HCLAS-X: Hierarchical and Cascaded Lyrics Alignment System Using Multimodal Cross-Correlation

In this work, we address the challenge of lyrics alignment, which involves aligning the lyrics and vocal components of songs. This problem requires the alignment of two distinct modalities, namely text and audio. To overcome this challenge, we propose a model that is trained in a supervised manner, utilizing the cross-correlation matrix of latent representations between vocals and lyrics. Our system is designed in a hierarchical and cascaded manner. It predicts synced time first on a sentence-level and subsequently on a word-level. This design enables the system to process long sequences, as the cross-correlation uses quadratic memory with respect to sequence length. In our experiments, we demonstrate that our proposed system achieves a significant improvement in mean average error, showcasing its robustness in comparison to the previous state-of-the-art model. Additionally, we conduct a qualitative analysis of the system after successfully deploying it in several music streaming services

The regulatory roles of motile cilia in CSF circulation and hydrocephalus

This article was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science, and Technology of Korea (2016R1D1A1B02008770, 2016M3A9B8914057, 2018M3C7A1056285, and 2021R1A4A1027355).Background Cerebrospinal fluid (CSF) is an ultra-filtrated colorless brain fluid that circulates within brain spaces like the ventricular cavities, subarachnoid space, and the spine. Its continuous flow serves many primary functions, including nourishment, brain protection, and waste removal. Main body The abnormal accumulation of CSF in brain cavities triggers severe hydrocephalus. Accumulating evidence had indicated that synchronized beats of motile cilia (cilia from multiciliated cells or the ependymal lining in brain ventricles) provide forceful pressure to generate and restrain CSF flow and maintain overall CSF circulation within brain spaces. In humans, the disorders caused by defective primary and/or motile cilia are generally referred to as ciliopathies. The key role of CSF circulation in brain development and its functioning has not been fully elucidated. Conclusions In this review, we briefly discuss the underlying role of motile cilia in CSF circulation and hydrocephalus. We have reviewed cilia and ciliated cells in the brain and the existing evidence for the regulatory role of functional cilia in CSF circulation in the brain. We further discuss the findings obtained for defective cilia and their potential involvement in hydrocephalus. Furthermore, this review will reinforce the idea of motile cilia as master regulators of CSF movements, brain development, and neuronal diseases.Publisher PDFPeer reviewe

Hippocampal sclerosis and encephalomalacia as prognostic factors of tuberculous meningitis-related and herpes simplex encephalitis-related epilepsy

AbstractBackgroundTuberculous meningitis (TBM) and herpes simplex encephalitis (HSE) are common neurological diseases involving the brain parenchyma, and both can result in chronic epilepsy. Here, we identified possible variables affecting the prognosis of central nervous system (CNS) infection-related epilepsy.MethodsThe clinical seizure characteristics and demographic data of 20 TBM- and 55 HSE-related epilepsy patients were compared. Statistically significant prognostic variables were identified using multiple regression analysis.ResultsSex, age at infection, age at epilepsy onset, presence of seizures at the time of infection, latency period, and seizure characteristics between two groups were similar except for the pattern of brain lesions observed on the MRI and their overall prognosis. Patients with hippocampal sclerosis (HS) only comprised 30% and 52.7% of the TBM and HSE groups, respectively. Encephalomalacia had a positive effect in the HSE group while HS had a negative effect in this group, but no significant effects were found in the TBM group. Through a multiple regression analysis with a correction for group effects, HS was associated with a poor prognosis. However, encephalomalacia was concomitantly associated with a good prognosis. In addition, a short latency period, with a one-year interval, and being male were both associated with a good prognosis, while the age at the onset of epilepsy was associated with a poor prognosis.ConclusionsThis study suggests that HS and encephalomalacia could have mutual but contradictory effects on the prognosis of CNS infection-related epilepsy

Tyrosine phosphorylation of Ras GAP by the Src kinases.

Cellular Ras has an essential function in oncogenic signal transduction pathways downstream of the viral Src kinase. GTPase-activating protein (GAP), discovered as a key regulator of Ras, also interacts with the Src kinase. To study the functional role of GAP in Src oncogenesis, interactions between the Src kinase and GAP were investigated using a baculovirus expression system. In this system, it was demonstrated that the viral and cellular Src kinases specifically associate with and phosphorylate GAP. Further studies using GAP deletion mutants suggest that the Src homology 2 (SH2) region of GAP interacts with phosphorylated residues in Src. To determine the precise residues in GAP phosphorylated by the Src kinases, phosphopeptide mapping experiments using either in vitro or in vivo labeled proteins were performed. This analysis showed that Tyr-457 in bovine GAP is the major site phosphorylated by the Src kinases both in vitro and in vivo. Tyr-457 in GAP is located immediately adjacent to SH2 domains implicated in GAP association with cellular phosphoproteins, including p62. To investigate whether this specific phosphorylation in GAP is involved in its association with cellular proteins, an epitope-tagged GAP mutant containing a substitution of Phe-457 in place of Tyr-457 was constructed and expressed in Src transformed rodent fibroblasts. GAP-associated proteins were analyzed using epitope specific antibodies reacting only with exogenously expressed GAP. These experiments showed that Tyr-457 phosphorylation of GAP stabilizes its association with p62, particularly at cell membranes. Therefore, one role of tyrosine phosphorylation in GAP may be to recruit p62 to cell membranes where Ras is localized. These results are consistent with a model in which phosphorylation of GAP by activated tyrosine kinases stimulates Ras signalling pathways through formation of GAP complexes with p62 at cell membranes.Ph.D.Microbiology and ImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/103823/1/9409778.pdfDescription of 9409778.pdf : Restricted to UM users only

Prognostic Implications of Epilepsy Onset Age According to Relapse Pattern in Patients with Four-Year Remission

A total of 472 epilepsy patients with a 4-year remission period were divided into 10-year age groups according to age of onset. The relapse patterns during at least 3 years of follow-up were classified as early relapse (ER), late relapse (LR), and seizure-free (SF). The remission probability and multiplicity of prognostic factors were evaluated using univariate and multivariate multinomial logistic analyses. The weighted risk score based on odd ratios (ORs) was used for comparisons of the relative risk of relapse between groups. The group with onset in their 20s had the lowest remission probability among the groups. The risks of relapse in the LR patients and the relative weighted risk score of ER patients in the group with onset in their 20s were 3.11 and 19.44, respectively, which was the highest risk among the age groups. Patients without remission within 1 year had the highest relapse risk, with an OR of 7.18 in ER patients. The OR of relapse in patients with >10 generalized tonic–clonic (GTC) seizures was the second most important prognostic factor in LR patients. The distinct risk and corresponding prognostic factors in LR and ER patients reflected inherent differences between these relapse patterns

The p110γ PI-3 kinase is required for EphA8-stimulated cell migration

AbstractThis study provides evidence that treatment with preclustered ephrin A5-Fc results in a substantial increase in the stability of the p110γ PI-3 kinase associated with EphA8, thereby enhancing PI-3 kinase activity and cell migration on a fibronectin substrate. In contrast, co-expression of a lipid kinase-inactive p110γ mutant together with EphA8 inhibits ligand-stimulated PI-3 kinase activity and cell migration on a fibronectin substrate, suggesting that the mutant has a dominant negative effect against the endogenous p110γ PI-3 kinase. Significantly, the tyrosine kinase activity of EphA8 is not important for either of these processes. Taken together, our results demonstrate that the stimulation of cell migration on a fibronectin substrate by the EphA8 receptor depends on the p110γ PI-3 kinase but is independent of a tyrosine kinase activity

Identification of Phosphotyrosine Binding Domain-Containing Proteins as Novel Downstream Targets of the EphA8 Signaling Function▿ †

Eph receptors and ephrins have been implicated in a variety of cellular processes, including morphology and motility, because of their ability to modulate intricate signaling networks. Here we show that the phosphotyrosine binding (PTB) domain-containing proteins AIDA-1b and Odin are tightly associated with the EphA8 receptor in response to ligand stimulation. Both AIDA-1b and Odin belong to the ankyrin repeat and sterile alpha motif domain-containing (Anks) protein family. The PTB domain of Anks family proteins is crucial for their association with the juxtamembrane domain of EphA8, whereas EphA8 tyrosine kinase activity is not required for this protein-protein interaction. In addition, we found that Odin is a more physiologically relevant partner of EphA8 in mammalian cells. Interestingly, overexpression of the Odin PTB domain alone attenuated EphA8-mediated inhibition of cell migration in HEK293 cells, suggesting that it acts as a dominant-negative mutant of the endogenous Odin protein. More importantly, small interfering RNA-mediated Odin silencing significantly diminished ephrinA5-induced EphA8 signaling effects, which inhibit cell migration in HEK293 cells and retract growing neurites of Neuro2a cells. Taken together, our findings support a possible function for Anks family proteins as scaffolding proteins of the EphA8 signaling pathway