48670 research outputs found
Sort by
The Historical and Contemporary Significance of Anscombe and Foot\u27s Metaethical Thought
No full textIn this dissertation, I argue that Anscombe and Foot’s metaethical thought was not only significant for the history of metaethics in the twentieth-century, but continues to be significant for contemporary thought. In Part One, I argue that the historical significance of Anscombe and Foot’s metaethical thought consisted in their revival and unique development of an approach to metaethics called Ethical Naturalism, which was a philosophical position that had all but disappeared from the theoretical map for several decades. Additionally, I argue that their work was historically significant for showing the relevance of Wittgenstein’s late theoretical philosophy for ethics and metaethics. In Part Two, I argue that the unique brand of Ethical Naturalism that was initially articulated by Anscombe and Foot has opened up exciting new pathways in contemporary metaethics. In particular, it made possible the development of a family of views called “NeoAristotelian Naturalism”, according to which it is possible to explain objective normative truths in terms of natural facts about what human beings are like. I argue that NeoAristotelian Naturalism is a promising, yet underdeveloped, position in contemporary metaethics
Ubiquitin Specific Protease 6 (USP6): A Novel Hot TME Agonist Inhibits Ewing Sarcoma through Natural Killer Cell Activation
No full textNatural Killer (NK) cell regulation by cancer cells requires extensive exploration for developing NK-cell based immunotherapies. Ewing sarcoma (ES) is an insidious pediatric cancer that has not benefited from immunotherapy, due to its immunologically cold nature. We previously reported that Ubiquitin-Specific Protease 6 (USP6) functions as a tumor suppressor in ES by inducing a highly immunostimulatory hot tumor microenvironment (TME), with increased infiltration and activation of multiple immune lineages. We found that USP6 expression in ES cells inhibited xenograft growth in nude mice, but not NSG mice, implicating a role for the innate immune system, particularly cytotoxic NK cells. Therefore, we hypothesize that NK cells are essential for USP6-mediated tumor suppression and seek to determine the mechanism by which their cytolytic function is activated by USP6. We discovered that NK cells are essential for ES inhibition by USP6, as NK cell depletion completely reverses USP6-mediated suppression of ES in RAG2-/- mice. USP6 expression in ES cells directly stimulates NK cell activation and degranulation in vitro, and functions by increasing surface levels of multiple NK-activating ligands. USP6 also induces surface upregulation of receptors for the apoptosis-inducing ligand TRAIL, providing an additional route for enhanced sensitivity to NK killing. Furthermore, USP6/ES and NK cells participate in a paracrine immunostimulatory feedforward loop, wherein interferon-γ (IFNγ) secreted by the activated NK cells feeds back on USP6/ES cells to induce synergistic expression of chemokines - CXCL9 and CXCL10. Remarkably, expression of USP6 in subcutaneous ES xenografts induces systemic activation of NK cells and an abscopal response in which growth of distal tumors is inhibited, coincident with increased infiltration and activation of NK cells. These observations suggest that USP6 expression in primary tumors might be able to inhibit growth of metastatic ES tumors, which will be substantial in meeting a major clinical need
Structural Basis of a Transcription Pre-Initiation Complex on a Divergent Promoter
No full textWhile a long history of molecular biology research has been directed toward the deciphering the fundamental mechanisms of life, a structural understanding of eukaryotic transcriptional activation has remained a longstanding goal in biology. Key observations in early transcriptional activation of RNA Polymerase II transcription, have highlighted the role of sequence specific transcription factors (ssTFs) in the recruitment of Mediator and the transcription machinery to transcriptional enhancers. Observations of bidirectional transcription and stable divergent pre-initiation complex (PIC) formation relative such loci point to the existence of a previously uncharacterized ssTF- and Mediator-dependent intermediate. Through characterization of such assembly intermediates on an endogenous divergently transcribed loci, we have identified common structural intermediates and characterized them by cryo-electron microscopy (CryoEM). The resulting architecture reveals how two distinct Mediator bound PICs form a dimer through the Mediator Tail module, induced by an activator protein localized near the dimerization interface. The Tail dimer is associated with ~80-bp upstream DNA, such that two flanking core promoter regions are positioned and oriented in a suitable form for PIC assembly in opposite directions. Additionally, cryo-electron tomography was used to visualize the progress of PIC assembly on the two core promoter regions, providing direct evidence for the role of the Tail dimer in supporting divergent transcription. Altogether, these results provide a structural basis for ssTF- and Mediator-dependent bidirectional transcription activation, the proposed innate state of transcriptional activation, and provide a first-ever visualization of recruitment-based transcription activation through the Mediator Complex
Restoration of a Qing Dynasty Historic Palette in Chinese Official-Style Architectural Polychrome Painting with Formulations from Treatise Sanchu Huitong Huazuo Xianxing Zeli
Get PDFDecorative polychrome painting is one of the defining features of Chinese official-style architecture. Lack of understanding in and documentation of polychrome painting’s historic appearance often lead to inappropriate color restoration. Recently, there are attempts in restoring historic palettes based on field experience and historic craftmanship treatises, but few of them focus on Qing dynasty or compound colors, especially small colors. This thesis studies ten formulations of compound color in an 18th century Qing dynasty treatise Sanchu Hutong Huazuo Xianxing Zeli and recreates twenty mockups with techniques documented by traditional craftsmen and experienced conservators. Observation shows that the restored samples indicate that the appearance of these compound colors varies with the pigments and binder used, their proportion, particle size, and mixing. Quantitative color measurement and cross-sectional analysis could serve as a reference for future polychrome painting pigment studies
A Retrospective Pilot Study of the Clinical and Histopathological Features of Oral Lichen Planus: Comparison of the Diagnostic Criteria
No full textObjective:
The purpose of this study was to compare published Oral Lichen Planus (OLP) diagnostic criteria.
Study Design:
After obtaining IRB approval, electronic health records at a tertiary care academic medical center from 2015 to 2021 were reviewed. Adult patients with OLP (ICD-10 code L43 and its subcategories) were included. Cases were excluded if histological analysis or outcomes were not reported.
Results:
341 charts were reviewed. Patient mean age was 66.2±11.7 years and 74.4% were female. 79.7% had OLP lesions in multiple anatomical locations within the oral cavity. 90.3% had bilateral involvement. Skin and genital lesions were reported as 15.5% and 13.7% respectively. 86.5% of cases had plaque, reticular or Wickham striae (WS), whereas 17.8% had atrophy, erosion, or ulceration. When applying the available diagnostic criteria to this cohort, 100% of cases agreed with 1978 WHO criteria, 60.9% with 2003 modified WHO, 74.5% with 2016 AAOMP, and 70.4% with 2020 WHO. Clinicopathologic features agreed with all 4 published criteria in 60.9% of cases.
Conclusions:
The 1978 WHO criteria may lack specificity, while 2003 WHO could be too specific clinically and histologically. The 2016 AAOMP criteria may be too strict histologically, while the 2020 WHO criteria may be too strict clinically. Further prospective studies are needed to reconcile diagnostic criteria
Anatech SCE-108 Barrel Asher standard operating procedure
Get PDFhttps://repository.upenn.edu/scn_sop/1010/thumbnail.jp
The Inception & The Projection of the Female Body in Biomedicine: An Exploration of Transitory Fertility in Cobbs Creek, West Philadelphia
Get PDFThe relationship between the psychosocial experience of fertility and its biological basis in women is under-researched and undertheorized. In order to create standard assessments informed by both the mental and the physical states of female fertility, qualitative work is necessary to augment our biological knowledge and provide an ethnographic lens on how women contextualize fertility outside of a biomedicine. Here, I introduce the concept of transitory fertility, a term I use to describe moments of perceived variability in fertility status among women. It is a concept currently unrecognized in biomedicine. Women who may be physically able to conceive naturally experience emotions similar to ‘infertile’ women when trying to become pregnant. Qualitative evidence of the ideas surrounding the female body and fertility is presented from the perspective of women in the low-wealth neighborhood of Cobbs Creek, West Philadelphia in partnership with Sayre Health Center (SHC). Cobbs Creek is a medically underserved area currently composed of 73% African Americans. In 2017, 35.0% of SHC service area population was below the federal poverty line compared to 13.5% of Pennsylvania. Over 6 months, semi-structured interviews were conducted virtually with women. Preliminary analyses illuminate the limits of biomedical constructs to contend with shame and anxiety surrounding fertility. Further, the stress associated with fertility struggles may contribute to reduced ability to conceive in women. The creation of a scale to measure transitory fertility will allow for the study of the relationship between women’s perceptions of fertility, their biological fertility, and their ability to become pregnant
An Osteological Study of Spina Bifida in the Nariokotome Homo erectus Skeleton
Get PDFSpina bifida, a type of neural tube defect apparent at birth, has been sporadically documented in paleopathological analyses. It occurs most frequently in the sacrum and has clinical manifestations ranging from mild to severe. However, reporting and interpreting spina bifida from archaeological sacral remains has been difficult because no consensus has been reached about the anatomical indicators of sacral spina bifida. Such a diagnosis is also complicated by the fact that the sacrum is the most variable region of the spine, with many of the morphometric variants being considered normal. This project explored sacral variation in a fossil hominin specimen designated KNM-WT 15000, also known as Nariokotome Boy. This Homo erectus skeleton had been initially suggested to be pathological, due to exhibiting traces of congenital skeletal abnormalities, including spina bifida. However, it has become a subject of controversy, as more recent studies refute this claim. Thus, the objective of the present study was to evaluate these competing claims through the comparative analysis of sacral morphology in KNM-WT 15000 and two prehistoric reference samples from the archaeological sites of Tepe Hissar and Hasanlu in modern-day Iran. The results indicate that the sacrum of KNM-WT 15000 falls within normal morphometric variation compared to the reference samples except in the first sacral vertebra, where an occurrence of spina bifida could be suggested
Penn Library\u27s Ms. Codex 1657 - Colecci[ón] de vari[os] tracta[dos]. (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1130/thumbnail.jp
In Vitro Comparative Study Between Full-Arch Conventional Implant Impressions and Full-Arch Digital Implant Impressions with Snap-on Scan Bodies
Get PDFStatement of Problem: Digital impression techniques are widely used in everyday cases. There is sufficient evidence to support this technique in partially edentulous patients but the evidence supporting the use of intraoral scanners (IOS) in restorative digital workflows for edentulous patients is still limited.
Purpose: The aim of the present in vitro study was to measure and compare the accuracy of full- arch conventional implant impressions with open and closed-trays, full-arch digital implant impressions with intraoral scanners (IOS), and three-dimensional (3D) printed casts from the full-arch digital implant impressions.
Material and methods: Six implants were placed into a mandibular model. Snap-on scan bodies were inserted into the implants and scanned with a high-resolution reference scanner and exported in standard tessellation language (.STL) format (Group Control). Splinted open-tray impressions (Group 1, n=5) and closed-tray impressions (Group 2, n=5) were made and stone casts were fabricated. Digital impressions (Group 3, n=5) were made with an intra-oral scanner and the .STL files were exported to fabricate 3D printed casts. Snap-on scan bodies were inserted into analogs in Groups 1, 2, and 3 and scanned with the reference scanner. Using a 3D inspection software, impression techniques were compared to the control. Root mean square (RMS) values were calculated from the control and superimposed digitized casts from different impression techniques.
Results: Group 3 had the lowest mean dimensional difference when superimposed with Group Control, then Groups 4, 1, and 2. Significant differences were found in RMS values between Group Control and digitized models fabricated from different techniques (P\u3c0.05). Post Hoc (Tukey) test revealed that Group 3 (P\u3c0.001) was significantly different from other groups while no significant difference was found between Groups 1, 2, and 4 (P\u3e0.001).
Conclusions: 3D printed models from full-arch digital impression of Snap-on scan bodies seem to be as accurate as stone models fabricated from full-arch conventional impression techniques. Closed-tray full-arch impression technique using dual-functioning Snap-on scan bodies seem to be as accurate as the splinted open-tray full-arch technique