had elevated markers of oxidative stress and inflammation, which may help delineate responsiveness to therapy. Whether Treg/IL-2 treatments can slow disease progression requires a larger clinical study (ClinicalTrials.gov number, NCT04055623).
CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that Treg infusions and IL-2 injections are safe and effective for patients with ALS
Vastus medialis cross-sectional area is positively associated with patella cartilage and bone volumes in a pain-free community-based population
INTRODUCTION: Although vastus medialis and lateralis are important determinants of patellofemoral joint function, their relationship with patellofemoral joint structure is unknown. The aim of this study was to examine potential determinants of vastus medialis and lateralis cross-sectional areas and the relationship between the cross-sectional area and patella cartilage and bone volumes. METHODS: Two hundred ninety-seven healthy adult subjects had magnetic resonance imaging of their dominant knee. Vastus medialis and lateralis cross-sectional areas were measured 37.5 mm superior to the quadriceps tendon insertion at the proximal pole of the patella. Patella cartilage and bone volumes were measured from these images. Demographic data and participation in vigorous physical activity were assessed by questionnaire. RESULTS: The determinants of increased vastus medialis and lateralis cross-sectional areas were older age (P <or= 0.002), male gender (P < 0.001), and greater body mass index (P <or= 0.07). Participation in vigorous physical activity was positively associated with vastus medialis cross-sectional area (regression coefficient [beta] 90.0; 95% confidence interval [CI] 38.2, 141.7) (P < 0.001) but not with vastus lateralis cross-sectional area (beta 10.1; 95% CI -18.1, 38.3) (P = 0.48). The cross-sectional area of vastus medialis only was positively associated with patella cartilage volume (beta 0.6; 95% CI 0.23, 0.94) (P = 0.001) and bone volume (beta 3.0; 95% CI 1.40, 4.68) (P < 0.001) after adjustment for potential confounders. CONCLUSIONS: Our results in a pain-free community-based population suggest that increased cross-sectional area of vastus medialis, which is associated with vigorous physical activity, and increased patella cartilage and bone volumes may benefit patellofemoral joint health and reduce the long-term risk of patellofemoral pathology
Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes
Background & Aims: Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols,
for direct comparison with fresh fetal and adult hepatocytes.
Methods: Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes.
Results: HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material,
HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests,
devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics.
Conclusions: HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes
Bisphosphonate Modulates Cementoblast Behavior In Vitro
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142297/1/jper1890.pd
Marketing Actions and the Value of Customer Assets: A Framework for Customer Asset Management
This article develops a framework for assessing how marketing actions affect customers’lifetime value to the firm. The framework is organized around four critical actions that firms must take to effectively manage the asset value of the customer base: database creation, market segmentation, forecasting customer purchase behavior, and resource allocation. In this framework, customer lifetime value is treated as a dynamic construct, that is, it influences the eventual allocation of marketing resources but is also influenced by that allocation. By viewing customers as assets and systematically managing these assets, a firm can identify the most appropriate marketing actions to acquire, maintain, and enhance customer assets and thereby maximize financial returns. The article discusses in detail how to assess customer lifetime value and manage customers as assets. Then, it identifies key research challenges in studying customer asset management and the managerial challenges associated with implementing effective customer asset management practices.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Global transpiration data from sap flow measurements: the SAPFLUXNET database
Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land–atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The “sapfluxnetr” R package – designed to access, visualize, and process SAPFLUXNET data – is available from CRAN
Global transpiration data from sap flow measurements: the SAPFLUXNET database
Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land?atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets,while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes.Fil: Poyatos, Rafael. Universitat Autònoma de Barcelona; EspañaFil: Granda, Víctor. Universitat Autònoma de Barcelona; EspañaFil: Flo, Víctor. Universitat Autònoma de Barcelona; EspañaFil: Adams, Mark A.. Swinburne University of Technology; Australia. University of Sydney; AustraliaFil: Adorján, Balázs. University of Debrecen; HungríaFil: Aguadé, David. Universitat Autònoma de Barcelona; EspañaFil: Aidar, Marcos P. M.. Institute of Botany; BrasilFil: Allen, Scott. University of Nevada; Estados UnidosFil: Alvarado Barrientos, M. Susana. Instituto de Ecología A.C.; MéxicoFil: Anderson Teixeira, Kristina J.. Smithsonian Tropical Research Institute; PanamáFil: Aparecido, Luiza Maria. Arizona State University; Estados Unidos. Texas A&M University; Estados UnidosFil: Arain, M. Altaf. McMaster University; CanadáFil: Aranda, Ismael. National Institute for Agricultural and Food Research and Technology; EspañaFil: Asbjornsen, Heidi. University of New Hampshire; Estados UnidosFil: Robert Baxter. Durham University; Reino UnidoFil: Beamesderfer, Eric. McMaster University; Canadá. Northern Arizona University; Estados UnidosFil: Carter Berry, Z.. Chapman University; Estados UnidosFil: Berveiller, Daniel. Université Paris Saclay; Francia. Centre National de la Recherche Scientifique; FranciaFil: Blakely, Bethany. University of Illinois at Urbana-Champaign; Estados UnidosFil: Boggs, Johnny. United States Forest Service; Estados UnidosFil: Gil Bohrer. Ohio State University; Estados UnidosFil: Bolstad, Paul V.. University of Minnesota; Estados UnidosFil: Bonal, Damien. Université de Lorraine; FranciaFil: Bracho, Rosvel. University of Florida; Estados UnidosFil: Brito, Patricia. Universidad de La Laguna; EspañaFil: Brodeur, Jason. McMaster University; CanadáFil: Casanoves, Fernando. Centro Agronómico Tropical de Investigación y Enseñanza; Costa RicaFil: Chave, Jérôme. Université Paul Sabatier; FranciaFil: Chen, Hui. Xiamen University; ChinaFil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Tecnológica Nacional. Facultad Regional Santa Cruz. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Nacional de la Patagonia Austral. Centro de Investigaciones y Transferencia de Santa Cruz; Argentin
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