Study of Radiation Embitterment and Degradation Processes of Li2ZrO3 Ceramic under Irradiation with Swift Heavy Ions

The work is devoted to the study of radiation damage and subsequent swelling processes of the surface layer of Li2ZrO3 ceramics under irradiation with heavy Xe22+ ions, depending on the accumulation of the radiation dose. The samples under study were obtained using a mechanochemical synthesis method. The samples were irradiated with heavy Xe22+ ions with an energy of 230 MeV at irradiation fluences of 1011–1016 ion/cm2. The choice of ion types is due to the possibility of simulating the radiation damage accumulation processes as a result of the implantation of Xe22+ ions and subsequent atomic displacements. It was found that, at irradiation doses above 5 × 1014 ion/cm2, point defects accumulate, which leads to a disordering of the surface layer and a subsequent decrease in the strength and hardness of ceramics. At the same time, the main process influencing the decrease in resistance to radiation damage is the crystal structure swelling as a result of the accumulation of defects and disordering of the crystal lattice.

RELIABILITY OF CORRODED STIFFENED PLATE SUBJECTED TO UNIAXIAL COMPRESSIVE LOADING

The work is focused on the reliability of corroded stiffened plates subjected to compressive uniaxial load based on the progressive collapse approach as stipulated by the Common Structural Rules for Bulk Carriers and Oil Tankers, employing the limit state design. Two different cases have been investigated. In the first model, the corrosion degradation led to uniform thickness loss, whereas the mechanical properties were unchanged, as given in the Rules. In the second model, the plate thickness degradation was followed by mechanical properties reduction. The uncertainties related to the mechanical properties, thicknesses, and initial imperfections of the corroded stiffened plate were taken into account. Several initial design solutions of stiffened plates, as well as different severity levels of corrosion degradation were investigated. The results show that structural reliability significantly decreases with corrosion development, especially when in addition to the initial imperfections and corrosion plate thickness reduction, corroded plate surface roughness and the changes in the mechanical properties were considered. The uncertainties, their origins and confidence levels are discussed. It was found that non-linear time-dependent corrosion degradation accounting not only for the thickness reduction due to corrosion wastage but also the subsequent decrease of mechanical properties lead to a significant reduction in the reliability index. Additionally, it was defined that the reliability estimate is very sensitive to the uncertainties related to the initial thickness and the spread of corrosion degradation as a function of the time. Incorporating the probability of corrosion detection into the original reliability model introduces additional information about the validity of structural degradation that may lead to a higher beta reliability index estimate compared to the original model.

Case Report: Early 68Ga-PSMA-PET Metabolic Assessment and Response to Systemic Treatment for First-Line Metastatic Clear Cell Renal Cell Carcinoma; About Two Clinical Cases

Early evaluation of response to anticancer treatment in metastatic renal cell carcinoma (RCC) is challenging as responses are sometimes delayed, as mixed responses can occur, and as conventional imaging have some limitations. As PSMA has been previously identified in neovasculature of clear cell RCC (ccRCC), 68Ga-PSMA-Positron Emitted Tomography (PET) could appear as an interesting tool to evaluate therapeutic response. We describe the association of an early decrease in 68Ga metabolism (at 8 weeks after treatment onset) and further radiological response (at 12 weeks after treatment onset) to treatment in two patients with different sensitivity to axitinib–pembrolizumab combination. Interestingly, one of these patients presented an initial progressive disease on pembrolizumab alone and a subsequent response to axitinib alone in the disease course; these response profiles were associated with absence of decrease and subsequent decrease in the 68Ga metabolism, respectively. Even if further prospective trials are needed, 68Ga-PSMA-PET may appear as a promising way for early prediction of response to ccRCC systemic treatment.

Sortie-based aircraft component demand rate to predict requirements

PurposeForecasting techniques improve supply chain resilience by ensuring that the correct parts are available when required. In addition, accurate forecasts conserve precious resources and money by avoiding new start contracts to produce unforeseen part requests, reducing labor intensive cannibalization actions and ensuring consistent transportation modality streams where changes incur cost. This study explores the effectiveness of the United States Air Force’s current flying hour-based demand forecast by comparing it with a sortie-based demand forecast to predict future spare part needs.Design/methodology/approachThis study employs a correlation analysis to show that demand for reparable parts on certain aircraft has a stronger correlation to the number of sorties flown than the number of flying hours. The effect of using the number of sorties flown instead of flying hours is analyzed by employing sorties in the United States Air Force (USAF)’s current reparable parts forecasting model. A comparative analysis on D200 forecasting error is conducted across F-16 and B-52 fleets.FindingsThis study finds that the USAF could improve its reparable parts forecast, and subsequently part availability, by employing a sortie-based demand rate for particular aircraft such as the F-16. Additionally, our findings indicate that forecasts for reparable parts on aircraft with low sortie count flying profiles, such as the B-52 fleet, perform better modeling demand as a function of flying hours. Thus, evidence is provided that the Air Force should employ multiple forecasting techniques across its possessed, organically supported aircraft fleets. The improvement of the forecast and subsequent decrease in forecast error will be presented in the Results and Discussion section.Research limitations/implicationsThis study is limited by the data-collection environment, which is only reported on an annual basis and is limited to 14 years of historical data. Furthermore, some observations were not included because significant data entry errors resulted in unusable observations.Originality/valueThere are few studies addressing the time measure of USAF reparable component failures. To the best of the authors’ knowledge, there are no studies that analyze spare component demand as a function of sortie numbers and compare the results of forecasts made on a sortie-based demand signal to the current flying hour-based approach to spare parts forecasting. The sortie-based forecast is a novel methodology and is shown to outperform the current flying hour-based method for some aircraft fleets.

Observation Based Budget and Lifetime of Excess Atmospheric Carbon Dioxide

The global budgets of CO2 and of excess CO2 (i.e., above preindustrial) in the biogeosphere are examined by a top-down, observationally constrained approach. Global stocks in the atmosphere, mixed-layer and deep ocean, and labile and obdurate terrestrial biosphere, and fluxes between them are quantified; total uptake of carbon by the terrestrial biosphere is constrained by observations, but apportionment to the two terrestrial compartments is only weakly constrained, requiring examination of sensitivity to this apportionment. Because of near equilibrium between the atmosphere and the mixed-layer ocean and near steady state between the atmosphere and the labile biosphere, these three compartments are tightly coupled. For best-estimate present-day anthropogenic emissions the turnover time of excess carbon in these compartments to the deep ocean and obdurate biosphere is 67 to 158 years. Atmospheric CO2 over the Anthropocene is accurately represented by a five-compartment model with four independent parameters: two universal geophysical quantities and two, specific to CO2, treated as variable. The model also accurately represents atmospheric radiocarbon, particularly the large increase due to atmospheric testing of nuclear weapons and the subsequent decrease. The adjustment time of excess atmospheric CO2, evaluated from the rate of decrease following abrupt cessation of emissions, is 78 to 140 years, consistent with the turnover time, approaching a long-time floor of 15–20 % of the value at the time of cessation. The lifetime of excess CO2 found here, several-fold shorter than estimates from current carbon-cycle models, indicates that cessation of anthropogenic emissions atmospheric would result in substantial recovery of CO2 toward its preindustrial value in less than a century.

THE EFFICIENCY OF THE WATER PURIFICATION PROCESS FROM BACTERIA DEPENDING ON THE GAS NATURE

A study of the influence of different gas nature on the efficiency of water purification from rod-shaped bacteria of the Bacillus cereus type is presented. The action of oxygen, carbon dioxide and inert argon and helium were used. The investigated water was model microbial water obtained on the basis of deaerated distilled water with the introduction of a pure culture of bacteria in the amount of 7 · 104 CFU/cm3. The total duration of the process was 2 hours at a reaction medium with temperature of 288 ± 1 K. The change in the number of microorganisms from the duration of gas bubbling is shown, depending on its nature. The degrees of destroyed microorganisms were calculated after each sampling of water (Dd), which was taken after each 30 min of the process. Studying the influence of different modes of water treatment, the largest number of destroyed bacterial cells was studied in an atmosphere of carbon dioxide (Dd = 91.0 %), and the smallest - in an atmosphere of oxygen (Dd = 34.73%). A two-stage process of number of microorganisms change was detected in the oxygen atmosphere: an increase in the first stage during 1800 s and a subsequent decrease in the second stage. After CO2 bubbling with a rate of 0.2 cm3/s through an aqueous medium with a volume of 75 cm3, the microbial count decreased by two orders of magnitude, which is apparently due to an increase in the acidity of the test medium. Having found a high efficiency of CO2 on the process of bacterial cells destruction, this gas should be used in water treatment processes, as well as in combination with other reagents or physical methods of water treatment to enhance the destructive effect on micro-objects.

Effect of Additional Buoyancy Swimsuits on Performance of Competitive Swimmers

Background: When in water, the Centers of Buoyancy (CoB) and Mass (CoM) of the human body are positioned cranially and caudally, respectively. With increasing distance between these centers, the sinking torque of the lower limbs increases, with a subsequent decrease in swimming performance due to increased drag. Objective: To clarify the effect of additional buoyancy swimsuits on swimming performance. Methods: The subjects were eight competitive male swimmers of mean ±SD age 21±2 years. Swimming performance was compared between Conventional (CS) and Additional Buoyancy Swimsuits (ABS). CoM and CoB were identified on land and in water, respectively, with the swimmers maintaining a horizontal posture. CoM was measured by the reaction board method. CoB was calculated as the force exerted in the vertical direction accompanied by changes in inspiratory volume. Swimming velocity and Blood Lactate (BL) concentration value during 200 m front crawl in trials at four different speeds (curve test) were recorded as swimming performance. Results: No significant difference in inspiratory volume was observed between CS and ABS (small effect size, d=0.28). The distance between CoM and CoB was significantly shorter for CS than ABS (p < 0.001; large effect size, d=1.08). Both swimming velocity at BL of 4 mmol·L-1 and maximal effort were significantly faster for ABS (p < 0.042; 0.008), with large effect size (d=0.91; 0.98). However, there was no significant difference in maximal BL between CS and ABS (small effect size, d=0.37). Conclusion: ABS improves swimming performance by streamlining the horizontal posture.

Deciphering the molecular mechanism of the cancer formation by chromosome structural dynamics

Cancer reflects the dysregulation of the underlying gene network, which is strongly related to the 3D genome organization. Numerous efforts have been spent on experimental characterizations of the structural alterations in cancer genomes. However, there is still a lack of genomic structural-level understanding of the temporal dynamics for cancer initiation and progression. Here, we use a landscape-switching model to investigate the chromosome structural transition during the cancerization and reversion processes. We find that the chromosome undergoes a non-monotonic structural shape-changing pathway with initial expansion followed by compaction during both of these processes. Furthermore, our analysis reveals that the chromosome with a more expanding structure than those at both the normal and cancer cell during cancerization exhibits a sparse contact pattern, which shows significant structural similarity to the one at the embryonic stem cell in many aspects, including the trend of contact probability declining with the genomic distance, the global structural shape geometry and the spatial distribution of loci on the chromosome. In light of the intimate structure-function relationship at the chromosomal level, we further describe the cell state transition processes by the chromosome structural changes, suggesting an elevated cell stemness during the formation of the cancer cells. We show that cell cancerization and reversion are highly irreversible processes in terms of the chromosome structural transition pathways, spatial repositioning of chromosomal loci and hysteresis loop of contact evolution analysis. Our model draws a molecular-scale picture of cell cancerization from the chromosome structural perspective. The process contains initial reprogramming towards the stem cell followed by the differentiation towards the cancer cell, accompanied by an initial increase and subsequent decrease of the cell stemness.

Multi-Recombinase Mouse Models of Flt3-Driven Leukemia Identifies Distinct Trajectories of Mutational Cooperativity and Leukemic Transformation

Genomic studies in acute myeloid leukemia (AML) have generated a near complete catalogue of genes mutated at varying frequencies both across patients and in individual leukemias. The high variability of mutation burden within a given leukemia is suggestive of a stepwise evolutionary process composed of early, clonal, mutations and subsequent subclonal events. The receptor tyrosine kinase, FLT3, is the most commonly mutated gene in AML, with mutations frequently manifesting as internal tandem duplications (ITDs) in the juxtamembrane domain leading to constitutive kinase activation. Although FLT3 is commonly a subclonal mutational event, FLT3 ITD mutations portend a poor prognosis particularly when combined with DNMT3A and NPM1, earlier mutations that drive clonal expansion. Notwithstanding its role as a subclonal driver, previous preclinical FLT3 models have utilized retroviral overexpression or germline mutant expression at the endogenous locus precluding accurate temporal modeling of disease. These efforts have prohibited evaluation of FLT3 mutational acquisition in the context observed in AML patients. Here, we report the development of an endogenously targeted, Flp inducible, Flt3 ITD mouse allele which can be somatically activated subsequent to cooperating disease alleles. When activated with a tamoxifen inducible FlpoER, Flt3 mutant mice developed rapid leukocytosis peaking at 4-6 weeks post activation and resolving by 8-10 weeks, a finding not previously observed in constitutive models. This leukocytosis was disproportionately monocytic and accompanied by pronounced anemia and thrombocytopenia. Long term, these mice develop a myeloproliferative disease , reminiscent of previously reported constitutive alleles. In competitive transplantation studies, Flt3 mutant cells initiated disease and outcompeted wild-type cells. Despite this competitive advantage, disease was incapable of transplanting into secondary recipients. We further observed a non-cell autonomous depletion of SLAM+ LSKs suggesting the Flt3 mutant cells cannot propagate disease in self-renewing stem cells. To evaluate how this allele influenced leukemic evolution we crossed this Flt3 ITD allele to a Flp inducible Npm1 c mouse where a pulse of tamoxifen simultaneously activated both alleles. The combination of mutant Npm1 and Flt3 resulted in progressive leukocytosis which did not resolve. Within 6 weeks of mutational activation, these mice developed a lethal AML with robust anemia, thrombocytopenia, leukocytosis and expanded cKIT+ blasts in the blood. RNA-sequencing and immunophenotyping by CyTOF revealed distinct patterns of differentiation, gene-expression and downstream signaling.In an effort to model sequential mutational acquisition, we crossed the Flp Flt3 ITD allele to a Cre-inducible Dnmt3a R878H. Cre mRNA was electroporated into lineage negative bone marrow cells to activate the Dnmt3a R878H allele and transplanted into lethally irradiated recipients. Four weeks post engraftment, Flt3 ITD was activated with a pulse of tamoxifen. In contrast to the Flt3-Npm1 model, we observed an increase and subsequent decrease in WBC similar to the kinetics observed in Flt3 ITD only mice. However, by 20 weeks we observed a robust and consistent increase in WBC accompanied by an emergence of cKIT+ cells in the blood. Histopathology indicated that &gt;50% of mice expressing both alleles in sequence developed AML marked by increased blasts in the marrow, with moderate anemia and thrombocytopenia compared to the Flt3-Npm1 models. Critically, in contrast to Flt3 ITD only mice, acquisition of the Flt3 ITD in Npm1 or Dnmt3a mutant HPSCs induced fully transplantable AML with immunophenotypic characteristics seen in human AML with these same genotypes. Collectively these results demonstrate that different co-occurring mutations are capable of transforming Flt3 ITD mutant cells, albeit with distinct latencies and mechanisms of cooperativity. In summary, our studies utilizing novel multi-recombinase models of leukemogenesis reveal new insights into the early phase of oncogene activation, and how cooperating alleles influence this response. This inducible Flt3 ITD allele represents a significant advance in modeling clonal evolution in myeloid malignancies and provides a critical isogenic platform for preclinical development of novel leukemia therapeutic regimens. Figure 1 Figure 1. Disclosures Bowman: Mission Bio: Honoraria, Speakers Bureau. Xiao: Stemline Therapeutics: Research Funding. Miles: Mission Bio: Honoraria, Speakers Bureau. Trowbridge: Fate Therapeutics: Patents & Royalties; H3 Biomedicine: Research Funding. Levine: Amgen: Honoraria; Lilly: Honoraria; Mission Bio: Membership on an entity's Board of Directors or advisory committees; Imago: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Ajax: Membership on an entity's Board of Directors or advisory committees; QIAGEN: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Zentalis: Membership on an entity's Board of Directors or advisory committees; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Janssen: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; Incyte: Consultancy; Auron: Membership on an entity's Board of Directors or advisory committees; Prelude: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees.

A Deep Learning Technique for Classification of Breast Cancer Disease

In recent years researchers are intensely using machine learning and employing AI techniques in the medical field particularly in the domain of cancer. Breast cancer is one such example and many studies have proposed CAD systems and algorithms to efficiently detect cancer cells and tumors. Breast cancer is one of the dreadful cancers accounting for a large portion of deaths caused due to cancer worldwide mostly affecting women, needs early detection for proper diagnosis, and subsequent decrease in death rate. Thus, for efficient classification, we implemented different ML techniques on Wisconsin dataset [1] namely SVM, KNN, Decision Tree, Random Forest, Naive Bayes using accuracy as a performance metric, and as per observance, SVM has shown better results when compared to other algorithms. Also, we worked on Breast Histopathology Images [2] scanned at 40x which had images of IDC which is one of the most common types of breast cancers. And to work with the image dataset along with EDA we used high-end techniques like a mobile net where smote a resampling was used to handle imbalanced class distribution, CNN, SVC, InceptionResNetV2 where frameworks like Tensor Flow, Keras were loaded for supporting the environment and smoothly implement the algorithms.