Subsequent Transformation Research Articles

New insights of the nucleation and subsequent phase transformation in duplex stainless steel

The solidification behavior, especially involving multi-phase, of duplex stainless steel (DSS) directly determines its microstructures. However, thermodynamic calculations and other reports, which indicates that δ-ferrite is always thermodynamically stable as the primary phase, cannot precisely describe the nucleation and subsequent phase transformations in DSS. Both high temperature confocal microscopy (HTCM) and differential thermal analysis (DTA) are well-established tools for studying solidification behaviors and phase transformation. Here, an in-house build apparatus was employed to investigate the solidification process of DSS. It enables contemporaneous in-situ observation of the surface and thermal analysis of the bulk thermal events. Meanwhile, N2 and Ar are used as protective gas. Dual-peak DTA signals of solidification were recorded under an N2 atmosphere. Furthermore, through the real-time comparison between the DTA signals and the in-situ observations, a solid-state phase transition was accurately located. We propose the following new insight into the solidification mechanism for DSS, by combining experimental results, thermodynamic arguments (Gibbs free energy), and microstructural characterization using electron back scattered diffraction (EBSD): The γ nucleates and grows via a competitive nucleation process, and completely transforms into δ-ferrite in a solid-state phase transformation. After that, part of the δ-ferrite transforms into γ, and the duplex structure remains (L → γ → δ → δ + γ). Heterogeneous nucleation of γ on the liquid surface was also observed, which is quite different from the nucleation and growth pattern of δ-ferrite. These new insights contribute to the improvement of solidification mechanisms of high nitrogen stainless steels and, in turn, microstructures and physical properties of steels in the course of materials production processes.

Electron-Donor Functional Groups, Band Gap Tailoring, and Efficient Charge Separation: Three Keys To Improve the Gaseous Iodine Uptake in MOF Materials.

Metal-organic frameworks (MOFs) have been largely investigated worldwide for their use in the capture of radioactive iodine due to its potential release during nuclear accident events and reprocessing of nuclear fuel. The present work deals with the capture of gaseous I2 under a continuous flow and its subsequent transformation into I3- within the porous structures of three distinct, yet structurally related, terephthalate-based MOFs: MIL-125(Ti), MIL-125(Ti)_NH2, and CAU-1(Al)_NH2. The synthesized materials exhibited specific surface areas (SSAs) with similar order of magnitude: 1207, 1099, and 1110 m2 g-1 for MIL-125(Ti), MIL-125(Ti)_NH2, and CAU-1(Al)_NH2, respectively. Because of that, it was possible to evaluate the influence of other variables over the iodine uptake capacity─such as band gap energies, functional groups, and charge transfer complexes (CTC). After 72 h of contact with the I2 gas flow, MIL-125(Ti)_NH2 was able to trap 11.0 mol mol-1 of I2, followed by MIL-125(Ti) (8.7 mol mol-1), and by CAU-1(Al)_NH2 (4.2 mol mol-1). The enhanced ability to retain I2 in the MIL-125(Ti)_NH2 was associated with a combined effect between its amino group (which has a great affinity toward iodine), its smaller band gap (2.5 eV against 2.6 and 3.8 eV for CAU-1(Al)_NH2 and MIL-125(Ti), respectively), and its efficient charge separation. In fact, the presence of a linker-to-metal charge transfer (LMCT) mechanism in MIL-125(Ti) compounds separates the photogenerated electrons and holes into the two distinct moieties of the MOF: the organic linker (which stabilizes the holes) and the oxy/hydroxy inorganic cluster (which stabilizes the electrons). This effect was observed using EPR spectroscopy, whereas the reduction of the Ti4+ cations into the paramagnetic Ti3+ species was evidenced after irradiation of the pristine Ti-based MOFs with UV light (<420 nm). In contrast, because CAU-1(Al)_NH2 exhibits a purely linker-based transition (LBT)─with no EPR signals related to Al paramagnetic species─it tends to exhibit faster recombination of the photogenerated charge carriers as, in this case, both electrons and holes are located over the organic linker. Furthermore, the transformation of the gaseous I2 into In- [n = 5, 7, 9, ...] intermediates and then into I3- species was evaluated using Raman spectroscopy by following the evolution of their respective bands at about 198, 180, and 113 cm-1. This conversion─which is favored by an effective charge separation and smaller band gaps─increases the I2 uptake capacity of the compounds by creating specific adsorption sites for these anionic species. In fact, because the -NH2 groups act as an antenna to stabilize the photogenerated holes, both In- and I3- are adsorbed into the organic linker via an electrostatic interaction with these positively charged entities. Finally, changes regarding the EPR spectra before and after the iodine loading were considered to propose a mechanism for the electron transfer from the MOFs structure to the I2 molecules considering their different characteristics.

General Approach to Enantiopure 1-Aminopyrrolizidines: Application to the Asymmetric Synthesis of the Loline Alkaloids.

The synthesis of a range of loline alkaloids is reported. The C(7) and C(7a) stereogenic centers for the targets were formed by the established conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 5-benzyloxypent-2-enoate, ensuing enolate oxidation to give an α-hydroxy-β-amino ester, and then formal exchange of the resultant amino and hydroxyl functionalities (via the intermediacy of the corresponding aziridinium ion) to give an α-amino-β-hydroxy ester. Subsequent transformation gave a 3-hydroxyprolinal derivative which was converted to the corresponding N-tert-butylsulfinylimine. Mannich-type reaction with the enolate derived from O-Boc protected methyl glycolate then formed the remaining C(1) and C(2) stereogenic centers for the targets. The 2,7-ether bridge was formed by a displacement reaction, completing construction of the loline alkaloid core. Facile manipulations then gave a range of loline alkaloids, including loline itself.

Separating Oil and Vinegar with a Single Trace

Due to recent cryptanalytical breakthroughs, the multivariate signature schemes that seemed to be most promising in the past years are no longer in the focus of the research community. Hence, the cryptographically mature UOV scheme is of great interest again. Since it has not been part of the NIST process for standardizing post-quantum cryptography so far, it has not been studied intensively for its physical security.In this work, we present a side-channel attack on the latest implementation of UOV. In the first part of the attack, a single side-channel trace of the signing process is used to learn all vinegar variables used in the computation. Then, we employ a combination of the Kipnis-Shamir attack and the reconciliation attack to reveal the complete secret key. Our attack, unlike previous work, targets the inversion of the central map and not the subsequent linear transformation. It further does not require the attacker to control the message to be signed.We have verified the practicality of our attack on a ChipWhisperer-Lite board with a 32-bit STM32F3 ARM Cortex-M4 target mounted on a CW308 UFO board. We publicly provide the code and both reference and target traces. Additionally, we discuss several countermeasures that can at least make our attack less efficient.

Glucagon cell hyperplasia and neoplasia: a recently recognized endocrine receptor disease.

Glucagon cell hyperplasia and neoplasia (GCHN) is the name of an endocrine receptor disease, whose morphology was first described in 2006. Three years later this rare disease was found to be to be caused by an inactivating mutation of the glucagon receptor (GCGR) gene. Functionally, the genetic defect mainly affects glucagon signaling in the liver with changes in the metabolism of glycogen, fatty acids and amino acids. Recent results of several studies in GCGR knockout mice suggested that elevated serum amino acid levels probably stimulate glucagon cell hyperplasia with subsequent transformation into glucagon cell neoplasia. This process leads over time to numerous small and some large pancreatic neuroendocrine tumors which are potentially malignant. Despite high glucagon serum levels, the patients develop no glucagonoma syndrome. In 2015 GCHN was identified as an autosomal recessive hereditary disorder.

Melt-Processed Halide Perovskite Thin Films from a Two-Dimensional Ruddlesden-Popper Phase Precursor.

While halide perovskite thin films have enormous potential for photovoltaics and other optoelectronics, the use of environmentally hazardous solvents during their deposition and processing poses a barrier to their commercialization. In this work, we demonstrated the deposition of melt-processable precursors and subsequent transformation into halide perovskite thin films without using environmentally hazardous solvents. We melted the wide-bandgap layered perovskites [(C6H5CH(CH3)CH2NH3)2PbI4:β-Me-PEA2PbI4] at ∼210 °C and blade coated them into films. The β-Me-PEA2PbI4 films were subsequently transformed to perovskite-phase methylammonium or formamidinium lead iodide films using a cation-exchange process in an alcohol-based solvent. Lastly, we demonstrate the potential and limitations of a completely solvent-free approach that uses solid-state transformation of a β-Me-PEA2PbI4 film. This work represents a substantial step toward eliminating environmentally hazardous solvents and enables inexpensive industrial-scale liquid-phase deposition processes that do not require expensive systems for handling and disposing of environmentally hazardous solvents.

Exploring the Complexities of Dissolved Organic Matter Photochemistry from the Molecular Level by Using Machine Learning Approaches.

Dissolved organic matter (DOM) sustains a substantial part of the organic matter transported seaward, where photochemical reactions significantly affect its transformation and fate. The irradiation experiments can provide valuable information on the photochemical reactivity (photolabile, photoresistant, and photoproduct) of molecules. However, the inconsistency of the fate of irradiated molecules among different experiments curtailed our understanding of the roles the photochemical reactions have played, which cannot be properly addressed by traditional approaches. Here, we conducted irradiation experiments for samples from two large estuaries in China. Molecules that occurred in irradiation experiments were characterized by the Fourier transform ion cyclotron resonance mass spectrometry and assigned probabilistic labels to define their photochemical reactivity. These molecules with probabilistic labels were used to construct a learning database for establishing a suitable machine learning (ML) model. We further applied our well-trained ML model to "un-matched" (i.e., not detected in our irradiation experiments) molecules from five estuaries worldwide, to predict their photochemical reactivity. Results showed that numerous molecules with strong photolability can be captured solely by the ML model. Moreover, comparing DOM photochemical reactivity in five estuaries revealed that the riverine DOM chemistry largely determines their subsequent photochemical transformation. We offer an expandable and renewable approach based on ML to compatibly integrate existing irradiation experiments and shed insight into DOM transformation and degradation processes.

RELATIONSHIP BETWEEN DISEASES OF ORAL MUCOSA AND GASTROINTESTINAL TRACT

A large number of scientific publications are devoted to diseases of the oral mucosa. This is due to their significant variety, prevalence, complexity of diagnosis and treatment, and medical and social significance as a determinant of precancerous diseases with subsequent malignant transformation. The data of professional studies show that most lesions of the oral mucosa are multifactorial and arise along with pathologies of various organs and systems, in particular, immune, cardiovascular, nervous, endocrine, and quite often, with diseases of the gastrointestinal tract. The purpose of this study was a retrospective analysis of professional literary sources devoted to a medically and socially relevant issue, the relationship between diseases of the oral mucosa and pathologies of the gastrointestinal tract. Bibliosemantic and analytical methods were used in the study. The analysis of data from the specialized literature shows the variety of diseases of the mucous membrane of the oral cavity and their close relationship with general somatic pathology. Clinical observations have revealed a significant correlation between chronic diseases such as gastritis, peptic ulcer disease (in the stomach and duodenum), chronic colitis, and enterocolitis, and various lesions of the oral mucous membrane. The severity of these lesions is dependent on the specific form and duration of the underlying gastrointestinal condition. Scientists attribute this relationship to the similarities in morphological structure, shared functions, common blood supply, and innervation. Professional sources substantiate the role of Helicobacter pylori infection and dysbiosis in the development and progression of oral mucosal lesions. The treatment of oral mucous membrane diseases places a significant emphasis on etiotropic therapy. However, when this approach is not feasible, pathogenetic or symptomatic treatment options are utilized.

Precipitation processes of Al-1.7 at% Cu and the influence of Au micro-alloying studied by dilatometry

Micro-alloying represents an important pathway in the design of modern Al-based alloys. It affects the precipitation kinetics during heat treatment which is crucial for optimization of the microstructure. In this study, difference dilatometry is applied to study precipitation processes in Al-1.7 at% Cu alloys with varying Au-content. A quantitative analysis is given for the base Al-Cu alloy on the formation of the metastable θ′-precipitate phase (Al2Cu) and its subsequent dissolution and transformation to the stable θ-precipitate phase (Al2Cu) upon time-linear heating starting from the state of supersaturated solid solution. The dilatometric analysis is enabled by the subtle balance of the relative length changes that arises, on the one hand, from the specific volume increase of the supersaturated Al matrix upon precipitation of the excess alloy component (Cu) and, on the other hand, from the specific volume variation associated with the formation of the precipitates. The relation between the observed relative changes and the amount of precipitates is supported by complementary simulation studies of the precipitation processes using MatCalc software. Micro-alloying with Au is found to promote the θ′-formation by an increasing nucleation and growth rate. In addition to the quantitative length change analysis, information on the kinetics of the θ′-formation is deduced from Kissinger analysis of the maximum rates of length change with temperature for different heating rates.

Neodymium promoted ceria and alumina supported nickel catalysts for CO2 methanation reaction

Two series of catalysts containing 20 wt.% nickel, promoted with different amounts of neodymium from 1 to 10 wt.% were prepared by the impregnation method, using nano-CeO2 and γ-Al2O3 as supports. Ceria supported nickel catalysts showed high activity in CO2 methanation reaction and weak activity changes were observed with an increase in Nd content. X-ray diffraction, hydrogen chemisorption and transmission electron microscopy studies evidenced a decrease in the average size of nickel crystallites and an increase in the active surface area of catalysts. The temperature-programmed reduction, oxidation and CO2 desorption, XPS, Raman and in-situ FTIR spectroscopy indicated complex changes in the nature of their redox and base centres. Non-promoted alumina supported nickel catalyst despite higher surface area showed lower activity than similar catalyst with ceria as support. However, an introduction of Nd-promoter led to strong increase in their activity. Such effect was mainly ascribed to the increase in their basicity, facilitation of CO2 activation and subsequent transformation of the intermediate surface species to methane with participation of hydrogen atoms activated on metallic nickel crystallites.

Fatigue and recrystallization evolution of carbide-free bainitic layer under high-stress rolling sliding contact

The rolling contact fatigue behavior of a newly developed bearing steel with carbide-free bainite, modified by a combination of tungsten inert gas surface melting and subsequent isothermal transformation was investigated. The rolling sliding tests were conducted to determine the vibration response and rolling contact fatigue life. The rolling contact fatigue life of the bainitic layer is 6.623 × 106 cycles, significantly higher than that of the commercial GCr15 steel sample (4.496 × 106 cycles). Focused ion beam technology and transmission Kikuchi diffraction studies on fatigue-tested samples showed that the toughness of the bainitic layer could be improved by the bainitic ferrite and retained austenite, which recrystallizes and forms nanocrystals during the rolling contact fatigue process. Furthermore, high-resolution transmission electron microscope study elucidated that the bainitic layer has better dislocation slip ability and is more prone to recrystallization on the rolling contact fatigue surface, preventing the rapid expansion of fatigue cracks. Moreover, the effect of dissolution of the Fe3C in GCr15 steel on the structure of distorted body-centered cubic crystals and pitting defects was also comparatively investigated.

Revisiting Balassa-Samuelson Hypothesis for Asia – A Critical Appraisal of Literature

Purpose: The present study is aimed at presenting a critical appraisal of the empirical literature on the Balassa-Samuelson hypothesis for emerging and developing Asian countries. Design/methodology/approach: A critical appraisal of the relevant studies is carried out across various important dimensions of the empirical estimation of the Balassa-Samuelson hypothesis including the scheme of sectoral division followed, definitions and proxy variables used for constructing real exchange rate and price series, choice of output and employment series and their subsequent transformation, empirical methodology followed and (theoretically) different variants of the hypothesis chosen for empirical estimation. Findings: Only a handful of studies have investigated the Balassa-Samuelson hypothesis for Asia. Nevertheless, these studies are characterized by a variety of irregularities in dealing with different important features of the theory, which may be of critical importance for yielding consistent empirical estimates. In multi-country studies for Asia, serious inconsistencies are observed whilst handling these critical aspects of the hypothesis. Such irregularities may hold serious implications for model estimates since the empirical evidence from Asia is very mixed, and in many cases, not even robust. Practical implications: The inconsistencies highlighted in this review paper hold strong implications for future research in this area. The selection of price indicators for the construction of real exchange rate series, choice of econometric methodology and the theoretical framework followed are aspects of the empirical verification of the Balassa-Samuelson hypothesis that need to be handled with great caution since they turn out to be most sensitive in relation to yielding intuitively correct and robust model estimates. Originality: To our knowledge, so far, no study on Asia has presented such an extensive appraisal of literature on the productivity-real exchange rate nexus. The present study is therefore novel in the sense that it critically evaluates studies on Asia against all those features of the Balssa-Samuelson theory which may stand responsible for yielding mixed and even contrasting empirical estimates for Asia.

Hot-rolled Al-added medium Mn steel (Fe-8Mn-2.85Al-1Si-0.2C): Microstructural evolution and tensile behavior

In this study, a low Al (<3%) added medium manganese steel has been developed through melting casting route in an open-air induction furnace. The cast steel ingot has been intercritical annealed at 720 °C after hot deformation, that includes hot forging and hot rolling treatment, respectively. Microstructure characterization coupled with X-ray diffraction (XRD) has been performed after each processing step to understand the extent of austenite formation and its subsequent transformation to ferrite/martensite. The processed steel possesses the ultimate tensile strength, yield strength and ductility of 1000±20 MPa,700±10 MPa and 18.5 ± 0.5, respectively. To understand the possible cause of enhanced strength and deformation mode rietveld analysis has been carried out. It reveals that developed (final processed) steel possesses ∼18% (volume%) of austenite that subsequently reduced to ∼6.139% after tensile testing, indicating significant transformation of austenite to martensite (continuous and enhanced TRIP effect). The morphological characteristic of martensite in developed steel has been investigated using transmission electron microscopy (TEM). It reveals lath morphology of martensite due to low carbon content. The TEM and 3D atom probe analysis reveals the precipitation of intergranular type kappa (k) carbide in intercritically annealed specimens due to probable segregation of C and Al. However, volume fraction of the same is low. The SFE of the steel has been found to be ∼16 mJ m− 2, calculated by the modified Olson and Cohen method that also concludes TRIP is the preferred deformation mechanism in the developed steel.

Engineered Monoamine Oxidase-Catalyzed Deracemization of Sterically Hindered Acylaminomethyl-tetrahydroisoquinoline: Asymmetric Synthesis of (R)-(−)-Praziquantel and Its Analogues

At present, praziquantel (PZQ) is the only drug utilized in clinics for the control and treatment of all forms of schistosomiasis, which is a neglected tropical disease infecting over 200 million people. As only the R-isomer of PZQ is biologically active and devoid of associated undesired properties, the development of a stereoselective, sustainable, and cost-effective synthesis of (R)-PZQ is of paramount significance. Herein, a known monoamine oxidase variant, MAO-N-D11D, which showed a specific activity of merely 0.003 U/mg toward 1-cyclohexanecarboxylaminomethyl-tetrahydroisoquinoline (THIQ) (1a), a synthetic intermediate to PZQ, was extensively engineered using combinatorial active-site saturation test/iterative saturation mutagenesis and site-saturation mutagenesis, resulting in the identification of an evolved variant, referred to as LJY-FM, exhibiting 134-fold elevated specific activity (0.401 U/mg) and 260-fold enhanced catalytic efficiency (26,989 min–1 M–1) toward 1a relative to MAO-N-D11D, respectively. After optimizing protein expression and reaction conditions, gram-scale deracemization of 50 mM of 1a catalyzed by variant LJY-FM was executed in the presence of ammonia borane, with (R)-1a, a critical intermediate to (R)-PZQ, being furnished with 76% isolated yield and 96% ee. Subsequent transformation of (R)-1a to (R)-PZQ was achieved in 82% yield. Moreover, eight 1-acylaminomethyl-THIQ derivatives, (R)-1b to (R)-1i, were prepared in 44–99% isolated yields with 90 to >99% ee through a LJY-FM-catalyzed deracemization process. To the best of our knowledge, our work represents the first application of monoamine oxidase to the synthesis of (R)-PZQ or its synthetic intermediates. We expect the efficient, stereoselective, and sustainable synthesis of (R)-PZQ established in the current study to be harnessed for the eventual development of a cost-effective, green production route of this antischistosomal agent, thereby leading to the realization of replacing the clinical use of praziquantel by (R)-praziquantel in the future.

Картографическая реконструкция природопользования на основе ретроспективных топографических карт

Taking the most developed part of the Baikal basin as example a digital cartographic reconstruction of the regional nature management of the early XX century is compiled; it enables establishing the physical and geographical characteristics of the territory economic use in the past. As a result of nature management objects retrospective layers vectorization and subsequent transformation of their shp files into the ArcGIS environment spatial object classes, two cartographic sets of such classes were formed. They characterize two types of regional nature use, traditional pastoral and invasive agricultural. As a result of layer-by-layer geoinformation modeling of cartographic sets on a modern topographic basis and a digital relief model, primary areas of settlement and economic use of the territory were established, and various mapping of spatial and temporal life support structures of nature management different types was performed. For operational digital visualization, a technological solution is proposed for storing and mapping sets of classes of spatial objects through arrangement of a file-based geodata of the ArcGIS information environment. Cartographic reconstructions of pastoral and agricultural nature management at the beginning of the XX century are presented, as well as its general cartographic reconstruction on landscape basis.

Illustration of Joule dissipation on the time-dependent stagnation point flow of nanofluid through a porous surface

The proposed flow problem is to analyze the behavior of dissipative heat on the time-dependent stagnation motion of nanofluids through a permeable surface. A novel approach to thermal buoyancy through the permeable medium enriches the flow properties. In the recent industrial applications for the cooling processes of the device, like the physiological application of the blood flow inside the capillary tube-like artery, drug delivery system, etc., the role of nanofluid is crucial. The proposed model equipped with various physical properties is used to design and subsequent transformation into a non-dimensional form is obtained for a set of similarity variables. Proposed models with different physical properties are designed and subsequent dimensionless transformations are obtained for a similar set of variables. In addition, shooting based Runge-Kutta fourth-order numerical technique is used to solve boundary value problems for nonlinear ordinary systems. The characteristics of the diversified quantities are presented graphically as well as numerically on the flow profile and other profiles. Furthermore, statistical approaches such as t-tests for simulated results of rate coefficients are also presented and validated with the obtained results. However, the important outcomes are presented as; the fluid velocity is controlled by the inclusion of the particle concentration as well as the magnetic parameter further the particle concentration and the dissipative heat encountered by the inclusion of Eckert number enhances the fluid temperature.

Phase stability and phase transformation related to Nb/Ta additions in a Ni-based superalloy

Alloys based on Inconel 725, and with elevated levels of Nb and Ta, have been designed for application in environments requiring high strength and corrosion resistance at elevated temperatures. The present study further examines the phase stability and subsequent phase transformation in those alloys following aging and long-term exposure of up to 10,000 h at 700 °C. Changes in the microstructure were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Two alloy bases with different Ti/Al ratio were considered. Following aging, the Nb/Ta additions favor the development of γ′/γ″ co-precipitates in the low Ti/Al ratio alloy, whereas the high Ti/Al ratio counterpart only contained γ″ precipitates. Upon 10,000 h exposure, complex geometrical closed-packed (GCP) phases formed from the γ′/γ″ co-precipitates in a layer-by-layer manner, i.e., the plate-like δ phase precipitates became decorated by blocky α-Cr and enveloped by a wavy γ′ film. Increasing the concentration of Nb and/or Ta did not change the basic characteristic of this phase transformation; however, the precipitate number density increased in the grain interior. On the other hand, the Ta addition in the alloy with low Ti/Al ratio promoted the formation of Ta-rich η precipitates at the grain boundaries while Nb promoted δ precipitates. The underlying phase transformation behavior of the layer-by-layer structure is likely initiating from the γ″-δ phase transition that ejects Cr and Ti into the neighboring phases, thus resulting in local phase separation into α-Cr and γ′ thin film. This phase transformation process had a significant impact on the phase morphologies in the high Nb/Ta alloys exposed at 700 °C for 10,000 h, with experimental results contradicting those from computational prediction.

Uterine Endometrial Stromal Tumors With Pure Low-Grade Morphology Harboring YWHAE::NUTM2 Fusions: Report of a Case Series Emphasizing Potential for High-Grade Transformation and Aggressive Behavior.

Uterine endometrial stromal sarcomas (ESS) with YWHAE::NUTM2 gene fusions are typically morphologically high-grade tumors composed of atypical round cells, sometimes associated with a low-grade fibromyxoid component; they are currently included in the category of high-grade ESS (HGESS). We report 5 morphologically pure low-grade endometrial stromal tumors harboring YWHAE::NUTM2 fusions, including 1 endometrial stromal nodule (ESN) and 4 low-grade endometrial stromal sarcomas (LGESS), an association only occasionally reported previously. Patients ranged from 30 to 51 (mean=43) years and tumors from 4.5 to 7.5cm (mean=5.7). All were stage I at diagnosis (confined to the uterus). Microscopically, the 4 LGESS showed extensive "tongue-like" invasion of the myometrium, and the ESN was entirely confined to the endometrium with no myometrial invasion. All tumors were composed entirely of morphologically uniform bland ovoid cells resembling proliferative endometrial stroma. A fibromyxoid component was seen in 1 LGESS and the ESN; in the LGESS, this was the sole component. Atypical round cells characteristic of YWHAE::NUTM2 HGESS were not identified. Mitotic count ranged from <1 to 13 per 10 high-power fields (mean: 3). CD10 was positive in 2/4 (focal), estrogen receptor in 5/5 (focal=1; diffuse=4), progesterone receptor in 5/5 (focal=1; diffuse=4) and cyclin D1 was diffusely positive in 3/4. Follow-up was available in all 5 patients and ranged from 6 to 159 months (mean=72). Two patients with LGESS had recurrent disease at 15 and 155 months; 1 showed predominantly LGESS with rare round cells in the initial recurrence and pure HGESS in a subsequent recurrence, while the other patient's recurrent tumor was predominantly HGESS (90%) in a background of focal fibromyxoid LGESS (10%). Both patients rapidly progressed and died of disease within 5 months of high-grade recurrence. We show that rare cases of morphologically pure low-grade endometrial stromal tumors, some but not all with a fibromyxoid component, harbor YWHAE::NUTM2 fusions and may recur rapidly, with transformation to HGESS and aggressive behavior. Our findings suggest that at least a subset of YWHAE::NUTM2 HGESS evolves from LGESS. We suggest that cyclin D1 and CD10 staining should be performed in all LGESS. Diffuse staining for cyclin D1 and/or negative or focal staining for CD10 should suggest the possibility of a YWHAE::NUTM2 fusion, and appropriate molecular testing should be undertaken. Since no single morphological or immunohistochemical parameter is entirely sensitive for fusion status, we also suggest that testing for a YWHAE::NUTM2 gene fusion should be considered in all cases of LGESS and, if a fusion is present, this should raise the possibility of subsequent high-grade transformation and aggressive behavior, even though such cases should still be categorized as LGESS. Although seemingly rare, ESN and LGESS with YWHAE::NUTM2 fusions may be under-recognized due to a lack of routine fusion testing.

Abstract 3045: Role of CD10 negative stroma in the development of precursor lesion of endometriosis associated ovarian cancer

Abstract Introduction: Ovarian clear cell carcinoma (OCCC) is a rare, aggressive, chemo-resistant subtype of epithelial ovarian cancer, and is associated with a significantly worse five-year survival compared to other ovarian cancer types. This is in part due to its distinct cell of origin which is thought to arise within sites of endometriosis. Atypical endometriosis is considered a precursor lesion of endometriosis-associated ovarian cancers, including OCCC. However, the mechanism underlying the development of atypical endometriosis and subsequent malignant transformation is still unknown. We recently demonstrated the existence of a OCCC tumor-promoting mesenchymal stem cell (enMSCs), marked by the loss of CD10 expression, within the endometriotic microenvironment. Further, we demonstrated that CD10 negative enMSCs selectively enhance OCCC growth, but not high-grade serous ovarian cancer (HGSOC) growth which provides further evidence that the endometriotic microenvironment is uniquely supportive of OCCC tumorigenesis. Thus, we hypothesized that loss of stromal CD10 expression leads to the creation of the precursor microenvironment for OCCC. Methods: EnMSCs and endometriosis epithelial cells were isolated from endometriosis tissue. Tissues were collected from women who undergo surgery for benign endometriosis. Based on surface CD10 expression, enMSCs were divided into CD10 negative or positive populations. Endometriosis epithelium proliferation was assessed using in vitro assays. Long term organoid of CD10 negative enMSCs and endometriosis epithelium were implanted into NSG mice to assess tumor initiation capacity. Results: Our data showed that co-culture with CD10 negative enMSCs enhanced the proliferation of endometriosis epithelium. Further, CD10 negative enMSCs enhanced the sphere formation capacity (sphere number and sphere size) of endometriosis epithelial cells when compared to endometriosis epithelium co-cultured with CD10 positive enMSCs or cultured alone. Furthermore, long term growth of organoids containing CD10 negative enMSCs and endometriosis epithelium stimulated the development of cytologic atypia in the epithelial cells. Strikingly, these organoids, when injected into the fat pad of NSG mice, initiated localized tumors. In summary, our data highlighted the role of CD10 negative enMSCs in the development of cytologic atypia in endometriosis epithelium and inducing tumor formation in vivo. This work has the potential for significant clinical impact as identification of a stromal biomarker for OCCC development would have important implications in the clinical management of women with endometriosis, including determining the need for risk-reducing surgery. Further, this work has the potential to identify new targets to disrupt the unique microenvironment of OCCC, thus providing new therapeutic strategies for this deadly disease. Citation Format: Huda Issa Atiya, Lan Coffman. Role of CD10 negative stroma in the development of precursor lesion of endometriosis associated ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3045.

Abstract 2456: Transcriptional signatures of stem cell phenotypes in normal and clonal hematopoiesis

Abstract Clonal hematopoiesis (CH) is an age-related clonal expansion of hematopoietic stem cells (HSCs). Factors that shape the progression of CH are only beginning to be characterized. HSCs are a heterogeneous population of cells with distinct clonal outputs over time, which are hypothesized to be largely scripted in epigenetic and transcriptional cell state. Molecular properties of HSC states that mediate clonal behaviors of two major driver mutations in CH - DNMT3A and TET2 - represent potential therapeutical targets. Recent studies have identified the landscape of human CH mutant cells compared to non-mutated ones. However, the notion of a specific molecular target identified in CH cells associated with selective advantage or predisposition for subsequent transformation requires a formal validation by longitudinal studies. To uncover molecular underpinnings of CH-driven clonal phenotypes in human HSCs in vivo, we combined clonal analysis using heritable expressed DNA barcodes with single-cell transcriptomics using transplant in immunodeficient mice. We developed a statistical approach to associate transcriptional differences of HSCs with the clone phenotypes, such as size and HSC density, across more than a hundred of detected clones. It revealed robust transcriptional signatures underlying clone size and HSC density, which are largely complementary to transcriptional programs activated in TET2 and DNMT3A mutant HSCs. Of note, the clone size and density of HSCs in the clone tend to be uncoupled and associated with distinct transcriptional processes. Citation Format: Ruslan Soldatov, Giulia Schiroli, Peter Kharchenko, David Scadden. Transcriptional signatures of stem cell phenotypes in normal and clonal hematopoiesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2456.