The structural basis of actinomycin D–bindinginduces nucleotide flipping out, a sharp bendand a left-handed twist in CGG triplet repeats

The potent anticancer drug actinomycin D (ActD)functions by intercalating into DNA at GpC sites,thereby interrupting essential biological processesincluding replication and transcription. Certainneurological diseases are correlated with the expansionof (CGG)n trinucleotide sequences, whichcontain many contiguous GpC sites separated by asingle G:G mispair. To characterize the binding ofActD to CGG triplet repeat sequences, the structuralbasis for the strong binding of ActD to neighbouringGpC sites flanking a G:G mismatch has beendetermined based on the crystal structure of ActDbound to ATGCGGCAT, which contains a CGGtriplet sequence. The binding of ActD molecules toGCGGC causes many unexpected conformationalchanges including nucleotide flipping out, a sharpbend and a left-handed twist in the DNA helix via atwo site-binding model. Heat denaturation, circulardichroism and surface plasmon resonance analysesshowed that adjacent GpC sequences flanking aG:G mismatch are preferred ActD-binding sites. Inaddition, ActD was shown to bind the hairpin conformationof (CGG)16 in a pairwise combination andwith greater stability than that of other DNAintercalators. Our results provide evidence of apossible biological consequence of ActD bindingto CGG triplet repeat sequences

Lightly Weighted Automatic Audio Parameter Extraction for the Quality Assessment of Consensus Auditory-Perceptual Evaluation of Voice

The Consensus Auditory-Perceptual Evaluation of Voice is a widely employed tool in clinical voice quality assessment that is significant for streaming communication among clinical professionals and benchmarking for the determination of further treatment. Currently, because the assessment relies on experienced clinicians, it tends to be inconsistent, and thus, difficult to standardize. To address this problem, we propose to leverage lightly weighted automatic audio parameter extraction, to increase the clinical relevance, reduce the complexity, and enhance the interpretability of voice quality assessment. The proposed method utilizes age, sex, and five audio parameters: jitter, absolute jitter, shimmer, harmonic-to-noise ratio (HNR), and zero crossing. A classical machine learning approach is employed. The result reveals that our approach performs similar to state-of-the-art (SOTA) methods, and outperforms the latent representation obtained by using popular audio pre-trained models. This approach provide insights into the feasibility of different feature extraction approaches for voice evaluation. Audio parameters such as jitter and the HNR are proven to be suitable for characterizing voice quality attributes, such as roughness and strain. Conversely, pre-trained models exhibit limitations in effectively addressing noise-related scorings. This study contributes toward more comprehensive and precise voice quality evaluations, achieved by a comprehensively exploring diverse assessment methodologies.Comment: Published in IEEE 42th International Conference on Consumer Electronics (ICCE 2024

Disseminated peritoneal tuberculosis simulating advanced ovarian cancer: A retrospective study of 17 cases

AbstractObjectivesThe abdominopelvic cavity is one of the common sites for extrapulmonary tubercular infections. The rate of preoperative misdiagnoses between peritoneal tuberculosis (TB) and ovarian cancer is high because of overlapping nonspecific signs and symptoms. We attempted to analyze the experience within our hospital so as to establish the best means of discriminating between peritoneal TB and advanced ovarian cancer.MethodsSeventeen patients diagnosed as having peritoneal TB between July 1986 and December 2008 at the Obstetrics and Gynecology Department of our hospital with the initial presentation simulating advanced ovarian cancer were retrospectively reviewed and evaluated.ResultsPatients’ ages ranged from 24 years to 87 years (median, 38 years). Ten of 17 patients (60%) were younger than 40 years. All patients except one had elevated serum cancer antigen-125 levels with a mean of 358.8U/mL (range, 12–733U/mL). Computed tomographic (CT) scans showed ascites with mesenteric or omental stranding in all (100%), enlarged retroperitoneal lymph nodes in six (35.3%), and an adnexal mass in three (17.6%). Abdominal paracentesis was performed in seven cases, in which the findings revealed lymphocyte-dominant ascites without malignant cells. Surgical intervention by laparotomy was performed in 13 cases (76%) and by laparoscopy in three cases (18%), and a CT-guided peritoneal biopsy was performed in one case (6%). A frozen section was taken from 16 patients but not the patient who received a CT-guided peritoneal biopsy, and all revealed granulomatous inflammation. A final pathological examination confirmed a diagnosis of peritoneal TB. All patients responded to anti-TB treatment.ConclusionsIn view of these data, a clinical diagnosis of peritoneal TB should be considered in a relatively young female with nonspecific symptoms of abdominal distension and wasting, as well as lymphocytic ascites without malignant cells. Laparoscopy or a minilaparotomy to obtain tissue samples for frozen-section analysis may be the most direct and least-invasive approach for a diagnosis, thus avoiding unnecessary extended surgery in these patients

Revealing the Anti-Tumor Effect of Artificial miRNA p-27-5p on Human Breast Carcinoma Cell Line T-47D

microRNAs (miRNAs) cause mRNA degradation or translation suppression of their target genes. Previous studies have found direct involvement of miRNAs in cancer initiation and progression. Artificial miRNAs, designed to target single or multiple genes of interest, provide a new therapeutic strategy for cancer. This study investigates the anti-tumor effect of a novel artificial miRNA, miR P-27-5p, on breast cancer. In this study, we reveal that miR P-27-5p downregulates the differential gene expressions associated with the protein modification process and regulation of cell cycle in T-47D cells. Introduction of this novel artificial miRNA, miR P-27-5p, into breast cell lines inhibits cell proliferation and induces the first “gap” phase (G1) cell cycle arrest in cancer cell lines but does not affect normal breast cells. We further show that miR P-27-5p targets the 3′-untranslated mRNA region (3′-UTR) of cyclin-dependent kinase 4 (CDK4) and reduces both the mRNA and protein level of CDK4, which in turn, interferes with phosphorylation of the retinoblastoma protein (RB1). Overall, our data suggest that the effects of miR p-27-5p on cell proliferation and G1 cell cycle arrest are through the downregulation of CDK4 and the suppression of RB1 phosphorylation. This study opens avenues for future therapies targeting breast cancer

Look, the World is Watching How We Treat Migrants! The Making of the Anti-Trafficking Legislation during the Ma Administration

Employing the spiral model, this research analyses how anti-human trafficking legislation was promulgated during the Ma Ying-jeou (Ma Yingjiu) presidency. This research found that the gov- ernment of Taiwan was just as accountable for the violation of mi- grants’ human rights as the exploitive placement agencies and abusive employers. This research argues that, given its reliance on the United States for political and security support, Taiwan has made great ef- forts to improve its human rights records and meet US standards for protecting human rights. The reform was a result of multilevel inputs, including US pressure and collaboration between transnational and domestic advocacy groups. A major contribution of this research is to challenge the belief that human rights protection is intrinsic to dem- ocracy. In the same light, this research also cautions against Taiwan’s subscription to US norms since the reform was achieved at the cost of stereotyping trafficking victimhood, legitimising state surveillance, and further marginalising sex workers

AV-SUPERB: A Multi-Task Evaluation Benchmark for Audio-Visual Representation Models

Audio-visual representation learning aims to develop systems with human-like perception by utilizing correlation between auditory and visual information. However, current models often focus on a limited set of tasks, and generalization abilities of learned representations are unclear. To this end, we propose the AV-SUPERB benchmark that enables general-purpose evaluation of unimodal audio/visual and bimodal fusion representations on 7 datasets covering 5 audio-visual tasks in speech and audio processing. We evaluate 5 recent self-supervised models and show that none of these models generalize to all tasks, emphasizing the need for future study on improving universal model performance. In addition, we show that representations may be improved with intermediate-task fine-tuning and audio event classification with AudioSet serves as a strong intermediate task. We release our benchmark with evaluation code and a model submission platform to encourage further research in audio-visual learning.Comment: Submitted to ICASSP 2024; Evaluation Code: https://github.com/roger-tseng/av-superb Submission Platform: https://av.superbbenchmark.or

Visible Light Responsive Photocatalyst Induces Progressive and Apical-Terminus Preferential Damages on Escherichia coli Surfaces

BACKGROUND: Recent research shows that visible-light responsive photocatalysts have potential usage in antimicrobial applications. However, the dynamic changes in the damage to photocatalyzed bacteria remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Facilitated by atomic force microscopy, this study analyzes the visible-light driven photocatalyst-mediated damage of Escherichia coli. Results show that antibacterial properties are associated with the appearance of hole-like structures on the bacteria surfaces. Unexpectedly, these hole-like structures were preferentially induced at the apical terminus of rod shaped E. coli cells. Differentiating the damages into various levels and analyzing the percentage of damage to the cells showed that photocatalysis was likely to elicit sequential damages in E. coli cells. The process began with changing the surface properties on bacterial cells, as indicated in surface roughness measurements using atomic force microscopy, and holes then formed at the apical terminus of the cells. The holes were then subsequently enlarged until the cells were totally transformed into a flattened shape. Parallel experiments indicated that photocatalysis-induced bacterial protein leakage is associated with the progression of hole-like damages, further suggesting pore formation. Control experiments using ultraviolet light responsive titanium-dioxide substrates also obtained similar observations, suggesting that this is a general phenomenon of E. coli in response to photocatalysis. CONCLUSION/SIGNIFICANCE: The photocatalysis-mediated localization-preferential damage to E. coli cells reveals the weak points of the bacteria. This might facilitate the investigation of antibacterial mechanism of the photocatalysis