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T cells in jawed vertebrates comprise two lineages, αβ T cells and γδ T cells, defined by the antigen receptors they express—that is, αβ and γδ T cell receptors (TCRs), respectively. The two lineages have different immunological roles, requiring that γδ TCRs recognize more structurally diverse ligands1. Nevertheless, the receptors use shared CD3 subunits to initiate signalling. Whereas the structural organization of αβ TCRs is understood2,3, the architecture of γδ TCRs is unknown. Here, we used cryogenic electron microscopy to determine the structure of a fully assembled, MR1-reactive, human Vγ8Vδ3 TCR–CD3δγε2ζ2complex bound by anti-CD3ε antibody Fab fragments4,5. The arrangement of CD3 subunits in γδ and αβ TCRs is conserved and, although the transmembrane α-helices of the TCR-γδ and -αβ subunits differ markedly in sequence, packing of the eight transmembrane-helix bundles is similar. However, in contrast to the apparently rigid αβ TCR2,3,6, the γδ TCR exhibits considerable conformational heterogeneity owing to the ligand-binding TCR-γδ subunits being tethered to the CD3 subunits by their transmembrane regions only. Reducing this conformational heterogeneity by transfer of the Vγ8Vδ3 TCR variable domains to an αβ TCR enhanced receptor signalling, suggesting that γδ TCR organization reflects a compromise between efficient signalling and the ability to engage structurally diverse ligands. Our findings reveal the marked structural plasticity of the TCR on evolutionary timescales, and recast it as a highly versatile receptor capable of initiating signalling as either a rigid or flexible structure.

Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson’s disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations.Objective: To observe the effects of STN-DBS on cerebellar oscillations in patients with PD.Methods: We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity.Results: In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions.Conclusions: While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD.

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson’s disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations. To observe the effects of STN-DBS on cerebellar oscillations in patients with PD. We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity. In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions. While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for reducing motor symptoms in Parkinson’s disease (PD). However, its effects on brain activity, specifically in the cerebellum, are not well understood. This study aimed to investigate how STN-DBS affects cerebellar brain waves in PD patients. We recruited 15 PD patients undergoing STN-DBS and recorded their brain activity including cerebellar region using EEG. We compared the brain wave patterns during periods when the DBS was turned OFF and when it was turned ON, focusing on specific brain wave frequencies (theta and beta). The results showed a significant increase in brain wave power across all frequencies in the mid-cerebellar region during STN-DBS. Additionally, there was a strong link between beta power in the cerebellum and motor symptom severity when DBS was OFF, which was not present when DBS was ON. This relationship was specific to the cerebellum and not found in other brain regions. The findings suggest that STN-DBS significantly alters cerebellar brain activity and that these changes are related to improvements in motor symptoms. However, more research is needed to fully understand the functional significance and potential clinical applications of these findings for optimizing DBS treatment in PD patients.

To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes.

Using gamma and alpha spectrometers, the radioactive isotopes 226Ra, 210Pb, 232Th, and 40K were determined in three sediment cores from the Tam Giang-Cau Hai (TG), Thi Nai (TN), and Nai (DN) lagoons, and radiation risk indices were computed. The radioactivity concentrations of 210Pb, 40K, 232Th, and 226Ra were 55.46 Bq/kg, 675.78 Bq/kg, 67.22 Bq/kg, and 34.15 Bq/kg, respectively. The Raeq, ADR, AEDE, Iγr, AUI, Hex, and AGDE indices were 182.31 Bq/kg, 84.46 nGy/h, 0.10 mSV/y, 1.35, 1, 18, 0.49, and 598.71 µSV/y, respectively; the values of 40K, 232Th, AEDE, ADR, Iγr, and AGDE were greater than the global average and UNSCEAR values. The radioactivity and radiation risk indices decreased in the order DN > TN > TG.

Primary biological aerosol particles (PBAPs) and secondary organic aerosol (SOA) both contain organic compounds that share similar chemical and optical properties. Fluorescence is often used to characterize PBAPs; however, this may be hindered due to interferences from fluorophores in SOA. Despite extensive efforts to understand the aging of SOA under elevated particle acidity conditions, little is known about how these processes affect the fluorescence of SOA and thereby their interference with the measurements of PBAPs. The objective of this study is to investigate the fluorescence of SOA and understand the influence of acidity on the optical properties of organic aerosols and potential interference for the analysis of bioaerosols. The SOA was generated by O3- or OH-initiated oxidation of d-limonene or α-pinene, as well as by OH-initiated oxidation of toluene or xylene. The SOA compounds were then aged by exposure to varying concentrations of aqueous H2SO4for 2 days. Absorption and fluorescence spectrophotometry were used to examine the changes in the optical properties before and after aging. The key observation was the appearance of strongly light-absorbing and fluorescent compounds at pH = ∼−1, suggesting that acidity is a major driver of SOA aging. The aged SOA from biogenic precursors (d-limonene and α-pinene) resulted in stronger fluorescence than the aged SOA from toluene and xylene. The absorption spectra of the aged SOA changed drastically in shape upon dilution, whereas the shapes of the fluorescence spectra remained the same, suggesting that the fluorophores and chromophores in SOA are separate sets of species. The fluorescence spectra of aged SOA overlapped with the fluorescence spectra of PBAPs, suggesting that SOA exposed to highly acidic conditions can be confused with PBAPs detected by fluorescence-based methods. These processes are likely to play a role in the atmospheric regions where high concentrations of H2SO4persist, such as the upper troposphere and lower stratosphere.

Silicone-in-water emulsions have found widespread use as lubricants, water repellants, softeners, binders, antiblocking agents, antislip agents, and defoamers across a diverse range of markets including textiles, coatings, pharmaceuticals, and home and personal care. Stable incorporation of silicone emulsions into formulated products for these applications can be a challenge. This study seeks to enable formulation by investigating the impact of the degree of ethoxylation of sodium lauryl ether sulfate (SLES) surfactants on their ability to displace surfactant stabilizer at the silicone–water interfaces of polydimethylsiloxane (PDMS)-in-water emulsion droplets. Building this understanding will greatly enable the manufacture of home and personal care products prepared by introducing silicone emulsions into SLES-rich formulations. Nuclear magnetic resonance (NMR) measurements reveal that SLES can displace the triethanolamine dodecylbenzenesulfonate stabilizer at the droplet surfaces. Both capillary electrophoresis (CE) measurements and molecular dynamics simulations of the interfacial tension (IFT) between silicone and water measurements suggest that SLES mixtures with a higher average degree of ethoxylation are more surface active at the silicone─water interface. The molecular dynamics simulations predict a systematic decrease in PDMS–water IFT with increase in degree of ethoxylation (simulations predict a decrease of 1.3 mN/m per mole of ethylene oxide). Optical microscopy reveals that the presence of SLES at the droplet surfaces promotes the formation of loose flocs of droplets that break up upon dilution. Overall, these fundamental insights will aid in formulating silicone emulsions into products to achieve optimal performance.

The circadian clock (CC) has biological and clinical implications in gliomas. Most studies focused on CC effects on the tumor microenvironment and the application of chronotherapy. The present study focused on CC gene expression patterns and intracellular oncogenic activities. Glioma gene expression data were collected from The Human Cancer Genome Atlas (TCGA) project. After applying inclusion and exclusion criteria, we selected 666 patients from TCGA-GBM and TCGA-LGG projects and included important clinicopathological variables. The entire cohort was subjected to clustering analysis and divided into CC1 and CC2 subtypes based on statistical, biological, and clinical criteria. CC2 gliomas showed higher expression of BMAL1and CRY1and lower expression of CRY2and PER2(adjusted P< .001). CC2 gliomas had q higher activity of cell proliferation, metabolic reprogramming, angiogenesis, hypoxia, and many oncogenic signals (P< .001). The CC2 subtype contained a higher proportion of glioblastomas (P< .001) and had a worse prognosis (P< .001). Stratified Kaplan–Meier and multivariable Cox analyses illustrated that the CC subtype is an independent prognostic factor to clinicopathological characteristics (P< .001), genetic aberrations (P= .006), and biological processes (P< .001). Thus, this study shows statistical evidence of CC subtypes and their biological, and clinicopathological significance in adult gliomas.

Developing self-powered and flexible optoelectronic sensors with high responsivity and speed is crucial for modern applications, motivating continuous efforts to enhance their performance. Flexo-phototronics is a less-explored but promising technique to elevate the performance of optoelectronics. Therefore, this work addresses the potential of utilizing the flexo-phototronic effect to enhance the performance of a flexible and self-powered ultraviolet photodetector (UV PD) based on ZnAl:LDH (layered double hydroxides) nanosheets (Ns)/NiO heterostructure. The vertically oriented ZnAl:LDH Ns are synthesized via a simple method involving the immersion of a sputtered 10% Al-doped ZnO thin film in deionized water at room ambient conditions. The fabricated PD exhibits an impressive response to 365 nm UV light, with high sensitivity in the order of 103. The device’s photocurrent and responsivity are significantly enhanced by the flexo-phototronic effect, attributed to the flexoelectric properties of ZnAl:LDH Ns. Specifically, applying an inhomogeneous tensile strain of 2% boosted the device responsivity by 57.1% and improved its operational speed. Furthermore, a working model revealing the altered energy-band structure is demonstrated to elucidate the flexo-phototronic-induced boost in the photoresponse. The PD also demonstrated a sustainable performance under severe bending cycles, underlining the good flexibility of the device. The results presented in this study demonstrate a self-powered and flexible UV PD and provide a viable approach to augment the performance of optoelectronics through the flexo-phototronic effect.

One of the most common adverse outcomes of an upper blepharoplasty involving double-eyelid surgery is asymmetric upper eyelids due to unbalanced supratarsal folds or a difference in the palpebral fissure height. This study aimed to evaluate the efficacy and safety of transconjunctival levator aponeurosis-Müller muscle complex plication for correcting acquired ptosis following double-eyelid surgery. This retrospective study evaluated 18 patients who underwent transconjunctival levator aponeurosis-Müller muscle complex plication between June 2016 and June 2019 to correct acquired ptosis. On the basis of the main area of eyelid drooping, ptosis was categorized as central (mid-pupillary), medial (medial limbus), or lateral (lateral limbus). Preoperative and postoperative palpebral fissure heights were measured and compared. Three months postsurgery, the mean difference in palpebral fissure height between bilateral eyes decreased from 0.96 to 0.04 mm in the medial (P<0.001), from 0.93 to 0.00 mm in central (P=0.003), and from 1.30 to −0.03 mm in lateral ptosis (P=0.079). In 13 patients who underwent unilateral correction, the amount of plication was significantly associated with increased palpebral fissure height at the medial limbus (P=0.043) and mid-pupillary line (P=0.035). All patients reported a significant improvement in satisfaction. Five patients experienced acute postoperative complications, including chemosis, conjunctival injection, and foreign body sensation, all of which were resolved after a month of observation. No asymmetries or recurrences were observed. Transconjunctival levator aponeurosis-Müller muscle complex plication is a minimally invasive, safe, and effective technique for correcting acquired ptosis following upper eyelid surgery.

To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice.

AbstractSouthern Cross University introduced its first Bachelor of Speech Pathology program in 2013 but with the university experiencing attrition and lower success rates, a new pedagogical approach and innovation was needed. To address these issues, Southern Cross University implemented an intensive block model of education which consists of six terms that are 6-week long to increase enrolment and success. This model was called the Southern Cross Model (SCM). This article describes how speech pathology used codesign with hospital-based clinicians to modify their curriculum from a traditional 13-week semester to intensive terms where there is a component of self-directed learning accompanied by interactive tutorials and workshops. A case study is provided specifically looking at hospital settings, and the process involved in supporting a cohort to be ready to practice. Feedback from content designers, tutors, clinical educators and students is provided to identify the process and the impact of this change and plans for future evaluation are identified.

This paper presents the NOWJ team’s approach to the COLIEE 2023 Competition, which focuses on advancing legal information processing techniques and applying them to real-world legal scenarios. Our team tackled the four tasks in the competition, which involved legal case retrieval, legal case entailment, statute law retrieval, and legal textual entailment. We employ state-of-the-art machine learning models and innovative approaches, such as BERT, Longformer, BM25-ranking algorithm, and multi-task learning models. Our participation in the COLIEE 2023 has provided useful insights including the importance of the pre-processing and feature engineering, effectiveness of the multi-task models in combining different legal tasks to improve model’s performance. Although our team did not achieve state-of-the-art results, our findings identify areas for further research and improvements in legal information processing.

Nonmagnetic media can be magnetized by light via processes referred to as an inverse Faraday effect (IFE). With nonmagnetic metal nanostructures, the IFE is dominated by the presence of light-induced solenoidal surface currents or plasmons with orbital angular momenta, whose properties depend on both the light and nanostructure geometry. Here, through a systematic study of gold nanodisks with different sizes, we demonstrate order-of-magnitude enhancement of the IFE compared to a bare gold film. Large IFE signals occur when light excites the dipolar plasmonic resonance of the gold nanodisk. We observe that the spectral response of the IFE signal mirrors the spectral response of time-dependent thermo-transmission signals. Our careful quantitative experimental measurements and analysis offer insight into the magnitude of IFE in plasmonic structures for compact, low-power, magneto-optic applications.

An approach combining adsorption characterization and lubricity effectiveness of amine-based friction modifier molecules has been performed using chemically controlled surfaces, coated either with cobalt or carbon, while keeping the surface roughness constant and sub-nanometric. Through squeeze measurements and numerical modeling, we have identified the mechanical properties of both adsorbed amine films, as a function of the surface on which they were formed. On the one hand, we were able to evidence that the fluid structuring at the vicinity of the adsorbed boundary film differed as a function of the latter mechanical properties, directly resulting from its molecular organization. On the other hand, we showed that the coverage ratio of the monolayer associated with the shear elastic modulus of the boundary film governed the friction level. Changing the surface chemistry while keeping the roughness constant controls the final organization in the boundary layer, the correlated mechanical properties, and the level of friction dissipation.

We have identified the biosynthetic gene cluster (hvm) for the sterol O-acyltransferase inhibitor helvamide (1) from the genome of Aspergillus rugulosusMST-FP2007. Heterologous expression of hvmin A. nidulansproduced a previously unreported analog helvamide B (5). An α-ketoglutarate-dependent oxygenase Hvm1 was shown to catalyze intramolecular cyclization of 1to yield 5. The biosynthetic branch to the related hancockiamides and helvamides was found to be controlled by the substrate selectivity of monomodular nonribosomal peptide synthetases.

Background Core patient characteristic sets (CPCSs) are increasingly developed to identify variables that should be reported to describe the target population of epidemiological studies in the same medical area, while keeping the additional burden on the data collection acceptable.Methods We conduct a systematic review of primary studies and protocols that aim to develop a CPCS, using the PubMed database. We extract information on the study design and the characteristics of the proposed CPCS. The quality of Delphi studies is assessed by a tool proposed in the literature. All results are reported descriptively.Results Among 23 eligible studies, Delphi survey is the most frequently used technique to obtain consensus in CPCS development (69.6%, n= 16). Most studies do not include patients as stakeholders. The final CPCS rarely includes socioeconomic factors (26.1%, n= 6). Besides, 60.9% (n= 14) and 26.1% (n= 6) of the studies provide definitions and measurement methods for items in the CPCS, respectively.Conclusion This review identifies considerable variation and suboptimality in many methodological aspects of CPCS studies. To improve these shortcomings, guidance on the conduct and reporting of CPCS studies should be established in the future.

Background:Progestin-primed ovarian stimulation (PPOS) has been proposed as an alternative to conventional gonadotropin-releasing hormone (GnRH) antagonist protocol for ovarian stimulation in in vitrofertilization (IVF). The aim of PPOS is to provide an effective, patient-friendly treatment. However, studies comparing outcomes after the use of PPOS and GnRH antagonist protocol in IVF have shown mixed results. This study compared ongoing pregnancy rates after the use of PPOS versus GnRH antagonist protocol for ovarian stimulation in IVF.Methods:This prospective pilot study was conducted at a single IVF center. Women aged 18–35 years old with an anti-Müllerian hormone (AMH) level greater than or equal to 1.2ng/mL or an antral follicle count (AFC) greater than or equal to 5 who were undergoing their first IVF cycle were allocated to undergoing ovarian stimulation using PPOS (dydrogesterone 20mg/day started on the day of gonadotropin) or a GnRH antagonist protocol (fixed regimen from stimulation day 5). The primary outcome was the ongoing pregnancy rate (at 12 weeks’ gestation).Results:The study included 30 women (15 in each treatment group). Baseline characteristics were similar between groups. The ongoing pregnancy rate was 7/15 (46.7%) in the PPOS group and 8/15 (53.3%) in the GnRH antagonist group (P=0.95); the number of oocytes retrieved and fertilization rates were also comparable between groups. One case of mild ovarian hyperstimulation syndrome (OHSS) occurred in the GnRH antagonist group.Conclusions:This pilot study showed similar ongoing pregnancy rates after the use of a PPOS protocol and a conventional GnRH antagonist protocol for ovarian stimulation in IVF. Additional studies with larger sample sizes are needed to confirm these findings.

Background:Follicle-stimulating hormone (FSH) is widely used during assisted reproductive therapy to facilitate the development of multiple follicles. In turn, the number of oocytes retrieved has been shown to relate to the live birth rate. This retrospective study investigated the correlation between the total FSH dose used and the cumulative live birth rate in individuals who had undergone in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).Methods:This retrospective study included women undergoing IVF/ICSI using a gonadotropin-releasing hormone antagonist protocol who had a regular menstrual cycle and an expected normal response to ovarian stimulation. Cumulative live birth rate was defined as the first live birth following the use of all fresh and frozen transfers of embryos derived from one stimulated IVF/ICSI cycle.Results:The analysis included 7,130 stimulated cycles in 6,517 individuals (9,138 transfers). The mean age, antral follicle count, and anti-Müllerian hormone level were 32.7±4.6, 16.0±22.3, and 3.9±2.9ng/ml, respectively. The mean total FSH dose, total number of oocytes retrieved, and total FSH dose per oocyte retrieved were 2659.6±863.1IU, 13.1±7.0, and 392.4±382.9IU, respectively. There was a significant negative correlation between the total FSH dosage and the cumulative live birth rate in women aged ≤35years (r=−0.11, 95% confidence interval [−0.14, −0.08]; p<0.001) and in those aged >35years (r=−0.06, 95% confidence interval [−0.11, −0.02]; p=0.004).Conclusions:The cumulative live birth rate decreased as the total FSH dose increased. These findings suggest that physicians may wish to avoid prescribing a high dose of FSH in women undergoing IVF/ICSI who are predicted not to have a poor response.

Purpose: This work designs a procedure for structural damage assessment in beams under moving loads. The proposal is based on the respective alterations of hybrid vibrational factors with respect to the structural changes, whereby matching them for accurate predictions. These hybrid factors are extracted from the vibrational responses and then are employed for an artificial neural network (ANN) to assess the structural condition. Methods: An experiment is deployed to generate a databank for evaluation as well as ANN training. The maximal overlap discrete wavelet transform (MODWT) and the fast Fourier transform (FFT) are incorporated to split original signals into several power bands, which helps to exploit characteristics of individual vibrational modes: centroids and comparative powers of allocated spectra. The extracted hybrid factors are then fed into an ANN to predict the damage condition of the beam. The training process of this ANN uses a databank of extracted features from measured signals. Results: The paper successfully finds out the damage-sensitive feature through signal processing. Alternatively, the implemented experiment provides a rich databank for the ANN training, and the training performance reaches a high accuracy. Moreover, the testing results reveal the superior generalization of the ANN because of automatic predictions with high precision. This proves the contribution of the study that the exploited features are proper for structural assessment, and the trained ANN learns the correlation of vibration features and structural state well. Conclusions: The automation and effectiveness of the proposed approach are endorsed, which has high applicability and accuracy for damage assessment in beams. The proposed method is mainly devoted to identifying, quantifying, and localizing damage.