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Abstract: Delivery of electrical energy for sensing or therapeutic purposes often involves electrochemical phenomena at the electrode-electrolyte solution interface. Release of gaseous bubbles that accompanies delivery of pulsed electric fields to tissues in applications such as electrochemotherapy of tumours and irreversible electroporation or pulsed field ablation in cardiac electrophysiology needs to be understood and characterized. We present an in vitro study using pulsed field delivery into saline, employing multiple different treatment protocols, two electrode geometries (pair of needles and a modified RF catheter), and two imaging systems to elucidate the complex relationship between the electrical treatment protocol, temperature changes at and around the electrodes, and gas release due to pulse delivery. Our primary objective was to identify the key parameters responsible for bubble formation and to highlight the importance of the treatment parameters and their interplay – ranging from the temperature to appropriate choice of electrode geometry, and, most importantly, to the choice of the treatment protocol. We found that bubbles originating from electrochemical reactions are more prevalent in monophasic pulsing protocols, whereas in high frequency biphasic pulsing protocols the bubbles are mainly caused by boiling of the medium. Degassing of liquid due to lower solubility of gasses at elevated temperatures does seems to play a role, though a minor one. We also observed that bubbles caused by boiling collapse very rapidly, whereas electrochemically produced bubbles or those produced through degassing appear to have longer lifetimes. Therefore, the treatment protocols most suited to minimizing gas release are biphasic trains of short ($\mu$s) pulses with a significant inter-pulse delay (i.e. low duty cycle) to prevent excessive heating. Moreover, electrodes must be designed to avoid high local current densities. Our findings have broad implications extending from lab-on-achip cell electroporation devices to intracorporeal pulsed field applications in the cardiovascular system, particularly pulsed field ablation procedures.
Keywords: pulsed field ablation, gas release, electrochemistry, Joule heating, water phase transition
Published in DiRROS: 10.04.2025; Views: 92; Downloads: 42
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Keywords: additive manufacturing, Ti6Al4V, microstructure, corrosion, mechanical properties
Published in DiRROS: 10.04.2025; Views: 85; Downloads: 39
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Abstract: Understanding differences in life-history outcomes under variable abiotic conditions is essential for understanding species coexistence. At middle elevations, a mosaic of available sets of abiotic conditions could allow highland and lowland species of the same ecological guild to overlap. Therefore, these sites are excellent to study the influence of abiotic conditions on life history and, thus, spatial overlap patterns of competing species. To test differences in life-history outcomes, we selected a pair of closely related lacertids, Iberolacerta horvathi and Podarcis muralis, with an overlapping geographical range but a contrasting elevational distribution. To assess how abiotic and biotic factors contribute to the realized niches of both species, we first built dynamic energy budget (DEB) models for each species based on available functional and life-history data. Then, we used a mechanistic modelling framework (NicheMapR) to simulate the microclimatic conditions at 15 study sites across an elevational gradient and performed whole life-cycle simulations for both species to compare egg development times, lifespans, reproductive years, mean yearly basking and foraging times and yearly fecundity in syntopy and allotopy along the elevational gradient. Our simulations show that the variability of abiotic conditions along an elevational gradient affects life-history traits of both species. We found strong effects of species and elevation on life-history outcomes such as longevity, activity and fecundity. We also observed the effects of syntopy/allotopy on egg development times, activity and reproductive output. In addition, we found a significant interplay between elevation and species impacting fecundity where occupying higher elevation habitats resulted in a more pronounced reduction in fecundity in P. muralis. Furthermore, using two different thermal preferences for spring and summer, we show that some physiological and reproductive traits change with seasonal changes in thermal preferences. Based on our simulations, we conclude that the intermediate elevations that harbour the majority of syntopic populations exhibit high environmental variability that is likely facilitating species coexistence. Since our model predictions support that the current elevational distribution of the species is not only affected by abiotic factors, this suggests that past historical contingencies might have also played a significant role. Our study provides a framework using mechanistic models to understand current distribution patterns of two interacting species by comparing life-history differences between species based on responses to changing abiotic conditions along an elevation gradient.
Keywords: dynamic energy budget, ectotherms, elevation, Lacertidae, life history, microclimate, syntopy
Published in DiRROS: 10.04.2025; Views: 72; Downloads: 30
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Abstract: Cell therapy product (CTP) developers face the significant challenge of developing appropriate potency tests for their CTPs. A review of the known potency tests used for the 31 United States Food and Drug Administration-approved CTPs (US FDA) can guide developers in designing effective potency tests for future CTPs. Data on these tests were primarily collected from publicly available regulatory documentation on the US FDA website (90%) as well as other sources (literature, company communications, etc.). Based on these data, an estimated 104 total potency tests have been used for the 31 CTPs. Of these, 33 are redacted (32%), leaving 71 non-redacted potency tests. On average, each CTP has 3.4 potency tests (standard deviation 2.0). The 71 non-redacted potency tests were categorized into 5 bins: “Viability and count” (37 tests, 52%), “Expression” (19 tests, 27%), “Bioassays” (7 tests, 7%), “Genetic modification” (6 tests, 9%) and “Histology” (2 tests, 3%). Measurements of gene or protein expression were used by 20 of the 31 CTPs (65%), and 19 CTPs (61%) used measurements of cell viability or cell count as a potency test. “Viability and count” and “Expression” are the two tests that have most often been used together for the same product, occurring for 16 CTPs (52%). It is unclear if bioassays are commonly used as potency tests since only 7 of 31 CTPs (23%) reported bioassays as potency tests. However, due to redactions, as many 24 (77%) CTPs could potentially have a bioassay as a potency test. Additionally, 26 of the 31 CTPs (84%) cite physicochemical assays (non-bioassays) as a potency test. This analysis of potency tests for approved CTPs provides valuable insights for developing potency tests for new CTPs.
Keywords: cell therapy product, potency, potency test, regenerative medicine
Published in DiRROS: 10.04.2025; Views: 68; Downloads: 33
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Keywords: organizacija znanosti, raziskovalna infrastruktura, odprti podatki, repozitoriji, področni repozitorij
Published in DiRROS: 10.04.2025; Views: 105; Downloads: 34
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