bluuebunny/crossref_metadata_2025_split huggingface dataset:
$$U(1)_{B-L}$$ extension of the standard model with $$S_3$$ symmetry
Authors: Vien V. V. , Long H. N. , Cárcamo Hernández A. E. 
Published: August 2020

AbstractWe propose a renormalizable$$B-L$$B-LStandard Model (SM) extension based on$$S_3$$S3symmetry which successfully accommodates the observed fermion mass spectra and flavor mixing patterns as well as the CP violating phases. The small masses for the light active neutrinos are generated through a type I seesaw mechanism. The obtained physical parameters in the lepton sector are well consistent with the global fit of neutrino oscillations (Esteban et al. in J High Energy Phys 01:106, 2019) for both normal and inverted neutrino mass orderings. The model also predicts effective neutrino mass parameters of$${\langle m_{ee}\rangle }= {1.02\times 10^{-2}}\,{\mathrm {eV}},\, m_{\beta }= {1.25}\times 10^{-2}\,{\mathrm {eV}}$$⟨mee⟩=1.02×10-2eV,mβ=1.25×10-2eVfor normal hierarchy (NH) and$${\langle m_{ee}\rangle } ={5.03}\times 10^{-2}\, {\mathrm {eV}},\, m_{\beta } ={5.05}\times 10^{-2}\, {\mathrm {eV}}$$⟨mee⟩=5.03×10-2eV,mβ=5.05×10-2eVfor inverted hierarchy (IH) which are all well consistent with the future large and ultra-low background liquid scintillator detectors which has been discussed in Ref. (Zhao et al. in Chin Phys C 41(5):053001, 2017) or the limit of the effective neutrino mass can be reached by the planning of future experiments. The model results are consistent with and successfully accommodate the recent experimental values of the physical observables of the quark sector, including the six quark masses, the quark mixing angles and the CP violating phase in the quark sector.
Bi-Objective Optimization of Service-Oriented Location-Pricing Model Using Electromagnetism-Like Mechanism Algorithm
Authors: Alinezhad Alireza , Hajipour Vahid , Hosseinzadeh Sanaz 
Published: August 2020

This paper develops a multi-objective multi-layer location-pricing (MLLP) model with congested facilities in which the facilities act like a classic queuing system. The customers who arrive to this system receive service at all layers in a predetermined order to fulfill their demands. The goal is to determine (1) optimal number of the facilities required at each layer, (2) optimal allocation of customers to facilities, and (3) optimal price of providing service at each layer. The objective functions are to maximize the total profit of the system and to minimize the sum of travel and waiting times, simultaneously. The problem is formulated as a multi-objective nonlinear integer mathematical programming model. Since the problem is hard to be solved analytically, we present a multi-objective meta-heuristic algorithm (MHA) based on an electromagnetism-like mechanism (ELM) as a solution for multi-objective MLLP. This algorithm used an elitist mechanism to strengthen the structure of search engine in order to find better quality solutions. The results indicate the efficiency and effectiveness of the proposed algorithm in comparison with the traditional ELM.
Cut-enhanced PolyCube-maps for feature-aware all-hex meshing
Authors: Guo Hao-Xiang , Liu Xiaohan , Yan Dong-Ming , Liu Yang 
Published: August 2020

Volumetric PolyCube-Map-based methods offer automatic ways to construct all-hexahedral meshes for closed 3D polyhedral domains, but their meshing quality is limited by the lack of interior singularities and feature alignment. In the presented work, we propose
cut-enhanced PolyCube-Maps
, to introduce essential interior singularities and preserve most input features. Our main idea is simple and intuitive: by inserting proper parameterization seams into the initial PolyCube-Map via novel PolyCube cutting operations, the mapping distortion can be reduced significantly.

The cut-enhanced PolyCube-Map computation includes feature-aware PolyCube-Map construction and cut-enhanced PolyCube deformation. The former aims to preserve input feature edges during the initial PolyCube-Map construction. The latter introduces seams into the volumetric PolyCube shape by cutting it through selective PolyCube edges and deforms the modified PolyCube under the seamless constraints to compute a low-distortion PolyCube-Map. The hexahedral mesh induced by the final PolyCube-Map can be further enhanced by our mesh improvement algorithm.
We validate the efficacy of our method on a collection of more than one hundred CAD models and demonstrate its advantages over other automatic all-hex meshing methods and padding strategies. The limitations of cut-enhanced PolyCube-Maps are also discussed thoroughly.
Specular manifold sampling for rendering high-frequency caustics and glints
Authors: Zeltner Tizian , Georgiev Iliyan , Jakob Wenzel 
Published: August 2020

Scattering from specular surfaces produces complex optical effects that are frequently encountered in realistic scenes: intricate caustics due to focused reflection, multiple refraction, and high-frequency glints from specular microstructure. Yet, despite their importance and considerable research to this end, sampling of light paths that cause these effects remains a formidable challenge.
In this article, we propose a surprisingly simple and general sampling strategy for specular light paths including the above examples, unifying the previously disjoint areas of caustic and glint rendering into a single framework. Given two path vertices, our algorithm stochastically finds a specular subpath connecting the endpoints. In contrast to prior work, our method supports high-frequency normal- or displacement-mapped geometry, samples specular-diffuse-specular ("SDS") paths, and is compatible with standard Monte Carlo methods including unidirectional path tracing. Both unbiased and biased variants of our approach can be constructed, the latter often significantly reducing variance, which may be appealing in applied settings (e.g. visual effects). We demonstrate our method on a range of challenging scenes and evaluate it against state-of-the-art methods for rendering caustics and glints.
Incremental potential contact
Authors: Li Minchen , Ferguson Zachary , Schneider Teseo , Langlois Timothy , Zorin Denis , Panozzo Daniele , Jiang Chenfanfu , Kaufman Danny M. 
Published: August 2020

Contacts weave through every aspect of our physical world, from daily household chores to acts of nature. Modeling and predictive computation of these phenomena for solid mechanics is important to every discipline concerned with the motion of mechanical systems, including engineering and animation. Nevertheless, efficiently time-stepping accurate and consistent simulations of real-world contacting elastica remains an outstanding computational challenge. To model the complex interaction of deforming solids in contact we propose Incremental Potential Contact (IPC) - a new model and algorithm for variationally solving implicitly time-stepped nonlinear elastodynamics. IPC maintains an intersection- and inversion-free trajectory regardless of material parameters, time step sizes, impact velocities, severity of deformation, or boundary conditions enforced.
Constructed with a custom nonlinear solver, IPC enables efficient resolution of time-stepping problems with separate, user-exposed accuracy tolerances that allow independent specification of the physical accuracy of the dynamics and the geometric accuracy of surface-to-surface conformation. This enables users to decouple, as needed per application, desired accuracies for a simulation's dynamics and geometry.
The resulting time stepper solves contact problems that are intersection-free (and thus robust), inversion-free, efficient (at speeds comparable to or faster than available methods that lack both convergence and feasibility), and accurate (solved to user-specified accuracies). To our knowledge this is the first implicit time-stepping method, across both the engineering and graphics literature that can consistently enforce these guarantees as we vary simulation parameters.

In an extensive comparison of available simulation methods, research libraries and commercial codes we confirm that available engineering and computer graphics methods, while each succeeding admirably in custom-tuned regimes, often fail with instabilities, egregious constraint violations and/or inaccurate and implausible solutions, as we vary input materials, contact numbers and time step. We also exercise IPC across a wide range of existing and new benchmark tests and demonstrate its accurate solution over a broad sweep of reasonable time-step sizes and beyond (up to
h
= 2s) across challenging large-deformation, large-contact stress-test scenarios with meshes composed of up to 2.3M tetrahedra and processing up to 498K contacts per time step. For applications requiring high-accuracy we demonstrate tight convergence on all measures. While, for applications requiring lower accuracies, e.g. animation, we confirm IPC can ensure feasibility and plausibility even when specified tolerances are lowered for efficiency.
Abstract A10: Constitutive HIF activity enhances T-cell antitumor immunity and memory T-cell formation in the murine adoptive cell therapy model
Authors: Lauhan Colette R. , Witherden Deborah , Liikanan Ilkka , Goldrath Ananda 
Published: August 2020

Abstract
Purpose: To determine if unrestrained hypoxia inducible factor (HIF) activity in CD8 T cells improves antitumor response.
Methods: CD8 T cells were isolated from von Hippel Lindau (VHL)-deficient (VHL KO) mice, which have unrepressed HIF1 and HIF2 activity, as well as from VHL/HIF1/HIF2 triple-deficient (TKO) and WT mice. Following in vitro activation, T cells were transferred to melanoma (B16) tumor-bearing mice and monitored for tumor progression and survival. In other studies, activated VHL KO and TKO CD8 cells were mixed with WT CD8 cells and transferred to B16 or adenocarcinoma (MC38) tumor-bearing mice; after 7-10 days, donor T cells were analyzed from tumors, spleens, and draining lymph nodes (LN).
Results: Single transfer of VHL KO CD8 T cells to B16 tumor-bearing mice resulted in delayed tumor growth and prolonged survival compared to transfer of CD8 T cells from TKO or WT donors. Co-transfer of VHL KO cells with WT cells into B16 tumor-bearing mice resulted in superior accumulation of VHL KO cells in all tissues including tumors. In contrast, mixed transfer of TKO cells with WT cells to B16 tumor-bearing mice resulted in poorer accumulation of TKO cells in all tissues including tumors. VHL KO tumor-infiltrating lymphocytes (TILs) had superior expression of tissue resident memory (TRM) phenotype markers CD103 and CD69 compared to WT and TKO TILs. Similarly in the MC38 tumor model, VHL KO cells showed improved accumulation in all tissues compared to WT cells.
Conclusions: Here we demonstrate that VHL deletion in CD8 T cells results in superior efficacy in delaying tumor growth and improving recipient survival, greater accumulation in multiple solid tumor models, and increased development of the TRM phenotype. Further, TKO recipients demonstrated increased tumor growth, reduced survival, reduced TIL numbers, and absence of TRM phenotype following adoptive transfer, confirming the HIF dependency of the VHL-deletion phenotype. Taken together, these data demonstrate that T cells with constitutive HIF activity provide a more robust antitumor response. Therefore, manipulation of HIF regulation could offer new tools for enhanced T-cell efficacy in adoptive cellular therapy for solid tumors.
Citation Format: Colette R. Lauhan, Deborah Witherden, Ilkka Liikanan, Ananda Goldrath. Constitutive HIF activity enhances T-cell antitumor immunity and memory T-cell formation in the murine adoptive cell therapy model [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A10.
Abstract A54: Parallel targeting of RAF/MEK/ERK pathway in RAS-mutant embryonal rhabdomyosarcoma
Authors: Vaseva Angelina V. , Bandyopadhyay Abhik , Pozo Vanessa Del , Goodwin Craig M. , Gautam Prson , Wennerberg Krister , Wood Kris C. , Chen Yidong , Der Channing J. , Houghton Peter J. 
Published: August 2020

Abstract
RAS pathway mutations are found in nearly 75% of high-risk embryonal rhabdomyosarcoma (ERMS). While RAS oncoproteins are well-established therapeutic targets for many adult human cancers, still very little is known about the role of RAS mutations in the development and maintenance of ERMS. By sequencing, we identified cell lines and PDX tumors harboring activating mutations in H- or NRAS. Further, we showed that mutant H- or NRAS was critical for the growth of all RAS-mutant ERMS cell lines and that RAF/MEK/ERK signaling pathway, but not PI3K/AKT, was mediator of RAS dependency in these cells. However, in vivo treatment of RAS-mutant ERMS xenografts with the MEK inhibitor trametinib showed modest response as compared to BRAF-mutant astrocytoma xenografts. We reasoned that similarly to other RAS-driven cancers, ERMS cells and tumors are able to acquire resistance to inhibitors of the RAF/MEK/ERK pathway. We performed drug-sensitizing pooled CRISPR library screen and identified that inhibition of ERK2 potentiated trametinib treatment. We show that combining trametinib with ERK1/2 inhibitor leads to potent synergistic ERK inhibition and ERMS tumor growth suppression.
Citation Format: Angelina V. Vaseva, Abhik Bandyopadhyay, Vanessa Del Pozo, Craig M. Goodwin, Prson Gautam, Krister Wennerberg, Kris C. Wood, Yidong Chen, Channing J. Der, Peter J. Houghton. Parallel targeting of RAF/MEK/ERK pathway in RAS-mutant embryonal rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A54.
Abstract A62: A cerebral organoid model of pediatric glioma
Authors: Ismail Amin , Balamatsias Demis 
Published: August 2020

Abstract
Glioblastoma is the most devastating brain cancer with dismal prognosis both in adults and children and accounts for 16% of primary brain tumors. Despite aggressive therapeutic approaches, the majority of patients die within one year after diagnosis. Current in vivo modeling of glioblastoma involves xenografts either of cultured cell lines or human biopsies transplanted into mice. These models do not faithfully recapitulate the complex biology/pathogenesis of cancer. Here we used human pluripotent embryonic stem cells (or young children fibroblast-driven induced pluripotent stem cells) to create 3D structures with histology reminiscent of human fetal brain (the so-called cerebral organoids). Cerebral organoids combine the accurate multilineage differentiation and physiology of a developing brain with the easiness of manipulation of an in vitro system. We engineered these mini-brains to develop tumors by forced expression of combinations of epigenetic and genetic hits that have previously been shown to drive pediatric glioblastoma multiform (GMB). These include the expression of a mutant histone H3 variant H3F3A (mutated at K27M or G34R) or a gain of function of a mutant form of isocitrate dehydrogenase (IDH1R132H) in combination with the loss of ATRX histone remodeling factor and/or p53 tumor suppressor. Lentiviral transfection was used to express combination of these genetic and epigenetic hits into cerebral organoids. The mutated organoids exhibited tumorigenic growth that was histologically characterized. For example, the expression of H3K27M in combination with loss of both p53 and ATRX showed a remarkable dysplasia reminiscent of primary glioblastoma. Moreover, these organoids exhibited tumor rosette structures resembling those found in ependymoma. In contrast, organoids expressing K27M alone did not show such structures. Interestingly, IDH1R132H combined with p53 and ATRX loss resulted in different tumor morphology, suggestive of a possibility to model oncogenic dependence in pediatric GBM. Cerebral organoids could also be used as a model to study tumor invasion starting with glioma stem-like cells (GSCs, which are believed to be the tumor-initiating cells in GBM). Interestingly, the GSC cell line 923 (which does not invade mouse brain in vivo) invaded and formed a focal lesion in a cocultured organoid. The organoid-based cancer model presented here carries a promising potential to uncover the initiation and pathogenesis of pediatric tumors early in the developing brain.
Note: This abstract was not presented at the conference.
Citation Format: Amin Ismail, Demis Balamatsias. A cerebral organoid model of pediatric glioma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A62.
Abstract A68: Optical coherence tomography improves subclinical retinoblastoma management
Authors: Soliman Sameh E. , VandenHooven Cynthia , MacKeen Leslie , Gallie Brenda 
Published: August 2020

Abstract
Purpose: Optical coherence tomography (OCT) improved retinal assessment that is comparable to histopathologic sections. In retinoblastoma, OCT was reported to detect fovea-tumor relation, diagnose subclinical (new, residual and recurrent tumors), and suspect tumor spread into the optic nerve. We hypothesized that strategic incorporation of OCT into retinoblastoma management will improve outcomes and managing retinoblastoma at the subclinical level (clinically undetectable) provides means for less treatment burden.
Methods: A single-center, noncomparative retrospective review of all eyes with subclinical retinoblastoma was conducted. Any eye that had an OCT-guided procedure, whether diagnostic or therapeutic, utilizing OCT software was included. OCT-guided management included projecting embedded OCT software tools (scan cube size and direction, multiple scan frames, localizing and measuring vertical and horizontal calipers, enhanced depth imaging frames, and/or red free fundus photograph) on a separate colored fundus image to guide management to improve visual, life, and eye salvage outcomes.
Results: We used OCT-guided strategies in 83 children (114 eyes). Diagnostic strategies included posterior pole screening for invisible retinoblastoma (37 eyes), topographic localization of invisible tumors (15 eyes) or subclinical recurrence (29 tumors), topographic localization of fovea-tumor relation (31 eyes), and mapping of potential choroidal or optic nerve invasion to determine subsequent management (2 eyes each). Therapeutic strategies included laser photocoagulation for perifoveal residual (26) and invisible (11) tumors and verification of photocoagulation adequacy for invisible (11) new and recurrent (11) tumors. These procedures were scored for their influence to changed therapy.
Conclusion: Detailed OCT assessment improves retinoblastoma management and facilitates precision therapy to preserve vital visual structures (e.g., the center of vision), detect subtle subclinical tumors (new or recurrent), allow administration and adequacy of laser treatment, and map subclinical high-risk features. Developing OCT-guided strategies with full technical description facilitates reproducibility and allows precision therapy to be a reality.
Citation Format: Sameh E. Soliman, Cynthia VandenHooven, Leslie MacKeen, Brenda Gallie. Optical coherence tomography improves subclinical retinoblastoma management [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A68.
Abstract B21: Childhood Cancer Molecular Map (C2M2) to define medulloblastoma heterogeneity and predict treatment response
Authors: Yeerna Huwate , Briggs Benjamin , Rusert Jessica , Chavez Lukas , Mesirov Jill , Wechsler-Reya Robert , Tamayo Pablo 
Published: August 2020

Abstract
Background: Medulloblastoma is a heterogenous group of tumors that collectively are the most common malignant brain tumor of childhood. Advances in treatment are required as one third of patients die from the disease, and those who survive suffer severe long-term side effects from therapy. The ability to sequence entire genome, methylome, and transcriptome of tumors provides the opportunity to identify underlying drivers of malignancy, predict treatment response, and develop novel therapies. A lack of reproducibility when comparing identified genetic mutations with treatment response is challenging because a single genetic change does not reflect the cellular state of a cancer cell in its entirety, which is expressing a multitude of genes. Computational methods allow for the creation of mapping systems that may more accurately describe the cellular state and thereby predict treatment response.
Objective: We used Childhood Cancer Molecular Map (C2M2) to define medulloblastoma heterogeneity and predict treatment response using patient-derived xenografts (PDX).
Methods: RNA transcription abundance from medulloblastoma samples published by Cho et al. were used to create C2M2. This was accomplished by analyzing the distribution of transcriptional abundance for each gene across all samples in order to select the genes that display the most asymmetric and non-Gaussian behavior. This delineated a “context score” for each gene, emphasizing those over- and underexpressed, allowing for the creation of a unique signature to model cellular states. The medulloblastoma samples from Cho et al. were then plotted onto the map based upon their RNA transcriptional abundance signatures, creating clusters of similar cellular states. Likewise, RNA transcription abundance from 20 PDX samples, for which drug response was known, was then mapped.
Results: C2M2 identified ten cellular states for medulloblastoma by which to define patient samples: SHH DNA repair, SHH glutamate signaling, SHH RNA repair, WNT, Photoreceptor and MYC (in which Group 3 medulloblastoma falls), Neuronal migration, Neuronal MAPK activation and Axonal (in which Group 4 medulloblastoma falls), and Homeobox activation. PDX samples for which drug response was known clustered similarly onto the map.
Conclusion: C2M2 using RNA transcriptional abundance from medulloblastoma samples could be used to predict drug response.
Citation Format: Huwate Yeerna, Benjamin Briggs, Jessica Rusert, Lukas Chavez, Jill Mesirov, Robert Wechsler-Reya, Pablo Tamayo. Childhood Cancer Molecular Map (C2M2) to define medulloblastoma heterogeneity and predict treatment response [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B21.
Abstract B23: EWS-FLI1 partners with EWSR1 to regulate transcription in Ewing sarcoma
Authors: Ahmed Nasiha , Schwartz Jacob 
Published: August 2020

Abstract
Transcription factors are important regulators in normal cell proliferation and cancer. Ewing sarcoma is a pediatric bone cancer driven by a translocation between two transcription factor genes, EWSR1 and FLI1, leading to the expression of an aberrant transcription factor, EWS-FLI1. While FLI1 is not expressed, constitutive expression of EWSR1 is retained in Ewing sarcoma cells. However, very little is known about the effect of wild-type EWSR1 on EWS-FLI1 transcriptional activity. EWSR1 and EWS-FLI1 coimmunoprecipitate in a complex together in Ewing sarcoma cells and HEK293T cells. RNA-sequencing in Ewing sarcoma cells revealed a pool of genes coregulated by EWS-FLI1 and EWSR1. Furthermore, loss of EWSR1 in Ewing sarcoma cells inhibits anchorage-independent growth. Taken together, this suggests EWSR1 may play a key role in the transcriptional activity of EWS-FLI1 in Ewing sarcoma biology.
Citation Format: Nasiha Ahmed, Jacob Schwartz. EWS-FLI1 partners with EWSR1 to regulate transcription in Ewing sarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B23.