Stringed Instruments in Near East and Aegean: From 2800.B.C.—480.B.C.

κατά τη διάρκεια αυτήν πάνω από δύο χιλιάδων χρόνων, δημιουργήθηκαν στενοί δεσμοί με διάφορες θρησκευτικές και τελετουργικές μνημονικές παραστάσεις της μουσικής. Αυτά μπορούν να επισημανθούν ιδιαίτερα στους πολιτισμούς της Εγγύς Ανατολής,συμπεριλαμβανομένης της Μεσοποταμίας, της Αιγύπτου, της Ινδίας. και το Αιγαίο, συμπεριλαμβανομένου του κυκλαδίτικου νησιού ,της Κρήτης και της ηπειρωτικής Ελλάδας. Αν και διασχίζει τον ωκεανό και τον έδαφο, μας δείχνει ακόμα διάφορες συνδέσεις.Throughout these exceeding two thousand years, ancestral links were established through several religious and ceremonial mnemonic performances of music. These can be particularly indicated in the cultures of Near East, including Mesopotamia, Egypt, India; and Aegean area, including Cycladic island, Crete island and mainland Greece. Although crossing the ocean and land, it still seen various connections

Enhancing Pre-trained ASR System Fine-tuning for Dysarthric Speech Recognition using Adversarial Data Augmentation

Automatic recognition of dysarthric speech remains a highly challenging task to date. Neuro-motor conditions and co-occurring physical disabilities create difficulty in large-scale data collection for ASR system development. Adapting SSL pre-trained ASR models to limited dysarthric speech via data-intensive parameter fine-tuning leads to poor generalization. To this end, this paper presents an extensive comparative study of various data augmentation approaches to improve the robustness of pre-trained ASR model fine-tuning to dysarthric speech. These include: a) conventional speaker-independent perturbation of impaired speech; b) speaker-dependent speed perturbation, or GAN-based adversarial perturbation of normal, control speech based on their time alignment against parallel dysarthric speech; c) novel Spectral basis GAN-based adversarial data augmentation operating on non-parallel data. Experiments conducted on the UASpeech corpus suggest GAN-based data augmentation consistently outperforms fine-tuned Wav2vec2.0 and HuBERT models using no data augmentation and speed perturbation across different data expansion operating points by statistically significant word error rate (WER) reductions up to 2.01% and 0.96% absolute (9.03% and 4.63% relative) respectively on the UASpeech test set of 16 dysarthric speakers. After cross-system outputs rescoring, the best system produced the lowest published WER of 16.53% (46.47% on very low intelligibility) on UASpeech.Comment: To appear at IEEE ICASSP 202

Associations of [18F]-APN-1607 Tau PET Binding in the Brain of Alzheimer's Disease Patients With Cognition and Glucose Metabolism.

Molecular imaging of tauopathies is complicated by the differing specificities and off-target binding properties of available radioligands for positron emission tomography (PET). [18F]-APN-1607 ([18F]-PM-PBB3) is a newly developed PET tracer with promising properties for tau imaging. We aimed to characterize the cerebral binding of [18F]-APN-1607 in Alzheimer's disease (AD) patients compared to normal control (NC) subjects. Therefore, we obtained static late frame PET recordings with [18F]-APN-1607 and [18F]-FDG in patients with a clinical diagnosis of AD group, along with an age-matched NC group ([18F]-APN-1607 only). Using statistical parametric mapping (SPM) and volume of interest (VOI) analyses of the reference region normalized standardized uptake value ratio maps, we then tested for group differences and relationships between both PET biomarkers, as well as their associations with clinical general cognition. In the AD group, [18F]-APN-1607 binding was elevated in widespread cortical regions (P < 0.001 for VOI analysis, familywise error-corrected P < 0.01 for SPM analysis). The regional uptake in AD patients correlated negatively with Mini-Mental State Examination score (frontal lobe: R = -0.632, P = 0.004; temporal lobe: R = -0.593, P = 0.008; parietal lobe: R = -0.552, P = 0.014; insula: R = -0.650, P = 0.003; cingulum: R = -0.665, P = 0.002) except occipital lobe (R = -0.417, P = 0.076). The hypometabolism to [18F]-FDG PET in AD patients also showed negative correlations with regional [18F]-APN-1607 binding in some signature areas of AD (temporal lobe: R = -0.530, P = 0.020; parietal lobe: R = -0.637, P = 0.003; occipital lobe: R = -0.567, P = 0.011). In conclusion, our results suggested that [18F]-APN-1607 PET sensitively detected tau deposition in AD and that individual tauopathy correlated with impaired cerebral glucose metabolism and cognitive function

Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells

Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3–500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM). Like native antigens, this antigen preparation induces MR1 refolding and upregulates surface expression of human MR1, forms MR1 tetramers that detect MAIT cells in human PBMCs, and stimulates cytokine expression (IFNγ, TNF) by human MAIT cells. These antigens also induce MAIT cell accumulation in mouse lungs after administration with a co-stimulant. These chemical and immunological findings provide new insights into antigen properties and MAIT cell activation

MAIT cell-MR1 reactivity is highly conserved across multiple divergent species

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize small molecule metabolites presented by major histocompatibility complex class I related protein 1 (MR1), via an αβ T cell receptor (TCR). MAIT TCRs feature an essentially invariant TCR α-chain, which is highly conserved between mammals. Similarly, MR1 is the most highly conserved major histocompatibility complex-I–like molecule. This extreme conservation, including the mode of interaction between the MAIT TCR and MR1, has been shown to allow for species-mismatched reactivities unique in T cell biology, thereby allowing the use of selected species-mismatched MR1–antigen (MR1–Ag) tetramers in comparative immunology studies. However, the pattern of cross-reactivity of species-mismatched MR1–Ag tetramers in identifying MAIT cells in diverse species has not been formally assessed. We developed novel cattle and pig MR1–Ag tetramers and utilized these alongside previously developed human, mouse, and pig-tailed macaque MR1–Ag tetramers to characterize cross-species tetramer reactivities. MR1–Ag tetramers from each species identified T cell populations in distantly related species with specificity that was comparable to species-matched MR1–Ag tetramers. However, there were subtle differences in staining characteristics with practical implications for the accurate identification of MAIT cells. Pig MR1 is sufficiently conserved across species that pig MR1–Ag tetramers identified MAIT cells from the other species. However, MAIT cells in pigs were at the limits of phenotypic detection. In the absence of sheep MR1–Ag tetramers, a MAIT cell population in sheep blood was identified phenotypically, utilizing species-mismatched MR1–Ag tetramers. Collectively, our results validate the use and define the limitations of species-mismatched MR1–Ag tetramers in comparative immunology studies.</p

Associations between long-term blood pressure trajectory and all-cause and CVD mortality among old people in China

BackgroundOptimal blood pressure (BP) management strategy among the elderly remains controversial, with insufficient consideration of long-term BP trajectory. This study aimed to identify BP trajectory patterns as well as terminal BP trajectory among the Chinese elderly and to explore the relationships between BP trajectories and all-cause mortality and cardiovascular disease (CVD) mortality.MethodsWe included 11,181 participants older than 60 at baseline (mean age, 80.98 ± 10.71) with 42,871 routine BP measurements from the Chinese Longitudinal Healthy Longevity Survey. Latent class trajectory analysis and Cox proportional hazard model were conducted to identify trajectory patterns and their associations with mortality. Furthermore, we also applied mixed-effects model to identify terminal BP trajectories among the elderly.ResultsCompared with stable at normal high level trajectory, excess systolic BP (SBP) trajectory with decreasing trend was associated with a 34% (HR = 1.34, 95% CI: 1.23–1.45) higher risk of all-cause mortality. Considering the competing risk of non-CVD death, excess BP trajectory with decreasing trend had a more pronounced effect on CVD mortality, in which HR (95% CI) was 1.67 (1.17, 2.37). Similar results were also found in diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) trajectories. We further conducted a mixed-effects model and observed that SBP and PP trajectories first increased and began to decline slightly six years before death. In contrast, DBP and MAP showed continuous decline 15 years before death.ConclusionLong-term BP trajectory was associated with all-cause mortality, especially CVD mortality. Keeping a stable BP over time may be an important way for CVD prevention among the elderly

Focused helium and neon ion beam induced etching for advanced extreme ultraviolet lithography mask repair

The gas field ion microscope was used to investigate helium and neon ion beam induced etching of nickel as a candidate technique for extreme ultraviolet (EUV) lithography mask editing. No discernable nickel etching was observed for room temperature helium exposures at 16 and 30 keV in the dose range of 1 x 10(15)-1 x 10(18) He+/cm(2); however, transmission electron microscopy (TEM) revealed subsurface damage to the underlying Mo-Si multilayer EUV mirror. Subsequently, neon beam induced etching at 30 keV was investigated over a similar dose range and successfully removed the entire 50 nm nickel top absorber film at a dose of similar to 3 x 10(17) Ne+/cm(2). Similarly, TEM revealed subsurface damage in the underlying Mo-Si multilayer. To further understand the helium and neon damage, the authors simulated the ion-solid interactions with our EnvizION Monte-Carlo model, which reasonably correlated the observed damage and bubble formation to the nuclear energy loss and the implanted inert gas concentration, respectively. A critical nuclear energy density loss of similar to 80 eV/nm(3) and critical implant concentration of similar to 2.5 x 10(20) atoms/cm(3) have been estimated for damage generation in the multilayer structure. (C) 2014 American Vacuum Society

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL

Efficacy of chimeric antigen receptor T cell therapy and autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma: A systematic review

BackgroundWe aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).Research design and methodsWe searched eligible publications up to January 31st, 2022, in PubMed, Cochrane Library, Springer, and Scopus. A total of 16 publications with 3484 patients were independently evaluated and analyzed using STATA SE software.ResultsPatients who underwent CAR-T cell therapy showed a better overall response rate (ORR) and partial response (PR) than those treated with auto-HSCT (CAR-T vs. auto-HSCT, ORR: 80% vs. 73%, HR:0.90,95%CI:0.76-1.07,P = 0.001; PR: 20% vs. 14%, HR:0.65,95%CI:0.62-0.68,P = 0.034). No significant difference was observed in 6-month overall survival (OS) (CAR-T vs. auto-HSCT, six-month OS: 81% vs. 84%, HR:1.23,95%CI:0.63-2.38, P = 0.299), while auto-HSCT showed a favorable 1 and 2-year OS (CAR-T vs. auto-HSCT, one-year OS: 64% vs. 73%, HR:2.42,95%CI:2.27-2.79, P &lt; 0.001; two-year OS: 54% vs. 68%, HR:1.81,95%CI:1.78-1.97, P &lt; 0.001). Auto-HSCT also had advantages in progression-free survival (PFS) (CAR-T vs. auto-HSCT, six-month PFS: 53% vs. 76%, HR:2.81,95%CI:2.53-3.11,P &lt; 0.001; one-year PFS: 46% vs. 61%, HR:1.84,95%CI:1.72-1.97,P &lt; 0.001; two-year PFS: 42% vs. 54%, HR:1.62,95%CI:1.53-1.71, P &lt; 0.001). Subgroup analysis by age, prior lines of therapy, and ECOG scores was performed to compare the efficacy of both treatment modalities.ConclusionAlthough CAR-T cell therapy showed a beneficial ORR, auto-HSCT exhibited a better long-term treatment superiority in R/R DLBCL patients. Survival outcomes were consistent across different subgroups