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Attosecond spectroscopy of molecular charge transfer uncovers a 1.5-fs delay in population transfer
Abstract The transfer of population between two intersecting quantum states is the most fundamental event in many dynamical processes in physics, chemistry, biology, and material science. Any two-state description of such processes requires population leaving one state to instantaneously appear in the other. We show that coupling to additional states, present in all real-world systems, can cause a measurable delay in population transfer. Using attosecond spectroscopy supported by quantum-chemical calculations, we measure a delay of 1.46 ± 0.41 fs at a charge-transfer crossing in CF3I+, where an electron hole moves from the fluorine atoms to iodine. Our measurements also resolve the other fundamental quantum-dynamical processes involved in the charge-transfer reaction: a vibrational rearrangement time of 9.38 ± 0.21 fs (during which the vibrational wave packet travels to the state crossing) and a population-transfer time of 2.3–2.4 fs. Our work shows that delays in population transfer readily appear in otherwise-adiabatic reactions and predicts them to be on the order of a single-femtosecond for molecular valence-state crossings. These results have implications for many research areas, such as atomic and molecular physics, charge transfer, or light harvesting.
Bearing fault diagnosis based on improved DenseNet for chemical equipment
Cryo-EM led analysis of open and closed conformations of Chagas vaccine candidate TcPOP
Abstract Chagas disease, caused by the protozoan parasite Trypanosoma cruzi , remains a significant global public health concern. Despite its profound health impact in both endemic and non-endemic areas, no vaccine is available, and the existing therapies are outdated, producing severe side effects. The 80 kDa prolyl oligopeptidase of Trypanosoma cruzi (TcPOP) has been identified as a leading candidate for Chagas vaccine development. Here we report the three-dimensional structure of TcPOP in open and closed conformation, at a global resolution of 3.8 and 3.6 Å, respectively, determined using single-particle cryo-electron microscopy. Multiple conformations were observed and further characterized using plasmonic optical tweezers and hydrogen-deuterium exchange mass spectrometry. To assess the immunogenic potential of TcPOP, we immunized female mice and evaluated both polyclonal and monoclonal responses against the TcPOP antigen and its homologues. The anti-TcPOP polyclonal response demonstrates invasion blocking properties via parasite lysis. Polyclonal sera were cross-reactive with closely-related POPs but not with human homologues. Collectively, our findings provide structural and functional insights necessary to understand the immunogenicity of TcPOP for future Chagas vaccine development.
Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924
Abstract A growing body of knowledge implicates perturbed RNA homeostasis in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that currently has no cure and few available treatments. Dysregulation of the multifunctional RNA-binding protein TDP-43 is increasingly regarded as a convergent feature of this disease, evidenced at the neuropathological level by the detection of TDP-43 pathology in most patient tissues, and at the genetic level by the identification of disease-associated mutations in its coding gene TARDBP . To characterize the transcriptional landscape induced by TARDBP mutations, we performed whole-transcriptome profiling of motor neurons (MNs) differentiated from two knock-in iPSC lines expressing the ALS-linked TDP-43 variants p.A382T or p.G348C. Our results show that the TARDBP mutations significantly altered the expression profiles of mRNAs and microRNAs of the 14q32 cluster in MNs. Using mutation-induced gene signatures and the Connectivity Map database, we identified compounds predicted to restore gene expression toward wild-type levels. Among top-scoring compounds selected for further investigation, the NEDD8-activating enzyme inhibitor MLN4924 effectively improved cell viability and neuronal activity, highlighting a possible role for protein post-translational modification via NEDDylation in the pathobiology of TDP-43 in ALS.
Extrinsically microporous polymer membranes derived from thermally cross-linked perfluorinated aryl-ether-free polymers for gas separation
Abstract State-of-the-art membranes derived from polymers of intrinsic microporosity offer promising alternatives to energy-intensive, thermally driven separation techniques but often suffer from reduced performance under condensable gases or physical aging. Here, extrinsically microporous polymer membranes (EMPMs) are introduced as a distinct class of microporous membranes, fabricated from perfluorinated aryl-ether-free aromatic polymers via defluorination-induced thermal cross-linking. This process generates extrinsic micropores, increases intersegmental distances, and significantly enhances gas permeability. EMPMs exhibit a Brunauer-Emmett-Teller surface area of 552 m2 g−1 and demonstrate exceptional plasticization resistance under equimolar CO2/CH4 mixed gas at pressures up to 40 bar. CO2 permeability increases from 280 to 12,000 Barrer at 1 bar and 35 °C, while CO2/N2 selectivity reaches 46 at −20 °C, surpassing the 2019 polymeric upper bound. Furthermore, extrinsically microporous hollow fiber membranes prepared via dip-coating achieve a CO2 permeance of 2174 gas permeation units and CO2/N2 selectivity of 30 at −20 °C, highlighting their industrial relevance. This study establishes a scalable method for fabricating high-performance microporous polymeric membranes with exceptional stability for sustainable energy and environmental applications.
CATT haplotype of the FKBP5 gene and dissociative phenomenology
Abstract Survival mechanisms are evolutionary grown behaviors in life-threatening situations. They are thought to be determined by genetic patterns involved in stress systems, such as the control of the hypothalamic-pituitary-adrenal (HPA) axis. FK506 binding protein 5 (FKBP5) is a co-chaperone that is involved in modulating glucocorticoid receptor (GR) sensitivity in response to stress. Dissociation is thought to be one of these survival strategies and appears to be associated with common haplotypes of the FKBP5 gene formed by four single nucleotide polymorphisms (SNPs) (rs9296158, rs3800373, rs1360780, and rs9470080). The aim of the study was to examine the association between the FKBP5 haplotypes, type of childhood trauma and different types of dissociative phenomena. Dissociation encompasses a wide range of different phenomena. A common categorization has been made that distinguishes between ‘detachment’ and ‘compartmentalisation’ dissociation. Therefore, both categories were included in the study, including identity dissociation as the most severe form of compartmentalisation dissociation. We analyzed the association between six different types of dissociative phenomena, different types of childhood trauma and the FKBP5 haplotypes in 194 participants, primarily Black Americans of low socioeconomic status and high trauma burden, who participated in the Grady Trauma Project in Atlanta. We found that only identity dissociation was significantly associated with the CATT FKBP5 haplotype, regardless of the type of childhood trauma. In particular, individuals with one or two CATT haplotypes are 15 times more likely to develop identity dissociation than others. In conclusion, our findings indicate a link between gene variants involved in the regulation of stress systems and self-development under conditions of traumatic stress during the developmental period, which may be important for the study of disorders such as complex post-traumatic stress disorder.
Does ResearchGate have a growing credibility problem?
Janus effect of FeCo dual atom catalyst with Co as active center in acidic oxygen reduction reaction
Single port laparoscopic umbilical fold reinforcement surgery reduces the postoperative recurrence rate of pediatric giant inguinal hernia
Three positively charged binding sites on the eastern equine encephalitis virus E2 glycoprotein coordinate heparan sulfate- and protein receptor-dependent infection
Development of a hip osteoarthritis index for gait quality assessment: a data-driven comparative study
Limits on the computational expressivity of non-equilibrium biophysical processes
Adaptive control strategies for button motor actuated insect scale flapping wing MAV mechanisms
Abstract The development of Flapping Wing Micro Aerial Vehicles (FWMAVs) has gained significant attention due to their potential for energy-efficient, lightweight, and highly maneuverable flight inspired by nature. This study presents innovative designs and adaptive control strategies for insect-scale FWMAVs, utilizing compact button vibrator motors as actuators for wing flapping. These actuators offer advantages in size, weight, and power efficiency but pose challenges in achieving continuous and controlled motion due to mechanical, control, and durability constraints. The research explores multiple lever alignment configurations using simplified crank-slider mechanisms, driven by single and dual coreless DC motors powered by a 1–3.7 V DC supply. Detailed modeling in SIMSCAPE Multibody and structural movement analysis using Compmech GIM software facilitate the evaluation of variations in flapping frequency, velocity, and acceleration. Advanced control strategies, including Self-Regulatory Fractional Fuzzy Control (SRFFC) and Fractional PID (FPID), are assessed under simulated and real-world conditions to mitigate external disturbances. Additionally, an AI-based disturbance observer is implemented to enhance stability and optimize power efficiency by compensating for environmental disturbances. Performance metrics such as rise time, settling time, overshoot, and integral absolute error (IAE) demonstrate the superior efficiency and disturbance rejection capabilities of SRFFC compared to FPID. Experimental validation and real-time assessments of maneuvering capabilities, including leftward, rightward, and forward movements, further substantiate the proposed strategies. This study underscores the potential of SRFFC-driven designs and modular motor configurations to enhance the performance, control, and applicability of FWMAVs for advanced micro-aerial systems.
Sub-nanosecond polarization switching with anomalous kinetics in vdW ferroelectric WTe2
OFD1 inhibition induces BRCAness to create a therapeutic vulnerability to PARP inhibition in pancreatic cancer
Abstract BRCAness is a homologous recombination repair (HRR) deficiency phenotype mimicking BRCA1/2 loss, leading to PARP inhibitor sensitivity in BRCA-associated cancers including pancreatic cancer1–7. However, how to induce BRCAness in BRCA-proficient tumors remains unclear. We identify OFD1 as a positive regulator of BRCA1 in human pancreatic cancer cells and specimens, with its overexpression correlating with poor prognosis. OFD1 depletion impairs HRR and confers synthetic lethality with PARP inhibitors. Mechanistically, OFD1 interacts with E2F4 in the cytosol to prevent assembly of the transcriptional repressor DREAM complex at the BRCA1 promoter. Targeting OFD1 or disrupting its interaction with E2F4 promotes E2F4 nuclear translocation and DREAM complex formation, suppressing BRCA1 expression. OFD1 inhibition synergizes with olaparib in pancreatic cancer xenograft, spontaneous, and patient-derived xenograft models, and in other BRCA-associated cancer models. These findings reveal a mechanism of BRCA1 transcriptional regulation and highlight OFD1 as a therapeutic target to induce BRCAness in BRCA-proficient pancreatic cancer.
SON-dependent nuclear speckle rehabilitation alleviates proteinopathies
Higher-order and distributed synergistic functional interactions encode information gain in goal-directed learning
Enantioselective construction of cyclic quaternary stereocenters via dinuclear copper catalyzed asymmetric [3 + 2] propargylation/annulation
A rapid, simple, and economical method for the isolation of ribosomes and translational machinery for structural and functional studies
Perinatal outcomes of symptomatic chikungunya, dengue and Zika infection during pregnancy in Brazil: a registry-based cohort study
Abstract The previous literature shows mixed conclusions regarding the risk of adverse perinatal outcomes in pregnant women with symptomatic chikungunya, dengue, and Zika. We investigated this topic using a linked population-based Brazilian cohort from 2015 to 2020. The study included 6,993,395 live births. Among these, 6066 ( < 0.1%) mothers were notified with chikungunya during pregnancy, 19,022 (0.3%) with dengue, and 8396 (0.1%) with Zika. Symptomatic maternal chikungunya was associated with an increased risk of preterm birth (Hazard ratio: 1.10, 95%CI 1.01-1.22), low Apgar score 5’ (1.44, 1.14-1.82), and neonatal death (1.50, 1.15-1.96). Symptomatic maternal dengue was associated with preterm birth (1.07, 1.02-1.12), low birth weight (1.10, 1.04-1.15), congenital anomalies (1.19, 1.03-1.37), and low Apgar score 5’ (1.26, 1.09-1.45). Symptomatic maternal Zika was associated with all adverse birth outcomes, particularly congenital anomalies, which were over twice the risk (2.36; 1.91-2.67) compared to the unexposed group. This study provides evidence of the adverse consequences of arbovirus infections during pregnancy, including critical time windows by trimester. Our findings emphasise the importance of implementing effective measures to prevent chikungunya, dengue, and Zika infections during pregnancy and the associated adverse birth and neonatal outcomes, which may have long-term health consequences for mothers and their children.