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DOE OSTI2022

Development and assessment of a reactor system prognosis model with physics-guided machine learning

Autonomous control systems provide recommendations to help operators in decision-making during plant operations ranging from normal operation to accident management. An important step of autonomous control is prognosis. In nuclear engineering domain, prognosis is the process of predicting future conditions of a system or equipment based on present signs and symptoms of a fault. The prognosis model allows predicting future reactor states for possible candidate control strategies so that the outcomes can be evaluated to determine the best control strategy. The prognosis model requires representing direct relationships between the symptoms and the predictions. In nuclear engineering, computational simulations are approximate representations of the operation of the real system. However, prognosis with computational simulations requires high computation power and time due to possible large number of scenarios. Necessary computation resources can be reduced with machine learning (ML) approach for fast predictions by building a surrogate function using the simulation data. A critical issue is, ML models are ignorant of physical knowledge, and these models approximate statistical relationships between the system variables. This ignorance can produce results that are inconsistent with physical laws, even if an optimal result is achieved from a mathematical point of view. Physics-guided machine learning (PGML) is an approach to tackle this issue. Here, this work formulates and illustrates a framework to guide development and assessment of the ML-based prognosis model for autonomous control systems. The development of the prognosis model considers the training of a ML model which consists of optimizing many aspects of the ML approach. The assessment of the prognosis model considers training data limitations and uncertainties of the ML approach. Prognosis models with standalone ML and PGML are developed and assessed on the loss-of-flow scenario of Experimental Breeder Reactor II. The results indicate that PGML based prognosis model has the best performance compared to other prognosis models.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2024

Development and demonstration of a BISON–Griffin modeling framework for the design of targeted TRISO transient experiments in the Transient Reactor Test Facility

Uranium oxycarbide (UCO)-bearing tri-structural isotropic (TRISO) particle fuels are expected to be used in numerous U.S. commercial reactor applications within the next decade. Here, in this work, we reviewed historical particle fuel transient experiments to identify gaps in TRISO fuel performance transient testing. A BISON–Griffin modeling framework was then developed to conduct preliminary TRISO transient analyses and begin to address these gaps. The framework was demonstrated using limiting-case transient conditions from a prototypic high-temperature gas-cooled reactor (HTGR). It was then applied to develop a matrix of experiments that could be performed in the Transient Reactor Test Facility (TREAT) to (1) evaluate UCO-fueled particle performance at moderate and high heat rates, (2) assess whether historical testing involving UO 2 -fueled particles is applicable to modern UCO-fueled particles, (3) deconvolute the impacts of temperature and heat rate on particle transient response, and (4) collect the data needed for fuel performance model validation and/or further development.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2026

Development of a BISON validation case for the TRISO transient irradiations in NSRR using effective heat capacity methods

The current tristructural isotropic (TRISO) fuel assessment and validation database in BISON primarily covers steady- state irradiation and high-temperature furnace testing. Transient assessment cases are potentially needed to support U.S. industry efforts in designing and deploying commercial reactors using TRISO fuels. Historical transient tests in- volving TRISO fuels used highly conservative conditions compared to the typical high-temperature gas-cooled reactor accident scenarios. Despite this, modeling historical transient tests is fundamental for evaluating BISON’s predictive capabilities, adapting material properties for high-temperature and high-particle-power regimes, and developing a sys- tematic validation approach for TRISO transient applications. This work developed a 1D model of transient experiments carried out at the Nuclear Safety Research Reactor using BISON. BISON’s predictions of energy deposition, UO 2 melting onset, and molten volume fractions are compared against experimental measurements. Melting was modeled using an effective specific heat capacity model for UO 2 . We found that BISON’s predictions are in reasonable agreement with experimental data for low-energy-deposition cases, and that BISON overpredicts melting at higher energy depositions. We also discuss the potential causes of discrepancies between the simulated and measured results and propose ways to further develop the model. Although these simulations used conservative conditions compared to those expected for actual TRISO-fueled reactors, they extended the range of conditions reflected in the data in the existing BISON database for TRISO fuels.

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2016

OvAd1, a Novel, Potent, and Selective Chimeric Oncolytic Virus Developed for Ovarian Cancer by 3D-Directed Evolution

Effective therapeutics for ovarian cancer continue to be urgently needed, particularly for chemotherapy-resistant cases. Here we present both a 3D-Matrigel culture-based expansion of our directed evolution method for generation of oncolytic virotherapies and two promising ovarian-cancer targeted oncolytic viruses, OvAd1 and OvAd2. OvAd1 was developed using Matrigel cell cultures, whereas OvAd2 was developed in parallel using traditional monolayer tissue culture methods. Both viruses are potent against a panel of platinum-resistant ovarian cancer cell lines and are attenuated on normal cells in vitro, resulting in therapeutic windows of ~200-fold. We observed two benefits of the use of Matrigel-based cultures for directed evolution of these oncolytics: (1) use of Matrigel generated a bioselected pool that was more strongly attenuated on normal cells while retaining its potency against ovarian cancer cells, and (2) in an ovarian carcinomatosis model, the Matrigel-derived virus OvAd1 suppressed all tumor growth while the non-Matrigelderived virus was 50% effective. Neither virus stimulated formation of peritoneal adhesions as seen for Ad5-based therapies. Consequently, these viruses are novel candidates for development as new effective treatments for aggressive ovarian cancer.

3D cell culture↗

DOE OSTI2023

Development of sustainable low carbon Engineered Cementitious Composites with waste polyethylene fiber, sisal fiber and carbonation curing

Engineered cementitious composites (ECC) is an advanced fiber-reinforced cementitious composite with high tensile ductility. However, the binder and fiber system in ECC incur high economic and environmental cost. In this study, a low carbon ECC was developed by substituting virgin polyethylene fiber with waste polyethylene fiber (WPE) from waste marine fishing nets. Carbonation curing was applied to further reduce embodied carbon footprint via direct CO 2 mineralization. This research examined the low carbon ECC’s mechanical properties, including compressive strength and tensile strength and ductility. The CO 2 footprint and material costs of ECC were also investigated. The objective was to develop an ECC competitive to normal concrete economically and environmentally while maintain the unique ductile performance of ECC. Results suggest that carbonation-cured WPE reinforced ECC possesses 50% of the CO 2 footprint and 37% of the cost of traditional concrete. Meanwhile, this low carbon ECC maintains at least 4 MPa tensile strength and 6% tensile ductility. This research demonstrates the feasibility of developing construction materials with low environmental impact while maintaining high performance for civil infrastructure applications. As a result, the adoption of WPE in ECC provides a plausible pathway to recycle marine waste into the construction industry that urgently needs to be decarbonized.

42 ENGINEERING↗

DOE OSTI2025

Satellite remote sensing for environmental sustainable development goals: A review of applications for terrestrial and marine protected areas

With few years left to achieve the vital United Nations Sustainable Development Goals (SDGs), member nations must urgently leverage technological advancements in environmental monitoring to succeed. Remote sensing now provides decades of global observations at a variety of spatio-temporal scales and a litany of data products to guide comprehensive measures for climate action, and aquatic and terrestrial biota preservation. Protected areas, such as national parks and wildlife preserves, represent largely untapped resources for both applying robust conservation measures and testing ambitious new approaches to sustainable development that could jumpstart the much-needed adoption of strategies to efficiently pursue global sustainability. This review summarizes recent demonstrated utilities of remotely sensed data applied to protected areas for research related to SDG goals 13, 14, and 15: “Climate Action”, “Life below Water”, and “Life on Land”. We identify successful uses of such data for each SDG, identify areas for improvement, and provide recommendations from the literature on how to expand what others have done to achieve lofty goals with global impact. We demonstrate that remote sensing provides a valuable tool for achieving SDGs as it facilitates monitoring vegetation health, water quality and condition, and climate variables at large spatial and fine temporal scales, while also evaluating the effectiveness of management and conservation practices. Issues remain, however, in that there is currently no reference from which to relate goal progress to human livelihoods. Further, the current relationship between remotely sensed indices and ecological services that determine sustainable development omit steps that would establish this connection.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2019

Impact of shale gas development on regional water resources in China from water footprint assessment view

Shale gas production in China could strengthen energy security while cutting CO2 emissions for China. However, the availability of and access to water could become major issue for shale gas development in certain parts of China. This study aims to estimate the water intensity (WI) of shale gas extraction in China, and to examine the impact of regional shale gas development on local water resources, from the water footprint (WF) point of view. Results of this study indicate that WI of shale gas is in the range of 0.3-9.9 kg per m(3) shale gas produced. Fora single well, total WF is 549,994 m(3), includes 35,469 m(3) blue WF and 514.525 m(3) grey WF. A large amount of wastewater generated during gas production is the major impact factor to high grey WF. To achieve 80 billion m(3)/year of shale gas production in 2030, 27-792 million m(3) water will be demanded in that year. Water use for shale gas development will account for 0.03-0.4% and 0.1-1.5% of the local water supply, in the base case and the worst case, respectively. Although a large amount of water will be demand for shale gas production, it will not affect the local water supply significantly. (C) 2019 Elsevier B.V. All rights reserved.

regional water resources↗

DOE OSTI2021

Cyanobacteria in early soil development of deglaciated forefields: Dominance of non-heterocytous filamentous cyanobacteria and phosphorus limitation of N-fixing Nostocales

Cyanobacteria are integral to soil development in the earliest stages of primary succession by fixing carbon (C) and nitrogen (N) essential for organismal growth. Here, we examined soil cyanobacterial communities at the earliest stage of succession (<5 years) at two disparate glacial forefields to reveal cyanobacterial patterns central to ecosystem development. Despite vast differences in climate and the relative dominance of heterotrophic versus autotrophic bacteria in these forefields, we found common patterns in cyanobacterial community composition in early soils. This work adds to limited research suggesting the importance of non-heterocytous filamentous cyanobacteria in initial soil colonization and development of primary succession of glacier forefields. Further, a phosphorus (P) addition experiment suggests P-limitation as a mechanism underlying the restricted presence of ecologically important, putatively N-fixing, Nostocales in these emerging landscapes.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Countermeasures for treatment of chlorine-induced acute lung injury are needed. • Formulations containing rolipram, triptolide, or budesonide were produced. • Formulations with a wide range of release properties were developed. • Countermeasure formulations inhibited chlorine-induced lung injury in mice.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

Development and validation of the cavitation-induced erosion risk assessment tool

This work presents the development of a cavitation-induced erosion risk assessment (CIERA) tool that links multiphase flow simulation predictions with the progress towards material erosion. To develop a robust erosion modeling tool, the cavitation and erosion predictions for pressurized diesel fuel flow within a channel geometry were validated over a range of Reynolds and cavitation number conditions in two different aluminum channel geometries, one featuring a rounded inlet corner and the other with a sharp inlet corner. The multiphase flow development within the channel was modeled using a compressible mixture model, where phase change was represented with the homogeneous relaxation model and the turbulent flow evolution was modeled using a dynamic structure approach for Large Eddy Simulations. To improve representation of the incubation period before material rupture over existing approaches, a physics-based metric was derived based on the cumulative energy absorbed by the solid material from repeated hydrodynamic impacts. When the average peak pressure was related to the incubation period, the incubation period and its sensitivity to changes in flow conditions were found to be overpredicted. In contrast, predictions from CIERA provided a more accurate means to qualitatively and quantitatively predict the influence of flow conditions on the incubation period before material erosion. When the predicted stored energy was related to the solid material properties to estimate the incubation period, multiphase flow simulations demonstrated accurate representation of the sensitivity of erosion severity to changes in flow conditions. The use of CIERA led to quantitative agreement of the predicted incubation period within 5% of the experimentally measured incubation period.

42 ENGINEERING↗

DOE OSTI2016

The development of human mast cells. An historical reappraisal

The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34{sup +}/CD117{sup +}/CD13{sup +}multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, different MC phenotypes can develop in different tissues and organs. - Highlights: • Human mast cells originate from CD34/CD117/CD13 positive multipotent hematopoietic progenitors. • Stem cell factor is a major chemotactic factor for mast cells and their progenitors. • Different mast cell phenotypes can develop in different tissues and organs.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Functional analysis of the cfdp1 gene in zebrafish provides evidence for its crucial role in craniofacial development and osteogenesis

Highlights: • The zebrafish cfdp1 gene maps to chromosome 8 and is 2222 bp long with seven exons and six introns. • The cfdp1 gene is highly expressed since very early embryonic stages until the completion of organogenesis. • The zebrafish CFDP1 protein is highly abundant in the head structures. • CFDP1 is an essential protein that actively participates to the correct definition and morphogenesis of craniofacial territories in the zebrafish model system. The CFDP1 proteins have been linked to craniofacial development and osteogenesis in vertebrates, though specific human syndromes have not yet been identified. Alterations of craniofacial development represent the main cause of infant disability and mortality in humans. For this reason, it is crucial to understand the cellular functions and mechanism of action of the CFDP1 protein in model vertebrate organisms. Using a combination of genomic, molecular and cell biology approaches, we have performed a functional analysis of the cfdp1 gene and its encoded protein, zCFDP1, in the zebrafish model system. We found that zCFDP1 is present in the zygote, is rapidly produced after MTZ transition and is highly abundant in the head structures. Depletion of zCFDP1, induced by an ATG-blocking morpholino, produces considerable defects in craniofacial structures and bone mineralization. Together, our results show that zCFDP1 is an essential protein required for proper development and provide the first experimental evidence showing that in vertebrates it actively participates to the morphogenesis of craniofacial territories.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Modulating SIRT1 activity variously affects thymic lymphoma development in mice

Highlights: • Reduced SIRT1 levels protect against lymphoma induction by the chemical carcinogen N-nitroso-N-methylurea (NMU). • Conversely, reduced SIRT1 levels promote tumor formation in NPM-ALK driven lymphoma development. • Reduced SIRT1 levels promote formation of lung adenoma/adenocarcinomas in the NMU model. • Sirt1 is neither an oncogene nor a tumor suppressor. • Sirt1 may have a role in the complex processes of tumor surveillance. SIRT1 is a protein deacetylase with a broad range of biological functions, many of which are known to be important in carcinogenesis, however much of the literature regarding the role of SIRT1 in cancer remains conflicting. In this study we assessed the effect of SIRT1 on the initiation and progression of thymic T cell lymphomas. We employed mouse strains in which SIRT1 activity was absent or could be reversibly modulated in conjunction with thymic lymphoma induction using either the N-nitroso-N-methylurea (NMU) carcinogenesis or the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) transgene. Decreased SIRT1 activity reduced the development of thymic lymphomas in the NMU-treated mice but was permissive for the formation of lung adenomas. Conversely, in the NPM-ALK transgenic mice, decreased SIRT1 activity had a modest promoting effect in the development of thymic lymphomas. The results of the work presented here add to the growing body of evidence that sirt1 is neither an outright oncogene nor a tumor suppressor. These opposing results in two models of the same disease suggest that the influence of sirt1 on carcinogenesis may lie in a role in tumor surveillance.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Electron microscopy techniques employed to explore mitochondrial defects in the developing rat brain following ketamine treatment

Ketamine, an FDA-approved N-methyl-D-aspartate (NMDA) receptor antagonist, is commonly used for general pediatric anesthesia. Accumulating evidence has indicated that prolonged exposure to ketamine induces widespread apoptotic cell death in the developing brains of experimental animals. Although mitochondria are known to play a pivotal role in cell death, little is known about the alterations in mitochondrial ultrastructure that occur during ketamine-induced neurotoxicity. The objective of this pilot study was to utilize classic and contemporary methods in electron microscopy to study the impact of ketamine on the structure of mitochondria in the developing rat brain. While transmission electron microscopy (TEM) was employed to comprehensively study mitochondrial inner membrane topology, serial block-face scanning electron microscopy (SBF-SEM) was used as a complementary technique to compare the overall mitochondrial morphology from a representative treated and untreated neuron. In this study, postnatal day 7 (PND-7) Sprague-Dawley rats were treated with ketamine or saline (6 subcutaneous injections × 20 mg/kg or 10 ml/kg, respectively, at 2-h intervals with a 6-h withdrawal period after the last injection, n=6 each group). Samples from the frontal cortex were harvested and analyzed using TEM or SBF-SEM. While classic TEM revealed that repeated ketamine exposure induces significant mitochondrial swelling in neurons, the newer technique of SBF-SEM confirmed the mitochondrial swelling in three dimensions (3D) and showed that ketamine exposure may also induce mitochondrial fission, which was not observable in the two dimensions (2D) of TEM. Furthermore, 3D statistical analysis of these reconstructed mitochondria appeared to show that ketamine-treated mitochondria had significantly larger volumes per unit surface area than mitochondria from the untreated neuron. The ultrastructural mitochondrial alterations demonstrated here by TEM and SBF-SEM support ketamine’s proposed mechanism of neurotoxicity in the developing rat brain.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Loss of MBD2 affects early T cell development by inhibiting the WNT signaling pathway

Highlights: • MBD2 deficiency resulted in retardation of T cell differentiation at the DN3 stage. • Decreased proliferative capacity and increased apoptosis were detected in Mbd2{sup −/−} DN thymocytes. • MBD2 affects early T cell development by regulating the expression of key genes of WNT pathway. DNA methylation alters the expression of certain genes without any alteration to the DNA sequence and is a dynamic process during normal hematopoietic differentiation. As an epigenetic regulator, methyl-CpG-binding domain protein 2 (MBD2) is an important member of the MBD protein family and is acknowledged as a “reader” of DNA methylation. We used a mouse model to study the effects of MBD2 on the early development of T cells. Here, we found that MBD2 deficiency led to retardation of T cell differentiation at the DN3 stage. Meanwhile, decreased proliferative capacity and increased apoptosis were detected in Mbd2{sup −/−} DN thymocytes. Furthermore, we found the WNT pathway was significantly down-regulated in Mbd2{sup −/−} DN thymocytes: DKK1 (Dickkopf-1) expression was significantly increased, while TCF7 (transcription factor 7) and c-MYC were down-regulated. Thus, these findings established that MBD2 acted as a dominant regulator to imprint DN T cell development via the WNT pathway.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Dual role of Fam208a during zygotic cleavage and early embryonic development

Maintenance of genome stability is essential for every living cell as genetic information is repeatedly challenged during DNA replication in each cell division event. Errors, defects, delays, and mistakes that arise during mitosis or meiosis lead to an activation of DNA repair processes and in case of their failure, programmed cell death, i.e. apoptosis, could be initiated. Fam208a is a protein whose importance in heterochromatin maintenance has been described recently. In this work, we describe the crucial role of Fam208a in sustaining genome stability during cellular division. }The targeted depletion of Fam208a in mice using CRISPR/Cas9 led to embryonic lethality before E12.5. We also used the siRNA approach to downregulate Fam208a in zygotes to avoid the influence of maternal RNA in the early stages of development. This early downregulation increased arresting of the embryonal development at the two-cell stage and the occurrence of multipolar spindles formation. To investigate this further, we used the yeast two-hybrid (Y2H) system and identified new putative interaction partners Gpsm2, Svil, and Itgb3bp. Their co-expression with Fam208a was assessed by RT-qPCR profiling and in situ hybridization [1] in multiple murine tissues. Based on these results we proposed that Fam208a functions within the HUSH complex by interaction with Mphosph8 as these proteins are not only able to physically interact but also co-localise. We are bringing new evidence that Fam208a is a multi-interacting protein affecting genome stability on the cell division level at the earliest stages of development and by interaction with methylation complex in adult tissues. }In addition to its epigenetic functions, Fam208a appears to have an important role in the zygotic division, possibly via interaction with newly identified putative partners Gpsm2, Svil, and Itgb3bp.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and -related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

The development and applications of multidimensional biomolecular spectroscopy illustrated by photosynthetic light harvesting

The parallel and synergistic developments of atomic resolution structural information, new spectroscopic methods, their underpinning formalism, and the application of sophisticated theoretical methods have led to a step function change in our understanding of photosynthetic light harvesting, the process by which photosynthetic organisms collect solar energy and supply it to their reaction centers to initiate the chemistry of photosynthesis. The new spectroscopic methods, in particular multidimensional spectroscopies, have enabled a transition from recording rates of processes to focusing on mechanism. We discuss two ultrafast spectroscopies – two-dimensional electronic spectroscopy and two-dimensional electronic-vibrational spectroscopy – and illustrate their development through the lens of photosynthetic light harvesting. Both spectroscopies provide enhanced spectral resolution and, in different ways, reveal pathways of energy flow and coherent oscillations which relate to the quantum mechanical mixing of, for example, electronic excitations (excitons) and nuclear motions. The new types of information present in these spectra provoked the application of sophisticated quantum dynamical theories to describe the temporal evolution of the spectra and provide new questions for experimental investigation. While multidimensional spectroscopies have applications in many other areas of science, we feel that the investigation of photosynthetic light harvesting has had the largest influence on the development of spectroscopic and theoretical methods for the study of quantum dynamics in biology, hence the focus of this review. We conclude with key questions for the next decade of this review.

59 BASIC BIOLOGICAL SCIENCES↗