Variational Autoencoders for chord sequence generation conditioned on Western harmonic music complexity

In recent years, the adoption of deep learning techniques has allowed to obtain major breakthroughs in the automatic music generation research field, sparking a renewed interest in generative music. A great deal of work has focused on the possibility of conditioning the generation process in order to be able to create music according to human-understandable parameters. In this paper, we propose a technique for generating chord progressions conditioned on harmonic complexity, as grounded in the Western music theory. More specifically, we consider a pre-existing dataset annotated with the related complexity values and we train two variations of Variational Autoencoders (VAE), namely a Conditional-VAE (CVAE) and a Regressor-based VAE (RVAE), in order to condition the latent space depending on the complexity. Through a listening test, we analyze the effectiveness of the proposed techniques

Room Transfer Function Reconstruction Using Complex-valued Neural Networks and Irregularly Distributed Microphones

Reconstructing the room transfer functions needed to calculate the complex sound field in a room has several important real-world applications. However, an unpractical number of microphones is often required. Recently, in addition to classical signal processing methods, deep learning techniques have been applied to reconstruct the room transfer function starting from a very limited set of measurements at scattered points in the room. In this paper, we employ complex-valued neural networks to estimate room transfer functions in the frequency range of the first room resonances, using a few irregularly distributed microphones. To the best of our knowledge, this is the first time that complex-valued neural networks are used to estimate room transfer functions. To analyze the benefits of applying complex-valued optimization to the considered task, we compare the proposed technique with a state-of-the-art kernel-based signal processing approach for sound field reconstruction, showing that the proposed technique exhibits relevant advantages in terms of phase accuracy and overall quality of the reconstructed sound field. For informative purposes, we also compare the model with a similarly-structured data-driven approach that, however, applies a real-valued neural network to reconstruct only the magnitude of the sound field

A Presence- and Performance-Driven Framework to Investigate Interactive Networked Music Learning Scenarios

Cooperative music making in networked environments has been subject of extensive research, scientific and artistic. Networked music performance (NMP) is attracting renewed interest thanks to the growing availability of effective technology and tools for computer-based communications, especially in the area of distance and blended learning applications. We propose a conceptual framework for NMP research and design in the context of classical chamber music practice and learning: presence-related constructs and objective quality metrics are used to problematize and systematize the many factors affecting the experience of studying and practicing music in a networked environment. To this end, a preliminary NMP experiment on the effect of latency on chamber music duos experience and quality of the performance is introduced. The degree of involvement, perceived coherence, and immersion of the NMP environment are here combined with measures on the networked performance, including tempo trends and misalignments from the shared score. Early results on the impact of temporal factors on NMP musical interaction are outlined, and their methodological implications for the design of pedagogical applications are discussed

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease

MOLECULAR CHARACTERISATION OF A NOVEL ADP-RIBOSYLATING PUTATIVE TOXIN OF NEISSERIA MENINGITIDIS

Molecular characterisation of a novel ADP-ribosylating putative toxin of Neisseria meningitidis VEGGIi D, *BALDUCCI E, MASIGNANI V, DI MARCELLO F, SAVINO S, ARICO’ B, COMANDUCCI M, PIZZA M, RAPPUOLI R IRIS, Chiron SpA, Via Fiorentina 1, 53100 Siena Italy; *Dipartimento Scienze morfologiche e Biochimiche Comparate, Università degli Studi di Camerino, Camerino, Italy Session: Surface antigens Introduction: By computer analysis on the Neisseria meningitidis (serogroup B, MC 58 strain) genome sequence, a protein with a feature similar to known bacterial ADP-ribosylating toxins (CT produced by Vibrio cholerae, LT by Escherichia coli and PT by Bordetella pertussis) has been identified. Enzymatic assay has shown that this protein (NM-ADPRT) possesses both NAD glycohydrolase and ADP-ribosyltransferase activity. In this study we describe the identification of the putative catalytic residues, their site-directed mutagenesis, and the resulting activity of the mutants. Materials and methods: The novel NM-ADPRT and the correspondent mutants, were expressed in E. coli as C-terminus His-tag protein fusions. Site-directed mutagenesis was performed using the Multi Site-Directed Mutagenesis Kit (QuikChange). Recombinant NM-ADPRT forms were purified from E. coli in their soluble form by metal chelate affinity chromatography. Both the wild-type and the mutants were assayed for their ADP-ribosylation and NAD-glycohydolase activites, using [adenine –U-14C] NAD and agmatine as ADP-ribose acceptor. Antisera against NM-ADPRT and the mutant derivatives were obtained by immunization of CD1 mice. 20μg of each recombinant protein were given i.p. together with CFA for the first dose and IFA for the second (day 21) and the third (day 35) booster doses. Blood sample were taken on days 34 and 49. Immune sera were used in western blot and tested in a bactericidal assay. Results and discussion: On the basis of sequence homology of NM-ADPRT with LT, CT and PT we have identified the putative residues involved in enzymatic activity. These residues have been changed by site-directed mutagenesis and the purified mutant toxins have been tested for both ADP-ribosylating and NAD-glycohydrolase activities. Interestingly, some of the mutants show reduced or abolished enzymatic activity indicating that the identified residues play a role in catalysis. Antisera against the wild-type and mutant toxins have bactericidal activity. The titers induced by two mutants were higher than those induced by the wild-type form. These data suggest that the mutations introduced could influence not only the enzymatic activity but also the in vivo stability of the toxin. Conclusion: A novel ADP-ribosyltransferase has been identified in meningococcus B. Catalytic residues have been predicted by sequence homology and their role in catalysis has been confirmed by site-directed mutagenesis. These molecules are also able to induce a bactericidal response

Unconsciousness or unresponsiveness in akinetic mutism? Insights from a multimodal longitudinal exploration

The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour-based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology-based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients

Reduction of sleep-like perilesional slow waves and clinical evolution after stroke: A TMS-EEG study

Objective: Recent studies indicate that brain injuries often lead to the occurrence of sleep-like slow waves in perilesional cortical areas. These slow waves may disrupt local cortico-cortical interactions and contribute to behavioral impairments but are, in principle, reversible. This study employs Transcranial Magnetic Stimulation (TMS) combined with Electroencephalography (EEG) to monitor changes in perilesional slow waves and local cortical interactions examining their relation to changes in stroke severity. Methods: Twelve patients with post-acute/chronic unilateral ischemic cortical stroke participated in a longitudinal study with two assessment points. Each assessment included a neurological evaluation using the National Institutes of Health Stroke Scale (NIHSS) and TMS-EEG recordings targeting perilesional cortical areas. Neurophysiological parameters, such as slow wave amplitude (SWa), high-frequency power (HFp) suppression, and the Perturbational Complexity Index-state transition (PCIst), were extracted from the perilesional EEG responses to TMS to quantify local sleep-like slow waves and cortical interactions. Results: We observed a perilesional reduction in sleep-like slow waves and a restoration of local cortical interactions. Notably, these changes significantly correlated with patients' clinical evolution as assessed by the NIHSS score. Conclusions: These findings highlight the potential of TMS-EEG as an objective tool for tracking neurological evolution post-stroke. Significance: Targeting sleep-like cortical dynamics may be relevant for devising post-stroke rehabilitation strategies

NarE: a novel ADP-ribosyltransferase from Neisseria meningitidis.

Mono ADP-ribosyltransferases (ADPRTs) are a class of functionally conserved enzymes present in prokaryotic and eukaryotic organisms. In bacteria, these enzymes often act as potent toxins and play an important role in pathogenesis. Here we report a profile-based computational approach that, assisted by secondary structure predictions, has allowed the identification of a previously undiscovered ADP-ribosyltransferase in Neisseria meningitidis (NarE). NarE shows structural homologies with E. coli heat-labile enterotoxin (LT) and cholera toxin (CT) and possesses ADP-ribosylating and NAD-glycohydrolase activities. As in the case of LT and CT, NarE catalyses the transfer of the ADP-ribose moiety to arginine residues. Despite the absence of a signal peptide, the protein is efficiently exported into the periplasm of Neisseria. The narE gene is present in 25 out of 43 strains analysed, is always present in ET-5 and Lineage 3 but absent in ET-37 and Cluster A4 hypervirulent lineages. When present, the gene is 100% conserved in sequence and is inserted upstream of and co-transcribed with the lipoamide dehydrogenase E3 gene. Possible roles in the pathogenesis of N. meningitidis are discussed

Stratification of unresponsive patients by an independently validated index of brain complexity.

OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior

A Randomized, Double-Blind, Controlled Trial Protocol for Therapeutic Neuroscience Education in Chronic Migraine Patients: A Clinical–Neurophysiological Combined Study Design

Chronic migraine (CM) is a highly disabling condition, affecting about 2% of the global population. Non-pharmacological treatments can be optimal for their non-invasive nature. This prospective, randomized, double-blind, controlled trial aimed to test the efficacy of therapeutic neuroscience education (TNE) in CM. Early response biomarkers were also evaluated. A total of 80 CM patients were consecutively enrolled and randomly allocated to TNE or a general education program. Treatment effectiveness was evaluated at baseline (T1) and 2 months after the end of treatment (T4). We collected the responses to disability and comorbidity questionnaires at the start (T1) and end of treatment (T3, 10 weeks after start). Early response biomarkers were evaluated at screening (T0) and mid-way through the process (T2, 5 weeks after start). We expected that TNE would provide a greater benefit than the general education program, which served as the primary outcome of this study. We also expected that a change in clinical and neurophysiological measures could potentially occur, reflecting plasticity-induced reorganization and predicting clinical response. This is the first study selectively exploring the effect of TNE as a standalone treatment for CM. A new, effective treatment regime without interactions with other medication could be of great interest as an addition to migraine therapeutic strategies