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Active Filaments on Curved Surfaces:From Single Filaments to Dilute Suspensions
Get PDFCurvature plays a central organizational role in active polymer dynamics. Using large-scale Langevin-dynamics simulations, we study active semiflexible filaments confined to smooth curved surfaces and map how curvature, bending rigidity, and activity interact. We find geodesic alignment, curvature lensing, and curvature-induced trapping. In particular, regions of negative Gaussian curvature localize filaments and hinder global surface exploration. These results show how surface geometry can be used to control the organization and transport of active matter on curved substrates
Detection and identification of vacancy defects in antimony selenide
No full textAntimony selenide (Sb2Se3) has an optimal bandgap and absorption coefficient for thin film solar cell applications and comprises earth abundant elements. The rate of increase in reported power conversion efficiencies has slowed due to a persistently large open circuit voltage deficit attributed to detrimental concentrations of point defects. Here we use depth-profiling positron annihilation lifetime spectroscopy to study Sb2Se3 crystals and thin films. The method is specific to neutral and negative charge states of vacancy-related defects. Both monovacancy and divacancy defects are identified in intrinsic and n-type samples but no monovacancy defects are detected in the p-type sample. Comparison of the experimental positron lifetimes with density functional theory calculated values provide evidence for the observation of Sb monovacancies in the –3 state and of Se monovacancies in the –2 state. The results are consistent with recent density function theory predictions that the Sb and the Se monovacancy defects both have accessible negative charge states
Revisiting Type 2 Inflammation and Airway Hyper-responsiveness in COPD
Get PDFAirway hyper-responsiveness (AHR) is well established in asthma but remains under-recognized in chronic obstructive pulmonary disease (COPD). The recognition of COPD heterogeneity, particularly eosinophilic COPD and asthma COPD overlap, has increased interest in AHR as a clinical marker of type 2 (T2) inflammation. This phenotype is present in 20% to 40% of patients with COPD and has become a focus of clinical trials exploring biologics targeting IL-4, IL-5, IL-13, and thymic stromal lymphopoietin. We aim to review current evidence on AHR in COPD, its relationship with inflammatory phenotypes, diagnostic modalities, and therapeutic implications. AHR in COPD reflects both structural and inflammatory mechanisms. Direct challenges such as methacholine predominantly assess airway geometry, whereas indirect challenges such as mannitol reflect more activity of T2 inflammation and correlates consequently with eosinophils and fractional exhaled nitric oxide. Patients with AHR may derive greater benefit from inhaled corticosteroids than AHR-negative patients. Although AHR reduction has been demonstrated with biologics in asthma, no study has evaluated their effects on AHR in COPD. AHR represents a clinically relevant and promising treatable trait in COPD, particularly in T2-high phenotypes. Standardized challenges combined with the integration of inflammatory markers and targeted trials of biologics are needed to clarify its role in personalized COPD management and therapeutic decision-making
Evaluating progesterone receptor agonist megestrol plus letrozole for women with early-stage estrogen-receptor-positive breast cancer:the window-of-opportunity, randomized, phase 2b, PIONEER trial
Get PDFThe use of progestogens in breast cancer has been controversial. Recent preclinical studies have shown that ligand-bound progesterone receptor interacts directly with the estrogen receptor (ER) and reprograms ER transcriptional activity. Progestogen cotreatment enhances the antitumor activity of antiestrogen therapy in mouse xenografts. We report PIONEER, a 198-participant, three-arm, randomized phase 2b window-of-opportunity study for women with early-stage ER+ breast cancer, which evaluated letrozole with or without megestrol at 40 mg or 160 mg daily. The primary endpoint was the change in tumor proliferation measured by Ki67 immunohistochemistry. Secondary and exploratory endpoints included a comparison of low versus higher dose of megestrol, safety, tolerability and biomarker subgroup analyses. The trial met its primary endpoint, with a greater reduction in proliferation seen when megestrol was added to letrozole. This effect was accompanied by reduced ER genomic binding at canonical binding sites in paired tumor biopsies, indicating reduced ER transcriptional activity. These results support further evaluation of low-dose megestrol, which has two mechanisms for potentially improving breast cancer outcomes in combination with standard antiestrogen therapy: alleviating hot flashes and thereby helping with treatment adherence, as well as a direct antiproliferative effect (NCT03306472).</p
Disease Remission and Surgical Outcomes of Endoscopic Transsphenoidal Surgery for Cushing Disease:A Single Center Experience
Get PDFIntroduction: Transsphenoidal surgery is the primary treatment for patients with Cushing disease (CD). This study assessed the surgical and endocrinologic outcomes of patients with CD following endoscopic pituitary surgery using strict biochemical criteria to guide surveillance in patients not achieving early remission. Methods: The medical records of all patients with CD who underwent endoscopic transsphenoidal surgery at a single institution between 2004 and 2025 were reviewed. Remission was defined as a fasting serum cortisol level <50 nmol/L (1.8 μg/dL) either basal or after 1 mg dexamethasone. Results: A total of 125 patients were diagnosed with CD and had a primary endoscopic transsphenoidal surgery during the study period (median age 48 years [range: 14–79 years; M:F 93:32). Fifty-seven patients (45.6%) had a microadenoma, 41 (32.8%) had a macroadenoma, and 26 (20.8%) had no demonstrable focal lesion on pituitary magnetic resonance imaging (MRI) (MRI-negative CD). The median length of follow-up was 3.1 years (range: 1 month to 16.7 years). Initial remission rates 3 months after surgery were: 72.0% for patients with MRI-negative CD, 77.2% for microadenomas, and 48.7% for macroadenomas. Age, male sex, MRI-negative, and single operation were predictors of remission. Patients who achieved remission at 3 months were significantly more likely to be in remission at last follow-up after accounting for patient and tumor characteristics. The 5-year recurrence rate following remission was 6.9%. Conclusion: Endoscopic transsphenoidal surgery is an effective first-line treatment for patients with CD but a significant minority will relapse. Close biochemical surveillance of patients who fail to achieve remission may support the use of early adjuvant radiotherapy.</p
Identification of a signalling pathway that modulates Fragile X-Related (FXR)2 function and is implicated in intellectual disability
No full textIn situ reaction-strengthening of ice-templated porous geopolymers for high anisotropy and robustness
Get PDFIce-templating enables ordered porous architectures but fails in geopolymers due to suppressed reactions at cryogenic temperatures and water loss during sublimation, yielding fragile scaffolds. We propose an in situ reaction strategy that converts ice from a passive porogen into a controlled-release solvent. By introducing a staged low-temperature polymerization (−5 °C to +5 °C) before sublimation, the gradually melting ice initiates geopolymerization in situ, forming a C-(A)-S-H gel that strengthens pore walls. This approach prevents collapse, ensures faithful ice-template replication, and yields porous geopolymers with compressive strength above 6.5 MPa, far exceeding conventional counterparts (<2 MPa). The materials exhibit pronounced anisotropy (σz/σy > 3.6) and well-defined lamellar pores. This strategy addresses a key limitation in ice-templating and opens pathways for fabricating high-performance porous materials from water-dependent reactive systems
The Palgrave International Handbook of Multiple and Multi-Dimensional Educational and Life Transitions
No full textThis is an international, interdisciplinary and research-based handbook about various educational and life transitions. This handbook has 30 chapters, divided into five parts according to their focus: theoretical/conceptual, multiple transitions, multi-dimensional transitions, dynamic environment, and research/practice/education. Editor Jindal-Snape's Multiple and Multi-dimensional Transitions (MMT) Theory runs as a thread through and between each chapter. MMT Theory takes a complex view of transitions and proposes that each individual experiences multiple transitions simultaneously, and in doing so can trigger transitions for significant others, and vice versa. Chapters lean into this complexity as they delve into childhood and youth transitions into education and care and between school and work, as well as professional transitions into leadership, and family and life transitions.The handbook is the first reference work to establish transitions research as a field in its own right. It presents two new frameworks and principles for undertaking effective multiple and multi-dimensional transitions research and practice. This handbook will be of relevance to researchers and professionals, from a range of sectors, disciplines and regions. The engaging style of the chapters, make complex concepts accessible to those with varied levels of expertise in transitions research and practice
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