Effect of macromolecular crowding in DNA folding

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2022, Tutora: Isabel Pastor del CampoThe effect of macromolecular crowding has already been studied in protein folding, but there are almost no precedents about its impact on the DNA folding. In this work, we have studied the folding of a DNA hairpin in the presence of different concentrations of PEG as a crowder agent using optical tweezers. The obtained results suggest that macromolecular crowding impacts in the studied DNA hairpin folding/unfolding process by varying its folding free energy and its coexistence force, becoming a more stable structure. Nevertheless, further studies are required to collect more data and explore other conditions to infer consistent conclusions on this topi

Implementation and automatization of validation tests for the simulation of Nuclear Medicine studies

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Niñerola Baizán, Aida, Aguiar Fernández, Pablo, Silva-Rodríguez, JesúsNowadays, Nuclear Medicine techniques are of great importance in the clinical practice, especially in Neurology and Oncology, for both Diagnostics and Treatment. Focusing on imaging techniques, quantitative methods have shown to be an alternative to the traditional interpreting of images to give support to the clinician for a more accurate diagnostic. The lack of ground-truths has difficulted the implementation of these quantitative methods in the clinical practice, and consequently the use of simulation has raised as a solution for obtaining reference images. In particular, SimPET is a platform that aims to simulate and reconstruct Positron Emission Tomograph (PET) images while being able to model any scanner by introducing its parameters. The introduction of a new scanner requires a validation process to ensure it works in accordance of the manufacturer’s specifications. To do so, the NEMA protocols are a set of tests to allow a comparison with these specifications. In this work we are developing an implementation in Python and automatization of these tests to allow the easy validation of new scanners for SimPET. Four of the five specified tests were implemented, concerning the Spatial Resolution and the Sensitivity of the tomograph, and the Image Quality and the fraction of Scattering of the reconstructed images. The results were tested and compared with the experimental ones of the Discovery ST scanner. The results show that the values of Resolution and Sensitivity do not strictly coincide with the experimental ones, and further work on tuning the adjustments of the simulation need to be done. For the Image Quality test we obtained parameters that seem to be in accordance with the theoretical behaviour, but the lack of comparative results does not allow us to extract relevant conclusions. In the case of the Scatter Fraction test, we have shown that the suggested method does not work for very low activities. Thus, due to time and computational limitations further work needs to be done in the development of the techniques, but this work has shown the feasibility of its implementation

Extending calibration-free force measurements to optically-trapped rod-shaped samples

Optical trapping has become an optimal choice for biological research at the microscale due to its non-invasive performance and accessibility for quantitative studies, especially on the forces involved in biological processes. However, reliable force measurements depend on the calibration of the optical traps, which is different for each experiment and hence requires high control of the local variables, especially of the trapped object geometry. Many biological samples have an elongated, rod-like shape, such as chromosomes, intracellular organelles (e.g., peroxisomes), membrane tubules, certain microalgae, and a wide variety of bacteria and parasites. This type of samples often requires several optical traps to stabilize and orient them in the correct spatial direction, making it more difficult to determine the total force applied. Here, we manipulate glass microcylinders with holographic optical tweezers and show the accurate measurement of drag forces by calibration-free direct detection of beam momentum. The agreement between our results and slender-body hydrodynamic theoretical calculations indicates potential for this force-sensing method in studying protracted, rod-shaped specimens

Influence of experimental parameters on the laser heating of an optical trap

In optical tweezers, heating of the sample due to absorption of the laser light is a major concern as temperature plays an important role at microscopic scale. A popular rule of thumb is to consider that, at the typical wavelength of 1064 nm, the focused laser induces a heating rate of B = 1 degrees C/100 mW. We analysed this effect under different routine experimental conditions and found a remarkable variability in the temperature increase. Importantly, we determined that temperature can easily rise by as much as 4 degrees C at a relatively low power of 100 mW, for dielectric, non-absorbing particles with certain sets of specific, but common, parameters. Heating was determined from measurements of light momentum changes under drag forces at different powers, which proved to provide precise and robust results in watery buffers. We contrasted the experiments with computer simulations and obtained good agreement. These results suggest that this remarkable heating could be responsible for changes in the sample under study and could lead to serious damage of live specimens. It is therefore advisable to determine the temperature increase in each specific experiment and avoid the use of a universal rule that could inadvertently lead to critical changes in the sample

Bounds on the capacity and power of quantum batteries

Quantum batteries, composed of quantum cells, are expected to outperform their classical analogs. The origin of such advantages lies in the role of quantum correlations, which may arise during the charging and discharging processes performed on the battery. In this theoretical work, we introduce a systematic characterization of the relevant quantities of quantum batteries, i.e., the capacity and the power, in relation to such correlations. For these quantities, we derive upper bounds for batteries that are a collection of non-interacting quantum cells with fixed Hamiltonians. The capacity, that is, a bound on the stored or extractable energy, is derived with the help of the energy-entropy diagram, and this bound is respected as long as the charging and discharging processes are entropy preserving. While studying power, we consider a geometric approach for the evolution of the battery state in the energy eigenspace of the battery Hamiltonian. Then, an upper bound for power is derived for arbitrary charging process, in terms of the Fisher information and the energy variance of the battery. The former quantifies the speed of evolution, and the latter encodes the non-local character of the battery state. Indeed, due to the fact that the energy variance is bounded by the multipartite entanglement properties of batteries composed of qubits, we establish a fundamental bound on power imposed by quantum entanglement. We also discuss paradigmatic models for batteries that saturate the bounds both for the stored energy and the power. Several experimentally realizable quantum batteries, based on integrable spin chains, the Lipkin-Meshkov-Glick and the Dicke models, are also studied in the light of these newly introduced bounds.We acknowledge the Spanish Ministry MINECO (National Plan 15 Grant: FISICATEAMO No. FIS2016-79508- P, SEVERO OCHOA No. SEV-2015-0522, FPI), European Social Fund, Fundació Cellex, Generalitat de Catalunya (AGAUR Grant No. 2017 SGR 1341 and CERCA/Program), EU FEDER, ERC AdG OSYRIS, EU FETPRO QUIC, and the National Science Centre, Poland-Symfonia Grant No. 2016/20/W/ST4/00314. M.N.B. gratefully acknowledges financial supports from Max-Planck Institute fellowship and from SERB-DST, Government of India, and A.R. thanks supports from CELLEX-ICFO-MPQ fellowship. We also thank M. Polini for fruitful discussions and for drawing our attention to Ref. [34], and an anonymous referee for motivating the finding of Corollary.Postprint (author's final draft

Optimization of atmospheric transport models on HPC platforms

The performance and scalability of atmospheric transport models on high performance computing environments is often far from optimal for multiple reasons including, for example, sequential input and output, synchronous communications, work unbalance, memory access latency or lack of task overlapping. We investigate how different software optimizations and porting to non general-purpose hardware architectures improve code scalability and execution times considering, as an example, the FALL3D volcanic ash transport model. To this purpose, we implement the FALL3D model equations in the WARIS framework, a software designed from scratch to solve in a parallel and efficient way different geoscience problems on a wide variety of architectures. In addition, we consider further improvements in WARIS such as hybrid MPI-OMP parallelization, spatial blocking, auto-tuning and thread affinity. Considering all these aspects together, the FALL3D execution times for a realistic test case running on general-purpose cluster architectures (Intel Sandy Bridge) decrease by a factor between 7 and 40 depending on the grid resolution. Finally, we port the application to Intel Xeon Phi (MIC) and NVIDIA GPUs (CUDA) accelerator-based architectures and compare performance, cost and power consumption on all the architectures. Implications on time-constrained operational model configurations are discussed.We thank M.S. Osores from the Argentinean National Scientific and Technical Research Council (CONICET) for providing hourly column heights for the Cordón Caulle eruption simulation and the constructive comments from two anonymous reviewers. This work was supported by NVIDIA through the UPC/BSC GPU Center of Excellence, and the Spanish Ministry of Science and Technology through the TIN2012-34557 project. Finally, we dedicate this work to our colleague and co-author Nacho Navarro, who sadly passed away during the reviewing process.Peer ReviewedPostprint (author's final draft

Understanding Optical Trapping Phenomena: a Simulation for Undergraduates

Optical trapping is an attractive and multidisciplinary topic that has become the center of attention to a large number of researchers. Moreover, it is a suitable subject for advanced students that requires a knowledge of a wide range of topics. As a result, it has been incorporated into some syllabuses of both undergraduate and graduate programs. In this paper, basic concepts in laser trapping theory are reviewed. To provide a better understanding of the underlying concepts for students, a Java application for simulating the behavior of a dielectric particle trapped in a highly focused beam has been developed. The program illustrates a wide range of theoretical results and features, such as the calculation of the force exerted by a beam in the Mie and Rayleigh regimes or the calibration of the trap stiffness. Some examples that are ready to be used in the classroom or in the computer lab are also supplied

Holographic optical tweezers combined with back-focal-plane displacement detection

A major problem with holographic optical tweezers (HOTs) is their incompatibility with laser-based position detection methods, such as back-focal-plane interferometry (BFPI). The alternatives generally used with HOTs, like high-speed video tracking, do not offer the same spatial and temporal bandwidths. This has limited the use of this technique in precise quantitative experiments. In this paper, we present an optical trap design that combines digital holography and back-focal-plane displacement detection. We show that, with a particularly simple setup, it is possible to generate a set of multiple holographic traps and an additional static non-holographic trap with orthogonal polarizations and that they can be, therefore, easily separated for measuring positions and forces with the high positional and temporal resolutions of laser-based detection. We prove that measurements from both polarizations contain less than 1% crosstalk and that traps in our setup are harmonic within the typical range. We further tested the instrument in a DNA stretching experiment and we discuss an interesting property of this configuration: the small drift of the differential signal between traps

Characterization of intra- and inter-host norovirus P2 genetic variability in linked individuals by amplicon sequencing

Noroviruses are the main cause of epidemics of acute gastroenteritis at a global scale.Although chronically infected immunocompromised individuals are regarded as potential reservoirs for the emergence of new viral variants, viral quasispecies distribution and evolution patterns in acute symptomatic and asymptomatic infections has not been extensively studied. Amplicons of 450 nts from the P2 coding capsid domain were studied using nextgeneration sequencing (454/GS-Junior) platform. Inter-host diversity between symptomatic and asymptomatic acutely infected individuals linked to the same outbreak as well as their viral intra-host diversity over time were characterized. With an average of 2848 reads per sample and a cutoff frequency of 0.1%, minor variant haplotypes were detected in 5 out of 8 specimens. Transmitted variants could not be confirmed in all infected individuals in one outbreak. The observed initial intra-host viral diversity in asymptomatically infected subjects was higher than in symptomatic ones. Viral quasispecies evolution over time within individuals was host-specific, with an average of 2.8 nt changes per day (0.0062 changes per nucleotide per day) in a given symptomatic case. Nucleotide polymorphisms were detected in 28 out of 450 analyzed nucleotide positions, 32.14% of which were synonymous and 67.86% were non-synonymous. Most observed amino acid changes emerged at or near blockade epitopes A, B, D and E. Our results suggest that acutely infected individuals, even in the absence of symptoms, which go underreported and may enhance transmission, may contribute to norovirus genetic variability and evolution

Involvement of Mechanical Cues in the Migration of Cajal-Retzius Cells in the Marginal Zone During Neocortical Development

Emerging evidence points to coordinated action of chemical and mechanical cues during brain development. At early stages of neocortical development, angiogenic factors and chemokines such as CXCL12, ephrins, and semaphorins assume crucial roles in orchestrating neuronal migration and axon elongation of postmitotic neurons. Here we explore the intrinsic mechanical properties of the developing marginal zone of the pallium in the migratory pathways and brain distribution of the pioneer Cajal-Retzius cells. These neurons are generated in several proliferative regions in the developing brain (e.g., the cortical hem and the pallial subpallial boundary) and migrate tangentially in the preplate/marginal zone covering the upper portion of the developing cortex. These cells play crucial roles in correct neocortical layer formation by secreting several molecules such as Reelin. Our results indicate that the motogenic properties of Cajal-Retzius cells and their perinatal distribution in the marginal zone are modulated by both chemical and mechanical factors, by the specific mechanical properties of Cajal-Retzius cells, and by the differential stiffness of the migratory routes. Indeed, cells originating in the cortical hem display higher migratory capacities than those generated in the pallial subpallial boundary which may be involved in the differential distribution of these cells in the dorsal-lateral axis in the developing marginal zone