Social contact structures and time use patterns in the Manicaland Province of Zimbabwe.

BACKGROUND: Patterns of person-to-person contacts relevant for infectious diseases transmission are still poorly quantified in Sub-Saharan Africa (SSA), where socio-demographic structures and behavioral attitudes are expected to be different from those of more developed countries. METHODS AND FINDINGS: We conducted a diary-based survey on daily contacts and time-use of individuals of different ages in one rural and one peri-urban site of Manicaland, Zimbabwe. A total of 2,490 diaries were collected and used to derive age-structured contact matrices, to analyze time spent by individuals in different settings, and to identify the key determinants of individuals' mixing patterns. Overall 10.8 contacts per person/day were reported, with a significant difference between the peri-urban and the rural site (11.6 versus 10.2). A strong age-assortativeness characterized contacts of school-aged children, whereas the high proportion of extended families and the young population age-structure led to a significant intergenerational mixing at older ages. Individuals spent on average 67% of daytime at home, 2% at work, and 9% at school. Active participation in school and work resulted the key drivers of the number of contacts and, similarly, household size, class size, and time spent at work influenced the number of home, school, and work contacts, respectively. We found that the heterogeneous nature of home contacts is critical for an epidemic transmission chain. In particular, our results suggest that, during the initial phase of an epidemic, about 50% of infections are expected to occur among individuals younger than 12 years and less than 20% among individuals older than 35 years. CONCLUSIONS: With the current work, we have gathered data and information on the ways through which individuals in SSA interact, and on the factors that mostly facilitate this interaction. Monitoring these processes is critical to realistically predict the effects of interventions on infectious diseases dynamics

Heavy-Fermion Instability in Double-Degenerate Plasmas

In this work we study the propagations of normal frequency modes for quantum hydrodynamic (QHD) waves in the linear limit and introduce a new kind of instability in a double-degenerate plasma. Three different regimes, namely, low, intermediate and high magnetic field strengths are considered which span the applicability of the work to a wide variety of environments. Distinct behavior is observed for different regimes, for instance, in the laboratory-scale field regime no frequency-mode instability occurs unlike those of intermediate and high magnetic-field strength regimes. It is also found that the instability of this kind is due to the heavy-fermions which appear below a critical effective-mass parameter ($\mu_{cr}=\sqrt{3}$) and that the responses of the two (lower and upper frequency) modes to fractional effective-mass change in different effective-mass parameter ranges (below and above the critical value) are quite opposite to each other. It is shown that, the heavy-fermion instability due to extremely high magnetic field such as that encountered for a neutron-star crust can lead to confinement of stable propagations in both lower and upper frequency modes to the magnetic poles. Current study can have important implications for linear wave dynamics in both laboratory and astrophysical environments possessing high magnetic fields

ISPRED-SEQ: Deep Neural Networks and Embeddings for Predicting Interaction Sites in Protein Sequences

The knowledge of protein–protein interaction sites (PPIs) is crucial for protein functional annotation. Here we address the problem focusing on the prediction of putative PPIs considering as input protein sequences. The issue is important given the huge volume of protein sequences compared to experimental and/or computed structures. Taking advantage of protein language models, recently developed, and Deep Neural networks, here we describe ISPRED-SEQ, which overpasses state-of-the-art predictors addressing the same problem. ISPRED-SEQ is freely available for testing at https://ispredws.biocomp.unibo.it

DeepREx-WS: A web server for characterising protein–solvent interaction starting from sequence

Protein–solvent interaction provides important features for protein surface engineering when the structure is absent or partially solved. Presently, we can integrate the notion of solvent exposed/buried residues with that of their flexibility and intrinsic disorder to highlight regions where mutations may increase or decrease protein stability in order to modify proteins for biotechnological reasons, while preserving their functional integrity. Here we describe a web server, which provides the unique possibility of integrating knowledge of solvent and non-solvent exposure with that of residue conservation, flexibility and disorder of a protein sequence, for a better understanding of which regions are relevant for protein integrity. The core of the webserver is DeepREx, a novel deep learning-based tool that classifies each residue in the sequence as buried or exposed. DeepREx is trained on a high-quality, non-redundant dataset derived from the Protein Data Bank comprising 2332 monomeric protein chains and benchmarked on a blind test set including 200 protein sequences unrelated with the training set. Results show that DeepREx performs at the state-of-the-art in the field. In turn, the Web Server, DeepREx-WS, supplements the predictions of DeepREx with features that allow a better characterisation of exposed and buried regions: i) residue conservation derived from multiple sequence alignment; ii) local sequence hydrophobicity; iii) residue flexibility computed with MEDUSA; iv) a predictor of secondary structure; v) the presence of disordered regions as derived from MobiDB-Lite3.0. The web server allows browsing, selecting and intersecting the different features. We demonstrate a possible application of the DeepREx-WS for assisting the identification of residues to be variated in protein surface engineering processes

CoCoNat: a novel method based on deep learning for coiled-coil prediction

MOTIVATION: Coiled-coil domains (CCD) are widespread in all organisms and perform several crucial functions. Given their relevance, the computational detection of CCD is very important for protein functional annotation. State-of-the-art prediction methods include the precise identification of CCD boundaries, the annotation of the typical heptad repeat pattern along the coiled-coil helices as well as the prediction of the oligomerization state. RESULTS: In this article, we describe CoCoNat, a novel method for predicting coiled-coil helix boundaries, residue-level register annotation, and oligomerization state. Our method encodes sequences with the combination of two state-of-the-art protein language models and implements a three-step deep learning procedure concatenated with a Grammatical-Restrained Hidden Conditional Random Field for CCD identification and refinement. A final neural network predicts the oligomerization state. When tested on a blind test set routinely adopted, CoCoNat obtains a performance superior to the current state-of-the-art both for residue-level and segment-level CCD. CoCoNat significantly outperforms the most recent state-of-the-art methods on register annotation and prediction of oligomerization states. AVAILABILITY AND IMPLEMENTATION: CoCoNat web server is available at https://coconat.biocomp.unibo.it. Standalone version is available on GitHub at https://github.com/BolognaBiocomp/coconat

Trees and Shrubs Monitoring Using an Ecological Approach: The Conclusion of the Restoration Project of Borgotrebbia Landfill (Northern Italy)

Plants growth monitoring in restored landfills are poorly available in literature. These data might be of critical importance for the evaluation and improvement of current and future restoration projects. Our study was focused on the plant\u2019s growth monitoring during a Life project (LIFE10 ENV/IT/000400 NEW LIFE), designed to restore a closed landfill (located in Northern Italy) using reconstituted soils. The growth monitoring was conducted on mortality rate, stress symptoms and phenological cycle completion of 10 plant species (trees and shrubs). Data were acquired during the 12 months following the end of the restoration with an ecological approach, using Landolt\u2019s indices and CSR functional strategy. It was observed that the stress-tolerant and the heliphilous ruderal species were the ones that best adapt to the restored environment (dead plants: 0 - 39%; unhealthy plants: 24 - 42%), whereas the most competitive species were the ones with highest mortality (17 - 43%) and stress symptoms (43 - 51%)

Quantitative analysis of videokymography in normal and pathological vocal folds: a preliminari study.

Videokymography (VKG) captures high-speed images of the vocal folds independently of the periodicity of the acoustic signal. The aim of this study was to preliminarily assess a software package that can objectively measure specific parameters of vocal fold vibration. From August 2009 until December 2010, we prospectively evaluated 40 subjects (Group A, 18 normal subjects; Group B, 14 patients with benign lesions of the middle third of the vocal fold, such as polyps and cysts; Group C, 8 patients treated by endoscopic excision of vocal fold benign lesions) by videoendoscopy, videolaryngostroboscopy, and VKG. A VKG camera was coupled to a 70 telescope and video was recorded during phonation. Images were objectively analyzed by a post-processing software tool (VKG-Analyser) with a user-friendly interface developed by our group. Different parameters were considered, including the ratio between the amplitude of the vibration of one vocal fold with respect to the contralateral (Ramp), the ratio between the period of one vocal fold vibration and the opposite one (Rper), and the ratio between the duration of the open and closed phase within a glottal cycle (Roc). Mean values for Ramp, Rper, and Roc in Group A were 1.05, 1.04, and 1.35, respectively; in Group B were 1.63, 0.92, and 0.97, respectively; and in Group C were 1.13, 0.91, and 1.85, respectively. Quantitative analysis of videokymograms by the herein presented tool, named VKG-Analyser, is useful for objective evaluation of the vibratory pattern in normal and pathologic vocal folds. Important future developments of this tool for the study of both physiologic and pathologic patterns of vocal fold vibration can be expected

Two-Body Random Ensembles: From Nuclear Spectra to Random Polynomials

The two-body random ensemble (TBRE) for a many-body bosonic theory is mapped to a problem of random polynomials on the unit interval. In this way one can understand the predominance of 0+ ground states, and analytic expressions can be derived for distributions of lowest eigenvalues, energy gaps, density of states and so forth. Recently studied nuclear spectroscopic properties are addressed.Comment: 8 pages, 4 figures. To appear in Physical Review Letter

Case Report: REL-1017 Reduces Abnormal Clinician Administered Dissociative States Scale Scores in Patients with Major Depressive Disorder

BACKGROUND: Dissociative symptoms may be found in a subset of patients with major depressive disorders (MDD). The Clinician-Administered Dissociative States Scale (CADSS) is a 23-item scale for the measurement of present-state dissociative symptoms with good inter-rater reliability and construct validity that can discriminate patients with dissociative disorders. The total CADSS score is derived by adding the score for each of the 23 items. A score of 4 or more on the CADSS is considered abnormal and clinically meaningful. Uncompetitive N-methyl-d-aspartic acid receptor (NMDAR) channel blockers have been proposed as a treatment for post-traumatic stress disorder (PTSD). REL-1017 is a novel, low potency, NMDAR channel blocker currently in Phase 3 studies for MDD. METHODS: This retrospective case series describes a subset of patients from a double-blind, randomized, placebo-controlled, in-patient 7-day, phase 2 trial of oral, once daily, 25 mg (75 mg loading dose on day 1, first dose) and 50 mg REL-1017 (100 mg loading dose on day 1, first dose) as an adjunctive treatment for MDD. This subset of patients was selected based on abnormal CADSS score at baseline, pre-treatment with the study drug. As part of REL-1017 safety evaluation, the CADSS was administered at four timepoints to all study patients: (a) 30 to 60 minutes pre-treatment at baseline on day 1; (b) 2 hours post-treatment on day 1 (after the first dose of study drug); (c) 2 hours post-treatment on day 7 (after the last dose); and (d) prior to discharge on day 9 (2 days after the last dose). RESULTS: Among the 62 randomized patients, four patients had a CADSS score of at least 4 on day 1 before study drug administration (2 patients in the 25 mg arm [CADSS score 22 and 4]; 1 patient in the 50 mg arm [CADSS score 35]; 1 patient in the placebo arm [CADSS score 6]). Among these 4 patients, starting on day 1, 2 hours post-treatment, the 2 subjects in the 25 mg subgroup (75 mg loading dose) and 1 subject in the 50 mg subgroup (100 mg loading dose) showed a clinically meaningful decrease in their CADSS score, while the single patient in the placebo group showed no change. CADSS scores on Day 1 pre-treatment, day 1 post-treatment, day 7 post last treatment, and on day 9 prior to discharge were 22-2-6-0; 4-0-0-0; 35-14-9-0, and 6-6-n/a-n/a, for the two patients in the 25 mg REL-1017 subgroup, the single patient in the 50 mg REL-1017 subgroup, and the single patient in the placebo group, respectively. CONCLUSIONS: These retrospective case report data potentially signal that REL-1017 may determine rapid and sustained improvement in patients with MDD and concurrent clinically meaningful dissociative symptoms assessed by a CADSS score of 4 or above. Ongoing phase 3 trials with REL-1017 are expected to enroll a total of 1200 outpatients with MDD. These studies will potentially generate additional data that may support the initiation of controlled studies with REL-1017 for the treatment of PTSD. FUNDING: Relmada Therapeutics