The Role of Noxa/MCL-1 in Head and Neck Squamous Cell Carcinoma (HNSCC) Treatment

Head and neck cancer is the sixth leading type of cancer with 90 percent of head and neck cancer arising from squamous cell lining on the epithelium of the oral and nasal cavity, pharynx, and salivary gland. Even with tremendous achievements on chemotherapeutic drugs and therapies, the long-term prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) has shown little improvement over the last three decades. Cisplatin is one of widely used chemotherapeutic drugs for multiple cancers, including head and neck cancer, but the prolonged use of this drug is limited by its toxicity and by the development of resistance. To overcome these major roadblocks to improved prognosis requires mechanism-based therapeutic strategies to maximize the antitumor effect of drugs while limiting their toxicities. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of BCL-2 family-dependent mitochondrial apoptosis. DNA damage activates a tumor suppressor p53 to induce apoptosis. One of its functions is to induce the expression of several pro-apoptotic proteins such as Noxa, which binds to an anti-apoptotic BCL-2 family protein, MCL-1 (myeloid leukemia cell-1) to inactivate its pro-survival function and induce apoptosis. We examined Noxa expression and apoptosis induced by cisplatin in p53-wild-type HN30 and HN31, p53-truncated and inactive HN4 and HN12, and p53-deleted HN22 and HN8 HNSCC cell lines. We found that Noxa was induced in HN30 and HN31 cells and down-regulation of Noxa by shRNA (short-hairpin RNA) decreased apoptosis, indicating Noxa contribution to cisplatin-induced apoptosis. Interestingly, cisplatin treatment induced Noxa and apoptosis even in p53-deleted HN22 and HN8 cells, suggesting the existence of the p53-independent pathways for the induction of Noxa. Based on these observations, we hypothesized that modulation of Noxa/MCL-1 axis could mimic cisplatin-induced cell death. We found that Noxa overexpression induced cell death in all cell lines tested regardless of p53 status. This finding could be applicable as a potential therapeutic strategy to treat head and neck cancer

Non-Abelian Anyon Collider

A collider, where particles are injected to a beam splitter from opposite sides, has been used for identifying quantum statistics of identical particles. The collision leads to bunching of the particles for bosons and antibunching for fermions. In recent experiments, a collider was applied to a fractional quantum Hall regime hosting Abelian anyons. The observed negative cross correlation of electrical currents cannot be understood with fermionic antibunching. Here we predict, based on a conformal field theory and non-perturbative treatment of non-equilibrium anyon injection, that the collider provides a tool for direct observation of the braiding statistics of various Abelian and non-Abelian anyons. Its dominant process is not direct collision between injected anyons, contrary to common expectation, but braiding between injected anyons and an anyon excited at the collider. The dependence of the resulting negative cross correlation on the injection currents distinguishes non-Abelian SU(2)$_k$ anyons, Ising anyons, and Abelian Laughlin anyons.Comment: Main text: 7 pages, 3 figures, Supplementary text: 8 pages, 3 figure

Vocoder-free End-to-End Voice Conversion with Transformer Network

Mel-frequency filter bank (MFB) based approaches have the advantage of learning speech compared to raw spectrum since MFB has less feature size. However, speech generator with MFB approaches require additional vocoder that needs a huge amount of computation expense for training process. The additional pre/post processing such as MFB and vocoder is not essential to convert real human speech to others. It is possible to only use the raw spectrum along with the phase to generate different style of voices with clear pronunciation. In this regard, we propose a fast and effective approach to convert realistic voices using raw spectrum in a parallel manner. Our transformer-based model architecture which does not have any CNN or RNN layers has shown the advantage of learning fast and solved the limitation of sequential computation of conventional RNN. In this paper, we introduce a vocoder-free end-to-end voice conversion method using transformer network. The presented conversion model can also be used in speaker adaptation for speech recognition. Our approach can convert the source voice to a target voice without using MFB and vocoder. We can get an adapted MFB for speech recognition by multiplying the converted magnitude with phase. We perform our voice conversion experiments on TIDIGITS dataset using the metrics such as naturalness, similarity, and clarity with mean opinion score, respectively.Comment: Work in progres

Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient (Vav1−/−) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of Vav1−/− mice than in WT mice. Furthermore, the bone status of Vav1−/− mice was analyzed in situ and the femurs of Vav1−/− mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an αvβ3 integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption

Disturbance of greedy publishing to academia

Questionable publications have been accused of "greedy" practices; however, their influence on academia has not been gauged. Here, we probe the impact of questionable publications through a systematic and comprehensive analysis with various participants from academia and compare the results with those of their unaccused counterparts using billions of citation records, including liaisons, e.g., journals and publishers, and prosumers, e.g., authors. The analysis reveals that questionable publications embellished their citation scores by attributing publisher-level self-citations to their journals while also controlling the journal-level self-citations to circumvent the evaluation of journal-indexing services. This approach makes it difficult to detect malpractice by conventional journal-level metrics. We propose journal-publisher-hybrid metric that help detect malpractice. We also demonstrate that the questionable publications had a weaker disruptiveness and influence than their counterparts. This indicates the negative effect of suspicious publishers in the academia. The findings provide a basis for actionable policy making against questionable publications.Comment: 16 pages of main text including 4 figures + 32 pages of supplementary information including 30 supplementary figure

Predicting COVID-19 transmission in a student population in Seoul, South Korea, 2020–2021

Background As coronavirus disease 2019 (COVID-19) transmission depends on factors such as demography, comorbidity, and patterns of daily activity, a better understanding of the societal factors of the infection among students would be useful in planning prevention strategies. However, no studies to date have focused on societal factors associated with COVID-19 transmission among students. Purpose This study aimed to characterize the factors of a student population associated with COVID-19 transmission in the metropolitan city of Seoul, South Korea. Methods We analyzed the epidemiological data for laboratory-confirmed (reverse transcription polymerase chain reaction) COVID-19 cases collected by the Korea Disease Control and Prevention Agency and Ministry of Education from January 2020 to October 2021. We calculated the global Moran’s index, local Moran’s index, and Getis-Ord’s index. A spatial regression analysis was performed to identify sociodemographic predictors of COVID-19 at the district level. Results The global spatial correlation estimated by Moran’s index was 0.082 for the community population and 0.064 for the student population. The attack rate of adults aged 30– 59 years (P=0.049) was associated with an increased risk of COVID-19 attack rates in students, whereas the number of students per primary- (P=0.003) and middle- (P=0.030) school class was inversely associated with risk of COVID-19 attack among students. Conclusion We found that COVID-19 transmission was more attributable to the community-level burden in students than adults. We recommend that public health initiatives target initiatives that protect students from COVID-19 when the community carries a high burden of infection