bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partition-based 3 + 2-axis tool path generation for freeform surface machining using a non-spherical tool
Authors: Hao Jiancheng , Li Zhaoyu , Li Xiangyu , Xie Fubao , He Dong , Tang Kai 
Published: August 2022

Abstract
When machining a complex freeform part, using a non-spherical tool could significantly improve the machining efficiency, as one can adaptively adjust the tool posture to maximize its contact area with the part surface. However, since adjusting the tool posture requires changing the tool orientation, a five-axis machine tool is needed, which is extremely expensive as compared to a conventional three-axis machine tool. Moreover, for a complex freeform surface with high curvature variation, to match its curvature change, the tool axis has to drastically change accordingly, thus inducing high velocity and acceleration on the machine tool’s rotary axes. To address these issues, in this paper we propose a partition-based 3 + 2-axis strategy for machining a general complex freeform surface with a non-spherical tool. As only a finite small number of distinct tool orientations are needed for 3 + 2-axis machining, an indexed three-axis machine tool suffices, thus relieving the need of an expensive five-axis machine tool. In addition, the much-increased rigidity of the three linear axes of the machine tool will greatly improve the kinematics and dynamics of the machine tool and thus enhance the machining accuracy. Experiments in both computer simulation and physical machining are carried out, whose results confirm that, when compared to using a conventional spherical cutter, by using a non-spherical cutter and adaptively adjusting the contacting tool posture and the feed direction, significant improvement in machining efficiency could be achieved, e.g., more than 50% achieved in our experiments.
β-cell dynamics in type 2 diabetes and in dietary and exercise interventions
Authors: Lv Chengan , Sun Yuchen , Zhang Zhe Yu , Aboelela Zeyad , Qiu Xinyuan , Meng Zhuo-Xian 
Published: August 2022

ABSTRACT
Pancreatic β-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes (T2D). Recent clinical and experimental studies have suggested that the functional capacity of β-cells, particularly in the first phase of insulin secretion, is a primary contributor to the progression of T2D and its associated complications. Pancreatic β-cells undergo dynamic compensation and decompensation processes during the development of T2D, in which metabolic stresses such as endoplasmic reticulum stress, oxidative stress, and inflammatory signals are key regulators of β-cell dynamics. Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D, especially in the early stages. Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague, accumulating evidence has implicated the improvement of β-cell functional capacity. In this review, we summarize recent advances in the understanding of the dynamic adaptations of β-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions on β-cell dysfunction in T2D. This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D, and more importantly, it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.
The Woman at the Well as a Witness in John Revisited
Authors: Wasserman Tommy 
Published: August 2022

Abstract
There is a major emphasis on testimony and witnesses in the Gospel of John, and scholars have analysed this trait in the context of a literary trial, or a cosmic lawsuit. The Samaritan woman (John 4) who testifies concerning Jesus is an unexpected witness. Could the author expect his contemporary readers to receive her testimony? This article surveys the status of women as witnesses in in the Graeco-Roman world in general and first-century Judaism in particular. There was a strong expectation that women should not testify in law-courts, where they were instead represented by male guardians with few exceptions. An analysis of John 4:4–42 gives further clues for the evaluation of the Samaritan woman as a legal witness. First, she expresses surprise that Jesus talks with her as a Samaritan. Second, the disciples are astonished that Jesus speaks to a woman. Third, the information about her previous marriages would likely further diminish her status as a witness. In conclusion, the presentation of the Samaritan woman as a key witness in John does not reflect the convention of contemporary culture, whether Graeco-Roman or Jewish. On the contrary, in regard to divine law, she is elevated to a status equal to male witnesses. A two-level reading of the Fourth Gospel further suggests that this feature reflects a different attitude toward women in early Christianity, if not a particular community connected with the Johannine writings.
National identity and anti-immigrant sentiment: Experimental evidence from Mexico
Authors: Acevedo Jesse , Meseguer Covadonga 
Published: August 2022

Abstract
In this article, we explore how historical patterns of identity construction shape today’s attitudes towards immigrants in Mexico. Immigrants in Mexico constitute a very small percentage of the country’s population. Yet some immigrants, in particular those of Asian origin, face a strong anti-immigrant sentiment as measured in terms of opinions and opposition to their social and political incorporation. We trace contemporary anti-Chinese sentiment back to historical processes of Mexican colonisation, which resulted in a particular politics of Chinese incorporation at the turn of the 19th century. This incorporation was violently contested during and after the revolution, leading to a construction of a national identity based on openly excluding the Chinese community. Using experimental evidence, we show that anti-Asian prejudice today is well explained by looking at ethnic traits and civic norms that are endorsed by natives as being constitutive of Mexican national identity.
Revisiting the evidences for spectral anomalies in distant blazars: New data on the photon-ALP mixing
Authors: Cenedese Francesco , Franceschini Alberto , Galanti Giorgio 
Published: August 2022

ABSTRACT
We re-examine possible dependencies on redshift of the spectral parameters of blazars observed at very-high energies (VHEs) with Imaging Atmospheric Cherenkov telescopes. This is relevant to assess potential effects with the source distance of the photon to axion-like particle mixing that would deeply affect the propagation of VHE photons across the Universe. We focus our spectral analysis on 38 BL Lac objects (32 high-peaked and 6 intermediate-peaked) up to redshift z ≃ 0.5, and a small sample of 5 Flat Spectrum Radio Quasars up to z = 1 treated independently to increase the redshift baseline. The 78 independent spectra of these sources are first of all carefully corrected for the gamma–gamma interaction with photons of the Extragalactic Background Light that are responsible for the major redshift-dependent opacity effect. Then, the corrected spectra are fitted with simple power laws to infer the intrinsic spectral indices Γem at VHE, to test the assumption that such spectral properties are set by the local rather than the global cosmological environment. We find some systematic anticorrelations with redshift of Γem that might indicate, although with low-significance, a spectral anomaly potentially requiring a revision of the photon propagation process. More conclusive tests with higher statistical significance will require the observational improvements offered by the forthcoming new generation of Cherenkov arrays (CTA, ASTRI, LHAASO).
Understanding the spatial variation of Mg ii and ionizing photon escape in a local LyC leaker
Authors: Seive Thomas , Chisholm John , Leclercq Floriane , Zeimann Gregory 
Published: August 2022

ABSTRACT
Ionizing photons must have escaped from high-redshift galaxies, but the neutral high-redshift intergalactic medium makes it unlikely to directly detect these photons during the Epoch of Reionization. Indirect methods of studying ionizing photon escape fractions present a way to infer how the first galaxies may have reionized the Universe. Here, we use HET/LRS2 observations of J0919 + 4906, a confirmed z≈ 0.4 emitter of ionizing photons to achieve spatially resolved (12.5 kpc in diameter) spectroscopy of Mg iiλ2796, Mg iiλ2803, [O ii]λλ3727, 3729, [Ne iii]λ3869, H γ, [O iiI]λ4363, H β, [O iii]λ4959, [O iii]λ5007, and H α. From these data, we measure Mg ii emission, which is a promising indirect tracer of ionizing photons, along with nebular ionization and dust attenuation in multiple spatially resolved apertures. We find that J0919 + 4906 has significant spatial variation in its Mg ii escape and thus ionizing photon escape fraction. Combining our observations with photoionization models, we find that the regions with the largest relative Mg ii emission and Mg ii escape fractions have the highest ionization and lowest dust attenuation. Some regions have an escape fraction that matches that required by models to reionize the early Universe, while other regions do not. We observe a factor of 36 spatial variation in the inferred LyC escape fraction, which is similar to recently observed statistical samples of indirect tracers of ionizing photon escape fractions. These observations suggest that spatial variations in neutral gas properties lead to large variations in the measured LyC escape fractions. Our results suggest that single sightline observations may not trace the volume-averaged escape fraction of ionizing photons.
The feasibility of constraining DM interactions with high-redshift observations by JWST
Authors: Kurmus Ali , Bose Sownak , Lovell Mark , Cyr-Racine Francis-Yan , Vogelsberger Mark , Pfrommer Christoph , Zavala Jesús 
Published: August 2022

ABSTRACT
Observations of the high redshift universe provide a promising avenue for constraining the nature of the dark matter (DM). This will be even more true with the advent of the James Webb Space Telescope (JWST). We run cosmological simulations of galaxy formation as part of the Effective Theory of Structure Formation (ETHOS) project to compare high redshift galaxies in cold dark matter (CDM) and alternative DM models which have varying relativistic coupling and self-interaction strengths. The interacting DM scenarios produce a cutoff in the linear power spectrum on small-scales, followed by a series of ‘dark acoustic oscillations’. We find that DM interactions suppress the abundance of galaxies below $M_\star \sim 10^8\, {\rm M}_\odot$ for the models considered. The cutoff in the power spectrum delays structure formation relative to CDM. Objects in ETHOS that end up at the same final masses as their CDM counterparts are characterized by a more vigorous phase of early star formation. While galaxies with $M_\star \lesssim 10^6\, {\rm M_\odot }$ make up more than 60 per cent of star formation in CDM at z ≈ 10, they contribute only about half the star formation density in ETHOS. These differences diminish with decreasing redshift. We find that the effects of DM self-interactions are negligible compared to effects of relativistic coupling (i.e. the effective initial conditions for galaxy formation) in all properties of the galaxy population we examine. Finally, we show that the clustering strength of galaxies at high redshifts depends sensitively on DM physics, although these differences are manifest on scales that may be too small to be measurable by JWST.
BSCI-02 CSF PROTEOMICS AS A MINIMALLY-INVASIVE STRATEGY FOR DISTINGUISHING BRAIN METASTASES FROM OTHER PRIMARY BRAIN MALIGNANCIES
Authors: Mansouri Alireza , Mikolajewicz Nicholas , Khan Shahbaz , Glantz Michael , Moffat Jason , Zadeh Gelareh , Kislinger Thomas 
Published: August 2022

Abstract

BACKGROUND
Accurate diagnosis and prognostication of intra-axial brain tumors hinges on invasive brain sampling, which carries risk of morbidity. Minimally invasive sampling of proximal fluids, also known as liquid biopsy, can mitigate this risk. Although the cerebrospinal fluid (CSF) is the ideal liquid biopsy source, the traditionally high volumes required for impactful analyses have deterred progress. The objective of this study was to identify diagnostic and prognostic CSF proteomic signatures in glioblastoma (GBM), brain metastases (BM), and central nervous system lymphoma (CNSL).

METHODS
CSF samples were retrospectively retrieved from the Penn State Neuroscience Biorepository and profiled using shotgun proteomics with low sample volumes. Proteomic signatures were identified using machine learning classifiers and survival analyses.

RESULTS
Using 30µL CSF volumes, we recovered 800 unique peptides across 73 samples [20 normal pressure hydrocephalus (NPH, non-tumor control), 22 GBM, 17 BM, and 14 CNSL]. Externally-validated proteomic-based classifiers identified malignancy with AUROC of 0.94 and distinguished individual tumor entities from others with AUROC ≥0.96. More clinically relevant triplex classifiers, comprised of just 3 peptides, distinguished individual tumor entities with AUROC ≥0.90. Novel biomarkers were identified among the top classifiers, including TFF3 and CACNA2D2, and characterized using single-cell RNA sequencing data. Survival analyses validated previously implicated prognostic signatures, including blood brain barrier disruption.

DISCUSSION
Reliable classification of intra-axial malignancies using low CSF volumes is feasible, which has ramifications for longitudinal tumor surveillance. Novel biomarkers identified here necessitate future validation. Based on emerging evidence, upfront implantation of CSF reservoirs in brain tumor patients warrants consideration.
BSCI-03 THE ROLE OF LONP1 IN DRIVING ENHANCED PMT IN THE ‘LEADING EDGE’ NICHE IN GLIOBLASTOMA
Authors: Douglas Christopher , Lomeli Naomi , Bota Daniela 
Published: August 2022

Abstract
Glioblastoma (GBM), a high grade brain tumor, possesses poor overall survival with less than 5% surviving past five years. Previously, the TCGA classifications for GBM have included the mesenchymal, proneural, classical and neural subtypes with their own respective expression profiles and survival. Recent omics analysis has revealed other key aspects of GBM pathology, including intratumoral heterogeneity spanning all subtypes and enhanced stemness and treatment resistance and other hallmarks of proneural mesenchymal transition (PMT) following treatment with first-line standard of care treatment with radiation therapy and temozolomide (TMZ). Invading glioma stem cells (GSC) with high Nestin and hypoxia-inducible factor 1 alpha (HIF-1α) expression have been theorized to contribute to recurrence. HIF-1α acts as a master regulator driving increased stemness, invasiveness and angiogenesis. Interestingly, HIF-1α and nuclear respiratory factor-2 both upregulate Lon peptidase 1 (LonP1) in response to increased hypoxia or reactive oxygen species (ROS) production. LonP1 has been shown to drive increased metastasis, tumor growth and epithelial-mesenchymal transition (EMT), an analog of PMT, in colon cancer, melanoma and other cancer types. In a recently elucidated GBM organoid model, we present new findings demonstrating the importance of LonP1 in driving enhanced, transient PMT near the ‘invading edge’. This includes the enhanced expression of several key drivers of PMT and phenotypic hallmarks, such as increased invasiveness, proliferation and poorer survival.
BSCI-05 REPURPOSING PROPOFOL FOR THE TREATMENT OF BRAIN METASTASES
Authors: Penning Donald , Cazacu Simona , Nizar Raphael , Goldstein Hodaya , Kazimirsky Gila , Brown Stephen , Rogers Lisa , Brodie Chaya 
Published: August 2022

Abstract

BACKGROUND
Recent clinical studies suggest beneficial effects of propofol anesthesia on tumor progression and patient survival in solid tumors but reported benefits are modest. One potential reason is the relatively short, single exposure to propofol, limited to the surgical period. Brain metastases (BM) are the most common brain tumors in adults. Metastatic tumors develop following infiltration of the brain from primary tumors such as lung, breast, melanoma, and colorectal cancers. BM are treated with combination therapies, including surgery, radiotherapy, chemotherapy, and immunotherapy, however the prognosis of most patients with BM remains dismal. In this report we investigated the effects of propofol plus radiation on cancer stem cells derived from human lung cancer brain metastases (BM-CSCs) and their cross-talk with microglia.

OBJECTIVES
Our hypothesis is that propofol can be repurposed as a treatment of BM in addition to its anesthetic uses. To test this, we first examined the cytotoxic effects of propofol on cancer stem cells established from BM-CSCs alone and with radiation. Also, we studied the effects of propofol on the cross-talk of BM-CSCs and microglia.

RESULTS
We found that propofol 1) exerted inhibitory effect on BM-CSCs self-renewal, stemness and cell proliferation; 2) increased cell death of cancer cells but not normal neural elements; 3) sensitized BM-CSCs to radiation; 4) inhibited the pro-tumorigenic BM-CSCs/ microglia cross-talk by promoting M1 phenotypes of co-cultured microglia.

CONCLUSIONS
Propofol exerted anti-tumor effects on BM-CSCs including inhibition of cell renewal, proliferation, and mesenchymal transition. Propofol at sensitized BM-GSCs to radiation and at higher concentrations induced cell death. Propofol exerted anti-tumor cytotoxicity also by inhibiting the pro-tumorigenic CSC-microglia cross-talk via secreted extracellular vesicles (EVs). Propofol effects can be exploited as a general anesthetic of choice during tumor resection and should be examined as an anti-tumor agent in sub-anesthetic doses either alone or in combination with radiation.
BSCI-13 DEVELOPMENT OF NOVEL ANTI-BRAIN METASTASIS INHIBITORS
Authors: Kieliszek Agata , Mobilio Daniel , Bassey-Archibong Blessing , Johnson Jarrod , McKenna Dillon , Venugopal Chitra , Magolan Jakob , Singh Sheila 
Published: August 2022

Abstract
The current standard of care (surgery and radiation) for brain metastases (BM) is inadequate as BM have a 90% mortality rate within one year of diagnosis, posing a large unmet clinical need. The Singh lab has generated a large in-house biobank of patient-derived BM cell lines that are established from BM patient tumor samples. We use these BM cell lines to generate murine orthotopic xenograft models of BM and interrogate the biological processes that lead to BM. These models have successfully recapitulated all the stages of their respective BM cascades and additionally captured a “pre-metastatic” population of BM cells that have just seeded the brains of mice before forming mature, clinically detectable tumors. Pre-metastatic cell populations are impossible to detect in human patients but represent a therapeutic window wherein metastasizing cells can be targeted and eradicated before establishing clinically detectable and difficult to treat brain tumors. RNA sequencing of pre-metastatic BM cells revealed a unique deregulated transcriptomic profile that is specific to pre-metastatic cells despite the tumor of origin. Connectivity Map analysis was applied to the gene expression signatures of pre-metastatic BM cells to identity a compound (Drug A) which selectively inhibits BM cell proliferation but is not blood-brain barrier (BBB) penetrant and has not been previously considered in the context of brain metastasis. We synthesized a BBB-penetrant analogue of Drug A and found, using our patient-derived xenograft (PDX) models, that it increased survival benefit relative to both placebo and Drug A. Beginning with this promising scaffold, we will conduct structure-activity hypothesis-driven medicinal chemistry campaigns to optimize this scaffold for brain permeation while maintaining selective anti-BM activity. Development of novel small molecules that target pre-metastatic BM cells could slow or prevent the formation of BM and dramatically improve the prognosis of at-risk cancer patients.
BSCI-14 THE ROLE OF ICAM1 IN GLIOBLASTOMA TUMOUR ASSOCIATED MACROPHAGES UNDER HYPOXIC CONDITIONS
Authors: Devaraja Kaviya , Mansouri Sheila , Zadeh Gelareh 
Published: August 2022

Abstract

BACKGROUND
Glioblastoma (GBM) is an aggressive and highly fatal brain cancer in adults. Existing treatment methods are ineffective and we are in need of new treatments that extend the overall survival and improve quality-of-life. Cell adhesion molecules (CAMs) are proteins that enable cells to communicate with one another and the surrounding environment. Intracellular adhesion molecule 1 (ICAM1) is a CAM expressed by TAMs in GBM. Tumour associated macrophages (TAMs) are thought to enhance tumour growth and proliferation, particularly within the characteristic hypoxic tumour microenvironment (TME) of GBM. I hypothesize that the expression of ICAM1 on the surface of TAMs contributes to GBM cell invasiveness, especially in the hypoxic TME, by enhancing the interaction between tumour cells and macrophages, thereby facilitating the migration and invasion of the tumour cells.

METHODOLOGY
Assess the expression levels of ICAM1 in primary and immortalized human and mouse macrophages under hypoxic conditions. Analyze the effect of ICAM1 deficiency on macrophage behaviour including migration, proliferation, and adhesion to tumour cells. Intracranially inject GL261 glioma cells in ICAM1 deficient and wild type mice.

RESULTS
ICAM1 is highly expressed in different cell types within the GBM microenvironment, including TAMs. The expression is particularly enhanced when primary or immortalized macrophages are treated with tumour cell-conditioned medium and is further exacerbated upon incubation of these cells in hypoxic conditions. The migration levels of bone marrow derived macrophage mouse cell type is higher in wild type cells than in ICAM1 deficient cells and higher when co-cultured with tumour cell condition media. ICAM1 deficient mice succumbed to GBM more quickly compared with wild type.

CONCLUSIONS
It is evident that the hypoxic tumour microenvironment increases the expression of ICAM1 in macrophages. The tumour microenvironment increases migration levels of macrophages. The expression of ICAM1 in TAMs in hypoxic TME promotes GBM cell invasiveness, proliferation, aggressiveness and migration.