250 research outputs found
Перспективи використання тонкодисперсних вуглецевих матеріалів
У останні десятиліття особливу увагу вчених привертає дослідження різних алотропних видозмін вуглецю, зокрема природних: алмазу, графіту, лонсдейліту, фулерену, вуглецевих нанотрубок (у тому числі шунгіту – природного нанотехн-логічного матеріалу) і штучних: карбіну, графену, аморфного вуглецю (кокс, вугілля, технічний вуглець, сажа, активоване вугілля). Водночас у техніці все більше розповсюдження отримують тонкодисперсні вуглецеві матеріали, зокрема тонкодисперсне вугілля та технічний вуглець, тонкоподрібнений аморфний вуглець, активоване вугілля, дослідженню яких присвячено ряд окремих досліджень, у т.ч. і авторів статті
Prognostic biomarkers in primary progressive multiple sclerosis: validating and scrutinizing multimodal evoked potentials
OBJECTIVE: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities. METHODS: Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0-6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression. RESULTS: Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45-0.69; p < 0.01) and follow-up (Rho: 0.59-0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R(2)adj: 0.24), while EDSS and age did not. Tibial qSEP (R(2)adj: 0.22) and qMEP (R(2)adj: 0.26) were the best single modality predictors, outperformed by their combination (R(2)adj: 0.32). CONCLUSIONS: Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information. SIGNIFICANCE: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS
Multimodal evoked potentials for functional quantification and prognosis in multiple sclerosis
A quality assessment of Spatial TDR soil moisture measurements in homogenous and heterogeneous media with laboratory experiments
Investigation of transient soil moisture profiles yields valuable information of near- surface processes. A recently developed reconstruction algorithm based on the telegraph equation allows the inverse estimation of soil moisture profiles along coated, three rod TDR probes. Laboratory experiments were carried out to prove the results of the inversion and to understand the influence of probe rod deformation and solid objects close to the probe in heterogeneous media. Differences in rod geometry can lead to serious misinterpretations in the soil moisture profile, but have small influence on the average soil moisture along the probe. Solids in the integration volume have almost no effect on average soil moisture, but result in locally slightly decreased moisture values. Inverted profiles obtained in a loamy soil with a clay content of about 16% were in good agreement with independent measurements
Spinal cord grey matter segmentation challenge
An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication
H3K9 Methyltransferases and Demethylases Control Lung Tumor-Propagating Cells and Lung Cancer Progression
Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition impairs lung adenocarcinoma progression in vivo. Therefore, inhibition of G9a is dangerous in certain cancer contexts, and targeting the histone demethylases is a more suitable approach for lung cancer treatment. Understanding cellular context and specific tumor populations is critical when targeting epigenetic regulators in cancer for future therapeutic development
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK092760)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK49216)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant U54DK110805)National Heart, Lung, and Blood Institute (Grant UO1-HL100001)National Heart, Lung, and Blood Institute (Grant U01HL134812)National Heart, Lung, and Blood Institute (Grant R01HL04880)National Institutes of Health (U.S.) (Grant R24OD017870-01
Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension
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