Temperature Excursions Research Articles

Subchronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice

Forecasted increases in the prevalence and severity of extreme weather events accompanying changes in climatic behavior pose potential risk to the reproductive capacity of humans and animals of ecological and agricultural significance. While several studies have revealed that heat stress induced by challenges such as testicular insulation can elicit a marked negative effect on the male reproductive system, and particularly the production of spermatozoa, less is known about the immediate impact on male reproductive function following subchronic whole-body exposure to elevated ambient temperature. To address this knowledge gap, we exposed unrestrained male mice to heat stress conditions that emulate a heat wave (daily cycle of 8 h at 35 °C followed by 16 h at 25 °C) for a period of 7 d. Neither the testes or epididymides of heat-exposed male mice exhibited evidence of gross histological change, and similarly, spermatozoa of exposed males retained their functionality and ability to support embryonic development. However, the embryos generated from heat-exposed spermatozoa experienced pronounced changes in gene expression linked to acceleration of early embryo development, aberrant blastocyst hatching, and increased fetal:placental weight ratio. Such changes were causally associated with an altered sperm small noncoding RNA (sncRNA) profile, such that these developmental phenotypes were recapitulated by microinjection of wild-type embryos sired by control spermatozoa with RNAs extracted from heat-exposed spermatozoa. Such data highlight that even relatively modest excursions in ambient temperature can affect male reproductive function and identify the sperm sncRNA profile as a particular point of vulnerability to this imposed environmental stress.

Numerical simulation of the temperature excursions of porous substrates during atomic layer deposition

Atomic layer deposition (ALD) processes are usually highly exothermic. For ALD on substrates with high specific surface area, the reaction heat per ALD cycle may lead to a substantial temperature rise of the substrates. The novelty of this study lies in quantifying the temperature excursions of porous substrates during ALD via numerical simulation and further addresses the issue of tuning this type of thermal effect. A comprehensive model has been developed and validated to investigate the ALD thermal effect with accounting for the roles of the precursor transport phenomena within the ALD reactor system, and the coupling among the precursor diffusion, heat transfer, film deposition, reaction heat generation within the porous substrates. The results show that the thermal effect of the sub-saturated ALD can change with different substrate thickness, precursor partial pressure profile, heat transfer coefficient, and kinetic parameters. In contrast, for saturated ALD with adiabatic condition, the maximum temperature rise of the substrate is a deterministic value, independent of the substrate thickness and precursor partial pressure profile. The thermal effect with the porous substrates can influence the ultimate deposit amount and its distribution for sub-saturated ALD and change the time required for attaining saturation for saturated ALD. The temperature rises of certain common substrates during typical half-ALD cycles have been simulated to demonstrate the capability of the present model in predicting the thermal effect of ALD.

The weather of 1740, the coldest year in central Europe in 600 years

Abstract. The winter of 1739/40 is known as one of the coldest winters in Europe since early instrumental measurements began. Many contemporary sources discuss the cold waves and compare the winter to that of 1708/09. It is less well known that the year 1740 remained cold until August and was again cold in October and that negative temperature anomalies were also found over Eurasia and North America. The 1739/40 cold season over northern mid-latitude land areas was perhaps the coldest in 300 years, and 1740 was the coldest year in central Europe in 600 years. New monthly global climate reconstructions allow us to address this momentous event in greater detail, while daily observations and weather reconstructions give insight into the synoptic situations. Over Europe, we find that the event was initiated by a strong Scandinavian blocking in early January, allowing the advection of continental cold air. From February until June, high pressure dominated over Ireland, arguably associated with frequent eastern Atlantic blocking. This led to cold-air advection from the cold northern North Atlantic. During the summer, cyclonic weather dominated over central Europe, associated with cold and wet air from the Atlantic. The possible role of oceanic influences (El Niño) and external forcings (eruption of Mount Tarumae in 1739) are discussed. While a possible El Niño event might have contributed to the winter cold spells, the eastern Atlantic blocking is arguably unrelated to either El Niño or the volcanic eruption. All in all, the cold year of 1740 marks one of the strongest, arguably unforced excursions in European temperature.

Current regulatory requirements for stability studies of biological medicinal products: a review

INTRODUCTION. The stability assessment of biological medicinal products (BMPs) requires special approaches and regulatory requirements. Therefore, BMPs require relevant national guidelines, which are an important prerequisite for the assurance of the safe and effective use of BMPs.AIM. This study aimed to analyse national and international requirements for the stability assessment of BMPs in order to use the results to inform future development of a unified regulatory approach to estimating and confirming shelf-life periods for BMPs.DISCUSSION. Most biotechnological medicinal products (BTMPs) are proteins and are highly sensitive to environmental factors by nature. Therefore, the shelf life of a BTMP is established on the basis of real-time stability studies. Stability testing under accelerated and stress conditions is conducted to support shelf-life claims and to characterise the mechanism of protein structure degradation. The results of accelerated and stress studies can be used to select the most sensitive stability-indicating parameters and testing methods. National and international regulatory authorities have developed specialised guidelines for stability studies of BMPs of various origins, and the stability assessment approaches in the regulatory system of the Eurasian Economic Union (EAEU) are harmonised with international standards. Special considerations associated with the stability of vaccines imply that stability studies of vaccines should not only establish shelf life but also investigate stability after reconstitution and after short-term temperature excursions from the recommended cold-chain conditions.CONCLUSIONS. Special stability testing considerations for various groups of BMPs (including BTMPs and immunobiologicals) indicate the need to develop and improve the system of requirements for BMP stability assessment. This will facilitate the optimisation of the life cycle of BMPs in the Russian Federation and the other EAEU member states.

Temperature Excursion Management: A Tier-Based Approach for Commercial Oral Solid Dosage Forms

Temperature excursions during product storage, transportation, and handling can deteriorate product quality. Following a temperature excursion event, the impact of the event on the product quality should be evaluated to determine if the product can be used or if it needs to be discarded. Pharmaceutical companies are required to have defined procedures for managing temperature excursions and performing impact assessment after an excursion occurs. In an increasingly complex supply chain, it is vital to develop processes that can expedite the review of these events. A tier-based approach is presented for analyzing the impact of temperature excursion on commercial small molecule drug products intended to be stored at room temperature. Utilization of each of the three tiers is based on whether the excursion temperature and/or excursion duration are within a predetermined, product-specific, allowable range. The stress study temperature defines the allowable temperature range, while the allowable duration is determined using a mathematical approach outlined in this article. Tier 1, specific to the product, allows products to be dispositioned for use without further assessment when temperature excursion events fall within both the product-specific allowable excursion temperature and duration ranges. Tier 2 applies when the excursion temperature is within the allowable range, but the duration exceeds it. Lot-specific release data is used for impact assessment in this tier. Finally, Tier 3 utilizes Arrhenius extrapolation to predict the final degradation and perform the impact assessment when the excursion temperature surpasses the allowable temperature range.Graphical

Temperature Excursions in Cold Chain Management-Assessing the Accuracy of Refrigerator Temperature Probes.

Background: Medications requiring refrigeration for stability are commonly used across hospitals. Temperature-sensitive medications may not have their temperature requirements maintained due to breaches in the cold chain, especially refrigerator failure. This is usually caused by malfunction of the refrigerator unit or by power outage. After multiple power outages at our institution involving refrigerators with temperature probes located in different areas of the refrigerator, we hypothesised that the fixed temperature probe may not accurately reflect the temperature of the medications themselves. Methods: We conducted simulations of power outages in a commonly used medication refrigerator, using additional temperature data loggers, placed on the refrigerator shelf and inside a cardboard box to replicate the temperature inside medication containers to determine if there was a difference in the time to breach cold chain conditions (>8°C) and to return to appropriate refrigerated temperatures (<8°C) when power was restored. Results: All data loggers took a longer time to breach cold chain conditions than the refrigerator probe (12.5 minutes vs 23-26 minutes) but took longer to return to acceptable temperature after power was restored (17.5 minutes vs 70.5-89 minutes). Conclusion: This exploratory research suggests that temperatures vary within a refrigerator depending on the type and location of probe and that medications within may take longer to breach cold chain conditions but also take longer to return to cold chain conditions compared with fixed refrigerator temperature probes. Further research is required to determine whether these variations occur across different sizes/brands of refrigerators and the effect on stability on refrigerated medications.

Comprehensive Analysis of Cetuximab Critical Quality Attributes: Impact of Handling on Antigen-Antibody Binding.

Cetuximab, formulated in Erbitux® (5 mg/mL), is a therapeutic monoclonal antibody (mAb) widely used in several cancer treatments. Currently, there is insufficient knowledge about the behavior of cetuximab with regard to the risk associated with its routine handling or unintentional mishandling in hospitals. Forced degradation studies can simulate these conditions and provide insights into the biophysical and biochemical properties of mAbs. In this study, we conducted a deep physicochemical and functional characterization of the critical quality attributes of cetuximab in control samples and under controlled degraded conditions, including freeze-thaw cycles, heat, agitation, and light exposure. To achieve this purpose, we used a set of proper analytical techniques, including CD, IT-FS, DLS, SE/UHPLC-UV, UHPLC-MS/MS, and ELISA, to check functionality based on antigen-antibody binding. The results revealed that light exposure was the stress stimuli with the greatest impact on the drug product, leading to the formation of non-natural oligomers, fragmentation, and oxidation of methionine residues. Additionally, cetuximab (Erbitux®, 5 mg/mL) showed a tendency to aggregate when submitted to 60 °C for 1 h. In terms of functionality, cetuximab (Erbitux®, 5 mg/mL) samples were found to be affected when subjected to freeze-thaw cycles, 60 °C (1 h), and when exposed to light (daylight with room temperature excursion and accelerated light exposure). Thus, we suggest that Erbitux® (5 mg/mL) should be shielded from these environmental conditions, as they compromise both the safety and efficacy of the drug product.

FORMULATION OPTIMIZATION AND CHARACTERIZATION OF NEWSTABLE READY TO USE (RTU) INJECTABLE FORMULATION OF ROCURONIUM BROMIDE

Commercially available injectable Rocuronium Bromide, a non-depolarizing neuromuscular blocker intended to store in a refrigerator at 2-8°C, requires an additional storage facility. The primary objectives of the present research were to design a stable, Ready to use (RTU) formulation of Rocuronium Bromide (RCB) Injection for Intravenous (IV) administration for storage at room temperature. Beta cyclodextrin (BCD) forms inclusion complexes with RCB. Edetate Disodium (EDTA) helps in achieving within the specification limit of Impurity C (Imp. C), a major metabolite of rocuronium bromide and Assay. Other excipients were selected to achieve a stable injectable formulation and cause less pain at the injection site. The formulation was optimized by Design of experiments (DoE) applying Central Composite Design (CCD) using Design Expert software and established design space where the formulation meets the desired acceptance criteria. The obtained optimized formulation can be terminally sterilized by moist heat and evaluated for thermal stability and robustness. The robustness of the formulation was established through Temperature excursion studies, pH sensitivity, and Oxygen sensitivity studies. Shelf life was estimated for 19 months when stored at 22°C which is an improvement to the currently available brands with 2-8°C storage. The formulation does not contain acetate buffer, which was identified as the root cause of the pain at the vascular site and may cause less vascular pain at the injection site. The current research work is encouraging in a positive way to achieve the objective of stable Rocuronium bromide injection at ambient conditions to enhance patient compliance.

A multi-center evaluation of a novel IVF cryostorage device in an active clinical setting

The objective of this study was to evaluate the function, and usability of a novel automated software-guided cryostorage system in an active IVF laboratory setting. The investigational device (ID) was installed at 3 IVF laboratories (sites: α, β, and γ). A total of 15 embryologists were trained to use the ID. Mock patient specimens containing mirrored live patient data were handled using the ID. Temperature readings were recorded every minute. Successful identification, storage, and retrieval of mock patient specimens by the ID were evaluated. To assess an LN2 pressure builder, the frequency of use and events of workflow interruption were logged. Student’s t-test was used to determine statistical significance. The ID was in active use for 164 days total. During this time, 329 mock patient egg and embryo cohorts were handled by the ID. The mean ± SD temperatures during active use were: α, − 176.57 ± 1.83 °C; β, − 178.21 ± 2.75 °C; γ, − 178.98 ± 1.74 and did not differ significantly. The highest recorded temperatures were: α, − 165.14 °C; β, − 157.41 °C; γ, − 164.45 °C. A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no mock specimen was exposed to a detrimental (> − 150 °C) temperature excursion. Over the 25 LN2 pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN2 pressure. The ID has advantages over the current manual-based cryostorage systems, including radio frequency identification (RFID) tracking, automation of manual tasks, and software guidance to ensure accurate specimen storage and retrieval. The results of this study indicate that the ID can be integrated into active IVF laboratories.

Capillary mediated vitrification is a novel technique that enables storage of antibody critical reagents at ambient temperature: Impact on binding, structure, and laboratory sustainability

Antibodies and antibody conjugates are essential components of life science research, but their inherent instability necessitates cold storage or lyophilization, posing logistical and sustainability challenges. Capillary-mediated vitrification has shown promise as a tool for improving biomolecule stability. In this study, we assess the feasibility of shipping and storing CMV-stabilized antibody reagents at ambient temperature using a purified rabbit polyclonal as a model system. The conditions tested included a simulated temperature excursion, ambient shipping, and storage for approximately two months at room-temperature. Antibody function was measured by both ELISA and Octet bio-layer interferometry kinetic measurements. Yield, aggregation, and thermal stability were assessed by UV/VIS, Size Exclusion Chromatography (SEC), thermal melting, and thermal aggregation studies. Results indicate >97 % protein yield and no impact on the binding activity. No evidence of aggregation or oligomer formation was detected. Addition of the vitrification buffer to the sample matrix resulted in an increase in the aggregation on-set temperature, indicating enhanced thermostability. A slight shift in both the SEC retention time for the main peak and a difference in aggregation behavior at high temperatures were noted post-vitrification. We hypothesize that these differences are related to the interaction of the protein with the saccharide component of the vitrification matrix and the stabilization mechanism of sugars. The cumulative data supports the use of Capillary Mediated Vitrification as a viable alternative to frozen reagent storage, with the potential to significantly impact reagent stability, assay performance, laboratory operations, and sustainability initiatives.

The 4.2 ka event is not remarkable in the context of Holocene climate variability

The “4.2 ka event” is a commonly described abrupt climate excursion that occurred about 4200 years ago. However, the extent to which this event is coherent across regional and larger scales is unclear. To objectively assess climate excursions in the Holocene we compile 1142 paleoclimate datasets that span all continents and oceans and include a wide variety of archive and proxy types. We analyze these data to determine the timing, significance and spatial imprint of climate excursions using an objective method that quantifies local, regional and global significance. Site-level excursions in temperature and hydroclimate are common throughout the Holocene, but significant global-scale excursions are rare. The most prominent excursion occurred 8200 years ago, when cold and dry conditions formed a large, significant excursion centered in the North Atlantic. We find additional significant excursions between 1600 and 1000 years ago, which agree with tree-ring data and annual-scale paleoclimate reconstructions, adding confidence and context to our findings. In contrast, although some datasets show significant climate excursions 4200 years ago, they do not occur in large, coherent spatial regions. Consequently, like most other periods in the Holocene, the “4.2 ka event” is not a globally significant climate excursion.

The Optical Corrector for the Dark Energy Spectroscopic Instrument

The Dark Energy Spectroscopic Instrument (DESI) is currently measuring the spectra of 40 million galaxies and quasars, the largest such survey ever made to probe the nature of cosmological dark energy. The 4 m Mayall telescope at Kitt Peak National Observatory has been adapted for DESI, including the construction of a 3.°2 diameter prime focus corrector that focuses astronomical light onto a 0.8 m diameter focal surface with excellent image quality over the DESI bandpass of 360–980 nm. The wide-field corrector includes six lenses, as large as 1.1 m in diameter and as heavy as 237 kilograms, including two counterrotating wedged lenses that correct for atmospheric dispersion over zenith angles from 0° to 60°. The lenses, cells, and barrel assembly all meet precise alignment tolerances on the order of tens of microns. The barrel alignment is maintained throughout a range of observing angles and temperature excursions in the Mayall dome by use of a hexapod, which is itself supported by a new cage, ring, and truss structure. In this paper we describe the design, fabrication, and performance of the new corrector and associated structure, focusing on how they meet DESI requirements. In particular, we describe the prescription and specifications of the lenses, design choices and error budgeting of the barrel assembly, stray light mitigations, and integration and test at the Mayall telescope. We conclude with some validation highlights that demonstrate the successful corrector on-sky performance, and we list some lessons learned during the multiyear fabrication phase.

The transient thermal ageing of Eurofer 97 by mitigated plasma disruptions

Plasma disruptions in a commercial-scale tokamak will impose high magnitude, short-duration thermal loads on its plasma-facing first wall. Despite a plethora of mitigation measures, these severe, off-normal events are likely to briefly expose the structural materials of the first wall to significant temperature excursions. Eurofer 97, the reference structural material for the plasma-facing first wall of the EU DEMO tokamak, is a reduced activation 9Cr steel with a normalised and tempered ferritic/martensitic microstructure. Repeated exposure to the thermal effects of disruptions over the operating lifetime of a reactor may promote a cumulative evolution of Eurofer 97′s microstructure, affecting key material properties crucial to first wall performance. This novel transient thermal degradation mechanism has been explored via a laser-based transient heating experiment, supported by time-dependent finite element thermal analysis studies of DEMO’s water-cooled lithium–lead first wall during a mitigated plasma disruption. Transient-affected samples of Eurofer 97 were characterised via scanning and transmission electron microscopy techniques (SEM/TEM), including electron backscatter diffraction (EBSD), energy-dispersive X-ray spectroscopy (EDX), and selective area electron diffraction (SAED). Microhardness and magnetisation testing data are also presented. A single 700 °C thermal transient was found sufficient to coarsen and partially recrystallise Eurofer 97′s tempered martensite sub-grains at the tungsten-Eurofer 97 interface. Further transient exposure at 700 °C resulted in the significant growth of equiaxed grains, the nucleation of intergranular Cr-rich M7C3 and M23C6 carbides, and the coarsening of V-rich and intra-granular Ta-rich MX precipitates. The microstructural effects of 850 °C transients are also reported. Notably, after 1,000 transients at 850 °C the hardness of Eurofer 97 was found to have decreased by 32 %.

Estimation-based model predictive control with objective prioritization for mutually exclusive objectives: Application to a power plant

This work presents an algorithm for estimation-based model predictive control with objective prioritization such that distinct objectives may be defined for mutually exclusive operational regions. The objective prioritization algorithm is built by using logical conditions that define regions of operation which are incorporated into the objective function, thus allowing smooth transitions between a bank of objectives. The control objective prioritization is cast in the framework of model predictive control that is coupled with an extended Kalman filter for estimation of critical yet unmeasured state variables. The algorithm is applied to the challenging control problem of an industrial superheater (SH)-reheater (RH) system of a natural gas combined cycle plant under load following operation where smooth transitions among various control objectives is desired – operation under nominal conditions, avoidance of spraying to saturation at the inlet of the SH and RH systems, and avoidance of main steam temperature excursions. The results from the estimator framework are compared with the industrial data from an operating power plant. The control algorithm is evaluated by simulating a servo control problem and disturbance rejection scenarios as expected under load-following operation of the power plant. This algorithm is generic and can be applied to accomplish local control policies for safety, economics, quality control, state constraints, and others. Topical HeadingProcess Systems Engineering

Evidence of Correlation between Membrane Phase Transition and Clonogenicity in Dehydrating Acinetobacter baumannii: A Combined Micro-Raman and AFM Study.

The Gram-negative bacterium Acinetobacter baumannii is one of the most resilient multidrug-resistant pathogens in hospitals. Among Gram-negative bacteria, it is particularly resistant to dehydration (anhydrobiosis), and this feature allows A. baumannii to persist in hospital environments for long periods, subjected to unfavorable conditions. We leverage the combination of μ-Raman spectroscopy and atomic force microscopy (AFM) to investigate the anhydrobiotic mechanisms in A. baumannii cells by monitoring the membrane (both inner and outer membranes) properties of four A. baumannii strains during a 16-week dehydration period and in response to temperature excursions. We noted that the membranes of A. baumannii remained intact during the dehydration period despite undergoing a liquid-crystal-to-gel-phase transition, accompanied by changes in the mechanical properties of the membrane. This was evident from the AFM images, which showed the morphology of the bacterial cells alongside modifications of their superficial mechanical properties, and from the alteration in the intensity ratio of μ-Raman features linked to the CH3 and CH2 symmetric stretching modes. Furthermore, employing a universal power law revealed a significant correlation between this ratio and bacterial fitness across all tested strains. Additionally, we subjected dry A. baumannii to a temperature-dependent experiment, the results of which supported the correlation between the Raman ratio and culturability, demonstrating that the phase transition becomes irreversible when A. baumannii cells undergo different temperature cycles. Besides the relevance to the present study, we argue that μ-Raman can be used as a powerful nondestructive tool to assess the health status of bacterial cells based on membrane properties with a relatively high throughput.

Correlating critical current density, quench protection, relaxation time and entropy in superconductors after disturbances—Intermediate summary

&lt;p&gt;This paper summarizes results recently obtained from simulation of transient temperature excursions in filamentary and thin film superconductors. Under multi-component heat transfer in the complicated conductor cross sections and materials composition of present High Temperature Superconductors, numerical, Finite Element and Monte Carlo simulations are applied to solve Fourier’s differential equation with high spatial and temporal resolution. The overall aim was to encircle the quench problem in superconductors and to provide new stability criteria from correlations between superconductor critical current density, density of electron pairs, and relaxation time and entropy. Relaxation, correlation and entropy analysis presented in this paper extends the spectrum of standard methods to avoid quench to a new tool. As results, quench starts always locally, and as a highlight of this investigation, a second “critical” temperature, &lt;em&gt;T&lt;sub&gt;Quench&lt;/sub&gt;&lt;/em&gt;, has been identified that with high probability exists below standard critical temperature. Entropy is the driving force for relaxation of the superconductor to new equilibrium after a disturbance.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;

Design and Optimization of Accumulator Pack

For an electric scooter, a lithium-ion battery with a Acro Butyl-nitrate (ABS) temperature management system was developed. Without the use of active cooling components like a fan, a blower, or a pump used in air/liquid-cooling systems, passive thermal management systems employing ABS can regulate the temperature excursions and maintain temperature uniformity in Li-ion batteries. Therefore, this new type of thermal management system can provide the benefits of a small, light, and energy-efficient system. The simulation results for a Li-ion battery sub-module with twenty 18650 Li-ion cells encased in ABS and a melting point of 114 to 120 °C are displayed. There are many important advantages to using aluminium fins manufactured from 0.7mm thick aluminium sheet between the battery cells in an accumulator pack. The relevance of them is explained in the following ways: Accumulator packs, particularly those used in high-power applications like scooters, can produce large amount of heat when in use. The performance, longevity, and safety of battery cells are all significantly impacted by heat. Aluminium fins serve as heat sinks and enhance heat dissipation by boosting the amount of heat-transfer surface area. Heat can be effectively transferred from the cells to the fins thanks to the thin aluminium sheet. Temperature Control: Battery cell efficiency and longevity depend on maintaining their temperature within a favorable range. By releasing more heat, aluminium fins assist in controlling the temperature. The fins aid in preventing overheating and preserving a more constant operating temperature by efficiently draining heat from the cells. Thermal Uniformity: The accumulator pack's thermal uniformity is enhanced by the inclusion of aluminium fins between the battery cells. Variations in cell temperature can cause performance imbalances and lower pack efficiency because uneven heat distribution can cause temperature differences among the cells. The fins aid in the even distribution of heat throughout the cells, reducing temperature variations and fostering consistent performance. Reduced Hotspots: Hotspots are small, high-temperature regions inside a battery pack that can hasten degradation and pose safety issues. Aluminium fins aid in heat dissipation, which reduces the development of hotspots. The fins' increased surface area enables more effective heat transport, which lowers the possibility of localized temperature accumulation. Improved Safety: Effective heat dissipation with aluminium fins can aid in accumulator packs' increased safety. Battery cells may experience thermal runaway or other dangerous situations as a result of high temperatures. The risk of thermal incidents is decreased by maintaining lower cell temperatures, improving operational safety in general. It's crucial to remember that parameters like spacing, size, and overall pack should be taken into account while designing and using aluminium fins. Additionally, by lowering the amount of heat that is released into the environment, liquid cooled heatsinks can be utilised to lessen the environmental effect of electronic equipment. The following are some benefits of employing liquid-cooled heatsinks: ● more efficient at cooling than heatsinks that use air cooling ● can be used to enhance the functionality and dependability of electronic equipment ● can be used to lessen how harmful electrical devices are to the environment. The following are some drawbacks of employing liquid-cooled heatsinks: ● more expensive than heatsinks that are air-cooled. ● more difficult to install and keep up ● Tend to leak more frequently. Keywords — CFD, 18650,ABS ,ALUMINUM FINS ,DRIVE CYCLE MODELS,EQUIVALENT CIRCUIT MODEL.

Abstract 3863: Flow cytometry using stabilized whole blood to assess innate and adaptive immune cells (Monocytes, NK, T, and B cells) in immunotherapies

Abstract Flow cytometry assays using fresh whole blood which are interrogating either an extremely rare cell subset or a depleting immunotherapy, may require samples to be processed from global clinical sites over a wide geographical area, which can pose a major challenge for clinical operations. Precision for Medicine (PfM) has addressed these operational challenges using commercial stabilizers which are added to the blood allowing samples to be frozen at -80°C and subsequently batch processed for sample testing. We have performed a fit for purpose assay qualification of a multiparameter flow cytometry panel allowing the immunophenotypic analysis of monocyte, T cell, B cell and NK immune populations using Cytodelics™ fixed/stabilized healthy donor whole blood. Additionally, the assay was verified in whole blood samples from multiple solid tumor disease states including melanoma, colorectal cancer, head &amp; neck, non-small cell lung cancer to demonstrate clinical application. In these oncology samples, we were able to assess both immune cell frequencies and their activation status in both fresh whole blood as well as fixed whole blood over a short-term sample stability study, where the samples had been stored at -80°C for several months. This data provides a representative example of the use of commercial stabilizing fixatives for clinical studies to extend the stability window of whole blood for subsequent assessment by flow cytometry. Fixed whole blood can be stored at -80°C, shipped on dry ice allowing multiple timepoints in a cohort to be assessed together, thus minimizing assay variability as compared to fresh whole blood analysis, and mitigating the impact of shipping delays and temperature excursions on the samples. With sufficient time for assay development there are several commercial stabilizers that can be tested to determine if the markers in the flow assay are compatible with these reagents, providing a valuable option to assess the impact of immunotherapies on the immune cells of interest and reducing operational challenges in global studies. Citation Format: Jackie Benko, Samantha Splitt, Angelina Bisconte, Laura Lozza, Rachel Owen, Deborah Phippard. Flow cytometry using stabilized whole blood to assess innate and adaptive immune cells (Monocytes, NK, T, and B cells) in immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3863.

Analysis of heat flow in modified transient plane source (MTPS) measurements of the thermal effusivity and thermal conductivity of materials.

An iterative algorithm for the diffusion of heat in layered structures is solved in cylindrical coordinates for the geometry used in measurements of thermophysical properties of materials by the modified transient plane source (MTPS) method. This solution for the frequency-domain temperature response is then used to model the transient temperature excursion and evaluate the accuracy of the measurements. We evaluate when the MTPS method is capable of separately determining the thermal conductivity and heat capacity per unit volume of a material. For a typical sensor design, data acquisition, and data analysis, the MTPS measurement has a small sensitivity to the thermal diffusivity of the sample when the thermal diffusivity is <5 mm2 s-1. We analyze the propagation of errors from uncertainties in the thermal contact between the sensor and the sample and evaluate the limitations of the MTPS method in accurately measuring samples with extremely low thermal effusivity, e.g., low density foam insulation. We find that uncertainties in the thickness of the contact region limit the accuracy of MTPS measurements when the data are analyzed in a conventional manner based on a single parameter, m-1, the inverse of the slope of the temperature excursion as a function of the square root of time.

Analysis of control rod driving mechanism nozzle rupture with loss of safety injection at the ATLAS experimental facility using MARS-KS and TRACE

Korea Atomic Energy Research Institute (KAERI) has operated an integral effect test facility, the Advanced Thermal-Hydraulic Test Loop for Accident Simulation (ATLAS), with reference to the APR1400 (Advanced Power Reactor 1400) for tests for transient and design basis accidents simulation. A test for a loss of coolant accident (LOCA) at the top of the reactor pressure vessel (RPV) had been conducted at ATLAS to address the impact of the loss of safety injections (LSI) and to evaluate accident management (AM) actions during the postulated accident. The experimental data has been utilized to validate system analysis codes within a framework of the domestic standard problem program organized by KAERI in collaboration with Korea Institute of Nuclear Safety. In this study, the test has been analyzed by using thermal-hydraulic system analysis codes, MARS-KS 1.5 and TRACE 5.0 Patch 6, and a comparative analysis with experimental and calculation results has been performed. The main objective of this study is the investigation of the thermal-hydraulic phenomena during a small break LOCA at the RPV upper head with the LSI as well as the predictability of the system analysis codes after the AM actions during the test. The results from both codes reveal that overall physical behaviors during the accident are predicted by the codes, appropriately, including the excursion of the peak cladding temperature because of the LSI. It is also confirmed that the core integrity is maintained with the proposed AM action. Considering the break location, a sensitivity analysis for the nodalization of the upper head has been conducted. The sensitivity analysis indicates that the nodalization gave a significant impact on the analysis result. The result emphasizes the importance of the nodalization which should be performed with a consideration of the physical phenomena occurs during the transient.