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1.
Carcinogenesis ; 44(1): 54-64, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36548952

RESUMO

Loss of heterozygosity and promoter hypermethylation of APC is frequently observed in human endometrial cancer, which is the most common gynecological cancer in the USA, but its carcinogenic driver status in the endometrial epithelium has not been confirmed. We have identified a novel population of progenitor endometrial epithelial cells (EECs) in mice that express lysozyme M (LysM) and give rise to approximately 15% of all EECs in adult mice. LysM is a glycoside hydrolase that is encoded by Lyz2 and functions to protect cells from bacteria as part of the innate immune system. Its expression has been shown in a subset of hematopoietic stem cells and in specialized lung and small intestinal epithelial cells. Conditional deletion of Apc in LysM + EECs results in significantly more epithelial cells compared to wild-type mice. At 5 months of age, the ApccKO mice have enlarged uterine horns with pathology that is consistent with endometrial hyperplasia with cystic endometrial glands, non-villous luminal papillae and nuclear atypia. Nuclear accumulation of ß-catenin and ERα, both of which are known to induce endometrial hyperplasia, was observed in the EECs of the ApccKO mice. These results confirm that loss of APC in EECs can result in a phenotype similar to endometrial hyperplasia.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Adulto , Feminino , Humanos , Camundongos , Animais , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Células Epiteliais/patologia , Endométrio/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Células-Tronco/metabolismo
2.
FASEB J ; 36(3): e22220, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35195928

RESUMO

Erythroid differentiation (ED) is a complex cellular process entailing morphologically distinct maturation stages of erythroblasts during terminal differentiation. Studies of actin filament (F-actin) assembly and organization during terminal ED have revealed essential roles for the F-actin pointed-end capping proteins, tropomodulins (Tmod1 and Tmod3). Tmods bind tropomyosins (Tpms), which enhance Tmod capping and F-actin stabilization. Tmods can also nucleate F-actin assembly, independent of Tpms. Tmod1 is present in the red blood cell (RBC) membrane skeleton, and deletion of Tmod1 in mice leads to a mild compensated anemia due to mis-regulated F-actin lengths and membrane instability. Tmod3 is not present in RBCs, and global deletion of Tmod3 leads to embryonic lethality in mice with impaired ED. To further decipher Tmod3's function during ED, we generated a Tmod3 knockout in a mouse erythroleukemia cell line (Mel ds19). Tmod3 knockout cells appeared normal prior to ED, but showed defects during progression of ED, characterized by a marked failure to reduce cell and nuclear size, reduced viability, and increased apoptosis. Tmod3 does not assemble with Tmod1 and Tpms into the Triton X-100 insoluble membrane skeleton during ED, and loss of Tmod3 had no effect on α1,ß1-spectrin and protein 4.1R assembly into the membrane skeleton. However, F-actin, Tmod1 and Tpms failed to assemble into the membrane skeleton during ED in absence of Tmod3. We propose that Tmod3 nucleation of F-actin assembly promotes incorporation of Tmod1 and Tpms into membrane skeleton F-actin, and that this is integral to morphological maturation and cell survival during erythroid terminal differentiation.


Assuntos
Citoesqueleto de Actina/metabolismo , Eritroblastos/citologia , Eritropoese , Leucemia Eritroblástica Aguda/metabolismo , Tropomodulina/metabolismo , Animais , Linhagem Celular Tumoral , Eritroblastos/metabolismo , Leucemia Eritroblástica Aguda/sangue , Camundongos , Multimerização Proteica , Espectrina/metabolismo , Tropomodulina/genética
3.
J Biol Chem ; 297(2): 100972, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34280433

RESUMO

Heme plays a critical role in catalyzing life-essential redox reactions in all cells, and its synthesis must be tightly balanced with cellular requirements. Heme synthesis in eukaryotes is tightly regulated by the mitochondrial AAA+ unfoldase CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit X), which promotes heme synthesis by activation of δ-aminolevulinate synthase (ALAS/Hem1) in yeast and regulates turnover of ALAS1 in human cells. However, the specific mechanisms by which CLPX regulates heme synthesis are unclear. In this study, we interrogated the mechanisms by which CLPX regulates heme synthesis in erythroid cells. Quantitation of enzyme activity and protein degradation showed that ALAS2 stability and activity were both increased in the absence of CLPX, suggesting that CLPX primarily regulates ALAS2 by control of its turnover, rather than its activation. However, we also showed that CLPX is required for PPOX (protoporphyrinogen IX oxidase) activity and maintenance of FECH (ferrochelatase) levels, which are the terminal enzymes in heme synthesis, likely accounting for the heme deficiency and porphyrin accumulation observed in Clpx-/- cells. Lastly, CLPX is required for iron utilization for hemoglobin synthesis during erythroid differentiation. Collectively, our data show that the role of CLPX in yeast ALAS/Hem1 activation is not conserved in vertebrates as vertebrates rely on CLPX to regulate ALAS turnover as well as PPOX and FECH activity. Our studies reveal that CLPX mutations may cause anemia and porphyria via dysregulation of ALAS, FECH, and PPOX activities, as well as of iron metabolism.


Assuntos
5-Aminolevulinato Sintetase/metabolismo , Endopeptidase Clp/metabolismo , Ferroquelatase/metabolismo , Heme/biossíntese , Ferro/metabolismo , Leucemia Eritroblástica Aguda/patologia , Mitocôndrias/metabolismo , Animais , Linhagem Celular Tumoral , Endopeptidase Clp/genética , Ativação Enzimática , Técnicas de Inativação de Genes/métodos , Leucemia Eritroblástica Aguda/enzimologia , Leucemia Eritroblástica Aguda/genética , Camundongos , Modelos Animais , Proteólise , Peixe-Zebra
4.
J Chem Inf Model ; 62(20): 4906-4915, 2022 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-36222558

RESUMO

The Reaction Mechanism Generator (RMG) database for chemical property prediction is presented. The RMG database consists of curated datasets and estimators for accurately predicting the parameters necessary for constructing a wide variety of chemical kinetic mechanisms. These datasets and estimators are mostly published and enable prediction of thermodynamics, kinetics, solvation effects, and transport properties. For thermochemistry prediction, the RMG database contains 45 libraries of thermochemical parameters with a combination of 4564 entries and a group additivity scheme with 9 types of corrections including radical, polycyclic, and surface absorption corrections with 1580 total curated groups and parameters for a graph convolutional neural network trained using transfer learning from a set of >130 000 DFT calculations to 10 000 high-quality values. Correction schemes for solvent-solute effects, important for thermochemistry in the liquid phase, are available. They include tabulated values for 195 pure solvents and 152 common solutes and a group additivity scheme for predicting the properties of arbitrary solutes. For kinetics estimation, the database contains 92 libraries of kinetic parameters containing a combined 21 000 reactions and contains rate rule schemes for 87 reaction classes trained on 8655 curated training reactions. Additional libraries and estimators are available for transport properties. All of this information is easily accessible through the graphical user interface at https://rmg.mit.edu. Bulk or on-the-fly use can be facilitated by interfacing directly with the RMG Python package which can be installed from Anaconda. The RMG database provides kineticists with easy access to estimates of the many parameters they need to model and analyze kinetic systems. This helps to speed up and facilitate kinetic analysis by enabling easy hypothesis testing on pathways, by providing parameters for model construction, and by providing checks on kinetic parameters from other sources.


Assuntos
Modelos Químicos , Cinética , Termodinâmica , Bases de Dados Factuais , Solventes
5.
Exp Eye Res ; 203: 108371, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33248069

RESUMO

Congenital aniridia is caused by heterozygous mutations in the PAX6 gene. In this disease, congenital iris and foveal hypoplasia is associated with juvenile onset cataract, glaucoma, and corneal keratopathy. In rodents, Pax6 mutations result in a congenital reduction in ocular size that is not typically described in human aniridia. Here, the ocular morphometry of aniridia patients is compared with the lens phenotype of Pax6+/tm1/Pgr mice to reveal whether there are species differences in Pax6 regulation of lens development and homeostasis. Ultrasound biometry (UBM) revealed that eleven percent of aniridia patients exhibited mild microphthalmia while the anterior chamber depth of aniridic eyes was significantly reduced from 6 months of age onward. Although aniridic lens thickness was normal from birth, it was significantly decreased in aniridic lenses older than 30. Notably, 86% of aniridic lenses exhibited cataractous changes in this cohort. In addition, a significant proportion of aniridia patients develop lens subluxation as they age associated with reduced lens diameter as measured by anterior segment optical coherence tomography (AS-OCT). Analysis of young adult Pax6+/tm1/Pgr mouse lenses by micro-computed tomography (microCT), bright field and dark field imaging revealed that they are reduced in size but did not exhibit overt cataracts at this age. Overall, this study reveals that congenital microphthalmia as assessed by axial length, or microphakia, as assessed by lens thickness, are not typical in human aniridia, although these are primary manifestations of Pax6 mutations in mice, suggesting that PAX6 regulates some aspects of lens development differently between these species.


Assuntos
Aniridia/patologia , Catarata/patologia , Cristalino/patologia , Microftalmia/patologia , Adolescente , Adulto , Idoso , Animais , Aniridia/genética , Câmara Anterior/patologia , Comprimento Axial do Olho/patologia , Catarata/genética , Criança , Pré-Escolar , Modelos Animais de Doenças , Feminino , Humanos , Lactente , Masculino , Camundongos , Camundongos Mutantes , Microftalmia/genética , Microscopia Acústica , Pessoa de Meia-Idade , Fator de Transcrição PAX6/genética , Fenótipo , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Adulto Jovem
6.
J Chem Inf Model ; 61(6): 2686-2696, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34048230

RESUMO

In chemical kinetics research, kinetic models containing hundreds of species and tens of thousands of elementary reactions are commonly used to understand and predict the behavior of reactive chemical systems. Reaction Mechanism Generator (RMG) is a software suite developed to automatically generate such models by incorporating and extrapolating from a database of known thermochemical and kinetic parameters. Here, we present the recent version 3 release of RMG and highlight improvements since the previously published description of RMG v1.0. Most notably, RMG can now generate heterogeneous catalysis models in addition to the previously available gas- and liquid-phase capabilities. For model analysis, new methods for local and global uncertainty analysis have been implemented to supplement first-order sensitivity analysis. The RMG database of thermochemical and kinetic parameters has been significantly expanded to cover more types of chemistry. The present release includes parallelization for faster model generation and a new molecule isomorphism approach to improve computational performance. RMG has also been updated to use Python 3, ensuring compatibility with the latest cheminformatics and machine learning packages. Overall, RMG v3.0 includes many changes which improve the accuracy of the generated chemical mechanisms and allow for exploration of a wider range of chemical systems.


Assuntos
Quimioinformática , Software , Cinética , Aprendizado de Máquina
7.
Educ Technol Res Dev ; 69(1): 263-268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33262560

RESUMO

This paper is in response to the article entitled "Identifying potential types of guidance for supporting student inquiry when using virtual and remote labs in science: a literature review" by Zacharia et al. (2015). In their review, Zacharia et al. (2015) adopted de Jong and Lazondo's (2014) framework of five inquiry phases for online labs: orientation, conceptualization, investigation, conclusion, and discussion. Zacharia et al. reviewed the literature on Computer-supported Inquiry Learning (CoSIL), and identified best practices for each phase. They concluded, for example, that the orientation/conclusion/discussion phases received the least amount of guidance, while there were many more tools and strategies for providing guidance in the conceptualization/investigation phases. In this paper, we adopt the same inquiry framework as Zacharia et al. (2015) and report strategies that we learned from STEM faculty about how they supported and guided virtual student lab-based learning in these five phases during the recent COVID-19 shutdown. While Zacharia et al. identified tools and processes for enabling all five inquiry phases, add additional practical examples of faculty implementing these phases online as part of COVID-19 emergency remote teaching, and we provide insights for extending the 5-phase framework for future research.

8.
Ann Rheum Dis ; 77(6): 808-818, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29625968

RESUMO

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Medicina Baseada em Evidências/métodos , Gastroenteropatias/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Uveíte Anterior/tratamento farmacológico , Trombose Venosa/tratamento farmacológico
9.
Rheumatology (Oxford) ; 57(12): 2200-2212, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30107448

RESUMO

Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. Results: We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. Conclusion: The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Oftalmopatias/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Anticoagulantes/uso terapêutico , Síndrome de Behçet/complicações , Ensaios Clínicos como Assunto , Oftalmopatias/etiologia , Gastroenteropatias/etiologia , Glucocorticoides/uso terapêutico , Humanos , Doenças do Sistema Nervoso/etiologia , Guias de Prática Clínica como Assunto , Doenças Vasculares/etiologia
10.
Exp Physiol ; 103(3): 358-369, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29205610

RESUMO

NEW FINDINGS: What is the central question of this study? The aim was to determine the effect of mid-portion Achilles tendinopathy (MAT) on free Achilles tendon three-dimensional morphology and volume at rest and under load in people with unilateral MAT. What is the main finding and its importance? Tendinopathic tendon had a larger resting tendon cross-sectional area and anteroposterior diameter relative to healthy tendon. When loaded, tendinopathic tendon experienced a reduction in transverse morphology (i.e. cross-sectional area, anteroposterior and mediolateral diameters) and overall volume reduction. In contrast, the healthy tendon remained isovolumetric and bulged along the anteroposterior axis. These findings suggest a fundamental reorganization of tendinopathic tendon matrix components and altered tendon fluid content when under load. ABSTRACT: Mid-portion Achilles tendinopathy (MAT) adversely affects free Achilles tendon (AT) structure and composition. However, it is not known how these pathological alterations associated with MAT change the normal three-dimensional (3-D) morphology of free AT at rest and under load throughout the entire free tendon length. Here, we used 3-D ultrasound to examine the effect of unilateral MAT on free tendon 3-D morphology [length, cross-sectional area (CSA), anteroposterior (AP) diameter and mediolateral (ML) diameter] and volume at rest and during a submaximal (50%) voluntary isometric plantarflexion contraction bilaterally in individuals with unilateral MAT (n = 10) compared with a matched healthy control group (n = 10). The tendinopathic free AT had a greater CSA relative to the control tendons along the entire tendon length, which was mainly driven by a greater tendon AP diameter. Under load, the tendinopathic tendon experienced greater longitudinal and transverse strains than the control tendons. In contrast to the control tendons, which experienced a reduction in tendon CSA and ML diameter, bulged along the AP axis and behaved isovolumetrically under load, the tendinopathic tendon experienced a reduction in tendon CSA, AP diameter and ML diameter and an overall volume reduction. Overall, these findings suggest that the magnitude of longitudinal strain and volume change and the corresponding magnitude and direction of transverse strain under load are altered in MAT compared with normal tendon. These findings are indicative of a fundamental reorganization of the tendon matrix and alterations in tendon fluid content and distribution under load in tendinopathic tendon.


Assuntos
Tendão do Calcâneo/diagnóstico por imagem , Contração Isométrica/fisiologia , Tendinopatia/diagnóstico por imagem , Suporte de Carga/fisiologia , Tendão do Calcâneo/fisiopatologia , Adulto , Fenômenos Biomecânicos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Descanso , Tendinopatia/fisiopatologia , Ultrassonografia
11.
Liver Int ; 37(1): 111-120, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27254473

RESUMO

BACKGROUND & AIMS: A proportion of patients with Budd-Chiari Syndrome (BCS) associated with stenosis or short occlusion of the hepatic vein (HV) or upper inferior vena cava (IVC) can be treated with recanalization by percutaneous venoplasty ± HV stent insertion. We studied the long-term outcomes of this approach. METHODS: Single-centre retrospective analysis of patients referred for radiological assessment ± intervention over a 27-year period. Of 155 BCS patients, 63 patients who underwent venoplasty were studied and compared to a previously reported series treated by TIPSS (n = 59). RESULTS: Patients treated with HV interventions (32 venoplasty alone, 31 endovascular stents): mean age, 34.9 ± 10.9; M:F ratio 27:36; median follow-up, 113.0 months; 62% of patients had ≥1 haematological risk factor. Technical success was 100%, with symptom resolution in 73%. Cumulative secondary patency at 1, 5, 10 years was 92%, 79%, 79% and 69%, 69%, 64% in the stenting and venoplasty groups respectively. Where long-term patency was not achieved, 10 patients required TIPSS, and 8 underwent surgery. Actuarial survival at 1, 5, 10 years was 97%, 89% and 85%. When compared to TIPSS, HV interventions resulted in similar patency and survival rates but significantly lower procedural complications (9.5% vs 27.1%) and hepatic encephalopathy (0% vs 18%). Patient age predicted survival following multivariate analysis. CONCLUSIONS: Our data support the stepwise approach to management of BCS, with very good outcomes from venoplasty combined with stenting when required. TIPSS should only be offered where HV interventions are not feasible or unsuccessful.


Assuntos
Síndrome de Budd-Chiari/cirurgia , Veias Hepáticas/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática , Adulto , Síndrome de Budd-Chiari/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Flebografia , Complicações Pós-Operatórias/epidemiologia , Análise de Regressão , Estudos Retrospectivos , Stents , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Reino Unido , Veia Cava Inferior/cirurgia , Adulto Jovem
12.
J Exp Biol ; 220(Pt 17): 3053-3061, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28620014

RESUMO

Mid-portion Achilles tendinopathy (MAT) alters the normal three-dimensional (3D) morphology of the Achilles tendon (AT) at rest and under a single tensile load. However, how MAT changes the 3D morphology of the AT during repeated loading remains unclear. This study compared the AT longitudinal, transverse and volume strains during repeated loading of the tendinopathic AT with those of the contralateral tendon in people with unilateral MAT. Ten adults with unilateral MAT performed 10 successive 25 s submaximal (50%) voluntary isometric plantarflexion contractions with both legs. Freehand 3D ultrasound scans were recorded and used to measure whole AT, free AT and proximal AT longitudinal strains and free AT cross-sectional area (CSA) and volume strains. The free AT experienced higher longitudinal and CSA strain and reached steady state following a greater number of contractions (five contractions) in the tendinopathic AT compared with the contralateral tendon (three contractions). Further, free tendon CSA and volume strain were greater in the tendinopathic AT than in the contralateral tendon from the first contraction, whereas free AT longitudinal strain was not greater than that of the contralateral tendon until the fourth contraction. Volume loss from the tendon core therefore preceded the greater longitudinal strain in the tendinopathic AT. Overall, these findings suggest that the tendinopathic free AT experiences an exaggerated longitudinal and transverse strain response under repeated loading that is underpinned by an altered interaction between solid and fluid tendon matrix components. These alterations are indicative of accentuated poroelasticity and an altered local stress-strain environment within the tendinopathic free tendon matrix, which could affect tendon remodelling via mechanobiological pathways.


Assuntos
Tendão do Calcâneo/fisiologia , Contração Isométrica , Ultrassonografia , Tendão do Calcâneo/diagnóstico por imagem , Adulto , Fenômenos Biomecânicos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
J Phys Chem A ; 121(37): 6896-6904, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28820268

RESUMO

A scarcity of known chemical kinetic parameters leads to the use of many reaction rate estimates, which are not always sufficiently accurate, in the construction of detailed kinetic models. To reduce the reliance on these estimates and improve the accuracy of predictive kinetic models, we have developed a high-throughput, fully automated, reaction rate calculation method, AutoTST. The algorithm integrates automated saddle-point geometry search methods and a canonical transition state theory kinetics calculator. The automatically calculated reaction rates compare favorably to existing estimated rates. Comparison against high level theoretical calculations show the new automated method performs better than rate estimates when the estimate is made by a poor analogy. The method will improve by accounting for internal rotor contributions and by improving methods to determine molecular symmetry.

14.
Nature ; 469(7328): 64-7, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-21150901

RESUMO

The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O ≥ 1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T > 2,500 K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.

15.
IEEE Trans Geosci Remote Sens ; Volume 55(Iss 4): 1897-1914, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31708601

RESUMO

This paper evaluates the retrieval of soil moisture in the top 5-cm layer at 3-km spatial resolution using L-band dual-copolarized Soil Moisture Active-Passive (SMAP) synthetic aperture radar (SAR) data that mapped the globe every three days from mid-April to early July, 2015. Surface soil moisture retrievals using radar observations have been challenging in the past due to complicating factors of surface roughness and vegetation scattering. Here, physically based forward models of radar scattering for individual vegetation types are inverted using a time-series approach to retrieve soil moisture while correcting for the effects of static roughness and dynamic vegetation. Compared with the past studies in homogeneous field scales, this paper performs a stringent test with the satellite data in the presence of terrain slope, subpixel heterogeneity, and vegetation growth. The retrieval process also addresses any deficiencies in the forward model by removing any time-averaged bias between model and observations and by adjusting the strength of vegetation contributions. The retrievals are assessed at 14 core validation sites representing a wide range of global soil and vegetation conditions over grass, pasture, shrub, woody savanna, corn, wheat, and soybean fields. The predictions of the forward models used agree with SMAP measurements to within 0.5 dB unbiased-root-mean-square error (ubRMSE) and -0.05 dB (bias) for both copolarizations. Soil moisture retrievals have an accuracy of 0.052 m3/m3 ubRMSE, -0.015 m3/m3 bias, and a correlation of 0.50, compared to in situ measurements, thus meeting the accuracy target of 0.06 m3/m3 ubRMSE. The successful retrieval demonstrates the feasibility of a physically based time series retrieval with L-band SAR data for characterizing soil moisture over diverse conditions of soil moisture, surface roughness, and vegetation.

16.
Br J Nurs ; 30(12): 694, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34170727
17.
J Exp Biol ; 218(Pt 24): 3894-900, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26519510

RESUMO

Our understanding of the immediate effects of exercise on Achilles free tendon transverse morphology is limited to single site measurements acquired at rest using 2D ultrasound. The purpose of this study was to provide a detailed 3D description of changes in Achilles free tendon morphology immediately following a single clinical bout of exercise. Freehand 3D ultrasound was used to measure Achilles free tendon length, and regional cross-sectional area (CSA), medio-lateral (ML) diameter and antero-posterior (AP) diameter in healthy young adults (N=14) at rest and during isometric muscle contraction, immediately before and after 3×15 eccentric heel drops. Post-exercise reductions in transverse strain were limited to CSA and AP diameter in the mid-proximal region of the Achilles free tendon during muscle contraction. The change in CSA strain during muscle contraction was significantly correlated to the change in longitudinal strain (r=-0.72) and the change in AP diameter strain (r=0.64). Overall findings suggest the Achilles free tendon experiences a complex change in 3D morphology following eccentric heel drop exercise that manifests under contractile but not rest conditions, is most pronounced in the mid-proximal tendon and is primarily driven by changes in AP diameter strain and not ML diameter strain.


Assuntos
Tendão do Calcâneo/anatomia & histologia , Tendão do Calcâneo/fisiologia , Exercício Físico/fisiologia , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Contração Isométrica , Masculino , Músculo Esquelético/fisiologia , Descanso
18.
Phys Chem Chem Phys ; 17(48): 32173-82, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26446401

RESUMO

Detailed kinetic models to aid the understanding of complex chemical systems require many thousands of reaction rate coefficients, most of which are estimated, some quite approximately and with unknown uncertainties. This motivates the development of high-throughput methods to determine rate coefficients via transition state theory calculations, which requires the automatic prediction of transition state (TS) geometries. We demonstrate a novel approach to predict TS geometries using a group-additive method. Distances between reactive atoms at the TS are estimated using molecular group values, with the 3D geometry of the TS being constructed by distance geometry. The estimate is then optimized using electronic structure theory and validated using intrinsic reaction coordinate calculations, completing the fully automatic algorithm to locate TS geometries. The methods were tested using a diisopropyl ketone combustion model containing 1393 hydrogen abstraction reactions, of which transition states were found for 907 over two iterations of the algorithm. With sufficient training data, molecular group contributions were shown to successfully predict the reaction center distances of transition states with root-mean-squared errors of only 0.04 Å.

19.
J Electrochem Soc ; 161(6): B111-B116, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-27330196

RESUMO

A double potential pulse scheme is reported for observation of cholesterol efflux from the plasma membrane of a single neuron cell. Capillary Pt disk microelectrodes having a thin glass insulator allow the 10 µm diameter electrode and cell to be viewed under optical magnification. The electrode, covalently functionalized with cholesterol oxidase, is positioned in contact with the cell surface resulting in enzyme catalyzed cholesterol oxidation and efflux of cholesterol from the plasma membrane at the electrode contact site. Enzymatically generated hydrogen peroxide accumulates at the electrode/cell interface during a 5 s hold-time and is oxidized during application of a potential pulse. A second, replicate potential pulse is applied 0.5 s after the first potential pulse to gauge background charge prior to significant accumulation of hydrogen peroxide. The difference in charge passed between the first and second potential pulse provides a measure of hydrogen peroxide generated by the enzyme and is an indication of the cholesterol efflux. Control experiments for bare Pt microelectrodes in contact with the cell plasma membrane show difference charge signals in the range of about 7-10 pC. Enzyme-modified electrodes in contact with the plasma membrane show signals in the range of 16-26 pC.

20.
BMC Public Health ; 14: 811, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-25100162

RESUMO

BACKGROUND: Sexting (sexual messaging via mobile devices) among adolescents may result in increased risky sexual practices, psychological distress and in some cases, suicide. There is very little research on sexting in developing nations, such as Peru. In particular, little is known about gender differences in the correlates of sexting. The purpose of this study was to determine the sexting prevalence and correlates of sexting among adolescent boys and girls in Cusco, Peru. METHODS: The study sample comprised 949 high school aged adolescents from Cusco, Peru. Adolescents responded to questions about demographics, sexting behavior, and risk/protective factors. Separate regression models were constructed to compare correlates of sexting for boys and sexting for girls. RESULTS: Twenty percent of the sample reported engaging in at least one instance of sexting. Boys reported higher rates of sexting than girls (35.17% vs. 13.19%, p = 0.000). Significant correlates for girls' sexting included having been cyberbullied and parental factors. For boys, hypertexting, fighting, parental factors, and parental rules about sexting were significant. CONCLUSIONS: Peruvian health officials with an interest in reducing the effects of sexting among adolescents may choose to target boys differently than girls. These efforts may include advising parents to set clear rules and expectations about sexting and the appropriate use of mobile devices.


Assuntos
Comportamento do Adolescente , Comportamento Sexual , Envio de Mensagens de Texto , Adolescente , Serviços de Saúde do Adolescente , Criança , Feminino , Humanos , Masculino , Peru/epidemiologia , Prevalência , Adulto Jovem
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