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Machine learning Sasakian and topology on contact Calabi-Yau -manifolds
No full textWe propose a machine learning approach to study topological quantities related to the Sasakian and -geometries of contact Calabi-Yau -manifolds. Specifically, we compute datasets for certain Sasakian Hodge numbers and for the Crowley-Nördstrom invariant of the natural -structure of the -dimensional link of a weighted projective Calabi-Yau -fold hypersurface singularity, for 7549 of the 7555 possible projective spaces. These topological quantities are then machine learnt with high performance scores, where learning the Sasakian Hodge numbers from the weights alone, using both neural networks and a symbolic regressor which achieve scores of 0.969 and 0.993 respectively. Additionally, properties of the respective Gröbner bases are well-learnt, leading to a vast improvement in computation speeds which may be of independent interest. The data generation and analysis further induced novel conjectures to be raised
Phosphoinositide 3-kinase δ activity in patients with systemic lupus erythematosus.
No full textINTRODUCTION: New biomarkers are needed for better stratification and personalized treatment of Systemic Lupus Erythematosus (SLE). Phosphoinositide 3-kinase δ (PI3Kδ) has been implicated in SLE pathogenesis. Here, we investigated whether a subset of SLE patients has increased PI3Kδ activity after T cell activation. METHODS: T cells were isolated from frozen PBMCs of 108 SLE patients, 19 healthy controls, and one patient with Activated PI3K Delta syndrome (APDS), which provided a benchmark of increased PI3Kδ activity. After 90-minute anti-CD3/CD28 stimulation, phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2) were measured using high-performance liquid chromatography-mass spectrometry. RESULTS: Higher levels of PIP3 (measured as the ratio of PIP3/PIP2) in stimulated T cells distinguished APDS patient from other subjects providing a useful biomarker of increased PI3Kδ activity. We observed no significant difference in T-cell PIP3 levels between SLE patients and healthy controls. However, a subset of SLE patients (n = 4) exhibited strong upregulation of PIP3 following T-cell stimulation, comparable to that observed in the APDS patient. PIP3 levels in stimulated T cells positively correlated with the frequency of CD4+ T cells and negatively correlated with the frequencies of CD8+, EMRA CD4+, and EMRA CD8+ T cells. CONCLUSIONS: We describe the range of variation of PI3Kδ activity in T cells from a large cohort of patients with SLE and from healthy subjects. Our findings suggest that increased PI3Kδ activity is not associated with SLE in general, although some SLE patients exhibit a particularly strong upregulation of PIP3 levels after T-cell stimulation. This subgroup of SLE patients warrants further investigation given the promising effect of PI3Kδ inhibitors in restoring normal immune regulation
Powered by Proximity? The Micro-Locational Behaviour of Knowledge-Intensive Businesses
No full textThis paper studies the emergence of Knowledge Intensive Business Services (KIBS) in cities and seeks to establish the economic factors that favour their development. KIBS have the capacity to produce and diffuse knowledge and innovation rapidly, thereby acting as catalysts for city-wide economic growth. While research on the agglomeration of KIBS has been largely conducted at the regional or national level, the intra-metropolitan scale has received considerably less attention despite the relevance of micro-location in the knowledge diffusion literature. Using an anonymised firm-level dataset of Singaporean firms, we use a spatially weighted Ellison-Glaeser index to demonstrate significant clustering of KIBS in urban locations. Furthermore, we find that client concentration and same KIBS type concentration are significant predictors of KIBS agglomeration, but proximity to firms of a different KIBS type and the business reputation of an area are not, potentially indicating that Marshallian localisation agglomeration economies are more powerful than Jacobian urbanisation economies for predicting the urban location patterns of KIBS
Kavos and the Special Deposits: The sanctuary on Keros and the origins of Aegean ritual practice: the excavations of 2006–2008. Volume II
Get PDFVolume II [of the Keros Project] describes the excavation and finds from the Special Deposits at Kavos at the sanctuary on Keros lying opposite the settlement on the islet of Dhaskalio (described in Volume I). The finds of marble from the Special Deposit South are described in Volume III, and the pottery in Volume V. The sanctuary at Kavos, dating from c. 2700 BC to 2400 BC has yielded the richest ritual deposits of the early bronze age Cyclades. The finds are presented here in their excavation contexts, and the significance of the Special Deposit South as a ritual deposit is examined in the context of Aegean prehistory.
The Supplementary Material, originally made available on a DVD affixed within the printed volume, consists of 4,254 images and 65 tables, as well as an appendix to Chapter 10 and a fuller version of the catalogue presented in Chapter 9. The material is organized in zipped folders named for the chapter in the book to which the material contained therein relates. A full description of these folders is provided in the "Contents" pdf
Health-related quality of life and cognitive functioning in survivors of oligodendroglioma: An international cross-sectional investigation.
Get PDFBACKGROUND: Patients with oligodendroglioma have a relatively favorable prognosis. The long-term impacts of the tumor itself and its treatment on health-related quality of life (HRQOL) and cognition remain largely unclear. We investigated associations between treatment and functioning of survivors of oligodendroglioma. METHODS: In this cross-sectional observational study, patients with oligodendroglioma, isocitrate dehydrogenase-mutant and 1p/19q-codeleted, diagnosed ≥ 5 years ago, were recruited. Patients completed patient-reported outcome measures (EORTC QLQ-C30; BN20; MOS Cognitive Complaints Scale) and cognitive tests (HVLT-R, TMT, COWAT). Associations between HRQOL and cognition outcomes, and clinical variables (time since diagnosis; age at diagnosis; progression; tumor location; treatments delivered; time since treatment; current medication) were explored with regression analyses. RESULTS: In total, 237 patients M = 9.9 years postdiagnosis (SD = 4.2, range 5.0-25.8) took part from 33 sites across 9 countries. Clinically relevant levels of impairment were noted in >40% of patients on EORTC QLQ-C30 scales for cognitive functioning (56.1%), emotional functioning (49.8%), fatigue (45.1%), and physical functioning (40.5%). In individuals, cognitive impairment ranged from 17.7% for processing speed to 46.0% for episodic verbal memory (delayed recall). Among other clinical factors such as current use of antiseizure medication or antidepressants, age, disease progression, time since diagnosis and time since treatment, and radiotherapy treatment (ever received) was linked to HRQOL and cognitive functioning outcomes (posthoc analyses for cumulative radiotherapy dose: not significant). CONCLUSIONS: In oligodendroglioma survivors, HRQOL and cognitive impairment are prevalent even years into follow-up. Supportive care and rehabilitation should be prioritized to mitigate these challenges and improve daily functioning. TRIAL REGISTRATION: NCT04708548
Entre agulhas e mãos: a "medicina chinesa" no Brasil da década de 1970
Get PDFThis article aims to understand the ways in which Chinese medicine was portrayed in the Brazilian press during the transnational context of counterculture in the 1970s. It seeks to analyse the social representations built around Chinese medicine, the dissemination of this medical rationale, main concepts, as well as its notions of healthcare, illness and healing. Focusing on manuals, newspaper articles and advertisements about acupuncture and daoyin aimed at the general public, we will look at the role multiple actors, beyond the biomedical community, played in the formation of Chinese medicine in Brazil. We selected printed manuals that also reverberated in the general press, especially in two wide-circulation newspapers, the Jornal do Brasil and Diário de Pernambuco. The several notions of health, illness and healing linked to ideas of tradition and modernity stand out as an essential paradox in the definition of Chinese medicine in Brazil
In vivo CRISPR screening identifies SAGA complex members as key regulators of hematopoiesis.
Get PDFThe biological mechanisms that sustain the vast blood production required for healthy life remain incompletely understood. To search for cell intrinsic regulators of hematopoiesis, we perform a genome-wide in vivo hematopoietic stem and progenitor cell (HSPC)-based CRISPR knockout screen. We discover SAGA complex members, including Tada2b and Taf5l, as key regulators of hematopoiesis. Loss of Tada2b or Taf5l strongly inhibits hematopoiesis in vivo, causing a buildup of immature hematopoietic cells in the bone marrow. The SAGA complex deposits histone H3 lysine 9 acetylation (H3K9ac) and removes histone H2B ubiquitination (H2Bub). Loss of Tada2b leads to a reduction in H3K9ac levels and altered H2Bub enrichment in HSPCs, implicating disruption of SAGA complex activity. This is associated with upregulation of interferon pathway genes, reduced mitochondrial activity, and increased megakaryocyte progenitor cell commitment. Loss of these factors also enhances the cell outgrowth and the interferon pathway in an in vivo human myelodysplastic syndrome cell line model. In summary, this study identifies the SAGA complex as an important regulator of hematopoiesis
RNAi in Pest Control: Critical Factors Affecting dsRNA Efficacy.
Get PDFIn recent years, agricultural crops have increasingly been attacked by more destructive insect pests, forcing modern farming to depend mainly on chemical insecticides. Although valuable, their widespread and intensive misuse has raised serious concerns about environmental and public health impacts. RNAi has been proposed as a safer alternative due to its high specificity, adaptability, and low ecological footprint. So far, dsRNA has proven effective in controlling various pest species, either through topical application or via genetically modified plants. Despite advances, large-scale implementation of RNAi remains challenging due to technical and biological hurdles that contribute to inconsistent performance. Key aspects such as dsRNA design, delivery techniques, and cellular uptake mechanisms still require refinement. Additionally, ensuring environmental stability, addressing biosafety concerns, and developing cost-effective production methods are essential for its practical application. In this review, we explore recent advances in the design and implementation of dsRNA, as well as the strategies that could support the successful integration of RNAi technology into pest management programs
Transdiagnostic interventions in prediagnostic youth with elevated distress: A meta-analysis of outcomes.
Get PDFOBJECTIVE: The current systematic review and meta-analysis identified nonpharmacological outpatient interventions with transdiagnostic effects in youth with elevated psychological distress who do not meet the diagnostic criteria. We examined common elements that may be associated with treatment effects. METHOD: Of the 10,208 studies identified, k = 68 were included involving 10,805 individuals with a Mage of 16.96 years (SD = 1.80; 66.67% female). We examined changes in depression, anxiety, suicidality, disordered eating, and quality of life using random-effects models in the R meta package. RESULTS: Cohen's d effect sizes (95% CIs) were 0.21 [0.11, 0.32] for depression (k = 64), 0.20 [0.11, 0.29] for anxiety (k = 57), and 0.11 [0.01, 0.21] for quality of life (k = 19). Heterogeneity was present (I2 ranging from 6.73 to 16.95%). Due to limited studies for eating (k = 5) and suicidality (k = 4), meta-analyses were not feasible for these outcomes. Moderator analyses indicated that adolescents (vs. children and emerging adults) derived significant benefits. Cognitive behavioral therapy was indicated as an effective transdiagnostic approach for depression and anxiety. The most frequent common elements across cognitive behavioral therapy approaches included cognitive literacy, emotional literacy, psychoeducation, goal setting, and problem solving. CONCLUSIONS: These results provide the first quantitative test of transdiagnostic intervention approaches that can improve mental health in vulnerable, symptomatic youth. Further attention is required to outcomes related to disordered eating and suicidality given their prevalence and serious consequences in youth. Dismantling studies of cognitive behavioral therapy are required to identify effective common elements that can drive better mental health outcomes in youth. (PsycInfo Database Record (c) 2025 APA, all rights reserved)
Colour plates (Kavos and the Special Deposits: The sanctuary on Keros and the origins of Aegean ritual practice: the excavations of 2006–2008. Volume II)
Get PDFVolume II [of the Keros Project] describes the excavation and finds from the Special Deposits at Kavos at the sanctuary on Keros lying opposite the settlement on the islet of Dhaskalio (described in Volume I). The finds of marble from the Special Deposit South are described in Volume III, and the pottery in Volume V. The sanctuary at Kavos, dating from c. 2700 BC to 2400 BC has yielded the richest ritual deposits of the early bronze age Cyclades. The finds are presented here in their excavation contexts, and the significance of the Special Deposit South as a ritual deposit is examined in the context of Aegean prehistory.
The Supplementary Material, originally made available on a DVD affixed within the printed volume, consists of 4,254 images and 65 tables, as well as an appendix to Chapter 10 and a fuller version of the catalogue presented in Chapter 9. The material is organized in zipped folders named for the chapter in the book to which the material contained therein relates. A full description of these folders is provided in the "Contents" pdf