bluuebunny/crossref_metadata_2025_split huggingface dataset:
Many-body approximations to the superfluid gap and critical temperature in pure neutron matter
Authors: Drissi Mehdi , Rios Arnau 
Published: May 2022

AbstractWe compute singlet pairing gaps and critical temperatures in pure neutron matter with different many-body approximations. Medium effects tend to reduce gaps and critical temperatures compared to the standard BCS ansatz. In the mean-field approximation, the ratio of these two quantities remains constant across a wide range of densities. This constant ratio is close to the universal prediction of BCS theory, whether three-neutron interactions are included or not. Using a more sophisticated many-body approach that incorporates the effect of short-range correlations in pairing properties, we find that the gap to critical temperature ratio in the low-density regime is substantially larger than the BCS prediction, independently of the interaction. In this region, our results are relatively close to experiments and theoretical calculations from the unitary Fermi gas. We also find evidence for a different density dependence of zero-temperature gaps and critical temperatures in neutron matter.
Unbiased elimination of negative weights in Monte Carlo samples
Authors: Andersen Jeppe R. , Maier Andreas 
Published: May 2022

AbstractWe propose a novel method for the elimination of negative Monte Carlo event weights. The method is process-agnostic, independent of any analysis, and preserves all physical observables. We demonstrate the overall performance and systematic improvement with increasing event sample size, based on predictions for the production of a W boson with two jets calculated at next-to-leading order perturbation theory.
A combination of the neutrino trimaximal mixings and $$\mu $$-$$\tau $$ reflection symmetry in the type-I seesaw model
Authors: Zhao Zhen-hua 
Published: May 2022

AbstractIn this paper, we make an attempt to combine the neutrino trimaximal (TM1 and TM2) mixings and $$\mu $$
μ
-$$\tau $$
τ
reflection symmetry in the type-I seesaw model. Such a scenario is highly restrictive and predictive: in addition to three right-handed neutrino masses, there are only five real parameters; all the lepton flavor mixing parameters except for $$\theta ^{}_{13}$$

θ
13

will be predicted. The relations between the model parameters and the measurable neutrino parameters will be derived. The implications of this scenario for leptogenesis will be explored in detail. A further reduction of this scenario to the more restrictive and predictive minimal seesaw model with only two right-handed neutrinos will also be considered. In addition, we will also discuss a possible approach to get the desired mass matrices and study the compatibility of the trimaximal $$\mu $$
μ
-$$\tau $$
τ
reflection symmetry with texture zeros.
On gauge-invariant deformation of reducible gauge theories
Authors: Lavrov P. M. 
Published: May 2022

AbstractNew method for construction of gauge-invariant deformed theory from an initial gauge theory proposed in our previous papers (Buchbinder and Lavrov in JHEP 06:854, 2021; Buchbinder and Lavrov in Eur Phys J C 81:856, 2021) for closed/open gauge algebras is extended to the case of reducible gauge algebras. The deformation procedure is explicitly described with the help of generating functions of anticanonical transformations depending on fields of the initial gauge action only. The deformed gauge-invariant action and the deformed gauge generators are described with the help of the generating functions in a closed and simple form. As an example of reducible gauge systems we consider the free fermionic p-form fields or, in another words, the antisymmetric tensor-spinor fields. It is proved that gauge-invariant deformation of fermionic p-form fields leads always to non-local deformed theory which does not contain a closed local sector. In its turn the model based on two fermionic 2-form fields and a real massive scalar field admits local interactions between these fields in local sector of the deformed action.
Mesozoic biological events and ecosystems in East Asia: introduction
Authors: Chang Su-Chin , Zheng Daran 
Published: May 2022

Abstract
Since the late twentieth century, palaeontological and geological evidence from East Asia has contributed to significant advances in the understanding of the Mesozoic world. Geological Society Special Publication 521 covers a wide range of topics that subdivide into four themes. These include: (1) clues and evidence from vertebrate fossils; (2) clues and evidence from invertebrate and plant fossils; (3) significant fossils from amber; and (4) palaeoenvironments and palaeoecosystems. The volume features 18 articles by 53 authors from different disciplines, including geochronology, palaeontology, stratigraphy, sedimentology, tectonics and geochemistry.
Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma
Authors: Dmello Crismita , Sonabend Aarón , Arrieta Victor A. , Zhang Daniel Y. , Kanojia Deepak , Chen Li , Gould Andrew , Zhang Jiangshan , Kang Seong Jae , Winter Jan , Horbinski Craig , Amidei Christina , Győrffy Balázs , Cordero Alex , Chang Catalina Lee , Castro Brandyn , Hsu Patrick , Ahmed Atique U. , Lesniak Maciej S. , Stupp Roger , Sonabend Adam M. 
Published: May 2022

Abstract

Purpose:
Paclitaxel (PTX) is one of the most potent and commonly used chemotherapies for breast and pancreatic cancer. Several ongoing clinical trials are investigating means of enhancing delivery of PTX across the blood–brain barrier for glioblastomas. Despite the widespread use of PTX for breast cancer, and the initiative to repurpose this drug for gliomas, there are no predictive biomarkers to inform which patients will likely benefit from this therapy.

Experimental Design:
To identify predictive biomarkers for susceptibility to PTX, we performed a genome-wide CRISPR knockout (KO) screen using human glioma cells. The genes whose KO was most enriched in the CRISPR screen underwent further selection based on their correlation with survival in the breast cancer patient cohorts treated with PTX and not in patients treated with other chemotherapies, a finding that was validated on a second independent patient cohort using progression-free survival.

Results:
Combination of CRISPR screen results with outcomes from patients with taxane-treated breast cancer led to the discovery of endoplasmic reticulum (ER) protein SSR3 as a putative predictive biomarker for PTX. SSR3 protein levels showed positive correlation with susceptibility to PTX in breast cancer cells, glioma cells, and in multiple intracranial glioma xenografts models. KO of SSR3 turned the cells resistant to PTX while its overexpression sensitized the cells to PTX. Mechanistically, SSR3 confers susceptibility to PTX through regulation of phosphorylation of ER stress sensor IRE1α.

Conclusions:
Our hypothesis generating study showed SSR3 as a putative biomarker for susceptibility to PTX, warranting its prospective clinical validation.
Therapeutic Implications for Intrinsic Phenotype Classification of Metastatic Castration-Resistant Prostate Cancer
Authors: Coleman Ilsa M. , DeSarkar Navonil , Morrissey Colm , Xin Li , Roudier Martine P. , Sayar Erolcan , Li Dapei , Corey Eva , Haffner Michael C. , Nelson Peter S. 
Published: May 2022

Abstract

Purpose:
To determine whether metastatic castration–resistant prostate cancers (mCRPC) partition into molecular phenotypes corresponding to intrinsic differentiation states and ascertain whether these subtypes exhibit specific druggable features and associate with treatment outcomes.

Experimental Design:
We used RNAseq, digital spatial profiling, and histological assessments from metastatic biopsies and patient-derived xenografts to segregate mCRPCs into subtypes defined by the PAM50 breast cancer classification algorithm. Subtype associations with treatment responses in preclinical models and patients were determined.

Results:
Using the PAM50 algorithm, we partitioned 270 mCRPC tumors into LumA (42%), LumB (24%), and Basal (34%) subtypes with classification largely driven by proliferation rates and androgen receptor (AR) activity. Most neuroendocrine tumors classified as Basal. Pathways enriched in the LumA subtype include TGFß and NOTCH signaling. LumB subtype tumors were notable for elevated MYC activity. Basal subtype tumors exhibited elevated IL6-STAT3 signaling and features of adult stem cell states. In patients where multiple tumors were evaluated, the majority had concordant PAM50 subtype determination, though a subset exhibited marked inter- and intratumor heterogeneity, including divergent classifications between primary and metastatic sites. In preclinical models, LumA subtype tumors were highly responsive to androgen deprivation and docetaxel chemotherapy whereas Basal tumors were largely resistant. In clinical cohorts patients with Basal subtype tumors demonstrated a shorter time on treatment with AR signaling inhibitors and docetaxel relative to patients with luminal subtypes.

Conclusions:
Subtyping of mCRPC based on cell differentiation states has potential clinical utility for identifying patients with divergent expression of treatment targets and responses to systemic therapy.
Genomic Analysis of a Spontaneous Model of Breast Cancer Metastasis to Bone Reveals a Role for the Extracellular Matrix
Authors: Eckhardt Bedrich L. , Parker Belinda S. , van Laar Ryan K. , Restall Christina M. , Natoli Anthony L. , Tavaria Michael D. , Stanley Kym L. , Sloan Erica K. , Moseley Jane M. , Anderson Robin L. 
Published: May 2022

Abstract
A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.
Bone Morphogenetic Protein-2 Stimulates Angiogenesis in Developing Tumors
Authors: Langenfeld Elaine M. , Langenfeld John 
Published: May 2022

Abstract
Bone Morphogenetic Protein-2 (BMP-2) is highly overexpressed in the majority of patient-derived lung carcinomas. However, a mechanism revealing its role in cancer has not been established. Here we report that BMP-2 enhances the neovascularization of developing tumors. Recombinant BMP-2 stimulated blood vessel formation in tumors formed from A549 cells injected s.c. into thymic nude mice. Recombinant BMP-2 also enhanced angiogenesis in Matrigel plugs containing A549 cells in nude mice. The BMP-2 antagonist noggin abrogated BMP-2-induced angiogenic response. Furthermore, antisense transfection of BMP-2 cDNA resulted in a decrease in blood vessel formation in the Matrigel assays. BMP-2 induced tube formation in both human aortic endothelial cells (HAEC) and umbilical vein endothelial cells. BMP-2 also stimulated proliferation of HAEC. The ability of BMP-2 to activate endothelial cells was further demonstrated by its ability to phosphorylate Smad 1/5/8 and ERK-1/2 and to increase expression of Id1. This study reveals that BMP-2 enhanced the angiogenic response in developing tumors. Furthermore, these data suggest that BMP-2 stimulation of angiogenesis may involve the activation of endothelial cells.
Nucleosomes Bind Fibroblast Growth Factor-2 for Increased Angiogenesis In vitro and In vivo
Authors: Tanner Jerome E. , Forté André , Panchal Chandra 
Published: May 2022

AbstractSolid tumors often display sites of necrosis near regions of angiogenesis in vivo. As tumor cell necrosis would result in the release of nucleosomes into the extracellular environment, we explored the potential role of nucleosomes in the promotion of angiogenesis. Data indicate that nucleosomes acted similar to heparin and bound to several heparin-binding, proangiogenic factors [i.e., fibroblast growth factor (FGF)-1, FGF-2, vascular endothelial growth factor, and transforming growth factor-β1]. Nucleosomes modestly enhanced FGF-2 growth of human umbilical vein endothelial cells when grown in restricted media as well as increased human umbilical vein endothelial cell migration and primitive blood vessel tube formation in vitro. On s.c. injection in mice, nucleosomes aided FGF-2 in promoting angiogenesis. These results suggest that nucleosomes released from dying tumor cells aid in the formation of blood vessels and may provide a novel means by which tumor cells increase angiogenesis.
Involvement of the Chemokine Receptor CXCR4 and Its Ligand Stromal Cell-Derived Factor 1α in Breast Cancer Cell Migration Through Human Brain Microvascular Endothelial Cells
Authors: Lee Byeong-Chel , Lee Tae-Hee , Avraham Shalom , Avraham Hava Karsenty 
Published: May 2022

AbstractIn this study, we have characterized the signaling pathways mediated by CXCR4 in breast cancer cells and its role in breast cancer cell invasion and migration. Stromal cell-derived factor 1α (SDF-1α; CXCL12) stimulation of breast cancer cells resulted in phosphoinositide 3-kinase (PI-3K) activation, AKT phosphorylation, and activation of the FKHRL1 transcription factor. In addition, SDF-1α induced activation of the focal adhesion kinase (FAK) as well as the migration of breast cancer cells. Expression of SDF-1α, the ligand of CXCR4, was about 2-fold higher in microdissected human breast epithelial cancer cells as compared with normal epithelial cells. Immunohistochemical analysis indicated that SDF-1α expression is consistently higher in primary breast tumor cells than in normal breast epithelial cells. Furthermore, SDF-1α induced blood vessel instability, through increased vascular permeability, resulting in the penetration of breast tumor cells through the human brain microvascular endothelial cells (HBMEC). Notably, the migration of breast cancer cells was inhibited by the PI-3K inhibitor, Wortmannin, and the Ca2+ inhibitor BAPTA/AM, indicating that transendothelial breast cancer cell migration induced by SDF-1α is mediated by activation of the PI-3K/AKT pathway and Ca2+-mediated signaling. Blockade of the CXCR4/SDF1 signaling pathway with anti-CXCR4 antibody also decreased transendothelial breast cancer cell migration as well as vascular permeability. This study focuses on novel interactions between highly relevant signaling pathways in breast cancer cells and brain microvascular endothelial cells and may provide insights into the molecular mechanisms of CXCR4/SDF-1α-mediated breast cancer metastasis to the brain.
Vascular Remodeling Marks Tumors That Recur During Chronic Suppression of Angiogenesis
Authors: Huang Jianzhong , Soffer Samuel Z. , Kim Eugene S. , McCrudden Kimberly W. , Huang Joe , New Tamara , Manley Christina A. , Middlesworth William , O'Toole Kathleen , Yamashiro Darrell J. , Kandel Jessica J. 
Published: May 2022

Abstract
The potential for avoiding acquired resistance to therapy has been proposed as one compelling theoretical advantage of antiangiogenic therapy based on the normal genetic status of the target vasculature. However, previous work has demonstrated that tumors may resume growth after initial inhibition if antiangiogenic blockade is continued for an extended period. The mechanisms of this recurrent growth are unclear. In these studies, we characterized molecular changes in vasculature during apparent resumption of xenograft growth after initial inhibition by vascular endothelial growth factor blockade, “metronome” topotecan chemotherapy, and combined agents in a xenograft murine model of human Wilms' tumor. Tumors that grew during antiangiogenic blockade developed as viable clusters surrounding strikingly remodeled vessels. These vessels displayed significant increases in diameter and active proliferation of vascular mural cells and expressed platelet-derived growth factor-B, a factor that functions to enhance vascular integrity via stromal cell recruitment. In addition, remodeled vessels were marked by expression of ephrinB2, required for proper assembly of stromal cells into vasculature. Thus, enhanced vascular stability appears to characterize tumor vessel response to chronic antiangiogenesis, features that potentially support increased perfusion and recurrent tumor growth.
Activation of Proteinase-Activated Receptor 1 Promotes Human Colon Cancer Cell Proliferation Through Epidermal Growth Factor Receptor Transactivation
Authors: Darmoul Dalila , Gratio Valérie , Devaud Hélène , Peiretti Franck , Laburthe Marc 
Published: May 2022

Abstract
Serine proteases are now considered as crucial contributors to the development of human colon cancer. We have shown recently that thrombin is a potent growth factor for colon cancer cells through activation of the aberrantly expressed protease-activated receptor 1 (PAR1). Here, we analyzed the signaling pathways downstream of PAR1 activation, which lead to colon cancer cell proliferation in HT-29 cells. Our data are consistent with the following cascade of events on activation of PAR1 by thrombin or specific activating peptide: (a) a matrix metalloproteinase–dependent release of transforming growth factor-α (TGF-α) as shown with TGF-α blocking antibodies and measurement of TGF-α in culture medium; (b) TGF-α-mediated activation of epidermal growth factor receptor (EGFR) and subsequent EGFR phosphorylation; and (c) activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and subsequent cell proliferation. The links between these events are shown by the fact that stimulation of cell proliferation and ERK1/2 on activation of PAR1 is reversed by the MMP inhibitor batimastat, TGF-α neutralizing antibodies, EGFR ligand binding domain blocking antibodies, and the EGFR tyrosine kinase inhibitors AG1478 and PD168393. Therefore, transactivation of EGFR seems to be a major mechanism whereby activation of PAR1 results in colon cancer cell growth. Finally, PAR1 activation induces Src phosphorylation, which is reversed by using the Src tyrosine kinase inhibitor PP2, suggesting that Src activation plays a permissive role for PAR1-mediated ERK1/2 activation and cell proliferation probably acting downstream of the EGFR. These data explain how thrombin exerts robust trophic action on colon cancer cells and underline the critical role of EGFR transactivation.
Development of Head and Neck Squamous Cell Carcinoma Is Associated With Altered Cytokine Responsiveness
Authors: Douglas Wade G. , Tracy Erin , Tan Dongfeng , Yu Jihnhee , Hicks Jr. Wesley L. , Rigual Nestor R. , Loree Thom R. , Wang Yanping , Baumann Heinz 
Published: May 2022

AbstractGrowth of head and neck squamous cell carcinoma (HNSCC) is generally associated with an inflammatory component. It is hypothesized that these tumor cells develop mechanisms to evade the growth inhibitory effects of cytokines that are present in the tumor microenvironment. This study determined the changes in responsiveness to inflammatory cytokines that accompany the transition of normal to transformed epithelial cells. Paired primary cultures of normal epithelial cells (NEC) and SCC cells were established from 16 patients. Receptor-mediated activation of signal transducer and activator of transcription and extracellular signal-regulated kinase pathways in response to cytokine treatments was identified by immunoblot analysis. Thymidine incorporation determined the impact of the cytokines on DNA synthesis. HNNEC and HNSCC displayed a prominent signaling in response to oncostatin M, interleukin-6, IFN-γ, and epidermal growth factor. Untreated HNSCC showed an elevated level of phosphorylated signal transducer and activator of transcription 3 and extracellular signal-regulated kinase (P &lt; 0.001) compared with HNNEC, suggesting constitutively activated pathways. Moreover, HNSCC cells phosphorylated significantly more signal transducer and activator of transcription 1 in response to oncostatin M (P = 0.002) and IFN-γ (P = 0.018) treatments. DNA synthesis of SCC cells was less inhibited by cytokines produced by endotoxin-stimulated macrophages (P = 0.016) than that of NEC. Low-dose oncostatin M slightly enhanced proliferation of SCC, whereas that of NEC was suppressed (P = 0.016). This study identified significant alterations in signal transduction pathways engaged by cytokines and which are associated with loss of growth inhibition of HNSCC. Increased signal transducer and activator of transcription phosphorylation, along with constitutively phosphorylated extracellular signal-regulated kinase in HNSCC, suggest that these pathways as molecular markers are important in the malignant transformation process and are potential targets for treatment.