Allowing the Actual Evapotranspiration Uncertainty in Hydrological Models: Coupling of Interval-Based Water Balance and METRIC Models

Against the paramount role of actual evapotranspiration (ET) in hydrological modeling, determining its values is mixed with different sources of uncertainties. In addition, estimation of ET with energy-based methods (e.g., METRIC) leads to different results with various acceptable initial and boundary conditions (such as land use and cold/hot pixels). The aim of the current research is to allow the uncertainty effects of ET as an interval-based input variable in hydrological modeling. The goal is achieved via feeding the uncertainty of computed ET values to the developed Interval-Based Water Balance (IBWB) model in terms of gray values. To this purpose, the comprehensive monthly water balance model (including surface and groundwater modules) has been revised to a new interval-based form. Moreover, the METRIC model has been used 20 times in each month of computational period to calculate the ET patterns with different hot/cold pixels to provide monthly ensemble ET values. For a comprehensive assessment, the selected water balance model has been calibrated with ensemble means of the computed ET with its classical type. The study area is a mountainous sub-basin of the Sefidrood watershed, Ghorveh-Dehgolan basin, with three alluvial aquifers in the North of Iran. Not only the paradigm shift from determinist to interval-based hydrologic structure improved the statistical metrics of the models’ responses, but also it decreased the uncertainty of the simulated streamflow and groundwater levels.

Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development.

Oleksii Chumakov’s Creative Activity

The article analyzes various aspects of Oleksii Chumakov’s creative activity. Oleksii Chumakov’s activity can be considered as striking in its variety of creative manifestations. His singing career is harmoniously combined with his work as a composer and arranger. The purpose of the article is to identify the specifics of stylistic dimensions of O. Chumakov’s work. The article analyzes various aspects of O. Chumakov’s activity, which impresses with the variety of creative manifestations. The artist harmoniously combines the singer’s career with composing and arranging skills. The research methodology consists oftheoretical methods (analysis, synthesis, generalization, biographical method), as well as empirical ones to observe the multifaceted work of O. Chumakov. The scientific novelty of the research is that the main features of O. Chumakov’s work are revealed, it is found out that the artist’s vocal skill is manifested in the use of soul singing. The style of Chumakov's compositions makes it possible to use the traditions of the gospel. The dominant directions in which his songs were written are funk, fusion, pop. Conclusions. It is noted that singers, who combine performance with composing, arranging, working in a recording studio, can rightly be considered professionals in their field. Having practical vocal skills, the composer takes into account the technical capabilities of singers, trying to emphasize their strengths. Oleksii Chumakov is also a presenter, writer and actor. All these qualities testify his versatility and high professionalism. In the concert performances of the singer, there is no bright effect or extraordinary scenography, because the performer prefers the ‘classical’ type of stage behaviour when the main emphasis is on the musical side of the compositions. Vocal skill, which manifests itself in the use of various vocal manners, intonation accuracy and stylistic sophistication, are the dominant elements of O. Chumakov’s performances.

Two Liberibacter Effectors Combine to Suppress Critical Innate Immune Defenses and Facilitate Huanglongbing Pathogenesis in Citrus

Genome sequence analyses predicted the presence of effectors in the gram-negative Candidatus Liberibacter asiaticus (CLas) even without the presence of a classical type III secretion system. Since CLas is not culturable, it is not possible to perform traditional gene knockout experiments to determine the role of various effectors in Huanglongbing (HLB) pathogenesis. Therefore, we followed an alternative functional genomics approach to examine the role of the CLas effectors in HLB pathogenesis in general and more specifically in suppressing citrus innate immune response. Here, we focused on the CLas effectors, P235 and Effector 3, to perform the following studies. First, proteomic studies by LC-MS/MS were conducted to screen the putative interacting citrus protein partners of P235 and Effector 3 from the healthy and CLas-infected Hamlin extracts and the most probable candidates were identified based upon their high protein scores from LC-MS/MS. Second, a transgenic tobacco split GFP system was designed for in planta detection of the most probable citrus interacting protein partners of P235 and Effector 3. Third, in vitro and in planta studies were performed to show that each of two effectors interacts with and inhibits the functions of multiple citrus proteins belonging to the innate immune pathways. These inhibitory interactions led to a high level of reactive oxygen species (ROS), blocking of bactericidal lipid binding protein (LTP), and induction of premature programmed cell death (PCD), thereby supporting CLas infection and HLB pathogenesis. Finally, an LTP mimic was designed to sequester and block the CLas effector and to rescue the bactericidal activity of LTP.

Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis

Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.

Clinical Impact of Molecular Subtyping of Pancreatic Cancer

Pancreatic ductal adenocarcinoma is a highly lethal malignancy, which has now become the seventh most common cause of cancer death in the world, with the highest mortality rates in Europe and North America. In the past 30 years, there has been some progress in 5-year survival (rates increasing from 2.5 to 10%), but this is still extremely poor compared to all other common cancer types. Targeted therapies for advanced pancreatic cancer based on actionable mutations have been disappointing, with only 3–5% showing even a short clinical benefit. There is, however, a molecular diversity beyond mutations in genes responsible for producing classical canonical signaling pathways. Pancreatic cancer is almost unique in promoting an excess production of other components of the stroma, resulting in a complex tumor microenvironment that contributes to tumor development, progression, and response to treatment. Various transcriptional subtypes have also been described. Most notably, there is a strong alignment between the Classical/Pancreatic progenitor and Quasi-mesenchymal/Basal-like/Squamous subtype signatures of Moffit, Collinson, Bailey, Puleo, and Chan-Seng-Yue, which have potential clinical impact. Sequencing of epithelial cell populations enriched by laser capture microscopy combined with single-cell RNA sequencing has revealed the potential genomic evolution of pancreatic cancer as being a consequence of a gene expression continuum from mixed Basal-like and Classical cell populations within the same tumor, linked to allelic imbalances in mutant KRAS, with metastatic tumors being more copy number-unstable compared to primary tumors. The Basal-like subtype appears more chemoresistant with reduced survival compared to the Classical subtype. Chemotherapy and/or chemoradiation will also enrich the Basal-like subtype. Squamous/Basal-like programs facilitate immune infiltration compared with the Classical-like programs. The immune infiltrates associated with Basal and Classical type cells are distinct, potentially opening the door to differential strategies. Single-cell and spatial transcriptomics will now allow single cell profiling of tumor and resident immune cell populations that may further advance subtyping. Multiple clinical trials have been launched based on transcriptomic response signatures and molecular subtyping including COMPASS, Precision Promise, ESPAC6/7, PREDICT-PACA, and PASS1. We review several approaches to explore the clinical relevance of molecular profiling to provide optimal bench-to-beside translation with clinical impact.

Transdisciplinary Status of the Ecological Modernization Theory and Its Role in the Development of Environmental Paradigm

The article examines the specificity of transdisciplinary orientations in modern scientific knowledge and reveals the multidimensionality of transdisciplinarity as a phenomenon of post-nonclassical science. Since transdisciplinarity is largely formed as a response to the challenge of increasing complexity and uncertainty of the future transformations in the “nature – man – society” system, the most appropriate area of transdisciplinary research today is environmental knowledge. In the example of the Ecological Modernization Theory (EMT), we investigate the interdisciplinary structure and transdisciplinary status of contemporary social ecology. The aim of the article is to analyze the various modes of transdisciplinarity in the structure of the ecological modernization theory and to identify its role in the dynamics of modern environmentalism. The epistemological status of EMT is explicated through philosophical and methodological reflection on the alternative discourses of sustainability as well as by using the principles of a systematic approach, methods of comparative analysis and semantic interpretation. The idea of sustainable development and the values of environmentalism are considered important factors in the formation of concepts and categories of this theory, its initial postulates and principles. The article substantiates the synthetic character of this theory, which meets the requirements of the post-non-classical type of scientific rationality. A conclusion is substantiated that EMT can be classified as a post-normal science. As a result of the analysis, it is argued that environmental philosophy has a special understanding of the goals of social development, principles of justice, social harmony, and human well-being. The reinterpretation of these concepts is a basis for adoption of novel theoretical schemes and methodological orientations in the system of modern socio-environmental studies.

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

Chronic kidney disease can progress to end-stage chronic renal disease (ESRD), which requires the use of replacement therapy (dialysis or kidney transplant) in life-threatening conditions. In ESRD, irreversible changes in the kidneys are associated with systemic changes of proinflammatory nature and dysfunctions of internal organs, skeletal muscles, and integumentary tissues. The common components of ESRD pathogenesis, regardless of the initial nosology, are (1) local (in the kidneys) and systemic chronic low-grade inflammation (ChLGI) as a risk factor for diabetic kidney disease and its progression to ESRD, (2) inflammation of the classical type characteristic of primary and secondary autoimmune glomerulonephritis and infectious recurrent pyelonephritis, as well as immune reactions in kidney allograft rejection, and (3) chronic systemic inflammation (ChSI), pathogenetically characterized by latent microcirculatory disorders and manifestations of paracoagulation. The development of ChSI is closely associated with programmed hemodialysis in ESRD, as well as with the systemic autoimmune process. Consideration of ESRD pathogenesis from the standpoint of the theory of general pathological processes opens up the scope not only for particular but also for universal approaches to conducting pathogenetic therapies and diagnosing and predicting systemic complications in severe nephropathies.

Quasi-split symmetric pairs of 𝑈(𝔰𝔩_{𝔫}) and Steinberg varieties of classical type

We provide a Lagrangian construction for the fixed-point subalgebra, together with its idempotent form, in a quasi-split symmetric pair of type A n − 1 A_{n-1} . This is obtained inside the limit of a projective system of Borel-Moore homologies of the Steinberg varieties of n n -step isotropic flag varieties. Arising from the construction are a basis of homological origin for the idempotent form and a geometric realization of rational modules.