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Keywords = tiny-TIM

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17 pages, 1715 KB  
Article
Dynamic Responses of Cherry Tomatoes to Salinity Stress: Growth, SPAD, Sap Ion Regulation and Leachate Chemical Composition Across Developmental Stages
by Alfonso Llanderal, Malena Suleika Pincay-Solorzano, Said Bermúdez, Stanislaus Antony Ceasar and Pedro García-Caparros
Agronomy 2026, 16(15), 1450; https://doi.org/10.3390/agronomy16151450 - 31 Jul 2026
Viewed by 349
Abstract
Tomato production is highly affected by salt stress conditions, especially under protected cultivation systems using low-quality irrigation water. This study assessed the effects of increasing electrical conductivity (EC) levels of the nutrient solution (2, 4, 6, and 8 dS m−1) on [...] Read more.
Tomato production is highly affected by salt stress conditions, especially under protected cultivation systems using low-quality irrigation water. This study assessed the effects of increasing electrical conductivity (EC) levels of the nutrient solution (2, 4, 6, and 8 dS m−1) on growth, biomass distribution, RGB-based spectral indices, physiological traits, petiole sap composition, and leachate chemistry in tomato plants (Solanum lycopersicum cv. Tiny Tim) cultivated in containers within a bamboo nethouse under tropical conditions. The results obtained reported that increasing salinity significantly reduced fresh and dry biomass (61.72 and 61.55% respectively) across all plant organs, with fruits showing the highest sensitivity. Leaf area index (LAI), SPAD values, leaf nitrogen (N) concentration, leaf relative humidity (LRH), and water uptake also declined progressively under saline conditions. In contrast, root and leaf biomass allocation increased under the highest salinity level. Spectral analyses reported reductions in red and blue RGB components and normalized red and blue index values, while normalized green index increased under higher salinity levels. Petiole sap analysis showed a progressive accumulation of sodium (Na+) and chloride (Cl) together with reductions in nitrate (NO3-N) and potassium (K+) concentrations, particularly during the reproductive stage. In contrast, °Brix, calcium (Ca2+), and phosphorus (P) concentrations increased under salinity, particularly during the reproductive stage. Leachate analyses confirmed salt accumulation in the substrate and reduced plant water uptake. Overall, petiole sap analysis and RGB-based spectral indices provide a rapid, non-destructive, and cost-effective tool for the early detection of salinity stress in tomato, enabling timely irrigation and fertigation adjustments to improve crop performance and resource-use efficiency under saline conditions. Full article
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20 pages, 2521 KB  
Article
TIM-1 and Tiny-TIM as Robust In Vitro Models for Oral Biopharmaceutics: Evidence from an International Ring Study
by Connor O’Farrell, Robert Havenaar, Mark McAllister, Bart Hens, Richard Barker, Álvaro López Mármol, Andrea Ansari, Tom Ooms, Ronald Schilderink, Robert Schwabe, James Butler, Malgorzata Stróžyk, Tânia Martins Garcia, Dyko Minekus, Inese Sarcevica, Kieran Smith, Irena Tomaszewska, Eleanor Jones, Hannah Batchelor and Susann Bellmann
Pharmaceutics 2026, 18(4), 400; https://doi.org/10.3390/pharmaceutics18040400 - 24 Mar 2026
Viewed by 1771
Abstract
Background/Objectives: Biorelevant in vitro dissolution testing is used increasingly to predict complex mechanisms in the gastrointestinal (GI) tract that determine oral bioavailability. However, the limited use of non-compendial systems is driven by the lack of widely accepted, standardized validation frameworks. This ongoing gap [...] Read more.
Background/Objectives: Biorelevant in vitro dissolution testing is used increasingly to predict complex mechanisms in the gastrointestinal (GI) tract that determine oral bioavailability. However, the limited use of non-compendial systems is driven by the lack of widely accepted, standardized validation frameworks. This ongoing gap continues to restrict their adoption relative to United States Pharmacopeia (USP) apparatus. While the physiological relevance and biopredictive capabilities of the tiny-TIM and TIM-1 in vitro GI models have been demonstrated in previous studies, their inter-laboratory reproducibility has not been systematically established. Therefore, this international ring study evaluates the reproducibility of in vitro simulations of GI transit and absorption of paracetamol in fasted- and fed-state conditions in tiny-TIM and TIM-1. Methods: Three laboratories used TIM-1 and five used tiny-TIM to simulate oral administration of a 500 mg paracetamol solution to a healthy adult. Paracetamol solution was selected as a well-characterized and widely available BCS I compound to minimize formulation and solubility effects and focus on system performance, enabling the generation of a generic validation dataset for the reproducibility of TIM experiments. Results: Paracetamol bioaccessibility profiles were repeatable and reproducible (all pairwise f2 > 50). Maximum differences in total bioaccessible paracetamol were 0.9% (TIM-1) and 2.8% (tiny-TIM) within laboratories and 3.4 and 5.9% between laboratories. Inter-lab variability at individual time points remained <4.0% (fasted) and 5.2% (fed). Both TIM models produced biopredictive metrics, correctly predicting no food effect on total paracetamol bioaccessibility and capturing delayed tmax. Gastric and intestinal environments showed repeatable pH, temperature, and GI transit characteristics, with fluctuations across transit stages that mirrored reported in vivo patterns. Conclusions: These results demonstrate that TIM systems can reproducibly simulate gastrointestinal conditions across laboratories and generate consistent measurements of drug product performance, despite the complexity of the dynamic processes involved. While this evaluation involving a single BCS I drug solution should not be directly extrapolated to experiments with poorly soluble compounds or different formulations, it supports the use of TIM systems as robust in vitro models in drug product development. This study provides a standardized, inter-laboratory, baseline performance dataset to support regulatory submissions incorporating TIM data and enable more confident interpretation of TIM experiments. Full article
(This article belongs to the Section Biopharmaceutics)
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43 pages, 2799 KB  
Review
A Review of Thermal Management Techniques Adopted for High-Power-Density GaN-Based Converters
by Mohamed Belguith, Sonia Eloued, Moncef Kadi, Jaleleddine Ben Hadj Slama and Mahmoud Hamouda
Chips 2026, 5(1), 4; https://doi.org/10.3390/chips5010004 - 22 Jan 2026
Cited by 8 | Viewed by 4778
Abstract
Power converters based on gallium nitride (GaN) are progressing swiftly owing to their exceptional efficiency and tiny dimensions, boosted by high power density and fast switching capabilities. Nevertheless, these benefits are accompanied by considerable thermal management issues that impact reliability, performance, and operational [...] Read more.
Power converters based on gallium nitride (GaN) are progressing swiftly owing to their exceptional efficiency and tiny dimensions, boosted by high power density and fast switching capabilities. Nevertheless, these benefits are accompanied by considerable thermal management issues that impact reliability, performance, and operational lifespan. This review examines advanced thermal management approaches for high-power-density GaN power converters, including active and passive cooling technologies, sophisticated packaging designs, and the use of novel materials like graphene and diamond to improve heat dissipation. The impacts of thermal boundary resistance, self-heating phenomena, and substrate selection on thermal performance are thoroughly analyzed. Strategies for enhancing printed circuit board (PCB) layouts, thermal vias, and the use of thermal interface materials (TIMs) are also emphasized. The study highlights co-design approaches that optimize thermal resistance and layout efficiency, supporting GaN operation under high-frequency conditions. This thorough investigation offers insights into addressing the thermal challenges linked to GaN technology, promoting its adoption in forthcoming power devices. Full article
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16 pages, 4734 KB  
Article
Zircon Internal Deformation and Its Effect on U-Pb Geochronology: A Case Study from the Himalayan High-Pressure Eclogites
by Hafiz U. Rehman
Minerals 2024, 14(8), 742; https://doi.org/10.3390/min14080742 - 24 Jul 2024
Cited by 2 | Viewed by 2678
Abstract
Zircon, with a chemical formula of ZrSiO4, is a widely used mineral for determining the crystallization age of igneous rocks. It is also used to constrain the timing of metamorphic events from its overgrowth or recrystallized domains. Furthermore, detrital zircon grains [...] Read more.
Zircon, with a chemical formula of ZrSiO4, is a widely used mineral for determining the crystallization age of igneous rocks. It is also used to constrain the timing of metamorphic events from its overgrowth or recrystallized domains. Furthermore, detrital zircon grains can provide information on the sedimentary provenance. Due to the trace amounts of uranium (parent) which decays into its daughter element (Pb), it is a prime geochronometer for the majority of magmatic and metamorphic rocks. With high-precision analytical instruments, such as TIMS, SIMS, and LA-ICP-MS, huge amounts of geochronological and trace element data from zircon have been generated around the globe to date. Target domains within zircon grains are analyzed to extract geochemical and geochronological records using spatially resolved techniques such as ion probes or laser ablation coupled with mass spectrometry. Before any such analysis, the zircon grains are examined for internal structures, growth zoning, and the presence of tiny inclusions. However, many researchers analyze multiple domains within single zircon grains for U-Pb isotope analysis with little regard for their internal structures, particularly crystallographic orientations. Hence, they may obtain mixed ages with variable discordance, leading to imprecise interpretation especially when the growth domains are not well-identified. Particularly, zircon grains that contain multi-growth domains or have local internal deformations within a single grain may not produce geologically meaningful age results if the analyses are conducted on mixed domains. This study presents a brief review on zircon geochronology, how to identify and visualize micro-deformations in metamorphic zircons through the EBSD analysis, and the effects of micro-deformation on age results. Examples from a case study conducted on zircons hosted in the Himalayan high-pressure eclogites are presented that show intra-grain plastically deformed domains and their effects on the corresponding age results. Full article
(This article belongs to the Section Mineral Geochemistry and Geochronology)
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16 pages, 4430 KB  
Article
Mucin-Protected Caco-2 Assay to Study Drug Permeation in the Presence of Complex Biorelevant Media
by Dong Ye, Álvaro López Mármol, Verena Lenz, Patricia Muschong, Anita Wilhelm-Alkubaisi, Manuel Weinheimer, Mirko Koziolek, Kerstin A. Sauer, Loic Laplanche and Mario Mezler
Pharmaceutics 2022, 14(4), 699; https://doi.org/10.3390/pharmaceutics14040699 - 24 Mar 2022
Cited by 16 | Viewed by 7367
Abstract
The poor solubility and permeability of compounds beyond Lipinski’s Rule of Five (bRo5) are major challenges for cell-based permeability assays. Due to their incompatibility with gastrointestinal components in biorelevant media, the exploration of important questions addressing food effects is limited. Thus, we established [...] Read more.
The poor solubility and permeability of compounds beyond Lipinski’s Rule of Five (bRo5) are major challenges for cell-based permeability assays. Due to their incompatibility with gastrointestinal components in biorelevant media, the exploration of important questions addressing food effects is limited. Thus, we established a robust mucin-protected Caco-2 assay to allow the assessment of drug permeation in complex biorelevant media. To do that, the assay conditions were first optimized with dependence of the concentration of porcine mucin added to the cells. Mucin-specific effects on drug permeability were evaluated by analyzing cell permeability values for 15 reference drugs (BCS class I–IV). Secondly, a sigmoidal relationship between mucin-dependent permeability and fraction absorbed in human (fa) was established. A case study with venetoclax (BCS class IV) was performed to investigate the impact of medium complexity and the prandial state on drug permeation. Luminal fluids obtained from the tiny-TIM system showed a higher solubilization capacity for venetoclax, and a better read-out for the drug permeability, as compared to FaSSIF or FeSSIF media. In conclusion, the mucin-protected Caco-2 assay combined with biorelevant media improves the mechanistic understanding of drug permeation and addresses complex biopharmaceutical questions, such as food effects on oral drug absorption. Full article
(This article belongs to the Special Issue Intestinal Drug Absorption)
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11 pages, 253 KB  
Article
Producing Cherry Tomatoes in Urban Agriculture
by Matthew L. Richardson and Caitlin G. Arlotta
Horticulturae 2022, 8(4), 274; https://doi.org/10.3390/horticulturae8040274 - 22 Mar 2022
Cited by 14 | Viewed by 7781
Abstract
Agriculture in urban and urbanizing areas will be increasingly critical to enhancing food security and food sovereignty, creating income, strengthening social interactions, and improving health outcomes in cities. We used three roofs, a hydroponic system, an aquaponic system, and field rows in an [...] Read more.
Agriculture in urban and urbanizing areas will be increasingly critical to enhancing food security and food sovereignty, creating income, strengthening social interactions, and improving health outcomes in cities. We used three roofs, a hydroponic system, an aquaponic system, and field rows in an urban environment to grow six dwarf tomato cultivars: ‘Micro Tom’, ‘Red Robin’, ‘Sweet ‘n’ Neat’, ‘Terenzo’, ‘Tiny Tim’, and ‘Tumbler.’ We measured the marketable yield and non-marketable yield, mass of non-marketable tomatoes exhibiting defects, and the content of 12 mineral nutrients in fruits. We found the productivity often varied among cultivars within a cropping system. ‘Terenzo’ and ‘Tumbler’ were always some of the most productive cultivars, whereas ‘Micro Tom’ was normally among the least productive cultivars. The production from ‘Red Robin’, ‘Tiny Tim’, and ‘Sweat ‘n’ Neat’ was more variable, sometimes producing high, moderate, or low mass. The mineral content was especially variable across the cultivars and we did not identify cultivars that were consistently high or low in mineral content across systems, indicating that the mineral content was highly influenced by a genotype x environment interaction. The amount of 5 minerals differed across cultivars in aquaponics, 9 differed in hydroponics, and 6–12 differed in the roof systems. A high-yielding cultivar should be selected first and production methods can then be modified to maximize the nutrient content. Full article
(This article belongs to the Special Issue Urban Horticulture - New Trends and Technologies)
17 pages, 8634 KB  
Article
Context-Dependent Tumorigenic Effect of Testis-Specific Mitochondrial Protein Tiny Tim 2 in Drosophila Somatic Epithelia
by Cristina Molnar, Anxela Louzao and Cayetano Gonzalez
Cells 2020, 9(8), 1842; https://doi.org/10.3390/cells9081842 - 6 Aug 2020
Cited by 1 | Viewed by 3648
Abstract
We have undertaken a study towards understanding the effect of ectopic expression of testis proteins in the soma in Drosophila. Here, we show that in the larval neuroepithelium, ectopic expression of the germline-specific component of the inner mitochondrial translocation complex tiny tim 2 [...] Read more.
We have undertaken a study towards understanding the effect of ectopic expression of testis proteins in the soma in Drosophila. Here, we show that in the larval neuroepithelium, ectopic expression of the germline-specific component of the inner mitochondrial translocation complex tiny tim 2 (ttm2) brings about cell autonomous hyperplasia and extension of G2 phase. In the wing discs, cells expressing ectopic ttm2 upregulate Jun N-terminal kinase (JNK) signaling, present extended G2, become invasive, and elicit non-cell autonomous G2 extension and overgrowth of the wild-type neighboring tissue. Ectopic tomboy20, a germline-specific member of the outer mitochondrial translocation complex is also tumorigenic in wing discs. Our results demonstrate the tumorigenic potential of unscheduled expression of these two testis proteins in the soma. They also show that a unique tumorigenic event may trigger different tumor growth pathways depending on the tissular context. Full article
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