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21
result(s) for
"Spivak, Igor"
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Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis
2020
Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH.
Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited prospectively through the STOPAH trial. The cohort was randomly divided into exploratory (n = 200) and validation sets (n = 628).
Patients with sAH had diminished serum transferrin but increased transferrin saturation. Among iron parameters, baseline transferrin was the best predictor of 28-day (area under the receiver operated characteristic 0.72 [95% confidence interval 0.67-0.78]) and 90-day survival (area under the receiver operated characteristic 0.65 [0.61-0.70]). Transferrin's predictive ability was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively).
In patients with sAH, serum transferrin predicts mortality with a performance comparable with commonly used composite scoring systems. Hence, this routinely available parameter might be a useful marker alone or as a component of prognostic models.
Journal Article
Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes
2023
People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref.
1
), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.
Hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality.
Journal Article
Low-Dose Molecular Ultrasound Imaging with E-Selectin-Targeted PBCA Microbubbles
by
Spivak, Igor
,
Kiessling, Fabian
,
Rix, Anne
in
Angiogenesis Inhibitors - pharmacology
,
Angiogenesis Inhibitors - therapeutic use
,
Animals
2016
Purpose
Our objective was to determine the lowest diagnostically effective dose for E-selectin-targeted poly
n
-butyl cyanoacrylate (PBCA)-shelled microbubbles and to apply it to monitor antiangiogenic therapy effects.
Procedures
PBCA-shelled microbubbles (MBs) coupled to an E-selectin-specific peptide were applied in mice carrying MLS or A431 carcinoma xenografts scaling down the MB dosage to the lowest level where binding could be examined with a 18-MHz small animal ultrasound transducer. Differences in E-selectin expression in the two carcinoma xenografts were confirmed by enzyme-linked immunosorbent assay (ELISA). In addition, MLS tumor-bearing mice under antiangiogenic therapy were monitored using E-selectin-targeted MBs at the lowest applicable dose. Therapy effects on tumor vascularization were verified by immunohistological analyses.
Results
The minimally required dosage was 7 × 10
7
MBs/kg body weight. This dosage was sufficient to enable E-selectin detection in high E-selectin-expressing MLS tumors, while low E-selectin-expressing A431 tumors required almost 2.5-fold higher doses. At the dose of 7 × 10
7
MBs/kg body weight, a decrease in E-selectin MB binding under antiangiogenic therapy could be assessed (being significant after 3 days of treatment;
p
< 0.0001), which was in line with the significant drop in E-selectin-positive area fractions that was found histologically (
p
< 0.05).
Conclusions
Molecular ultrasound imaging with our E-selectin-targeted MB and therapy monitoring was possible down to a dose of 7 × 10
7
MBs/kg body weight (equates to 66 μg PBCA/kg and 4.6 mg PBCA/70 kg). Improvements in choice of targets, MB composition, and other MB detection methods may improve sensitivity and lead to reliable detection results of clinically transferrable MBs at even lower dosage levels.
Journal Article
Deep ChArUco: Dark ChArUco Marker Pose Estimation
by
Chauhan, Vikram
,
Spivak, Igor
,
Malisiewicz, Tomasz
in
Artificial neural networks
,
Augmented reality
,
Computer vision
2019
ChArUco boards are used for camera calibration, monocular pose estimation, and pose verification in both robotics and augmented reality. Such fiducials are detectable via traditional computer vision methods (as found in OpenCV) in well-lit environments, but classical methods fail when the lighting is poor or when the image undergoes extreme motion blur. We present Deep ChArUco, a real-time pose estimation system which combines two custom deep networks, ChArUcoNet and RefineNet, with the Perspective-n-Point (PnP) algorithm to estimate the marker's 6DoF pose. ChArUcoNet is a two-headed marker-specific convolutional neural network (CNN) which jointly outputs ID-specific classifiers and 2D point locations. The 2D point locations are further refined into subpixel coordinates using RefineNet. Our networks are trained using a combination of auto-labeled videos of the target marker, synthetic subpixel corner data, and extreme data augmentation. We evaluate Deep ChArUco in challenging low-light, high-motion, high-blur scenarios and demonstrate that our approach is superior to a traditional OpenCV-based method for ChArUco marker detection and pose estimation.
Acidification of East Siberian Arctic Shelf waters through addition of freshwater and terrestrial carbon
2016
Uptake of atmospheric CO
2
contributes to ocean acidification. Measurements of seawater chemistry reveal that the extreme acidity of the East Siberian Arctic Shelf is driven by terrestrial organic matter and freshwater inputs.
Ocean acidification affects marine ecosystems and carbon cycling, and is considered a direct effect of anthropogenic carbon dioxide uptake from the atmosphere
1
,
2
,
3
. Accumulation of atmospheric CO
2
in ocean surface waters is predicted to make the ocean twice as acidic by the end of this century
4
. The Arctic Ocean is particularly sensitive to ocean acidification because more CO
2
can dissolve in cold water
5
,
6
. Here we present observations of the chemical and physical characteristics of East Siberian Arctic Shelf waters from 1999, 2000–2005, 2008 and 2011, and find extreme aragonite undersaturation that reflects acidity levels in excess of those projected in this region for 2100. Dissolved inorganic carbon isotopic data and Markov chain Monte Carlo simulations of water sources using salinity and δ
18
O data suggest that the persistent acidification is driven by the degradation of terrestrial organic matter and discharge of Arctic river water with elevated CO
2
concentrations, rather than by uptake of atmospheric CO
2
. We suggest that East Siberian Arctic Shelf waters may become more acidic if thawing permafrost leads to enhanced terrestrial organic carbon inputs and if freshwater additions continue to increase, which may affect their efficiency as a source of CO
2
.
Journal Article
Intense zonal freshwater transport in the Eurasian Arctic during ice-covered season revealed by in situ measurements
by
Kuskova, Ekaterina
,
Osadchiev, Alexander
,
Sedakov, Roman
in
704/106/829/2737
,
704/829/2737
,
Autumn
2023
The Kara Sea receives ~ 1/3 of total freshwater discharge to the Arctic Ocean, mainly from the large Ob and Yenisei rivers. The Ob-Yenisei plume covers wide area in the central part of the Kara Sea during ice-free season (June–October) and accumulates ~ 1000 km
3
of freshwater volume. In late autumn, the Kara Sea becomes covered by ice, which hinders in situ measurements at this area. As a result, the fate of the Ob-Yenisei plume below sea ice during winter and spring remains unclear. In this study, we report multiple in situ measurements performed in the Kara Sea shortly before and during ice-covered season. We demonstrate that late autumn convection in the plume shortly before ice formation significantly reduces friction between the plume and the subjacent sea. The subsequent formation of solid sea ice coverage isolates the plume from wind forcing. These two factors precondition the Ob-Yenisei plume to form an intense buoyancy-driven coastal current below sea ice. As a result, the plume advects eastward to the Laptev Sea through the Vilkitsky Strait during several months in November-February. Eventually, by late winter this huge freshwater volume disappears from the Kara Sea and contributes to freshwater content of the Laptev Sea. The obtained result improves our understanding of freshwater balance of the Kara and Laptev seas, as well as provides an important insight into the large-scale freshwater transport in the Eurasian Arctic, which remain largely unknown during ice-covered season.
Journal Article
Influence of estuarine tidal mixing on structure and spatial scales of large river plumes
by
Osadchiev, Alexander
,
Medvedev, Igor
,
Kulikov, Mikhail
in
Alliances
,
Bathymetry
,
Brackishwater environment
2020
The Yenisei and Khatanga rivers are among the largest estuarine rivers that inflow to the Arctic Ocean. Discharge of the Yenisei River is 1 order of magnitude larger than that of the Khatanga River. However, spatial scales of buoyant plumes formed by freshwater runoff from the Yenisei and Khatanga gulfs are similar. This feature is caused by different tidal forcing in these estuaries, which have similar sizes, climate conditions, and geomorphology. The Khatanga discharge experiences strong tidal forcing that causes formation of a diluted bottom-advected plume in the Khatanga Gulf. This deep and weakly stratified plume has a small freshwater fraction and therefore occupies a large area on the shelf. The Yenisei Gulf, on the other hand, is a salt-wedge estuary that receives a large freshwater discharge and is less affected by tidal mixing due to low tidal velocities. As a result, the low-salinity and strongly stratified Yenisei plume has a large freshwater fraction and its horizontal size is relatively small. The results show that estuarine tidal mixing determines freshwater fraction in these river plumes, which governs their depth and area after they spread from estuaries to coastal sea. Therefore, the influence of estuarine mixing on spatial scales of a large river plume can be of the same importance as the roles of river discharge rate and wind forcing. In particular, plumes with similar areas can be formed by rivers with significantly different discharge rates, as illustrated by the Yenisei and Khatanga plumes.
Journal Article
Structure and Inter-Annual Variability of the Freshened Surface Layer in the Laptev and East-Siberian Seas During Ice-Free Periods
by
Tilinina, Natalia
,
Osadchiev, Alexander
,
Frey, Dmitry
in
East-Siberian Sea
,
freshened surface layer
,
Laptev Sea
2021
This work is focused on the structure and inter-annual variability of the freshened surface layer (FSL) in the Laptev and East-Siberian seas during ice-free periods. This layer is formed mainly by deltaic rivers among which the Lena River contributes about two thirds of the inflowing freshwater volume. Based on in situ measurements, we show that the area of this FSL during certain years is much greater than the area of FSL in the neighboring Kara Sea, while the total annual freshwater discharge to the Laptev and East-Siberian seas is 1.5 times less than to the Kara Sea (mainly from the estuaries of the Ob and Yenisei rivers). This feature is caused by differences in morphology of the estuaries and deltas. Shallow and narrow channels of the Lena Delta are limitedly affected by sea water. As a result, undiluted Lena discharge inflows to sea from multiple channels and forms relatively shallow plume, as compared to the Ob-Yenisei plume, which mixes with subjacent saline sea water in deep and wide estuaries. Due to small vertical extents of FSL in the Laptev and East-Siberian seas, wind conditions strongly affect its spreading and determine its significant inter-annual variability, as compared to relatively stable FSL in the Kara Sea. During years with prevailing western and northern winds, FSL is localized in the southern parts of the Laptev and East-Siberian seas due to southward Ekman transport, meridional extent (<250 km) and area (∼250,000 km 2 ) of FSL are relatively small. During years with strong eastern winds FSL spreads northward over large area (up to 500,000 km 2 ), its meridional extent increases up to 500–700 km. At the same time, area and position of FSL do not show any dependence on significant variability of the annual river discharge volume and ice coverage during warm season.
Journal Article
The spatial and interannual dynamics of the surface water carbonate system and air–sea CO2 fluxes in the outer shelf and slope of the Eurasian Arctic Ocean
by
Gustafsson, Örjan
,
Repina, Irina A
,
Shcherbakova, Kseniia P
in
Air temperature
,
Air-sea flux
,
Arctic climate changes
2017
The Arctic is undergoing dramatic changes which cover the entire range of natural processes, from extreme increases in the temperatures of air, soil, and water, to changes in the cryosphere, the biodiversity of Arctic waters, and land vegetation. Small changes in the largest marine carbon pool, the dissolved inorganic carbon pool, can have a profound impact on the carbon dioxide (CO2) flux between the ocean and the atmosphere, and the feedback of this flux to climate. Knowledge of relevant processes in the Arctic seas improves the evaluation and projection of carbon cycle dynamics under current conditions of rapid climate change.Investigation of the CO2 system in the outer shelf and continental slope waters of the Eurasian Arctic seas (the Barents, Kara, Laptev, and East Siberian seas) during 2006, 2007, and 2009 revealed a general trend in the surface water partial pressure of CO2 (pCO2) distribution, which manifested as an increase in pCO2 values eastward. The existence of this trend was defined by different oceanographic and biogeochemical regimes in the western and eastern parts of the study area; the trend is likely increasing due to a combination of factors determined by contemporary change in the Arctic climate, each change in turn evoking a series of synergistic effects. A high-resolution in situ investigation of the carbonate system parameters of the four Arctic seas was carried out in the warm season of 2007; this year was characterized by the next-to-lowest historic sea-ice extent in the Arctic Ocean, on satellite record, to that date. The study showed the different responses of the seawater carbonate system to the environment changes in the western vs. the eastern Eurasian Arctic seas. The large, open, highly productive water area in the northern Barents Sea enhances atmospheric CO2 uptake. In contrast, the uptake of CO2 was strongly weakened in the outer shelf and slope waters of the East Siberian Arctic seas under the 2007 environmental conditions. The surface seawater appears in equilibrium or slightly supersaturated by CO2 relative to atmosphere because of the increasing influence of river runoff and its input of terrestrial organic matter that mineralizes, in combination with the high surface water temperature during sea-ice-free conditions.This investigation shows the importance of processes that vary on small scales, both in time and space, for estimating the air–sea exchange of CO2. It stresses the need for high-resolution coverage of ocean observations as well as time series. Furthermore, time series must include multi-year studies in the dynamic regions of the Arctic Ocean during these times of environmental change.
Journal Article
Improving the Conductivity of the PEDOT:PSS Layers in Photovoltaic Cells Based on Organometallic Halide Perovskites
2022
Among conductive polymers, PEDOT films find the widest application in electronics. For photovoltaic applications, studies of their optical properties, stability, and electrical conductivity are of greatest interest. However, the PEDOT:PSS transport layers, when used in photovoltaic cells, have a high electrical resistance, which prevents solar cells from increasing their efficiency. One of the promising ways to improve their electrical properties is the use of composite materials based on them, in which the conductivity can be increased by introducing various additives. In this work, conductive polymer films PEDOT:PSS (poly (3,4-ethylenedioxythiophene):polystyrene sulfonate acid) doped with a number of amines (Pentylamine, Octylamine, Diethylamine, Aniline with carbon nanotubes) were obtained and studied. It is shown that, depending on the concentration of dopants, the electrical conductivity of PEDOT:PSS films can be significantly improved. In this case, the light transmission of the films practically does not change. The process of improving the conductivity by treating the surface of the finished film with amines, followed by heat treatment, was studied. It is assumed that the improvement in conductivity is the result of the self-assembly of monolayers of organic molecules on the surface of the PEDOT:PSS film leading to its p-doping due to intermolecular interaction.
Journal Article