Browse Articles

Continental rifts losing driving forces can still complete breakup

Abstract The complex evolution of continental rift systems results from the intricate interplay of external driving forces and the rift system’s responses. For this reason, allowing plate kinematics to emerge from the force balance can provide deeper insights than imposing prescribed velocity boundary conditions. This study investigates the influence of temporally varying driving forces, possibly resulting from changes in slab dynamics, on rift evolution using numerical and semi-analytical models. We examined the effects of varying the timing ( $$t_i$$ ), duration ( $$\delta t$$ ), and magnitude ( $$\delta \tau$$ ) of boundary traction reductions on extension velocities ( $$V_\text {E}$$ ). Our models demonstrate that later initiation of traction reduction and slower reduction rates promote continental breakup. A 25% reduction in boundary traction can still lead to continental breakup under optimal conditions, while a 50% reduction generally results in failed rifts. Non-monotonic $$V_\text {E}$$ evolution, including temporary velocity increases during force reduction, is observed and explained by dynamic force balance. Our results show that a continental rift can accelerate towards breakup even when it is currently extending slowly due to a reduced driving force that can arise from many different situations.

Living in the Present Tense

Enhancing atomization and spray patterns of spray G in a gasoline direct injection system using biofuel blends with gasoline

Tirzepatide vs. Semaglutide for Obesity Treatment

How to spot fake scientists and stop them from publishing papers

Spatiotemporal dynamics of production-living-ecological space coordination in Ganzhou City from 2000 to 2020

Thirty Years of Hydroxyurea for Sickle Cell Anemia — Scientific Progress, Global Health Gaps

Multi-target tracking for star sensor based on CenterTrack deep learning model

Perioperative Durvalumab in Gastric Cancer

A surgical window of opportunity trial evaluating the effect of the PCSK9 inhibitor evolocumab on tumoral MHC-I expression and CD8+ infiltration in glioma

Abstract Many cancers evade immunosurveillance by downregulating surface major histocompatibility class (MHC)-I. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes MHC-I degradation and is elevated in glioma. Evolocumab is a clinically approved PCSK9 inhibitor which restores MHC-I expression in pre-clinical cancer models. However, monoclonal antibodies have limited blood brain/tumor barrier penetrance (BBB/BTB). We conducted a window-of-opportunity trial, evaluating evolocumab’s BBB/BTB penetrance and biological effect (PesKE; NCT04937413). Patients with newly diagnosed or recurrent glioma undergoing a clinically indicated biopsy or resection were enrolled (n = 32, M: 16, F: 16; control average age: 51.85, evolocumab: 53). Intervention participants (n = 6) received a single subcutaneous evolocumab dose pre-procedure, of which 4 provided research tissue. No significant adverse events were observed. Evolocumab was detected in all analyzed intervention tissue, with an average tumor: blood ratio of 0.0222 (SD ± 0.0190), akin to other monoclonals. Evolocumab quantitation was 4.44× greater in contrast-enhancing (mean 0.0068 fmol/mcg (SD ± 0.001)) vs non-contrast enhancing cases (mean 0.0015 fmol/mcg (SD ± 0.0004)). Proteomic analysis found positive trends between evolocumab and MHC-I subtypes (HLA-A-C, E-G), with a significant positive correlation with HLA-H (R 2  = 0.9584, p  = 0.021*). Tumor tissue with higher evolocumab titers demonstrated increased surface MHC-I and CD8 + T cell infiltration. Increased CD8 + TNF , FASLG and GZMA transcription was observed in high titer tissue compared to low titer tissue and untreated controls. Pre-resection evolocumab is well tolerated but exhibits BBB/BTB penetrance akin to other monoclonal antibodies. Increased tumoral evolocumab/PCSK9i may enhance tumoral MHC-I/effector CD8 + infiltration. Future work will explore combining evolocumab with BBB/BTB opening therapies like low-intensity focused ultrasound.

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation

Reply to: Uncertain climate effects of anthropogenic reactive nitrogen

Assessment of morphological and molecular diversity in tomato accessions using quantitative traits and RAPD markers

Time to Reconsider Mucoactive Agents for Airway Clearance

Leveraging known Pacific colonisation times to test models for the ancestry of Southeast Asians

Abstract The most widely accepted model for the colonization of Remote Oceania by Austronesian-speaking bearers of the Lapita complex ~ 3 ka (3000 years ago) links it to a broader Neolithic expansion from China, via Taiwan, ~ 4.5–6 ka. However, analyses of mitochondrial DNA haplogroup B4a1a1a, prevalent among Remote Oceanians today, have both supported and challenged this scenario. Here, we analyze 1364 B4a1a1 mitogenomes (234 novel) from 68 islands and compare age estimates with radiocarbon dates for colonization. We estimate the settlement of Remote Oceania ~ 3.2 [2.7; 3.75] ka, matching radiocarbon ages, and then extrapolate the age in Near Oceania. B4a1a1a arose around the northern coasts of New Guinea at least 6 ka, following Early Holocene dispersals from Asia. Technological advances (e.g., in sailing), fueled by interaction networks alongside the arrival of Late Holocene migrants from Taiwan or ISEA and putative environmental changes, likely triggered the expansion of Lapita colonists carrying B4a1a1a from New Guinea into Remote Oceania.

Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis

We need more than good science to fight infectious disease

Design and simulation of high efficiency KSnI3 based perovskite solar cells using DFT and SCAPS-1D

Involving Palliative Care to Improve Outcomes in Sickle Cell Disease

Exogenous gamma amino butyric acid (GABA) enhanced salinity tolerance in wheat by modulating morphological and anatomical traits