LaunchpadGPT: Language Model as Music Visualization Designer on Launchpad

Launchpad is a musical instrument that allows users to create and perform music by pressing illuminated buttons. To assist and inspire the design of the Launchpad light effect, and provide a more accessible approach for beginners to create music visualization with this instrument, we proposed the LaunchpadGPT model to generate music visualization designs on Launchpad automatically. Based on the language model with excellent generation ability, our proposed LaunchpadGPT takes an audio piece of music as input and outputs the lighting effects of Launchpad-playing in the form of a video (Launchpad-playing video). We collect Launchpad-playing videos and process them to obtain music and corresponding video frame of Launchpad-playing as prompt-completion pairs, to train the language model. The experiment result shows the proposed method can create better music visualization than random generation methods and hold the potential for a broader range of music visualization applications. Our code is available at https://github.com/yunlong10/LaunchpadGPT/.Comment: Accepted by International Computer Music Conference (ICMC) 202

How do leaders react when treated unfairly? Leader narcissism and self-interested behavior in response to unfair treatment

In this article we employ a trait activation framework to examine how unfairness perceptions influence narcissistic leaders’ self-interested behavior, and the downstream implications of these effects for employees’ pro-social and voice behaviors. Specifically, we propose that narcissistic leaders are particularly likely to engage in self-interested behavior when they perceive that their organizations treat them unfairly, and that this self-interested behavior in turn decreases followers’ pro-social behavior and voice. Data from a multisource, time-lagged survey of 211 team leaders and 1,205 subordinates provided support for the hypothesized model. Implications for theory and practice are discussed

DePARylation Is Critical for S Phase Progression and Cell Survival

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy

Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5\u27-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens revealed that ZATT also has a TDP2-independent role in promoting cell survival following ETO treatment. ZATT KO cells showed relatively higher ETO sensitivity than TDP2-KO cells, and ZATT/TDP2 DKO cells displayed additive hypersensitivity to ETO treatment. The study using a series of deletion mutants of ZATT determined that the N-terminal 1-168 residues of ZATT are required for interaction with TOP2 and this interaction is critical to ETO sensitivity. Moreover, depletion of ZATT resulted in accelerated TOP2 degradation after ETO or cycloheximide (CHX) treatment, suggesting that ZATT may increase TOP2 stability and likely participate in TOP2 turnover. Taken together, this study suggests that ZATT is a critical determinant that dictates responses to ETO treatment and targeting. ZATT is a promising strategy to increase ETO efficacy for cancer therapy

Genome-Wide CRISPR Screen Reveals the Synthetic Lethality between BCL2L1 Inhibition and Radiotherapy

Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 inhibition combined with RT dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models. Taken together, our results suggest that the combination of an apoptosis inhibitor such as a BCL2L1 inhibitor with RT may represent a promising anticancer strategy for solid cancers including breast cancer

FACS-Based Genome-Wide CRISPR Screens Define Key Regulators of DNA Damage Signaling Pathways

DNA damage-activated signaling pathways are critical for coordinating multiple cellular processes, which must be tightly regulated to maintain genome stability. To provide a comprehensive and unbiased perspective of DNA damage response (DDR) signaling pathways, we performed 30 fluorescence-activated cell sorting (FACS)-based genome-wide CRISPR screens in human cell lines with antibodies recognizing distinct endogenous DNA damage signaling proteins to identify critical regulators involved in DDR. We discovered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as modulators that regulate ATM protein level. Moreover, we discovered that GNB1L is a key regulator of DDR signaling via its role as a co-chaperone specifically regulating PIKK proteins. Collectively, these screens offer a rich resource for further investigation of DDR, which may provide insight into strategies of targeting these DDR pathways to improve therapeutic outcomes

Peliminary exploration on the differential diagnosis between meningioma and schwannoma using contrast-enhanced T1WI flow-sensitive black-blood sequence

IntroductionContrast-enhanced T1WI flow-sensitive black-blood (CE-T1WI FSBB) is a newly developed sequence which had not been widely used for differential diagnosis of brain tumors.MethodsTo quantify the pre-operative imaging features of intratumoral microbleeds and intratumoral vessels using CE-T1WI FSBB scan and study the differences in biological behavior of meningiomas and schwannomas underlying the imaging features. Seventy-three cases of meningiomas and 24 cases of schwannomas confirmed by postoperative pathology were included. Two neuroradiologists independently counted intratumoral vessels and intratumoral microbleeds based on CE-T1WI FSBB images. The vessel density index (VDI) and microbleed density index (MDI) were the number of intratumoral vessels and the number of intratumoral microbleeds divided by the tumor volume, respectively. The consistency test of intratumoral vessel count and intratumoral microbleed count based on CE-T1WI FSBB were summarized using 2-way random intraclass correlation coefficients (ICC). Mann–Whitney U-test and chi-square test were used to determine significant differences between meningiomas and schwannomas, and fibrous meningiomas and epithelial meningiomas. P<0.05 was considered statistically significant.ResultsThe ICC of intratumoral vessels count and intratumoral microbleeds count were 0.89 and 0.99, respectively. There were significant differences in the number of intratumoral microbleeds (P<0.01) and MDI values (P<0.01) between meningiomas and schwannomas. There were no differences in the number of intratumoral vessels (P=0.64), VDI (P=0.17), or tumor volume (P=0.33). There were also differences in the number of intratumoral microbleeds (P<0.01), the MDI value (P<0.01), and the sex of patients (P<0.05) between fibrous meningiomas and epithelial meningiomas.DiscussionCE-T1WI FSBB can be a new technique for differentiating schwannomas from meningiomas, and even different types of meningiomas. Schwannomas have a higher incidence of intratumoral hemorrhage, more intratumoral microbleeds, and higher MDI values than meningiomas, which provides a new basis for preoperative differential diagnosis and treatment decisions

Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity

BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy

An Improved Technique of Hybridization of PSO for the Optimal Coordination of Directional Overcurrent Protection Relays of IEEE Bus System

The use of a directional overcurrent protection relay (DOPR) to protect an electrical power system is a crucial instrument for keeping the system dynamic and avoiding undue interruption. The coordination of a DOPR’s primary and backup relays is modelled as a highly constrained optimization problem. The goal is to determine an ideal value that will reduce the overall working time of all primary relays. The coordination is accomplished by the use of particle swarm optimization hybridization (HPSO). Comprehensive simulation experiments are carried out to evaluate the efficacy of the proposed HPSO by employing the time multiplier setting (TMS) and plug setting (PS) as an optimization variable and constant, respectively. The HPSO has been examined satisfactorily utilizing certain IEEE benchmark test systems (9-bus and 14-bus). The outcomes are contrasted with earlier heuristics and evolutionary approaches. Based on the acquired findings, it is clear that the obtained results exceed the other conventional and state of the art procedures in terms of total DOPR operation and the computing time necessary to achieve the global optimal solution

An Improved Technique of Hybridization of PSO for the Optimal Coordination of Directional Overcurrent Protection Relays of IEEE Bus System

The use of a directional overcurrent protection relay (DOPR) to protect an electrical power system is a crucial instrument for keeping the system dynamic and avoiding undue interruption. The coordination of a DOPR’s primary and backup relays is modelled as a highly constrained optimization problem. The goal is to determine an ideal value that will reduce the overall working time of all primary relays. The coordination is accomplished by the use of particle swarm optimization hybridization (HPSO). Comprehensive simulation experiments are carried out to evaluate the efficacy of the proposed HPSO by employing the time multiplier setting (TMS) and plug setting (PS) as an optimization variable and constant, respectively. The HPSO has been examined satisfactorily utilizing certain IEEE benchmark test systems (9-bus and 14-bus). The outcomes are contrasted with earlier heuristics and evolutionary approaches. Based on the acquired findings, it is clear that the obtained results exceed the other conventional and state of the art procedures in terms of total DOPR operation and the computing time necessary to achieve the global optimal solution