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Methane Production by Methanogens In Simulated Subsurface Martian Environments
Methane has a typical atmospheric photochemical lifetime of ∼300 years on Mars, making contemporary reported detections (and non-detections) of methane a fiercely debated topic, due to the potential need for a present-day source. On Earth, most methane is produced by methanogenic microbes present in, e.g., ruminants, wetlands, lakes and permafrost. Of the four metabolic pathways on Earth, the hydrogenotrophic pathway is the most common, utilising CO2 and H2 as substrates. Both gases are present on Mars, plus liquid water and essential elements (CHNOPS) that are requirements for life, and organics. Surface conditions on Mars are sterilising, however, the temperature and pressure of the subsurface are potentially favourable to life and provide a shield to sterilising surface conditions, and are thus a possible habitat for methanogens. A meta-analysis was
conducted, motivated by these subsurface parameters, that redefined the statistical representation for several growth parameters for all type-strains of methanogens and analysed multiple parameters
simultaneously across multiple categories (e.g. metabolism), showing that the optimal average conditions in which to grow methanogens would be a meso-temperate (20 to 39◦C), hypersaline and slightly acidic environment. Two martian subsurface environments were simulated to determine whether environmental or chemical factors are inhibitory to methanogenesis. (1) Methanoculleus marisnigri was grown in a custom-built, high-pressure manifold at 60 bar and 25◦C to simulate the subsurface of Mars, although no methane was produced, due to a technical issue resulting in oxygenated medium. However, some cells survived five weeks of oxygenation. (2) Methanothermococcus okinawensis was grown in a simulated chemical environment at 1 bar and 60◦C, that included a regolith simulant, a proposed martian brine and a Mars-relevant organic source (carbonaceous chondrite). The simulated parameters of the chemical environment of subsurface Mars were not inhibitory to hydrogenotrophic methanogenesis, suggesting it is feasible (from a metabolic perspective) that subsurface methanogens could be producing contemporary methane on Mars
Physical modelling of DMFC performance heterogeneities and the recovery of reversible cathode degradation
In this work, a transient multiphase DMFC model in 2D has been developed with the aim to describe the physical processes inside a DMFC single cell with a focus on performance heterogeneities along the channel. The model featured the spatial discretisation of
the ACL and CCL, which proved essential for the investigation of local inhomogeneities in the cell as well as for understanding transient phenomena during the recovery of reversible cathode degradation.
The model has been thoroughly validated against experimental performance data from a macro-segmented cell, which also included impedance spectra as well as the overall methanol and water crossover. The local resolution of the cell performance helped to verify the modelling of physical processes for mass and charge transport on the global as
well as on the local scale. Such a locally resolved model validation can hardly be found in literature. A very good agreement of the model prediction with the experimental data regarding humidity-related phenomena inside the DMFC cathode as well as general mass transport
phenomena and their effect on the cell performance under various operating conditions has been achieved with just one set of model parameters. The simulation study has highlighted the complex interplay of gas and liquid phase inside the DMFC and its impact on material properties and transport processes inside the cell. Furthermore, the importance of interface processes at the PEM boundaries to the catalyst layers as well as inside the catalyst layer on the local cell behaviour could be shown. For the species transport inside the compositional fuel cell structure, the formation and presence of liquid water plays a dominant role. It could be shown that phase-dependent sorption processes at the DMFC membrane interface fundamentally determine the water
transfer from anode to cathode and consequently the distribution of liquid water inside the cell. The impact of the individual humidity-related transport mechanisms has been evaluated step by step in this work. The ionomer phases in the cell, i.e the bulk membrane as well as the ionomer thin-film in the CL, proved to be highly sensitive to the local water activity and phase conditions and exhibit a strong resistance to proton transport in the areas of the DMFC with poor humidification. Mass transport resistances in the heterogeneous CL microstructure due to liquid water accumulation could be successfully modelled on the continuum scale by integrating an ionomer-film model.
The validated cell model also proved fit to describe the transient processes within the cell during the recovery of reversible cathode degradation during a refresh cycle. Without any adjustments in the model, the dynamics in the local potential for electrons and ions as well as in the membrane in dependence on the conditions inside the DMFC were predicted with a very good accuracy in anode and cathode.
With its spatial resolution of the CCL, the model rendered a visualisation of the heterogeneous distribution of species and reactions in the course of the refresh sequence. Also the local formation of H2 in the DMFC anode during the absence of oxygen in the CCL could be successfully described with the model.
The simulation study showed that the methanol crossover through the DMFC membrane and the resulting methanol oxidation reactions in the CCL play an essential role during the refresh cycle. Especially the secondary, H2O-activated MOR reaction path in the CCL under oxygen-depleted conditions was identified as relevant for the achievement of
low local potentials in the DMFC cathode and thus for the full recovery of the cathode ECSA during the air break. A variation of air stop scenarios was simulated with the model and the impact of the local species distribution on the electrochemical processes within the cell was studied.
The variations included settings where the PtOx-surface species in the CCL would get entirely or only partially reduced. In a simulation of a longer air stop, the effect of methanol accumulation during the air
stop period could be visualised and its impact on the heterogeneities in the local cell voltage could be explained. Also the processes during an incomplete air stop, where oxygen is only partially depleted in the cathode catalyst layer, could be shown with the model. Two air stop variants resulting in a full recovery of the cathode ECSA were identified and examined. The simulation showed that while a flush with pure nitrogen on the one hand swiftly enables a full reduction of the platinum oxides in the CCL, it on the other hand limits the re-humidification of the membrane. By improving the model’s refresh boundary conditions, i.e. further limiting the diffusion of oxygen into the cell from external
during the air stop period (and thus presumably approximating the experimental conditions more closely), the best results in terms of platinum oxide reduction and ionomer rehydration were achieved
Optical Measurement of Airborne Particles on Unmanned Aircraft
Aerosols and clouds are persistent causes of uncertainty in climate and weather models,
which is due to their heterogeneous suspension and occurrence within the atmosphere, and
complex interactions which are chaotic and exist on small scales. Unmanned aerial vehicles
(UAVs) have grown in popularity, and are becoming more commonly used for general atmospheric
measurement, particularly measurement of aerosols and clouds. This thesis presents
and evaluates a synergy between two UAVs, a multi-rotor: the UH-AeroSAM octocopter and
a fixed-wing: the FMI-Talon, and an optical particle instrument: the Universal Cloud and
Aerosol Sounding System. Computational fluid dynamics with Lagrangian particle tracking
(CFD-LPT) was used as a tool for the characterisation of the velocity fields and particle
trajectories around both UAVs. In both instances CFD-LPT was used to develop an operational
envelope, with particular attention to angle of attack constraints and size distribution
perturbation, for the UAV – instrument synergy. UCASS was the first open path instrument
to be used on a UAV, and a good case has been made for its continued use, particularly
on fixed-wing UAVs, which exhibit less complex aerodynamics and superior stability in the
induced sampling airflow through the instrument
4D FLOW CMR in congenital heart disease
This thesis showed that the use of a cloud-based reconstruction applicationwith advanced eddy currents correction, integrated with interactiveimaging evaluation tools allowed for remote visualization and interpretationof 4D flow data and that was sufficient for gross visualizationof aortic valve regurgitation. Further, this thesis demonstrated that bulkflow and pulmonary regurgitation can be accurately quantified using 4Dflow imaging analyzed. Peak systolic velocity over the pulmonary valvemay be underestimated. However, the measurement of peak systolicvelocity can be optimized if measured at the level of highest velocity inthe pulmonary artery. Also correlated against invasive measurements (inan animal model), this thesis shows that aorta flow and pulmonary flowcan be accurately and simultaneously measured by 4D flow MRI.When applied in clinical practice, 4D flow has extra advantages, of beingable to visualize flow pattern, vorticity and to predict aortic growth. InASD patients it can measure shunt volume directly following the septumframe by frame. In Fontan patients in can visualize better than standardMRI the Fontan circuit and it can measure flow at multiple points alongthe Fontan circuit. We observed in our Fontan population that shunt lesionswere very common, most of the time via veno-venous collaterals.Further using advanced computations, we showed that WSS angle wasthe only independent predictor of aortic growth in BAV patients. We alsoshowed the feasibility of GLS analysis on 4D flow MRI and presented anintegrative approach in which flow and functional data are acquired inone sequence.From the technical point of view, 4D flow MRI has proved to complementthe traditional components of the standard cardiac MR exams, enablingin-depth insights into hemodynamics. At this moment it proved its addedvalue, but in most of the cases it is not able yet to replace the standardexam. This is still due to long scanning times and relatively longpost-processing times.<br/
Development of DNA origami-based tools for cancer treatment
DNA has been used as material for the assembly of objects at different scales. Particularly,
the introduction of DNA origami has been inspiring the design and construction of many
different versions of DNA nanostructures for, especially, biomedical applications. DNA
origami nanostructures are showing unique advantages, including structural homogeneity,
addressability, biocompatibility, and capacity to carry pharmaceuticals or biomolecules, for
the development of future cancer therapeutics. To fully unlock their potential, however, they
need to be tailored based on physiological and pathological molecular environments which
they interact with. In this thesis, we develop a few functionalized DNA origami
nanostructures to investigate specific questions of cancer biology or to overcome challenges
of cancer immunotherapy.
In PAPER I, we compare the physical characteristics of a compact lattice-based rod and a
wireframe-styled rod and revealed how they interact with cell spheroid tissue models
(CSTMs). Our data indicate that the wireframe structure, which has a lower local material
density in design, has higher local deformability than the lattice-based structure. We reveal
that these physical differences play important roles in the interaction between DNA origami
nanostructures and human cancer cells, showing that wireframe rods are more likely to stay
on the cell membrane, rather than being internalized, and this facilitates their deeper
penetration into CSTMs. These observations tell us that DNA origami design methods should
be carefully considered in DNA origami-based drug delivery applications.
In PAPER II, to explore the nanoscale clustering effect of death receptor 5 (DR5) on human
breast cancer cells, we develop flat sheet-like DNA origami nanostructures and functionalize
them with the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-
mimicking peptides which can recognize and bind with DR5, in differently sized hexagonal
patterns. Experiments of cancer cells and DNA origami incubation show that apoptosis can
be precisely controlled when we vary the size of peptide patterns between the range of 6 nm
to 26 nm. Interestingly, our data indicate that the interpeptide distance for effective apoptosis
is sub-10 nm. Our findings highlight the potency of precise spatial patterning of ligands on
apoptosis signaling.
In PAPER III, to limit cytotoxicity of the sub-10 nm peptide pattern, which we have screened
out in the work of PAPER II, only to tumors, we design a three-dimensional DNA origami
nanostructure containing a 6 nm wide and 12 nm deep cavity and use it to hide but display
the peptide pattern according to the acidity of the tissue microenvironment. Peptide display
is achieved by the protonation-triggered formation of the DNA triplex, during which a singlestranded DNA extension from the complementary strand of a mini-scaffold DNA wraps back to the mini-scaffold duplex. By varying the AT percentage in the mini-scaffold DNA, we can
control the triggering pH for the formation of the DNA triplex. We demonstrate the safety of
the DNA origami under physiological pH (pH 7.4) for non-cancer cells and its cytotoxicity
to cancer cells under the pH of solid tumors (pH 6.5).
In PAPER IV, to mimic functions of T cell engagers but mitigate corresponding adverse
effects mainly caused by “on-target, off-tumor” immune activation and cytokine release
syndrome, we develop a wireframe DNA origami based-nanorobot: a double-layered barrellike
origami with antibodies inside under its closed status. When the DNA nanorobot presents
as its open configuration, internal antibodies get exposed, functioning to engage T cells with
cancer cells and activate T cell immune killing. By spatiotemporally controlling the opening
of the DNA nanorobot via signals from cancer cells, tumor microenvironment, or external
stimulus, we aim to selectively redirect the cytotoxicity of T cells to solid cancers and
substantially mitigate corresponding adverse effects of current T cell engagers-based cancer
immunotherapy
Endogenous UMIs as quantifiable reporter elements – validation studies & applications in rAAV vectorology
In the creation of recombinant adeno-associated viral (rAAV) vectors, terminal DNA elements known ITRs (inverted terminal repeats) of the direct the intracellular synthesis and packaging of nonviral DNA. The need to clonally amplify ITR sequences in one form or another thereby underlies the existence of all rAAV clinical products and research materials worldwide. Their tendency to form strong nonduplex structures raises problems. The genetic precursors to rAAV vectors – typically prokaryotic plasmids – are known to possess heterogenous ITR sequences as a result of replicational instability, the effects of which on vector yield and efficacy are unclear and have not been systematically explored. To shed much-needed light on this decades-old problem, I utilised unique molecular identifiers (UMIs) as reporter elements for different rAAV plasmid preparations, so that massively parallel sequencing could be used to analyse their DNA and RNA derivatives through the course of production and in vivo gene transfer. The range of vector potencies observed, while not calamitous, definitively erases the notion that this problem can be further overlooked.
The success of this unconventional strategy proved to be an equally notable outcome, offering unprecedented insights into population kinetics, and achieving quantitative consistency between biological replicates comparable to q/dPCR measurement replicates of single samples. This triggered concerted efforts to formally investigate the capabilities of UMIs used in this fashion. The probabilistic principles underlying the technique were formalised and empirically validated, confirming precision capabilities akin if not superior to dPCR and qPCR at equivalent levels of stringency. Experiments also revealed a pattern of measurement bias with potentially adverse implications for other areas of count analysis including differential gene expression
TROPOMI/S5P Total Column Water Vapor validation against AERONET ground-based measurements
Water vapor plays an important role in the greenhouse effect, rendering it an atmospheric constituent that requires continuous and global monitoring by different types of remote sensing instruments. The TROPOspheric Monitoring Instrument Sentinel-5 Precursor (TROPOMI/S5P) Total Column Water Vapor (TCWV) is a new product retrieved from the visible blue spectral range (435–455 nm), using an algorithm that was originally developed for the GOME-2/MetOp sensors. For the purposes of this work, 2.5 years of continuous satellite observations at high spatial resolution are validated against co-located (in space and in time) precipitable water Level 2.0 (quality-assured) ground-based measurements from the NASA AERONET (AErosol RObotic NETwork). The network uses Cimel Sun photometers located at approximately 1300 stations globally to monitor precipitable water among other products. Based on data availability, 369 of the stations were used in this study. The two datasets, satellite- and ground-based, were co-located, and the relative differences of the comparisons were calculated and statistically analyzed. The Pearson correlation coefficient of the two products is found to be 0.91, and the mean bias of the overall relative percentage differences is of the order of −2.7 %. For the Northern Hemisphere midlatitudes (30–60∘ N), where the density of the ground-based stations is high, the mean relative bias was found to be −1.8 %, while in the tropics (±15∘) the TROPOMI TCWV product has a relative dry bias of up to −10 %. The effect of various algorithm and geophysical parameters, such as air mass factor, solar zenith angle, clouds and albedo, is also presented and discussed. It was found that the cloud properties affect the validation results, leading the TCWV to a dry bias of −20 % for low cloud heights (cloud top pressure (CTP) >800 hPa). Moreover, cloud albedo introduces a wet bias of 15 % when it is below 0.3 and a dry bias up to −25 % when the clouds are more reflective. Overall, the TROPOMI/S5P TCWV product, on a global scale and for moderate albedo and cloudiness, agrees well at -2.7±4.9 % with the AERONET observations but probably within about −8 % to −13 % with respect to the “truth”.</p
RaBit: Parametric Modeling of 3D Biped Cartoon Characters with a Topological-consistent Dataset
Assisting people in efficiently producing visually plausible 3D characters
has always been a fundamental research topic in computer vision and computer
graphics. Recent learning-based approaches have achieved unprecedented accuracy
and efficiency in the area of 3D real human digitization. However, none of the
prior works focus on modeling 3D biped cartoon characters, which are also in
great demand in gaming and filming. In this paper, we introduce 3DBiCar, the
first large-scale dataset of 3D biped cartoon characters, and RaBit, the
corresponding parametric model. Our dataset contains 1,500 topologically
consistent high-quality 3D textured models which are manually crafted by
professional artists. Built upon the data, RaBit is thus designed with a
SMPL-like linear blend shape model and a StyleGAN-based neural UV-texture
generator, simultaneously expressing the shape, pose, and texture. To
demonstrate the practicality of 3DBiCar and RaBit, various applications are
conducted, including single-view reconstruction, sketch-based modeling, and 3D
cartoon animation. For the single-view reconstruction setting, we find a
straightforward global mapping from input images to the output UV-based texture
maps tends to lose detailed appearances of some local parts (e.g., nose, ears).
Thus, a part-sensitive texture reasoner is adopted to make all important local
areas perceived. Experiments further demonstrate the effectiveness of our
method both qualitatively and quantitatively. 3DBiCar and RaBit are available
at gaplab.cuhk.edu.cn/projects/RaBit.Comment: CVPR 2023, Project page: https://gaplab.cuhk.edu.cn/projects/RaBit
Strategies to Improve Antineoplastic Activity of Drugs in Cancer Progression
The aim of this Special Issue is to collect reports regarding all the recent strategies, directed at the improvement of antineoplastic activity of drugs in cancer progression, engaging all the expertise needed for the development of new anticancer drugs: medicinal chemistry, pharmacology, molecular biology, and computational and drug delivery studies
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