bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical Investigation of Thermal-Hydraulic Performance of U-Tubes Enhanced With Ellipsoidal 45 deg Dimples
Authors: Sabir Rizwan , Khan Muhammad Mahabat , Sheikh Nadeem Ahmed 
Published: May 2022

Abstract
This study aims to numerically investigate thermal–hydraulic performance augmentation of ellipsoidal 45 deg dimpled U-tubes with various bend curvatures subjected to constant external heat flux (q′′=10kW/m2) for a range of Reynolds numbers (5000 ≤ Re ≤ 30,000). Three smooth U bends with curvatures radii of 0.695Dh, 1.5Dh, and 2.0Dh, where Dh is the hydraulic diameter of the smooth tube, are used in both smooth and enhanced tubes. A comparison of thermal-hydraulic characteristics of dimpled and smooth U-tubes is carried out using steady-state Reynolds averaged Navier–Stokes simulations. The analysis shows that the performance of the dimpled U-tube is superior to the smooth tube for all bend curvatures. The swirl flow patterns generated by the dimples induce early flow reattachment in the postbend section of the tube, which enhances its heat transfer rate. The dimpled U-tube having the shortest curvature radius significantly alters Dean vortices, which leads to a substantial improvement in its heat and flow performances. The dimpled U-tube having the shortest curvature radius enhances the thermal–hydraulic performance by 21.4% while for other curvature radii (1.5Dh, and 2.0Dh), the performance augmentations are found to be 10.7% and 8.9%, respectively.
U-Pb dating reveals multiple Paleoproterozoic orogenic events (Hamersley orogenic cycle) along the southern Pilbara margin (Australia) spanning the onset of atmospheric oxygenation
Authors: Rasmussen Birger , Zi Jian-wei , Muhling Janet 
Published: May 2022

Abstract
The early Paleoproterozoic was a time of unprecedented change in Earth's climate and surface environment. The key to resolving some of the controversies surrounding the timing and causes of these changes lies with supracrustal sequences, such as the 2.45–2.22 Ga Turee Creek Group in the southern Pilbara craton, northwestern Australia. The group preserves a predominantly siliciclastic sequence; however, its precise age, tectonic setting, and postdepositional history are disputed. Although it is interpreted to have been deposited in a foreland basin setting shortly after 2.45 Ga, the oldest well-recognized deformational event, marked by northward folding and thrusting, is the 2.20–2.15 Ga Ophthalmia orogeny. Evidence for a pre-Ophthalmia fabric-forming tectonic event north of the Archean Sylvania Inlier, southeast Pilbara craton, which is marked by tight to isoclinal folding, has been largely overlooked. In this area, we report in situ U-Pb geochronology of authigenic monazite and xenotime in shale with a well-developed tectonic cleavage from the ca. 2.63 Ga Jeerinah Formation. Monazite porphyroblasts, which are locally wrapped by strain fringes aligned in a tectonic cleavage, yielded weighted mean 207Pb/206Pb ages at 2370 ± 11 Ma and 2312 ± 8 Ma, whereas xenotime, which overprints a crenulation cleavage, gave a weighted mean 207Pb/206Pb age of 2291 ± 11 Ma, constraining fabric development to between 2.31 Ga and 2.29 Ga. Our results confirm the existence of a pre-Ophthalmia deformational event in the southeastern Pilbara craton, herein referred to as the Sylvania orogeny, which is part of an ~300 m.y. interval (2.45–2.15 Ga) of northward-directed compression (“Hamersley orogenic cycle”). This orogenic cycle is marked by east-west and northwest-southeast folding, cleavage development, veining, hydrothermal gold mineralization, and isotopic resetting across the southern Pilbara craton. Our results indicate that the syn–Great Oxidation Event Turee Creek Group was deposited in one or more foreland basins after 2.45 Ga. Our results provide a new tectonostratigraphic and geodynamic framework for understanding the timing and origin of geochemical records in a key succession deposited during an interval of global environmental change.
On radical ideals of non-commutative rings
Authors: Groenewald Nico 
Published: May 2022

Let [Formula: see text] denote the Jacobson radical of a commutative ring [Formula: see text]. In [H. A. Khashan and A. B. Bani-Ata, [Formula: see text]-ideals of commutative rings, Int. Electron. J. Algebra 29 (2021) 148–164], the notion of J-ideals was introduced. If [Formula: see text] denotes the prime radical of a commutative ring then in [U. Tekir, S. Koc and K. H. Oral, [Formula: see text]-Ideals of commutative rings, Filomat 31(10) (2017) 2933–2941], the notion of an [Formula: see text] ideal of a commutative ring was introduced and studied. In this note, we show that these results are special cases of a more general situation. We define [Formula: see text]-ideals for a special radical [Formula: see text] and prove that most of the results of the above-mentioned papers are satisfied for non-commutative rings as a special case.
MDM2 and Prognosis
Authors: Onel Kenan , Cordon-Cardo Carlos 
Published: May 2022

Abstract
The cellular stress response pathway regulated by the p53 tumor suppressor is critical to the maintenance of genomic integrity and to the prevention of oncogenic transformation. Intracellular levels of p53 are tightly regulated by an autoregulatory feedback loop comprised of p53 and MDM2. It might be predicted that disruption of this loop, either through p53 mutation or overexpression of MDM2, would be a negative prognostic marker for cancer development, likelihood of relapse, or response to therapy. In fact, although MDM2 overexpression is common in cancer, it can be both a positive and a negative predictor of outcome in different tumors, and its significance as a biomarker remains controversial. Data from a number of different tumor types are reviewed for the predictive significance of MDM2 expression, along with evidence for different mechanisms of MDM2 overexpression in these different tumors.
In light of the biological complexities underlying the p53-MDM2 loop, it is, perhaps, not surprising that no simple paradigm exists that is generally applicable. Much work remains to be done to elucidate the basic mechanisms underlying the physical interactions between the two proteins, the role of protein modifications in altering those interactions, and also the genetic and transcriptional deregulations by which protein levels are altered in human cancers. Only in this way will truly biologically relevant predictive factors emerge.
Cyclin-Dependent Kinase 6 Inhibits Proliferation of Human Mammary Epithelial Cells
Authors: Lucas Joseph J. , Domenico Joanne , Gelfand Erwin W. 
Published: May 2022

AbstractMany defects in cancer cells are in molecules regulating G1-phase cyclin-dependent kinases (cdks), which are responsible for modulating the activities of Rb family growth-suppressing proteins. Models for understanding how such defects affect proliferation assume that cdks are responsible for sequentially phosphorylating, and hence inactivating, the growth-suppressing functions of Rb family proteins, thus promoting cell cycle progression. However, cdks also play a role in formation of growth-suppressing forms of pRb family molecules, including the “hypophosphorylated” species of pRb itself. Here, it is shown that normal human mammary epithelial cells have a high amount of cdk6 protein and activity, but all breast tumor-derived cell lines analyzed had reduced levels, with several having little or no cdk6. Immunohistochemical studies showed reduced levels of cdk6 in breast tumor cells as compared with normal breast tissue in vivo. Cdk6 levels in two breast tumor cell lines were restored to those characteristic of normal human mammary epithelial cells by DNA transfection. The cells had a reduced growth rate compared with parental tumor cells; cells that lost ectopic expression of cdk6 reverted to the faster growth rate of parental cells. Cell lines with restored cdk6 levels accumulated higher amounts of the Rb family protein p130 as well as E2F4, a suppressing member of the E2F family of transcription factors, in their nuclei. The results suggest that cdk6 restrains rather than stimulates breast epithelial cell proliferation and that its loss or down-regulation could play a role in breast tumor development.
The Cytoskeleton Differentially Localizes the Early Growth Response Gene-1 Protein in Cancer and Benign Cells of the Prostate
Authors: Mora Gloria R. , Olivier Kenneth R. , Cheville John C. , Mitchell Richard F. , Lingle Wilma L. , Tindall Donald J. 
Published: May 2022

Abstract
Prostate cancer is the most prevalent malignancy and the second leading cause of cancer mortality in men. Early growth response gene-1 (EGR-1) plays a crucial role in the development and progression of prostate cancer. The presented data show that EGR-1 differs in cellular localization in benign cells compared with malignant prostate cells and that this localization is critical for the transcriptional activation of EGR-1-dependent genes. Immunohistochemistry of human prostate cancer specimens demonstrated higher levels of EGR-1 in malignant cells located predominantly in the cytoplasm, whereas benign cells contained lower levels of EGR-1 located predominantly in the nucleus. Benign prostate cells responded to mitogens in vitro, with increased levels of EGR-1, rapid nuclear translocation, and enhanced transcriptional activity, whereas malignant prostate cells did not exhibit the same responses, and the protein remained in the cytoplasm. The central aspect of this difference is the association of EGR-1 with microtubules, which is exclusive to the benign cells of the prostate and is requisite for the nuclear translocation and transcriptional activity of EGR-1. Our in vitro data demonstrate that the differences in EGR-1 between benign and malignant prostate cells extend beyond cellular levels, which was confirmed by immunohistochemistry in human tissues. Thus, we add the novel concept that microtubules regulate EGR-1 localization in benign prostate cells but not in malignant prostate cells.
Thombospondin-1 Disrupts Estrogen-Induced Endothelial Cell Proliferation and Migration and Its Expression Is Suppressed by Estradiol
Authors: Sengupta Krishanu , Banerjee Snigdha , Saxena Neela K. , Banerjee Sushanta K. 
Published: May 2022

Abstract
The natural hormone 17β-estradiol (17β-E2) is known to induce tumor angiogenesis in various target organs by activating positive regulators of angiogenesis. In this study, we show for the first time that in human umbilical vein endothelial cells (HUVECs), 17β-E2 transiently down-regulates the expression and secretion of a potent negative regulator of angiogenesis, thrombospondin-1 (TSP-1). This inhibitory effect of 17β-E2 is mediated through nongenomic estrogen receptor (ER)/mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) 1/2 and c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) signaling pathways, because this effect can be abolished by a pure ER antagonist (ICI 182,780) and inhibitors of downstream signaling proteins of MAPK signaling cascades, including MAPK kinase 1/2 and ERK1/2 inhibitor and JNK/SAPK inhibitor. To understand the functional role(s) of TSP-1 during estradiol-induced angiogenesis, we examined the growth and migration of endothelial cells in different experimental environments. Using a recombinant protein, we show that increments of TSP-1 protein concentration in culture medium significantly reduce the migration and proliferation of HUVECs stimulated by 17β-E2. Together, these studies suggest that TSP-1 can be considered an important negative factor in understanding the increased angiogenesis in response to estrogens.
Mitotic Aberration Coupled With Centrosome Amplification Is Induced by Hepatitis B Virus X Oncoprotein via the Ras-Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase-Mitogen-Activated Protein Pathway
Authors: Yun Chawon , Cho Hyeseon , Kim Su-Jeong , Lee Jae-Ho , Park Sun Yi , Chan Gordon K. , Cho Hyeseong 
Published: May 2022

Abstract
Multinucleated cells have been noted in pathophysiological states of the liver including infection with hepatitis B virus (HBV), the status of which is also closely associated with genomic instability in liver cancer. Here, we showed that hepatitis B virus X oncoprotein (HBx) expression in Chang cells results in a multinuclear phenotype and an abnormal number of centrosomes (n ≥ 3). Regulation of centrosome duplication in HBx-expressing ChangX-34 cells was defective and uncoupled from the cell cycle. HBx induced amplification of centrosomes, multipolar spindle formation, and chromosomal missegregation during mitosis and subsequently increased the generation of multinucleated cells and micronuclei formation. Treatment with PD98059, a mitogen-activated protein/extracellular signal-regulated kinase (MEK) 1/2 inhibitor, significantly reduced the number of cells with hyperamplified centrosomes and decreased the multinucleated cells and micronuclei formation. Consistently, the phospho-ERK level during cell progression was substantially higher in ChangX-34 cells than that of Chang cells. In contrast, neither wortmannin, an inhibitor of phosphoinositide-3 kinase, nor SB203589, an inhibitor of p38 mitogen-activated protein kinase (MAPK), showed any effects. Introduction of Ras dominant-negative (D/N) and MEK2 D/N genes into ChangX-34 cells significantly alleviated centrosome amplification, whereas introduction of the PKC D/N and PKB D/N genes did not. Thus, our results demonstrate that the HBx induced centrosome hyperamplification and mitotic aberration by activation of the Ras-MEK-MAPK. Intervention of this signaling pathway could suppress the centrosome amplification as well as mitotic aberration. These findings may provide a possible mechanism by which HBx promotes phenotypic progression by predisposing chromosomal alteration in HBV-infected liver.
Raf and RhoA Cooperate to Transform Intestinal Epithelial Cells and Induce Growth Resistance to Transforming Growth Factor β
Authors: Du Jianguo , Jiang Bo , Coffey Robert J. , Barnard John 
Published: May 2022

Abstract
Although unregulated activation of the Ras/Raf/mitogen-activated protein kinase kinase/Erk signaling pathway is believed to be a central mechanism by which many cell types undergo oncogenic transformation, recent studies indicate that activation of Raf kinase by oncogenic Ras is not sufficient to cause tumorigenic transformation in intestinal epithelial cells. Thus, identification of signaling proteins and pathways that interact with Raf to transform intestinal epithelial cells may be critical for understanding aberrant growth control in the intestinal epithelium. Functional interactions between Raf and the small GTPase RhoA were studied in RIE-1 cells overexpressing both activated Raf(22W) and activated RhoA(63L). Double transfectants were morphologically transformed, formed colonies in soft agar, grew in nude mice, overexpressed cyclin D1 and cyclooxygenase-2 (COX-2), and were resistant to growth inhibition by transforming growth factor (TGF) β. RIE-Raf and RIE-RhoA single transfectants showed none of these characteristics. Expression of a dominant-negative RhoA(N19) construct in RIE-Ras(12V) cells was associated with markedly reduced COX-2 mRNA, COX-2 protein, and prostaglandin E2 levels when compared with RIE-Ras(12V) cells transfected with vector alone. However, no change in transformed morphology, growth in soft agar, cyclin D1 expression, TGFα expression, or TGFβ sensitivity was observed. In summary, coexpression of activated Raf and RhoA induces transformation and TGFβ resistance in intestinal epithelial cells. Although blockade of RhoA signaling reverses certain well-described characteristics of RIE-Ras cells, it is insufficient to reverse the transformed phenotype and restore TGFβ sensitivity. Blockade of additional Rho family members or alternate Ras effector pathways may be necessary to fully reverse the Ras phenotype.
Multiple Aspects of the Phenotype of Mammary Epithelial Cells Transformed by Expression of Activated M-Ras Depend on an Autocrine Mechanism Mediated by Hepatocyte Growth Factor/Scatter Factor
Authors: Zhang Kai-Xin , Ward Katherine R. , Schrader John W. 
Published: May 2022

Abstract
Multiple aspects of the transformed phenotype induced in a murine mammary epithelial cell line scp-2 by expression of activated G22V M-Ras, including maintainance of cell number at low density, anchorage-independent growth, invasion of Matrigel, and secretion of matrix metalloproteinases (MMP) 2 and 9, were dependent on an autocrine mechanism. Conditioned medium from dense cultures of scp-2 cells expressing G22V M-Ras, but not from parental cells, induced activation of Erk and Akt in cells expressing G22V M-Ras, maintained the cell number and promoted anchorage-independent growth of cells expressing G22V M-Ras (although not the parental cells), and induced scattering of MDCK cells. The latter activities were blocked by neutralizing antibodies to hepatocyte growth factor/scatter factor (HGF/SF) and could be mimicked by HGF/SF. Anti-HGF/SF antibodies also inhibited invasion of Matrigel, and the production of MMP-2 and MMP-9, together with urokinase-type plasminogen activator, was secreted by G22V M-Ras scp-2 cells but not by parental cells. Invasion of Matrigel was blocked by an inhibitor of MMPs, BB94, and by the mitogen-activated protein kinase kinase 1/2 kinase inhibitor PD98059 but was only marginally affected by the phosphatidylinositol 3-kinase inhibitor LY294002. Autocrine HGF/SF was thus critical for expression of key features of the phenotype of mammary epithelial cells transformed by expression of activated M-Ras.
Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer
Authors: Borgoño Carla A. , Michael Iacovos P. , Diamandis Eleftherios P. 
Published: May 2022

AbstractTissue kallikreins are members of the S1 family (clan SA) of trypsin-like serine proteases and are present in at least six mammalian orders. In humans, tissue kallikreins (hK) are encoded by 15 structurally similar, steroid hormone–regulated genes (KLK) that colocalize to chromosome 19q13.4, representing the largest cluster of contiguous protease genes in the entire genome. hKs are widely expressed in diverse tissues and implicated in a range of normal physiologic functions from the regulation of blood pressure and electrolyte balance to tissue remodeling, prohormone processing, neural plasticity, and skin desquamation. Several lines of evidence suggest that hKs may be involved in cascade reactions and that cross-talk may exist with proteases of other catalytic classes. The proteolytic activity of hKs is regulated in several ways including zymogen activation, endogenous inhibitors, such as serpins, and via internal (auto)cleavage leading to inactivation. Dysregulated hK expression is associated with multiple diseases, primarily cancer. As a consequence, many kallikreins, in addition to hK3/PSA, have been identified as promising diagnostic and/or prognostic biomarkers for several cancer types, including ovarian, breast, and prostate. Recent data also suggest that hKs may be causally involved in carcinogenesis, particularly in tumor metastasis and invasion, and, thus, may represent attractive drug targets to consider for therapeutic intervention.
TEL/AML1 Overcomes Drug Resistance Through Transcriptional Repression of Multidrug Resistance-1 Gene Expression
Authors: Asakura Keiko , Uchida Hideo , Miyachi Hayato , Kobayashi Hiroyuki , Miyakawa Yoshitaka , Nimer Stephen D. , Takahashi Hiroyuki , Ikeda Yasuo , Kizaki Masahiro 
Published: May 2022

AbstractThe t(12;21)(p12;q22) chromosomal aberration, which is frequently observed in pediatric precursor B-cell acute lymphoblastic leukemia (ALL), generates the TEL/AML1 chimeric gene and protein. TEL/AML1-positive ALL has a favorable prognosis, and one possible reason is that this subtype of ALL rarely shows drug resistance. AML1/ETO, another AML1-containing chimeric protein, has been shown to transcriptionally repress the activity of the multidrug resistance-1 (MDR-1) gene promoter; thus, we examined whether TEL/AML1 also represses MDR-1 gene expression, possibly preventing the emergence of multidrug resistance. In this study, we show that the TEL/AML1 protein binds to the consensus AML1 binding site in the MDR-1 promoter and transcriptionally represses its activity. Following transient transfection of TEL/AML1 protein into Adriamycin-resistant K562/Adr cells, we also demonstrate that TEL/AML1 can down-regulate the expression of P-glycoprotein, a product of the MDR-1 gene, and restore the chemosensitivity to the cells. Furthermore, we report that MDR-1 mRNA levels in leukemic cells obtained from TEL/AML1-positive ALL patients are lower than those from TEL/AML1-negative ALL patients. Thus, TEL/AML1 protein acts as a transcriptional repressor of MDR-1 gene expression, and although TEL/AML1 has been implicated in leukemogenesis, its effects on the MDR-1 gene may contribute to the excellent prognosis of TEL/AML1-positive ALL with current therapy.
c-myb Heterozygous Mice Are Hypersensitive to 5-Fluorouracil and Ionizing Radiation
Authors: Ramsay Robert G. , Micallef Suzanne , Lightowler Sally , Mucenski Michael L. , Mantamadiotis Theo , Bertoncello Ivan 
Published: May 2022

Abstract
Hypersensitivity to chemo- and radiotherapy employed during cancer treatment complicates patient management. Identifying mutations in genes that compromise tissue recovery would rationalize treatment and may spare hypersensitive patients undue tissue damage. Genes that govern stem cell homeostasis, survival, and progenitor cell maintenance are of particular interest in this regard. We used wild-type and c-myb knock-out mice as model systems to explore stem and progenitor cell numbers and sensitivity to cytotoxic damage in two radiosensitive tissue compartments, the bone marrow and colon. Because c-myb null mice are not viable, we used c-myb heterozygous mice to test for defects in stem-progenitor cell pool recovery following γ-radiation and 5-fluorouracil treatment, showing that c-myb+/− mice are hypersensitive to both agents. While apoptosis is comparable in mutant and wild-type mice following radiation exposure, the crypt beds of c-myb+/− mice are markedly depleted of proliferating cells. Extrapolating from these data, we speculate that acute responses to cytotoxic damage in some patients may also be attributed to compromised c-myb function.