Miracle-dz/UniFAR-FTUs huggingface dataset:
Unsupervised Singing Voice Separation Using Gammatone Auditory Filterbank and Constraint Robust Principal Component Analysis

This paper presents an unsupervised singing voice separation algorithm which using an extension of robust principal component analysis (RPCA) with rank-1 constraint (CRPCA) based on gammatone auditory filterbank on cochleagram. Unlike the conventional algorithms that focus on spectrogram analysis or its variants, we develop an extension of RPCA on cochleagram using an alternative time-frequency representation based on gammatone auditory filterbank. We also apply time-frequency masking to improve the results of separated low-rank and sparse matrices by using CRPCA method. Evaluation results demonstrate that the proposed algorithm can achieve better separation performance on MIR-IK dataset.
Measuring Commuter Student Support and Success through Academic

This Research Work In Progress Paper presents an initiative to understand engineering commuter student support and success using a validated instrument to measure academic integration. There are many calls to increase the number of engineering students who graduate with a degree; however, there is little work in uncovering the support mechanisms that work for engineering commuter students. Therefore, this WIP paper looks to start to build a case for studying engineering commuter students in more detail by first looking at differences between how residential and commuter students integrate academically. Academic integration is defined by how students are able to access, effectively interact with, and are supported by engineering faculty and staff. Academic integration is an important construct, which contributes to a student's persistence and ultimate graduation. However, it is unknown if there are differences between the way residential and commuter engineering students access the support structures provided for them. Therefore, this paper answers one research question: How do residential and commuter engineering students differ in regards to academic integration in a first-year engineering context? During the spring semester of 2018, 175 first-year engineering students participated in a questionnaire with multiple items, one of which was the construct of academic integration. I measure academic integration using the engineering student integration instrument which consists of five Likert-type questions on a six-point scale ranging from 'strongly disagree' to 'strongly agree. ' Results show differences between residential and commuter engineering students with regards to academic integration. Measures of reliability and validity show the construct is acceptable.
Protective effects of pentoxifylline in pulmonary inflammation are adenosine receptor A2A dependent

Pentoxifylline (PTX) has been shown to exert anti‐inflammatory effects in experimental acute lung injury. However, results in humans were controversial. Recent in vitro studies suggested that the adenosine receptor A2A may be required for PTX to be effective. Therefore, we studied the association between A2A and PTX in a murine model of LPS‐induced pulmonary inflammation. PTX treatment (10 mg/kg) reduced cellular influx (by 40%), microvascular permeability (30%), and the release of chemotactic cytokines into the alveolar space (TNF‐α 60%, IL‐6 60%, and CXCL2/3 53%, respectively). These protective effects were abolished completely in A2A–/– mice and in wild‐type mice that had been treated with the selective A2A antagonist (1 mg/kg), but effects were not different in mice with altered adenosine levels. In vitro transmigration assays revealed a pivotal role of the endothelium in PTX‐mediated PMN migration, with a reduction of 50% (2 mM PTX). This effect was also A2A dependent. Further, oxidative burst of human PMNs was A2A‐dependently reduced by 53% after PTX treatment. In summary, PTX exhibits its anti‐inflammatory effects in LPS‐induced lung injury through an A2A‐dependent pathway. These results will help to better understand previous conflicting data on PTX in inflammation and will direct further studies to consider the predominant role of A2A. —Konrad, F. M. , Neudeck, G. , Vollmer, I. , Ngamsri, K. C. , Thiel, M. , Reutershan, J., Protective effects of pentoxifylline in pulmonary inflammation are adenosine receptor A2A dependent. FASEB J. 27, 3524–3535 (2013). www.fasebj. org
Transcutaneous Vagus Nerve Stimulation (tVNS) and the Dynamics of Visual Bistable Perception

Transcutaneous vagus nerve stimulation (tVNS) is widely used for clinical applications, but its mechanism of action is poorly understood. One candidate pathway that might mediate the effects of tVNS is an increase in GABAergic neurotransmission. In this study, we investigated the effect of tVNS on visual bistable perception, which is highly coupled to GABA. Participants were 34 healthy young subjects. We used a static (Necker cube) and a dynamic (structure from motion) bistable perception task. Each subject underwent tVNS as well as sham (placebo) stimulation for ∼45 min. We analyze effects of tVNS on percept durations by means of Bayesian multilevel regression. We find no evidence for a modulation of bistable perception dynamics through tVNS in either task, but the analyses do not ultimately confirm the null hypothesis either. We discuss different possible implications of our finding and propose that GABAergic effects of tVNS should be further investigated using more direct measures of GABA concentration, and, more generally, that a better understanding of the mechanisms of action of vagus nerve stimulation is needed. Finally, we discuss limitations of our study design, data analysis, and conclusions.
Music and Visual Art Training Modulate Brain Activity in Older Adults

Cognitive decline is an unavoidable aspect of aging that impacts important behavioral and cognitive skills. Training programs can improve cognition, yet precise characterization of the psychological and neural underpinnings supporting different training programs is lacking. Here, we assessed the effect and maintenance (3-month follow-up) of 3-month music and visual art training programs on neuroelectric brain activity in older adults using a partially randomized intervention design. During the pre-, post-, and follow-up test sessions, participants completed a brief neuropsychological assessment. High-density EEG was measured while participants were presented with auditory oddball paradigms (piano tones, vowels) and during a visual GoNoGo task. Neither training program significantly impacted psychometric measures, compared to a non-active control group. However, participants enrolled in the music and visual art training programs showed enhancement of auditory evoked responses to piano tones that persisted for up to 3 months after training ended, suggesting robust and long-lasting neuroplastic effects. Both music and visual art training also modulated visual processing during the GoNoGo task, although these training effects were relatively short-lived and disappeared by the 3-month follow-up. Notably, participants enrolled in the visual art training showed greater changes in visual evoked response (i.e., N1 wave) amplitude distribution than those from the music or control group. Conversely, those enrolled in music showed greater response associated with inhibitory control over the right frontal scalp areas than those in the visual art group. Our findings reveal a causal relationship between art training (music and visual art) and neuroplastic changes in sensory systems, with some of the neuroplastic changes being specific to the training regimen.
Phylogeography of Invasive Rats in New Zealand

Two species of invasive rats (Rattus norvegicus and R. rattus) arrived in New Zealand with Europeans in the mid to late 18th and 19th century respectively. They rapidly spread across the main islands of New Zealand and its offshore islands, displacing the historically introduced R. exulans. Today both species are widespread although the distribution of the sub-dominant R. norvegicus is patchy. Tissue samples were obtained from 425 R. rattus and 130 R. norvegicus across the New Zealand archipelago and neighbouring islands. We sequenced a standard 545 base pair section of the mitochondrial D-loop in order to construct a modern phylogeography of the two species and to make inference on historical invasion pathways and spread across the country. We found limited diversity in R. norvegicus haplotypes, with two widespread haplotypes across New Zealand and its offshore islands most likely corresponding to two independent invasions, potentially with English and Chinese origins. In contrast we found widespread diversity in R. rattus haplotypes across New Zealand and its offshore islands, most likely corresponding to at least four independent invasions to the main North and South Islands, Great Barrier Island archipelago, and Stewart Island archipelago. The most common R. rattus haplogroup was found throughout New Zealand and many of its offshore islands, as well as neighbouring islands in the Tasman Sea, and has been documented elsewhere across the Pacific, but with European origins. We also found both geographic partitioning and secondary invasions of haplotypes within the main North and South Island. In addition to distinct haplogroups differing by over three base pairs, which exhibit geographical partitioning suggestive of independent invasion events, for both species we also found instances of single base-pair differences within localities, elevating haplotype diversity. The geographical distribution of pelage colour morphs also correlates with haplotype distribution, lending further support to the hypothesis and role of independent invasion events.
Brain Differences Between Men and Women: Evidence From Deep Learning

Do men and women have different brains? Previous neuroimage studies sought to answer this question based on morphological difference between specific brain regions, reporting unfortunately conflicting results. In the present study, we aim to use a deep learning technique to address this challenge based on a large open-access, diffusion MRI database recorded from 1,065 young healthy subjects, including 490 men and 575 women healthy subjects. Different from commonly used 2D Convolutional Neural Network (CNN), we proposed a 3D CNN method with a newly designed structure including three hidden layers in cascade with a linear layer and a terminal Softmax layer. The proposed 3D CNN was applied to the maps of factional anisotropy (FA) in the whole-brain as well as specific brain regions. The entropy measure was applied to the lowest-level image features extracted from the first hidden layer to examine the difference of brain structure complexity between men and women. The obtained results compared with the results from using the Support Vector Machine (SVM) and Tract-Based Spatial Statistics (TBSS). The proposed 3D CNN yielded a better classification result (93.3%) than the SVM (78.2%) on the whole-brain FA images, indicating gender-related differences likely exist in the whole-brain range. Moreover, high classification accuracies are also shown in several specific brain regions including the left precuneus, the left postcentral gyrus, the left cingulate gyrus, the right orbital gyrus of frontal lobe, and the left occipital thalamus in the gray matter, and middle cerebellum peduncle, genu of corpus callosum, the right anterior corona radiata, the right superior corona radiata and the left anterior limb of internal capsule in the while matter. This study provides a new insight into the structure difference between men and women, which highlights the importance of considering sex as a biological variable in brain research.
Molecular Mechanisms of Synaptic Dysregulation in Fragile X Syndrome and Autism Spectrum Disorders

Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment. FXS patient exhibit a high comorbidity rate with autism spectrum disorders (ASDs). This makes FXS a model disease for understanding how synaptic dysregulation alters neuronal excitability, learning and memory, social behavior, and more. Since 1991, with the discovery of fragile X mental retardation 1 (FMR1) as the sole gene that is mutated in FXS, thousands of studies into the function of the gene and its encoded protein FMR1 protein (FMRP), have been conducted, yielding important information regarding the pathophysiology of the disease, as well as insight into basic synaptic mechanisms that control neuronal networking and circuitry. Among the most important, are molecular mechanisms directly involved in plasticity, including glutamate and γ-aminobutyric acid (GABA) receptors, which can control synaptic transmission and signal transduction, including short- and long-term plasticity. More recently, several novel mechanisms involving growth factors, enzymatic cascades and transcription factors (TFs), have been proposed to have the potential of explaining some of the synaptic dysregulation in FXS. In this review article, I summarize the main mechanisms proposed to underlie synaptic disruption in FXS and ASDs. I focus on studies conducted on the Fmr1 knock-out (KO) mouse model and on FXS-human pluripotent stem cells (hPSCs), emphasizing the differences and even contradictions between mouse and human, whenever possible. As FXS and ASDs are both neurodevelopmental disorders that follow a specific time-course of disease progression, I highlight those studies focusing on the differential developmental regulation of synaptic abnormalities in these diseases.
Nutrient and Stress Sensing in Pathogenic Yeasts

More than 1.5 million fungal species are estimated to live in vastly different environmental niches. Despite each unique host environment, fungal cells sense certain fundamentally conserved elements, such as nutrients, pheromones and stress, for adaptation to their niches. Sensing these extracellular signals is critical for pathogens to adapt to the hostile host environment and cause disease. Hence, dissecting the complex extracellular signal-sensing mechanisms that aid in this is pivotal and may facilitate the development of new therapeutic approaches to control fungal infections. In this review, we summarize the current knowledge on how two important pathogenic yeasts, Candida albicans and Cryptococcus neoformans, sense nutrient availability, such as carbon sources, amino acids, and ammonium, and different stress signals to regulate their morphogenesis and pathogenicity in comparison with the non-pathogenic model yeast Saccharomyces cerevisiae. The molecular interactions between extracellular signals and their respective sensory systems are described in detail. The potential implication of analyzing nutrient and stress-sensing systems in antifungal drug development is also discussed.
An interplay between Centrin2 and Centrin4 on the bi‐lobed structure in Trypanosoma brucei

Centrins are conserved calcium‐binding proteins important for various regulatory functions. In procyclic Trypanosoma brucei, TbCentrin2 and TbCentrin4 have distinct effects on cell division but both localize to the basal bodies that seed the flagellum, and a bi‐lobed structure important for organelle duplication and cell division. Here we show that TbCentrin2 and TbCentrin4 both bind to the basal bodies and bi‐lobed structure through the conserved C‐terminal domain. Molecular genetic manipulation of TbCentrin4 levels greatly affects TbCentrin2 association with the bi‐lobed structure. Using established synchronization methods, TbCentrin2 expression level is shown to be relatively constant throughout the cell cycle while TbCentrin4 level fluctuates, decreasing most during early S‐phase when the bi‐lobe undergoes duplication. These results thus suggest a co‐ordinated action between these two centrin proteins, where the cell cycle‐dependent TbCentrin4 expression could regulate the abundance of TbCentrin2 on the bi‐lobed structure.
Paradoxical Effect of Mitochondrial Respiratory Chain Impairment on Insulin Signaling and Glucose Transport in Adipose Cells*

Adipocyte function is crucial for the control of whole body energy homeostasis. Pathway analysis of differentiating 3T3-L1 adipocytes reveals that major metabolic pathways induced during differentiation involve mitochondrial function. However, it is not clear why differentiated white adipocytes require enhanced respiratory chain activity relative to pre-adipocytes. To address this question, we used small interference RNA to interfere with the induction of the transcription factor Tfam, which is highly induced between days 2 and 4 of differentiation and is crucial for replication of mitochondrial DNA. Interference with Tfam resulted in cells with decreased respiratory chain capacity, reflected by decreased basal oxygen consumption, and decreased mitochondrial ATP synthesis, but no difference in many other adipocyte functions or expression levels of adipose-specific genes. However, insulin-stimulated GLUT4 translocation to the cell surface and subsequent glucose transport are impaired in Tfam knockdown cells. Paradoxically, insulin-stimulated Akt phosphorylation is significantly enhanced in these cells. These studies reveal independent links between mitochondrial function, insulin signaling, and glucose transport, in which impaired respiratory chain activity enhances insulin signaling to Akt phosphorylation, but impairs GLUT4 translocation. These results indicate that mitochondrial respiratory chain dysfunction in adipocytes can cause impaired insulin responsiveness of GLUT4 translocation by a mechanism downstream of the Akt protein kinase.
TcdB from hypervirulent Clostridium difficile exhibits increased efficiency of autoprocessing

TcdB, an intracellular bacterial toxin that inactivates small GTPases, is a major Clostridium difficile virulence factor. Recent studies have found that TcdB produced by emerging/hypervirulent strains of C. difficile is more potent than TcdB from historical strains, and in the current work, studies were performed to investigate the underlying mechanisms for this change in TcdB toxicity. Using a series of biochemical analyses we found that TcdB from a hypervirulent strain (TcdBHV) was more efficient at autoprocessing than TcdB from a historical strain (TcdBHIST). TcdBHV and TcdBHIST were activated by similar concentrations of IP6; however, the overall efficiency of processing was 20% higher for TcdBHV. Using an activity‐based fluorescent probe (AWP19) an intermediate, activated but uncleaved, form of TcdBHIST was identified, while only a processed form of TcdBHV could be detected under the same conditions. Using a much higher concentration (200 µM) of the probe revealed an activated uncleaved form of TcdBHV, indicating a preferential and more efficient engagement of intramolecular substrate than TcdBHIST. Furthermore, a peptide‐based inhibitor (Ac‐GSL‐AOMK) was found to block the cytotoxicity of TcdBHIST at a lower concentration than required to inhibit TcdBHV. These findings suggest that TcdBHV may cause increased cytotoxicity due to more efficient autoprocessing.
Phosphoenolpyruvate phosphotransferase system regulates detection and processing of the quorum sensing signal autoinducer‐2

Autoinducer‐2 (AI‐2) a signal produced by a range of phylogenetically distant microorganisms, enables inter‐species cell–cell communication and regulates many bacterial phenotypes. Certain bacteria can interfere with AI‐2‐regulated behaviours of neighbouring species by internalizing AI‐2 using the Lsr transport system (encoded by the lsr operon). AI‐2 imported by the Lsr is phosphorylated by the LsrK kinase and AI‐2‐phosphate is the inducer of the lsr operon. Here we show that in Escherichia coli the phosphoenolpyruvate phosphotransferase system (PTS) is required for Lsr activation and is essential for AI‐2 internalization. Although the phosphorylation state of Enzyme I of PTS is important for this regulation, LsrK is necessary for the phosphorylation of AI‐2, indicating that AI‐2 is not phosphorylated by PTS. Our results suggest that AI‐2 internalization is initiated by a PTS‐dependent mechanism, which provides sufficient intracellular AI‐2 to relieve repression of the lsr operon and, thus induce depletion of AI‐2 from the extracellular environment. The fact that AI‐2 internalization is not only controlled by the community‐dependent accumulation of AI‐2, but also depends on the phosphorylation state of PTS suggests that E. coli can integrate information on the availability of substrates with external communal information to control quorum sensing and its interference.
Multiple ABC transporters are involved in the acquisition of petrobactin in Bacillus anthracis

In Bacillus anthracis the siderophore petrobactin is vital for iron acquisition and virulence. The petrobactin‐binding receptor FpuA is required for these processes. Here additional components of petrobactin reacquisition are described. To identify these proteins, mutants of candidate permease and ATPase genes were generated allowing for characterization of multiple petrobactin ATP‐binding cassette (ABC)‐import systems. Either of two distinct permeases, FpuB or FatCD, is required for iron acquisition and play redundant roles in petrobactin transport. A mutant strain lacking both permeases, ΔfpuBΔfatCD, was incapable of using petrobactin as an iron source and exhibited attenuated virulence in a murine model of inhalational anthrax infection. ATPase mutants were generated in either of the permease mutant backgrounds to identify the ATPase(s) interacting with each individual permease channel. Mutants lacking the FpuB permease and FatE ATPase (ΔfpuBΔfatE) and a mutant lacking the distinct ATPases FpuC and FpuD generated in the ΔfatCD background (ΔfatCDΔfpuCΔfpuD) displayed phenotypic characteristics of a mutant deficient in petrobactin import. A mutant lacking all three of the identified ATPases (ΔfatEΔfpuCΔfpuD) exhibited the same growth defect in iron‐depleted conditions. Taken together, these results provide the first description of the permease and ATPase proteins required for the import of petrobactin in B. anthracis.
Large‐scale study of the interactions between proteins involved in type IV pilus biology in Neisseria meningitidis: characterization of a subcomplex involved in pilus assembly

The functionally versatile type IV pili (Tfp) are one of the most widespread virulence factors in bacteria. However, despite generating much research interest for decades, the molecular mechanisms underpinning the various aspects of Tfp biology remain poorly understood, mainly because of the complexity of the system. In the human pathogen Neisseria meningitidis for example, 23 proteins are dedicated to Tfp biology, 15 of which are essential for pilus biogenesis. One of the important gaps in our knowledge concerns the topology of this multiprotein machinery. Here we have used a bacterial two‐hybrid system to identify and quantify the interactions between 11 Pil proteins from N. meningitidis. We identified 20 different binary interactions, many of which are novel. This represents the most complex interaction network between Pil proteins reported to date and indicates, among other things, that PilE, PilM, PilN and PilO, which are involved in pilus assembly, indeed interact. We focused our efforts on this subset of proteins and used a battery of assays to determine the membrane topology of PilN and PilO, map the interaction domains between PilE, PilM, PilN and PilO, and show that a widely conserved N‐terminal motif in PilN is essential for both PilM–PilN interactions and pilus assembly. Finally, we show that PilP (another protein involved in pilus assembly) forms a complex with PilM, PilN and PilO. Taken together, these findings have numerous implications for understanding Tfp biology and provide a useful blueprint for future studies.