Urban College of Boston

To further elucidate the modification effects of polyphosphoric acid (PPA) on different oil-source base asphalts from the perspective of the mechanical properties of asphalt colloidal components, an improved separation device was designed to isolate colloidal components from PPA-modified and unmodified asphalts derived from different oil-source regions. The rheological properties of the maltene components were evaluated across a broad temperature range using a dynamic shear rheometer. The nanomechanical properties of solid-state asphaltenes were examined using atomic force microscopy. The variations in polarity and solubility of resins and aromatics induced by PPA were quantified by thin-layer chromatography with flame-ionization detection (TLC-FID). The results indicated that PPA significantly increased the complex modulus of resins by 2.5 to 3 times. The enhancement effect of 115-grade PPA generally exceeded that of 105-grade PPA. TLC-FID confirmed that PPA simultaneously polymerized rigid aromatic fragments and cyclized alkyl segments in the aromatic and resin fractions. By polymerizing active sites in asphaltenes, PPA introduced a small amount of ultrahard substance into the Derjaguin–Muller–Toporov (DMT) modulus image of the asphaltenes, a phenomenon more pronounced with long-chain PPA. This resulted in increases of 7.4% to 25.6% in the maximum DMT modulus and 10 to 30 MPa in the average DMT modulus of the asphaltenes. This study innovatively investigated the effects of PPA on different oil-source asphalts from the perspective of the mechanical properties of the four components, revealing the material transformation mechanisms within asphalts under the influence of PPA and the reasons for the differences in modification effects among asphalts with different molecular structures. Moreover, the research methodology provides a reference for studies of other chemically modified asphalts.

The MDS-UPDRS was not specifically developed for early-stage Parkinson’s disease (PD). This study investigated a sub-score of MDS-UPDRS Part III to assess bradykinesia and rigidity, which would be more targeted and clinically meaningful to assess disease progression in early-stage PD. A cross-sectional Rasch model was applied to the Parkinson’s Progression Markers Initiative (PPMI) untreated PD cohort data (N = 423) to define an adequate item set. Additionally, we evaluated how the daily life items from MDS-UPDRS Part II relate to bradykinesia and rigidity severity. A sub-score of 15 MDS-UPDRS Part III items focusing on limb-related bradykinesia and rigidity demonstrated good measurement properties in early-stage PD. Items adequately targeted to the study sample, and a meaningful hierarchy supported the validity of the scale. The scale was invariant to symptomatic treatment intake. Onset of clinical signs was represented as a milestone in the emergence of impairment in patients’ daily functioning.

South Africa is experiencing a heterogeneous and rapid nutrition transition. Rural-origin Black South Africans frequently migrate to access employment opportunities in urbanized areas, which could place individuals at risk for obesity due to accompanying dietary and lifestyle changes. We utilize longitudinal data-four waves from 2018 to 2022-with detailed internal migration and health information, and negligible participant attrition from the Migrant Health Follow-Up Study, with origin households located in rural northeast South Africa-Agincourt. We employ lagged-dependent variable regressions to test whether (1) the number of waves one is away from their rural home (0-4) and (2) residing in a densely populated urban area (Gauteng province) relative to other locations or remaining in Agincourt over the four waves, are differentially associated with having abdominal obesity, indicated by the preferable measure of the waist circumference-to-height ratio (WHtR), at Wave 4-after adjusting for Wave 1 obesity and other variables, including fast food consumption. WHtR is operationalized as a binary indicator of abdominal obesity as well as a standardized, continuous one. Our analytic sample includes women (N = 895) and men (N = 1010). Our results show that internal migrant women and men face higher chances of having abdominal obesity at Wave 4 than their nonmigrant counterparts. For men, both the number of waves as a migrant and ever migrating to Gauteng are consistently, strongly associated with the chances of having abdominal obesity-considerably more so than women. As obesity rates rise throughout urbanizing low- and middle-income countries, this research emphasizes the importance of understanding the correlates of the risks of obesity that internal migrants will face.

Abstract Lysosomal dysfunction occurs in many neurodegenerative diseases, including Parkinson’s disease, and activating TFEB to enhance lysosomal biogenesis is a promising therapeutic strategy. To understand TFEB physiology in cells of the brain, we characterised TFEB expression using iPSC-derived models, and transcriptomic analysis of human and mouse brain tissue. Surprisingly, TFEB expression at the RNA and protein level was restricted to glia, whereas the related transcription factor, TFE3, was expressed ubiquitously. We identified HDAC1/2/3 as transcriptional repressors of neuronal TFEB and found the brain-penetrant HDAC inhibitor ACY-738 derepressed TFEB expression and enhanced TFE3 nuclear translocation in iPSC-dopaminergic neurons (iPSC-DaNs). We delineated the role of each transcription factor by genetic manipulation in iPSC-DaNs to reveal divergent roles in which TFEB activates mitochondrial biogenesis, whereas TFE3 enhances lysosomal biogenesis. Finally, we show TFE3 activation corrects the lysosomal dysfunction associated with GBA-N370S and SNCA-Triplication mutations in Parkinson’s patient-derived iPSC-DaNs, demonstrating therapeutic utility in neurodegeneration.

To characterize normal and disruptive symptoms and understand effect on daily life, a survey was administered to caregivers of individuals with developmental and epileptic encephalopathies (DEEs).

BackgroundThe phase 3, open-label, randomised, crossover MG0020 study investigated rozanolixizumab self-administration, efficacy, and safety in patients with generalised myasthenia gravis (gMG) using infusion pump and manual push methods.MethodsAdults with gMG received once-weekly rozanolixizumab for 18 weeks, comprising a 6-week Training Period and two 6-week Self-Administration Periods where patients were randomised 1:1 to Sequence 1 (infusion pump then manual push) or Sequence 2 (manual push then infusion pump). The primary endpoint was successful rozanolixizumab self-administration (choosing correct infusion site, administering subcutaneously, delivering intended dose), evaluated by a healthcare professional (HCP) at weeks 12 and 18. Secondary endpoints included treatment-emergent adverse events (TEAEs). Additional endpoints included change from baseline in total immunoglobulin G (IgG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) score, and patients’ administration method preference.ResultsSixty-two patients received treatment; 55 were randomised (Sequence 1: n = 28; Sequence 2: n = 27). The self-administration success rate was 100% with both methods. Decreases from baseline in IgG and MG-ADL score were maintained during self-administration with both methods. TEAEs occurred in 47/62 (75.8%) patients; most events (161/165 [97.6%]) were mild or moderate. Incidence was comparable for both methods. Most patients (35/55 [63.6%]) preferred self-administration to HCP administration (5/55 [9.1%]); more preferred manual push (25/55 [45.5%]) to infusion pump (17/55 [30.9%]).ConclusionsAll patients successfully self-administered rozanolixizumab; more patients preferred manual push. Efficacy and safety were consistent with the known HCP-administered profile. These results support rozanolixizumab self-administration and manual push administration in patients with gMG.Trial registration: NCT05681715 (registered 4 January 2023).Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-025-13420-6.

This paper proposes a system scheme based on RL78/I1A main control chip, which can realize real-time monitoring, precise control and intelligent lighting. The system includes awareness layer, control layer, network layer and comprehensive application layer. The field controller of the control layer can be used independently or networked. The system uses short time energy and short time average zero crossing rate to judge the voice control signal. The universal background model based on Gaussian mixture model is used to determine the identity of voice controller. The hardware subsystem consists of coordinator node module, controller node module and sensor node module. After debugging, it is found that the dimming curve of the system is stable, and the harmonic distortion and power consumption index are excellent. The expansion of lighting system is strong. The system has good extensibility.

Whitepaper #138 in the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033. Main topics: basic research; infrastructure/workforce/other programmatic. Additional topics: solar physics; state of the profession; space-based missions/projects; inner heliosphere; […]

While DNA-encoded macrocyclic libraries have gained substantial attention and several hit compounds have been identified from DNA-encoded library technology, efficient on-DNA macrocyclic methods are also required to construct DNA-linked libraries with a high degree of cyclization and DNA integrity. In this paper, we reported a set of on-DNA methodologies, including the use of an OPA-mediated three-component cyclization with native handles of amino acids and photoredox chemistries. These chemistries proceed smoothly under mild conditions in good to excellent conversions, successfully generating novel isoindole, isoindoline, indazolone, and bicyclic scaffolds.