Improving Speech Inversion Through Self-Supervised Embeddings and Enhanced Tract Variables

The performance of deep learning models depends significantly on their capacity to encode input features efficiently and decode them into meaningful outputs. Better input and output representation has the potential to boost models' performance and generalization. In the context of acoustic-to-articulatory speech inversion (SI) systems, we study the impact of utilizing speech representations acquired via self-supervised learning (SSL) models, such as HuBERT compared to conventional acoustic features. Additionally, we investigate the incorporation of novel tract variables (TVs) through an improved geometric transformation model. By combining these two approaches, we improve the Pearson product-moment correlation (PPMC) scores which evaluate the accuracy of TV estimation of the SI system from 0.7452 to 0.8141, a 6.9% increase. Our findings underscore the profound influence of rich feature representations from SSL models and improved geometric transformations with target TVs on the enhanced functionality of SI systems

Laboratory Detection and Neutralizing Activity of Exocellular AmpC β-lactamases by Anti bla-CMY

Detection of AmpC β-lactamases (AmpC-bls) is important for infection control purposes and therapeutic options. Here, we provided a diagnostic anti β-lactamase neutralization test (bla-NT); modified from broth microdilution (BM) for the detection of bls-AmpC, CMY, in multidrug resistant Escherichia coli and Klebsiella pneumoniae. Anti-bla neutralizing activity against these two bacteria was tested. Anti bla-CMY was prepared in rabbits and used in: bla-NT; investigating effect on bacterial colony forming unit (CFU); and in ELISA. In bla-NT, the anti-bla-CMY neutralized exocellular bls produced by the tested bacterial strains and resulted in an increase in the bacterial sensitivity to the tested antimicrobials and reduction in minimum inhibitory concentration. Interestingly, the anti-bla-CMY decreased the CFU and its morphology when added to the tested bacteria. ELISA-OD was significantly correlated with the drop in minimum inhibitory concentration and CFU counts at P-value ≤ 0.05 and 0.01, respectively. It could be concluded that, bla-NT could detect bls-AmpC and run parallel to BM in microbiology laboratory. Investigations are running to develop the test for quantitative detection of bls-AmpC

Audio Data Augmentation for Acoustic-to-articulatory Speech Inversion using Bidirectional Gated RNNs

Data augmentation has proven to be a promising prospect in improving the performance of deep learning models by adding variability to training data. In previous work with developing a noise robust acoustic-to-articulatory speech inversion system, we have shown the importance of noise augmentation to improve the performance of speech inversion in noisy speech. In this work, we compare and contrast different ways of doing data augmentation and show how this technique improves the performance of articulatory speech inversion not only on noisy speech, but also on clean speech data. We also propose a Bidirectional Gated Recurrent Neural Network as the speech inversion system instead of the previously used feed forward neural network. The inversion system uses mel-frequency cepstral coefficients (MFCCs) as the input acoustic features and six vocal tract-variables (TVs) as the output articulatory features. The Performance of the system was measured by computing the correlation between estimated and actual TVs on the U. Wisc. X-ray Microbeam database. The proposed speech inversion system shows a 5% relative improvement in correlation over the baseline noise robust system for clean speech data. The pre-trained model, when adapted to each unseen speaker in the test set, improves the average correlation by another 6%.Comment: EUSIPCO 202

Phenotypic and Genotypic Identification of Vancomycin Resistant Enterococci from Different Sources

Enterococci are reservoirs for transmission of the most clinically important antimicrobial resistances such as vancomycin resistance. Therefore, this work aimed to determine the occurrence of enterococci and their respective vancomycine resistance genes (vanA and vanB) from different sources. Two hundred and twenty-four samples from chickens, turkey, fish and human urine, as well as, two types of human food including milk (raw and milk from mastitic animals) and sausage were tested for isolation of Enterococcus species. The isolates were identified morphologically and biochemically using catalase test, sodium chloride tolerance and growth at pH 9.6 and 10- 45˚C. The vancomycin resistance profile of the isolates was verified by both disc diffusion and agar dilution methods. The genotypic enterococcal identification at both genus and species levels and their vancomycine resistance genes were also ascertained using PCR amplification of the respective genes for 28 isolates. Enterococci isolation rate was 70% of the examined samples with a higher percentage of vancomycine resistance (53.5%) and the minimum inhibitory concentrations (MICs) ranged from 16 to 512 µg/mL. Molecular identification of 28 enterococcal isolates revealed the dominance of E. faecalis (42.8%) and clarified a higher proportion of vanA (78.5%) and vanB (67.8%) genes. In conclusion, administration of the antimicrobials mainly vancomycin may be considered as a pronounced stress factor in the veterinary and human practices. In addition, VRE can act as a reservoir for vancomycin resistance

Thymoquinone suppression of the human hepatocellular carcinoma cell growth involves inhibition of IL-8 expression, elevated levels of TRAIL receptors, oxidative stress and apoptosis

Hepatocellular carcinoma (HCC) is the fourth most common solid tumor worldwide. The chemokine interleukin-8 (IL-8) is overexpressed in HCC and is a potential target for therapy. Although the transcription factor NF-κB regulates IL-8 expression, and while thymoquinone (TQ; the most bioactive constituent of black seed oil) inhibits NF-κB activity, the precise mechanisms by which TQ regulates IL-8 and cancer cell growth remain to be clarified. Here, we report that TQ inhibited growth of HCC cells in a dose- and time-dependent manner, caused G2M cell cycle arrest, and stimulated apoptosis. Apoptosis was substantiated by activation of caspase-3 and -9, as well as cleavage of poly(ADP-ribose)polymerase. TQ treatments inhibited expression of NF-κB and suppressed IL-8 and its receptors. TQ treatments caused increased levels of reactive oxygen species (ROS) and mRNAs of oxidative stress-related genes, NQO1 and HO-1. Pretreatment of HepG2 cells with N-acetylcysteine, a scavenger of ROS, prevented TQ-induced cell death. TQ treatment stimulated mRNA expression of pro-apoptotic Bcl-xS and TRAIL death receptors, and inhibited expression of the anti-apoptotic gene Bcl-2. TQ enhanced TRAIL-induced death of HepG2 cells, in part by up-regulating TRAIL death receptors, inhibiting NF-κB and IL-8 and stimulating apoptosis. Altogether, these findings provide insights into the pleiotropic molecular mechanisms of TQ-dependent suppression of HCC cell growth and underscore potential of this compound as anti-HCC drug

Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines

Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-β1, nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF-κB, STAT3 and COX-2 and decreased IκBα in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions

Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-jB signaling and IL-8 expression

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. The transcription factor NF-κB is overexpressed in human MB and is a critical factor for MB tumor growth. NF-κB is known to regulate the expression of interleukin-8 (IL-8), the chemokine that enhances cancer cell growth and resistance to chemotherapy. We have recently shown that thymoquinone (TQ) suppresses growth of hepatocellular carcinoma cells in part by inhibiting NF-κB signaling. Here we sought to extend these studies in MB cells and show that TQ suppresses growth of MB cells in a dose- and time-dependent manner, causes G2M cell cycle arrest, and induces apoptosis. TQ significantly increased generation of reactive oxygen species (ROS), while pretreatment of MB cells with the ROS scavenger N-acetylcysteine (NAC) abrogated TQ-induced cell death and apoptosis, suggesting that TQ-induced cell death and apoptosis are oxidative stress-mediated. TQ inhibitory effects were associated with inhibition of NF-κB and altered expression of its downstream effectors IL-8 and its receptors, the anti-apoptotic Bcl-2, Bcl-xL, X-IAP, and FLIP, as well as the pro-apoptotic TRAIL-R1, caspase-8, caspase-9, Bcl-xS, and cytochrome c. TQ-triggered apoptosis was substantiated by up-regulation of the executioner caspase-3 and caspase-7, as well as cleavage of the death substrate poly(ADP-ribose)polymerase. Interestingly, pretreatment of MB cells with NAC or the pan-caspase inhibitor zVAD-fmk abrogated TQ-induced apoptosis, loss of cyclin B1 and NF-κB activity, suggesting that these TQ-mediated effects are oxidative stress- and caspase-dependent. These findings reveal that TQ induces both extrinsic and intrinsic pathways of apoptosis in MB cells, and suggest its potential usefulness in the treatment of MB

Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression

IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma

Mechanisms of colorectal cancer cell growth and metastasis inhibition by CARP-1 functional mimetic-4

Introduction: Colorectal cancer (CRC) constitutes one of the most aggressive malignancies worldwide and in Malaysia. Due to high recurrence rate and toxic side effects associated with radiation and chemotherapies, new agents are urgently needed. CARP-1 is a peri-nuclear phospho-protein which plays a dynamic role in regulating cell growth and apoptosis. CARP-1 functional mimetics (CFMs) are a class of compounds that stimulate CARP-1. CFM-4, a lead compound, was shown to suppress growth and metastasis of various cancers, other than CRC. We hypothesized that CFM-4 inhibits proliferation and metastasis in CRC. Material and methods: CFM-4 anti-cancer effects of on CRC cells were investigated using MTT assay, Annexin V/Propidium iodide (PI) apoptosis assay, cell cycle analysis, quantitative real-time PCR (qRT-PCR) and Western blotting. Antimetastatic activities were assessed by migration, colony formation and invasion assays. Results: CFM-4 inhibited CRC cell proliferation and was much more potent than the classical anti-CRC 5-fluorouracil. These effects were shown to be mediated at least in part by stimulating apoptosis, as indicated in our Annexin V/PI assay results. Cell cycle analysis showed that CFM-4 induced G2/M phase arrest. Molecularly, qRT-PCR results revealed that CFM-4 promoted intrinsic apoptosis by upregulating expression of caspase-8 and -9, p53, PUMA and Noxa, and stimulated extrinsic apoptosis by enhancing expression of death receptors. CFM-4 upregulated NF-B signaling inhibitor A20-binding inhibitor protein and the PI3K negative regulator PTEN. Western blot analysis results revealed that CFM-4 enhanced expression of CARP-1, caspase-8 and executioner caspase-3. Metastatic properties of the CRC cells were reduced by CFM-4 through blocking their capabilities to form colonies, migrate and invade through the matrix-coated membranes. Conclusion: The potent antitumor and anti-metastatic properties of CFM-4 against CRC are due to collective pro-apoptotic, anti-proliferative and anti-metastatic activities. Together our data warrants further investigations of CFM-4 as potential anti-tumor agent for CRC malignancy and metastasis