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| 2. |
- Mamontov, Eugen, 1955, et al.
(author)
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The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
- 2006
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In: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
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Journal article (peer-reviewed)abstract
- Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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| 3. |
- Sieber, Arne Santa, et al.
(author)
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Compact recreational rebreather with innovative gas sensing concept and low work of breathing design
- 2013
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In: Marine Technology Society journal. - : Marine Technology Society Inc.. - 0025-3324 .- 1948-1209. ; 47:6, s. 27-41
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Journal article (peer-reviewed)abstract
- Recreational rebreathers are increasingly popular, and recreational diver training organizations now routinely offer training for rebreather diving. Few rebreathers on the market, however, fulfill the criteria of a dedicated recreational rebreather. These remain based on traditional sensor technology, which may be linked to rebreather use having an estimated 10 times the risk of mortality while diving compared with open circuit breathing systems. In the present work, a new recreational rebreather based on two innovative approaches is described. Firstly, the rebreather uses a novel sensor system including voltammetric and spectroscopic validation of galvanic pO2 sensor cells, a redundant optical pO2 sensor, and a two-wavelength infrared pCO2 sensor. Secondly, a new breathing loop design is introduced, which reduces failure points, improves work of breathing, and can be mass fabricated at a comparatively low cost. Two prototypes were assembled and tested in the laboratory at a notified body for personal protective equipment before both pool and sea water diving trials. Work of breathing was well below the maximum allowed by the European Normative. These trials also demonstrated that optical pO2 sensors can be successfully employed in rebreathers. The pCO2 sensor detected pCO2 from 0.0004 to 0.0024 bar. These new approaches, which include a new concept for simplified mechanical design as well as improved electronic control, may prove useful in future recreational diving apparatus.
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| 5. |
- Skedung, Lisa, et al.
(author)
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Feeling small : Exploring the Tactile Perception Limits
- 2013
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. 2617-
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Journal article (peer-reviewed)abstract
- The human finger is exquisitely sensitive in perceiving different materials, but the question remains as to what length scales are capable of being distinguished in active touch. We combine material science with psychophysics to manufacture and haptically explore a series of topographically patterned surfaces of controlled wavelength, but identical chemistry. Strain-induced surface wrinkling and subsequent templating produced 16 surfaces with wrinkle wavelengths ranging from 300 nm to 90 mu m and amplitudes between 7 nm and 4.5 mu m. Perceived similarities of these surfaces (and two blanks) were pairwise scaled by participants, and interdistances among all stimuli were determined by individual differences scaling (INDSCAL). The tactile space thus generated and its two perceptual dimensions were directly linked to surface physical properties - the finger friction coefficient and the wrinkle wavelength. Finally, the lowest amplitude of the wrinkles so distinguished was approximately 10 nm, demonstrating that human tactile discrimination extends to the nanoscale.
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| 6. |
- Nguyen, Tho D. K., et al.
(author)
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Visualization of Partial Exocytotic Content Release and Chemical Transport into Nanovesicles in Cells
- 2022
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In: Acs Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:3, s. 4831-4842
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Journal article (peer-reviewed)abstract
- For decades, "all-or-none"and "kiss-and-run"were thought to be the only major exocytotic release modes in cell-to-cell communication, while the significance of partial release has not yet been widely recognized and accepted owing to the lack of direct evidence for exocytotic partial release. Correlative imaging with transmission electron microscopy and NanoSIMS imaging and a dual stable isotope labeling approach was used to study the cargo status of vesicles before and after exocytosis; demonstrating a measurable loss of transmitter in individual vesicles following stimulation due to partial release. Model secretory cells were incubated with 13C-labeled l-3,4-dihydroxyphenylalanine, resulting in the loading of 13C-labeled dopamine into their vesicles. A second label, di-N-desethylamiodarone, having the stable isotope 127I, was introduced during stimulation. A significant drop in the level of 13C-labeled dopamine and a reduction in vesicle size, with an increasing level of 127I-, was observed in vesicles of stimulated cells. Colocalization of 13C and 127I- in several vesicles was observed after stimulation. Thus, chemical visualization shows transient opening of vesicles to the exterior of the cell without full release the dopamine cargo. We present a direct calculation for the fraction of neurotransmitter release from combined imaging data. The average vesicular release is 60% of the total catecholamine. An important observation is that extracellular molecules can be introduced to cells during the partial exocytotic release process. This nonendocytic transport process appears to be a general route of entry that might be exploited pharmacologically. © 2022 The Authors. Published by American Chemical Society.
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| 7. |
- Chapman, Henry N, et al.
(author)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Journal article (peer-reviewed)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 8. |
- Venkatakrishnan, Vignesh, 1987, et al.
(author)
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Novel inhibitory effect of galectin-3 on the respiratory burst induced by Staphylococcus aureus in human neutrophils
- 2023
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In: Glycobiology. - : OXFORD UNIV PRESS INC. - 1460-2423 .- 0959-6658. ; 33:6, s. 503-511
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Journal article (peer-reviewed)abstract
- Among the responders to microbial invasion, neutrophils represent the earliest and perhaps the most important immune cells that contribute to host defense with the primary role to kill invading microbes using a plethora of stored anti-microbial molecules. One such process is the production of reactive oxygen species (ROS) by the neutrophil enzyme complex NADPH-oxidase, which can be assembled and active either extracellularly or intracellularly in phagosomes (during phagocytosis) and/or granules (in the absence of phagocytosis). One soluble factor modulating the interplay between immune cells and microbes is galectin-3 (gal-3), a carbohydrate-binding protein that regulates a wide variety of neutrophil functions. Gal-3 has been shown to potentiate neutrophil interaction with bacteria, including Staphylococcus aureus, and is also a potent activator of the neutrophil respiratory burst, inducing large amounts of granule-localized ROS in primed cells. Herein, the role of gal-3 in regulating S. aureus phagocytosis and S. aureus-induced intracellular ROS was analyzed by imaging flow cytometry and luminol-based chemiluminescence, respectively. Although gal-3 did not interfere with S. aureus phagocytosis per se, it potently inhibited phagocytosis-induced intracellular ROS production. Using the gal-3 inhibitor GB0139 (TD139) and carbohydrate recognition domain of gal-3 (gal-3C), we found that the gal-3-induced inhibitory effect on ROS production was dependent on the carbohydrate recognition domain of the lectin. In summary, this is the first report of an inhibitory role of gal-3 in regulating phagocytosis-induced ROS production.
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| 9. |
- Yau, Estelle, et al.
(author)
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Global Sensitivity Analysis of the Rodgers and Rowland Model for Prediction of Tissue: Plasma Partitioning Coefficients: Assessment of the Key Physiological and Physicochemical Factors That Determine Small-Molecule Tissue Distribution
- 2020
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In: AAPS Journal. - : Springer Nature. - 1550-7416. ; 22:2, s. 1-13
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Journal article (peer-reviewed)abstract
- In physiologically based pharmacokinetic (PBPK) modelling, the large number of input parameters, limited amount of available data and the structural model complexity generally hinder simultaneous estimation of uncertain and/or unknown parameters. These parameters are generally subject to estimation. However, the approaches taken for parameter estimation vary widely. Global sensitivity analyses are proposed as a method to systematically determine the most influential parameters that can be subject to estimation. Herein, a global sensitivity analysis was conducted to identify the key drug and physiological parameters influencing drug disposition in PBPK models and to potentially reduce the PBPK model dimensionality. The impact of these parameters was evaluated on the tissue-to-unbound plasma partition coefficients (Kpus) predicted by the Rodgers and Rowland model using Latin hypercube sampling combined to partial rank correlation coefficients (PRCC). For most drug classes, PRCC showed that LogP and fraction unbound in plasma (fup) were generally the most influential parameters for Kpu predictions. For strong bases, blood:plasma partitioning was one of the most influential parameter. Uncertainty in tissue composition parameters had a large impact on Kpu and Vss predictions for all classes. Among tissue composition parameters, changes in Kpu outputs were especially attributed to changes in tissue acidic phospholipid concentrations and extracellular protein tissue:plasma ratio values. In conclusion, this work demonstrates that for parameter estimation involving PBPK models and dimensionality reduction purposes, less influential parameters might be assigned fixed values depending on the parameter space, while influential parameters could be subject to parameters estimation.
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| 10. |
- Lisney, Thomas J., et al.
(author)
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Using electroretinograms to assess flicker fusion frequency in domestic hens Gallus gallus domesticus
- 2012
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In: Vision Research. - : Elsevier BV. - 0042-6989 .- 1878-5646. ; 62, s. 125-133
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Journal article (peer-reviewed)abstract
- The assessment of flicker fusion frequency (FFF), the stimulus frequency at which a flickering light stimulus can no longer be resolved and appears continuous, and critical flicker fusion frequency (CFF; the highest frequency at any light intensity that an observer can resolve flicker) are useful methods for comparing temporal resolution capabilities between animals. Behavioural experiments have found that average CFFs in domestic chickens (Gallus gallus domesticus) are in the range of ca. 75-87 Hz, measured in response to full spectrum (i.e. white light plus UV) stimuli. In order to examine whether the chicken retina is able to detect flicker at higher frequencies, we used electroretinograms (ERGs) to assess FFF/CFF in adult hens from two commercial genotypes, Lohmann Selected Leghorns (LSLs) and Lohmann Browns (LBs). ERGs were recorded in response to flickering light at ten full spectrum light intensities ranging from 0.7 to 2740 cd m(-2). Two methods were used to determine FFF/CFF from the ERG recordings and these methods yielded very similar results, with average FFF ranging from ca. 20 Hz at 0.7 cd m(-2) to an average CFF of ca. 105 Hz at 2740 cd m(-2). In some individuals, CFFs of 118-119 Hz were recorded. The Intensity/FFF (I/FFF) curves are double-branched with a break point representing the rod-cone transition occurring between 2.5 and 5.9 cd m(-2). No significant differences in the I/FFF curves were found between the two genotypes. At stimulus light intensities >250 cd m(-2), the ERG-derived FFF and CFF values are all higher than those from behavioural studies using the same stimuli. Although hens do not appear to be able to consciously perceive flicker above approximately 90 Hz, the finding that the ERG responses are able to remain in phase with light flickering at frequencies >100 Hz means that the retinae of domestic poultry housed in artificial light conditions may be able to resolve flicker from fluorescent lamps. As range of detrimental effects have been reported in humans as a result of exposure to such "invisible flicker", the possibility exists that flicker from fluorescent lamps also acts as stressor in domesticated birds.
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