Improving Language Model-Based Zero-Shot Text-to-Speech Synthesis with Multi-Scale Acoustic Prompts

Zero-shot text-to-speech (TTS) synthesis aims to clone any unseen speaker's voice without adaptation parameters. By quantizing speech waveform into discrete acoustic tokens and modeling these tokens with the language model, recent language model-based TTS models show zero-shot speaker adaptation capabilities with only a 3-second acoustic prompt of an unseen speaker. However, they are limited by the length of the acoustic prompt, which makes it difficult to clone personal speaking style. In this paper, we propose a novel zero-shot TTS model with the multi-scale acoustic prompts based on a neural codec language model VALL-E. A speaker-aware text encoder is proposed to learn the personal speaking style at the phoneme-level from the style prompt consisting of multiple sentences. Following that, a VALL-E based acoustic decoder is utilized to model the timbre from the timbre prompt at the frame-level and generate speech. The experimental results show that our proposed method outperforms baselines in terms of naturalness and speaker similarity, and can achieve better performance by scaling out to a longer style prompt.Comment: Submitted to ICASSP 202

Systemically administered liposome-encapsulated Ad-PEDF potentiates the anti-cancer effects in mouse lung metastasis melanoma

BACKGROUND: The use of adenoviral vector for gene therapy is still an important strategy for advanced cancers, however, the lack of the requisite coxsackie-adenovirus receptor in cancer cells and host immune response to adenovirus limit the application of adenoviral vector in vivo. METHOD: We designed the antiangiogenic gene therapy with recombinant PEDF adenovirus (Ad-PEDF) encapsulated in cationic liposome (Ad-PEDF/Liposome), and investigated the anti-tumor efficacy of Ad-PEDF/Liposome complex on inhibition of tumor metastasis. RESULTS: We found that systemic administration of Ad-PEDF/liposome was well tolerated and resulted in marked suppression of tumor growth, and was more potent than uncoated Ad-PEDF to induce apoptosis in B16-F10 melanoma cells and inhibit murine pulmonary metastases in vivo. After Ad-luciferase was encapsulated with liposome, its distribution decreased in liver and increased in lung. The anti-Ad IgG level of Ad-PEDF/Liposome was significantly lower than Ad-PEDF used alone. CONCLUSION: The present findings provide evidences of systematic administration of cationic liposome-encapsulated Ad-PEDF in pulmonary metastatic melanoma mice model, and show an encouraging therapeutic effect for further exploration and application of more complexes based on liposome-encapsulated adenovirus for more cancers

Functionalizing tetraphenylpyrazine with perylene diimides (PDIs) as high-performance nonfullerene acceptors

Perylene diimide (PDI)-based small molecular acceptors with a three-dimensional structure are thought to be essential for efficient photocurrent generation and high power conversion efficiencies (PCEs). Herein, a couple of new perylene diimide acceptors (PPDI-O and PPDI-Se) have been designed and successfully synthesized using pyrazine as the core-flanking pyran and selenophene-fused PDIs, respectively. Compared to PPDI-O, PPDI-Se exhibits a blue-shifted absorption in the 400–600 nm range, a comparable LUMO level, and a more distorted molecular geometry. The PPDI-Se-based organic solar cell device with PDBT-T1 as the donor achieved the highest PCE of 7.47% and a high open-circuit voltage (Voc) of up to 1.05 V. The high photovoltaic performance of PPDI-Se-based devices can be attributed to its high LUMO energy level, complementary absorption spectra with donor materials, favorable morphology and balanced carrier transport. The results demonstrate the potential of this type of fullerene-free acceptor for high efficiency organic solar cells

Anti-tumor effect of adenovirus-mediated gene transfer of pigment epithelium-derived factor on mouse B16-F10 melanoma

<p>Abstract</p> <p>Background</p> <p>Angiogenesis plays an important role in tumor growth, invasion, and eventually metastasis. Antiangiogenic strategies have been proven to be a promising approach for clinical therapy for a variety of tumors. As a potent inhibitor of tumor angiogenesis, pigment epithelium-derived factor (PEDF) has recently been studied and used as an anticancer agent in several tumor models.</p> <p>Methods</p> <p>A recombined adenovirus carrying PEDF gene (Ad-PEDF) was prepared, and its expression by infected cells and in treated animals was confirmed with Western blotting and ELISA, respectively. Its activity for inhibiting human umbilical vein endothelial cell (HUVEC) proliferation was tested using the MTT assay. C57BL/6 mice bearing B16-F10 melanoma were treated with i.v. administration of 5 × 10⁸IU/mouse Ad-PEDF, or 5 × 10⁸IU/mouse Ad-Null, or normal saline (NS), every 3 days for a total of 4 times. Tumor volume and survival time were recorded. TUNEL, CD31 and H&E stainings of tumor tissue were conducted to examine apoptosis, microvessel density and histological morphology changes. Antiangiogenesis was determined by the alginate-encapsulated tumor cell assay.</p> <p>Results</p> <p>The recombinant PEDF adenovirus is able to transfer the PEDF gene to infected cells and successfully produce secretory PEDF protein, which exhibits potent inhibitory effects on HUVEC proliferation. Through inhibiting angiogenesis, reducing MVD and increasing apoptosis, Ad-PEDF treatment reduced tumor volume and prolonged survival times of mouse bearing B16-F10 melanoma.</p> <p>Conclusion</p> <p>Our data indicate that Ad-PEDF may provide an effective approach to inhibit mouse B16-F10 melanoma growth.</p

AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model

<p>Abstract</p> <p>Background</p> <p>Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression <it>in vivo</it>. The objective of this work was to evaluate the ability of AAV-mediated human PEDF (hPEDF) as a potent tumor suppressor and a potential candidate for cancer gene therapy.</p> <p>Methods</p> <p>Recombinant AAV₂encoding hPEDF (rAAV₂-hPEDF) was constructed and produced, and then was assigned for <it>in vitro </it>and <it>in vivo </it>experiments. Conditioned medium from cells infected with rAAV₂-hPEDF was used for cell proliferation and tube formation tests of human umbilical vein endothelial cells (HUVECs). Subsequently, colorectal peritoneal carcinomatosis (CRPC) mouse model was established and treated with rAAV₂-hPEDF. Therapeutic efficacy of rAAV₂-hPEDF were investigated, including tumor growth and metastasis, survival time, microvessel density (MVD) and apoptosis index of tumor tissues, and hPEDF levels in serum and ascites.</p> <p>Results</p> <p>rAAV₂-hPEDF was successfully constructed, and transmission electron microscope (TEM) showed that rAAV₂-hPEDF particles were non-enveloped icosahedral shape with a diameter of approximately 20 nm. rAAV₂-hPEDF-infected cells expressed hPEDF protein, and the conditioned medium from infected cells inhibited proliferation and tube-formation of HUVECs <it>in vitro</it>. Furthermore, in CRPC mouse model, rAAV₂-hPEDF significantly suppressed tumor growth and metastasis, and prolonged survival time of treated mice. Immunofluorescence studies indicated that rAAV₂-hPEDF could inhibit angiogenesis and induce apoptosis in tumor tissues. Besides, hPEDF levels in serum and ascites of rAAV₂-hPEDF-treated mice were significant higher than those in rAAV₂-null or normal saline (NS) groups.</p> <p>Conclusions</p> <p>Thus, our results suggest that rAAV₂-hPEDF may be a potential candidate as an antiangiogenic therapy agent.</p

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure