Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental Sound Extraction Using Onomatopoeic Words

An onomatopoeic word, which is a character sequence that phonetically imitates a sound, is effective in expressing characteristics of sound such as duration, pitch, and timbre. We propose an environmental-sound-extraction method using onomatopoeic words to specify the target sound to be extracted. By this method, we estimate a time-frequency mask from an input mixture spectrogram and an onomatopoeic word using a U-Net architecture, then extract the corresponding target sound by masking the spectrogram. Experimental results indicate that the proposed method can extract only the target sound corresponding to the onomatopoeic word and performs better than conventional methods that use sound-event classes to specify the target sound.
Hamilton-Jacobi equations on graphs with applications to semi-supervised learning and data depth

Shortest path graph distances are widely used in data science and machine learning, since they can approximate the underlying geodesic distance on the data manifold. However, the shortest path distance is highly sensitive to the addition of corrupted edges in the graph, either through noise or an adversarial perturbation. In this paper we study a family of Hamilton-Jacobi equations on graphs that we call the $p$-eikonal equation. We show that the $p$-eikonal equation with $p=1$ is a provably robust distance-type function on a graph, and the $p\to \infty$ limit recovers shortest path distances. While the $p$-eikonal equation does not correspond to a shortest-path graph distance, we nonetheless show that the continuum limit of the $p$-eikonal equation on a random geometric graph recovers a geodesic density weighted distance in the continuum. We consider applications of the $p$-eikonal equation to data depth and semi-supervised learning, and use the continuum limit to prove asymptotic consistency results for both applications. Finally, we show the results of experiments with data depth and semi-supervised learning on real image datasets, including MNIST, FashionMNIST and CIFAR-10, which show that the $p$-eikonal equation offers significantly better results compared to shortest path distances.
CHEX: Multiversion Replay with Ordered Checkpoints

In scientific computing and data science disciplines, it is often necessary to share application workflows and repeat results. Current tools containerize application workflows, and share the resulting container for repeating results. These tools, due to containerization, do improve sharing of results. However, they do not improve the efficiency of replay. In this paper, we present the multiversion replay problem, which arises when multiple versions of an application are containerized, and each version must be replayed to repeat results. To avoid executing each version separately, we develop CHEX , which checkpoints program state and determines when it is permissible to reuse program state across versions. It does so using system call-based execution lineage. Our capability to identify common computations across versions enables us to consider optimizing replay using an in-memory cache, based on a checkpoint-restore-switch system. We show the multiversion replay problem is NP-hard, and propose efficient heuristics for it. CHEX reduces overall replay time by sharing common computations but avoids storing a large number of checkpoints. We demonstrate that CHEX maintains lightweight package sharing, and improves the total time of multiversion replay by 50% on average.
Pacer: Comprehensive Network Side-Channel Mitigation in the Cloud

Network side channels (NSCs) leak secrets through packet timing and packet sizes. They are of particular concern in public IaaS Clouds, where any tenant may be able to colocate and indirectly observe a victim's traffic shape. We present Pacer, the first system that eliminates NSC leaks in public IaaS Clouds end-to-end. It builds on the principled technique of shaping guest traffic outside the guest to make the traffic shape independent of secrets by design. However, Pacer also addresses important concerns that have not been considered in prior work -- it prevents internal side-channel leaks from affecting reshaped traffic, and it respects network flow control, congestion control and loss recovery signals. Pacer is implemented as a paravirtualizing extension to the host hypervisor, requiring modest changes to the hypervisor and the guest kernel, and only optional, minimal changes to applications. We present Pacer's key abstraction of a cloaked tunnel, describe its design and implementation, prove the security of important design aspects through a formal model, and show through an experimental evaluation that Pacer imposes moderate overheads on bandwidth, client latency, and server throughput, while thwarting attacks based on state-of-the-art CNN classifiers.
Preservation of the Global Knowledge by Not-True Distillation in Federated Learning

In federated learning, a strong global model is collaboratively learned by aggregating clients' locally trained models. Although this precludes the need to access clients' data directly, the global model's convergence often suffers from data heterogeneity. This study starts from an analogy to continual learning and suggests that forgetting could be the bottleneck of federated learning. We observe that the global model forgets the knowledge from previous rounds, and the local training induces forgetting the knowledge outside of the local distribution. Based on our findings, we hypothesize that tackling down forgetting will relieve the data heterogeneity problem. To this end, we propose a novel and effective algorithm, Federated Not-True Distillation (FedNTD), which preserves the global perspective on locally available data only for the not-true classes. In the experiments, FedNTD shows state-of-the-art performance on various setups without compromising data privacy or incurring additional communication costs.
Artemisia vulgaris essential oil nanoemulsions (AVEO-NE), a novel anti-angiogenic agent and safe apoptosis inducer in MCF-7 human cancer cells

Abstract Artemisia vulgaris essential oil (AVEO) is known as a therapeutic agent. Several types of investigation have demonstrated its cytotoxic impact on human cancer cells. In the current study, AVEO nanoemulsion (AVEO-NE) was synthesized using an ultrasound-based emulsification method and its cytotoxic, apoptotic, antioxidant, and anti-angiogenic properties were evaluated for the MCF-7 cancer cell line by measuring the cell’s gene expression profile and performing MTT. Finally, the anti-angiogenic activity of AVEO-NE was verified by applying CAM assay analysis. The results showed that AVEO-NE exhibited significant cell-selective cytotoxic, apoptotic, and antioxidant activities by up-regulating Cas-9, CAT, and SOD gene expression. Moreover, the AVEO-NE meaningfully suppressed angiogenesis in MCF-7 cancer cells by down-regulating VEGF gene expression. Finally, the decreased number and length of chick embryo chorioallantoic membrane (CAM) blood vessels verified AVEO-NE’s anti-angiogenic activity. Therefore, AVEO-NE can potentially be employed as a safe cell-dependent anti-breast cancer drug delivery system.
Optimization of conditions for conjugation of outer membrane vesicles of Salmonella Typhimurium with oral delivery systems using response surface method

Background Outer membrane vesicles (OMVs) released from Salmonella Typhimurium can become the effective vaccine candidate. For efficient delivery through oral route, the OMVs are conjugated with some delivery systems. The current study was aimed at optimization of conditions required for conjugation of OMVs with nano- or microparticles for maximum entrapment of OMV in terms of protein concentration. Methods The OMVs of Salmonella Typhimurium were conjugated under three optimum conditions of pH, temperature and ratio (nanoparticles or microparticles: OMVs) predicted by response surface method. The efficiency of conjugation was determined by entrapment of OMVs in nano/microparticles. Result The pH and temperature were not influential conditions in case of conjugation of OMVs with chitosan nanoparticles (Ch-NP) and poly-lactide co-glycolide microparticles (PLG-MP) while they had influence in case of poly(anhydride) nanoparticles. In case of Ch-NP and PLG-MP, the optimum ratio for maximum entrapment was found to be 1:10 and 1:9 respectively. The optimum pH and temperature was found to be 7 and 24°C respectively for conjugation of poly(anhydride) nanoparticles. The optimized conditions did not alter the protein profile and immunogenic potential of conjugated vaccines.
Pushing the limits of HiFi assemblies reveals centromere diversity between two Arabidopsis thaliana genomes

Although long-read sequencing can often enable chromosome-level reconstruction of genomes, it is still unclear how one can routinely obtain gapless assemblies. In the model plant Arabidopsis thaliana, other than the reference accession Col-0, all other accessions de novo assembled with long-reads until now have used PacBio continuous long reads (CLR). Although these assemblies sometimes achieved chromosome-arm level contigs, they inevitably broke near the centromeres, excluding megabases of DNA from analysis in pan-genome projects. Since PacBio high-fidelity (HiFi) reads circumvent the high error rate of CLR technologies, albeit at the expense of read length, we compared a CLR assembly of accession Ey15-2 to HiFi assemblies of the same sample performed by five different assemblers starting from subsampled data sets, allowing us to evaluate the impact of coverage and read length. We found that centromeres and rDNA clusters are responsible for 71% of contig breaks in the CLR scaffolds, while relatively short stretches of GA/TC repeats are at the core of >85% of the unfilled gaps in our best HiFi assemblies. Since the HiFi technology consistently enabled us to reconstruct gapless centromeres and 5S rDNA clusters, we demonstrate the value of the approach by comparing these previously inaccessible regions of the genome between two A. thaliana accessions.
Directed differentiation of EA/TEF patient-derived induced pluripotent stem cells into esophageal epithelial organoids reveal SOX2 dysregulation at the anterior foregut stage

A series of well-regulated cellular and molecular events result in the compartmentalization of the anterior foregut into the esophagus and trachea. Disruption of the compartmentalization process leads to esophageal atresia/tracheoesophageal fistula (EA/TEF). Therefore, the objective is to differentiate pluripotent stem cells (PSCs), namely, embryonic stem cells and iPSCs from healthy individuals and iPSCs from EA/TEF type C patients, into mature 3-dimensional esophageal organoids expressing Involucrin, Keratin-4, -13, and p63. CXCR4, SOX17, and GATA4 expression was similar in both patient and healthy endodermal cells. Key transcription factor SOX2 was significantly lower in patient-derived anterior foregut. RNA sequencing revealed critical genes GSTM1 and RAB37 to be significantly lower in patient-derived anterior foregut. Furthermore, we observed an abnormal expression of NKX2.1 in the patient-derived mature esophageal organoids. We therefore hypothesize that a transient dysregulation of SOX2 and the abnormal expression of NKX2.1 in patient-derived cells could be responsible for the abnormal foregut compartmentalization.
Monoacylglycerol O-acyltransferase 1 is required for adipocyte differentiation in vitro but does not affect adiposity in mice

Objective Monoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme that converts monoacylglycerol to diacylglycerol, is highly expressed in adipocytes and may regulate lipolysis by re-esterifying fatty acids released during times when lipolytic rates are low. However, the role of Mogat1 in regulating adipocyte fat storage during differentiation and diet-induced obesity is relatively understudied. Methods Here we generated adipocyte-specific Mogat1 knockout mice and subjected them to a high-fat diet to determine the effects of Mogat1 deficiency on diet-induced obesity. We also used Mogat1 floxed mice to develop preadipocyte cell lines wherein Mogat1 could be conditionally knocked out to study adipocyte differentiation in vitro. Results In preadipocytes, we found that Mogat1 knockout at the onset of preadipocyte differentiation prevented the accumulation of glycerolipids and reduced the differentiation capacity of preadipocytes. However, the loss of adipocyte Mogat1 did not affect weight gain or fat mass induced by high-fat diet in mice. Furthermore, loss of Mogat1 in adipocytes did not affect plasma lipid or glucose concentrations or insulin tolerance. Conclusions These data suggest Mogat1 may play a role in adipocyte differentiation in vitro but not adipose tissue expansion in response to nutrient overload in mice. STUDY IMPORTANCE What is already known? Adipose tissue expansion through adipocyte precursor cell differentiation is critical for proper lipid storage during nutrient overload. Monoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme, is highly induced during adipocyte differentiation of human and mouse precursor cells and is reduced in patients with obesity and metabolic dysfunction. What does this study add? Mogat1 deletion during early adipocyte differentiation reduces differentiation capacity, adipogenic gene expression and lowers glycerolipid content of differentiated adipocytes. Adipocyte Mogat1 expression is dispensable for adiposity and metabolic outcomes high-fat fed mice and suggests compensation from other glycerolipid synthesis enzymes. How might these results change the direction of research? Understanding the molecular mechanisms of glycerolipid metabolism healthy adipose tissue expansion.
Centriole growth is not limited by a finite pool of components, but is limited by the Cdk1/Cyclin-dependent phosphorylation of Ana2/STIL

Centrioles duplicate once per cell cycle but it is unclear how daughter centrioles assemble at the right time and place and grow to the right size. Here we show that in early Drosophila embryos the cytoplasmic concentrations of the key centriole assembly proteins Asl, Plk4, Ana2, Sas-6 and Sas-4 are low, but remain constant throughout the assembly process— indicating that none of them are limiting for centriole assembly. The cytoplasmic diffusion rate of Ana2/STIL, however, increased significantly towards the end of S-phase as Cdk/Cyclin activity in the embryo increased. A mutant form of Ana2 that cannot be phosphorylated by Cdk/Cyclins did not exhibit the diffusion rate change, and allowed daughter centrioles to grow for an extended period. Thus, the Cdk/Cyclin-dependent phosphorylation of cytoplasmic Ana2 seems to reduce the efficiency of daughter centriole assembly towards the end of S-phase. This helps to ensure that daughter centrioles stop growing at the correct time, and presumably also helps to explain why centrioles cannot duplicate during mitosis when Cdk/Cyclin activity is high.
NaCl Triggers the Sessile-to-Motile Transition of Bacillus subtilis

Various chemical cues are known to alter the motile and sessile states of bacteria differentially and, in turn, the formation of biofilms. However, the underlying mechanisms at the cellular and molecular level remain less understood, which severely limits our ability to control biofilms. Here, we systematically studied the effects of NaCl on the dynamics of biofilm formation across various length scales and the associated changes in the regulation of gene expression in an undomesticated natural isolate of Bacillus subtilis. Interestingly, NaCl induced significant changes in the architecture of pellicles and yielded systematic increase in lateral expansion rates of biofilms when grown on an agar surface. At the microscopic level, both in the presence and absence of NaCl, bacteria displayed super-diffusive motion at times lesser than a second. However, at larger delay times, we observed an intriguing NaCl-induced transition from sub-diffusion behavior of individual bacterial cells to rapid diffusion behavior. In addition, NaCl reduced the dynamical heterogeneity of the bacterial cells within the biofilm. The reduced heterogeneity and the increased flagellation in a subpopulation of cells in the presence of NaCl corroborates well with the observed higher motility of the cells. Further, the cellular uptake of NaCl resulted in the downregulation of several genes underlying the formation of biofilms, revealing the role of chemical cues like NaCl in controlling the gene regulatory circuit underlying the sessile to motile transition. Our study opens a new avenue to decipher the competitive advantage provided to the subcellular populations by NaCl due to lifestyle switch in Bacillus subtilis.
Prolactin-induced AMPK stabilizes alveologenesis and lactogenesis through regulation of STAT5 signaling

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis at cellular and organismal levels. It has been shown to affect several steps of breast cancer progression in a context-dependent manner. However, its role in normal mammary gland development and physiology remains ill-explored. Here, we show that AMPK expression and activity increased within murine mammary epithelia from puberty to pregnancy with highest levels during lactation, and then declined during involution. In ex vivo cultures of mammary epithelial cells (MECs) in organotypic scaffolds, treatment with lactogenic hormone prolactin (PRL) enhanced AMPK expression and activity. To understand the role of AMPK on mammary morphogenesis in vivo, we generated mice with conditional knockout of AMPKα isoforms α1 and α2 (AMPKα KO) in MECs. AMPKα KO mammary glands showed accelerated alveolar development with increased epithelial content of both luminal and myoepithelial lineages, suggestive of hyperproliferation. AMPKα KO mice also showed elevated beta-casein expression during pregnancy and lactation. These observations were phenocopied upon treatment of ex vivo cultivated wild-type MECs with a cognate AMPK inhibitor. AMPKα null MECs showed increased phosphorylated STAT5 which is known to drive alveologenesis downstream of prolactin signaling. Our study identifies a novel interplay between AMPK and PRL-STAT5 signaling that determines mammary alveologenesis and differentiation.
Sympathetic blockage attenuates fasting-induced hepatic steatosis

Background and Aim Although it is clear that the central nervous system coordinates whole-body metabolism, the neural mechanism for hepatic steatosis remains unclear. This study is aimed to explore the neural mechanism of fasting-induced hepatic steatosis. Methods Mice were pretreated with 6-hydroxydopamine to block sympathetic nerve activity before fasting, and explored the potential effects of chemical sympathectomy on fasting-induced hepatic steatosis and transcriptional changes. Results Prolonged fasting led to obvious hepatic steatosis, low core temperature, and similar effects to cold-induced white adipose lipolysis. The alterations in hepatic mRNA expression revealed that the hepatic lipid accumulation did not result from the increase of hepatic lipogenesis or the decrease of fatty acid oxidation but from the enhanced fatty acid uptake as indicated by the upregulation of CD36. Blockage of the sympathetic nervous system via chemical sympathectomy attenuated fasting-induced hepatic steatosis and suppressed CD36 upregulation in the liver, but did not obviously alter the expression of genes associated with lipogenesis or fatty acid oxidation. Conclusions These findings indicate that the sympathetic nervous system orchestrates the mechanism for fasting-induced hepatic steatosis via modulating CD36 expression and adipose fat trafficking into the liver, which provides clues to reveal new targets for fatty liver diseases. HIGHLIGHTS Prolonged fasting causes obvious hepatic steatosis Sympathectomy attenuates fasting-induced hepatic steatosis Sympathectomy attenuates steatosis via suppressing CD36 upregulation IN BRIEF Prolonged fasting contributes to sympathetic hyperactivity, but its role in the pathogenesis of hepatic steatosis remains unclear. Here, we found prolonged fasting led to obvious hepatic steatosis, low core temperature, and subsequent sympathetic stimulation that promoted white adipose lipolysis, hepatic upregulation of CD36, and adipose fat trafficking into the liver.
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus. Here, Farley et al. perform untargeted lipidomics to assess how SARS-CoV-2 rewires host lipid metabolism. SARS-CoV-2 viral proteins specifically induce lipid droplet formation and dramatically change lipid metabolism to support infection; interfering with lipid metabolism using small molecule inhibitors decreases virus production.
A Count Model Analysis of Traded Contracts in the JEPX Forward Market

It is desirable that the number of forward contracts traded on the Japan Electric Power Exchange increase. However, few studies have clarified what factors have contributed to impacting the number of forward contracts traded. In this study, the authors analyzed the number of forward contracts using four count regression models. The negative binomial regression model and the zero‐inflated models were better able to express the expected counts, by incorporating the overdispersion and excess zeros present in the observed data. Among others, the spot market can carry positive influences on the expected counts, by about 12% for a 1 yen/kWh increase in price, and by about 27% for a 0.1%‐point increase in volumes. The zero‐inflated models revealed that as many as three‐fourth of the entire forward products have a high probability of zero counts, while the remaining one‐fourth may see an increased number of counts as the spot market price and/or the spot volume becomes higher.
Birth order differences in education originate in postnatal environments

Siblings share many environments and much of their genetics. Yet, siblings turn out different. Intelligence and education are influenced by birth order, with earlier-born siblings outperforming later-borns. We investigate whether birth order differences in education are caused by biological differences present at birth, that is, genetic differences or in-utero differences. Using family data that spans two generations, combining registry, survey, and genotype information, this study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). We show that there are no genetic differences by birth order as captured by polygenic scores (PGSs) for educational attainment. Furthermore, we show that earlier-born have lower birth weight than later-born, indicating worse uterine environments. Educational outcomes are still higher for earlier-born children when we adjust for PGSs and in utero variables, indicating that birth order differences arise post-natally. Finally, we consider potential environmental influences, such as differences according to maternal age, parental educational attainment, and sibling genetic nurture. We show that birth order differences are not biological in origin, but pinning down their specific causes remains elusive.