Experimental validation of the free-energy principle with in vitro neural networks

Empirical applications of the free-energy principle are not straightforward because they entail a commitment to a particular process theory, especially at the cellular and synaptic levels. Using a recently established reverse engineering technique, we confirm the quantitative predictions of the free-energy principle using in vitro networks of rat cortical neurons that perform causal inference. Upon receiving electrical stimuli—generated by mixing two hidden sources—neurons self-organised to selectively encode the two sources. Pharmacological up- and downregulation of network excitability disrupted the ensuing inference, consistent with changes in prior beliefs about hidden sources. As predicted, changes in effective synaptic connectivity reduced variational free energy, where the connection strengths encoded parameters of the generative model. In short, we show that variational free energy minimisation can quantitatively predict the self-organisation of neuronal networks, in terms of their responses and plasticity. These results demonstrate the applicability of the free-energy principle to in vitro neural networks and establish its predictive validity in this setting

Clinical application of endoscopic soft palate augmentation in the treatment of velopharyngeal insufficiency

Velopharyngeal structure augmentation with the injection of autologous fat tissue into the nasal mucosa of the soft palate has been reported previously. However, as the injection points in the velopharyngeal space cannot be observed directly, these injections may be difficult to perform accurately. This report describes a new endoscope-assisted approach in which the materials for velopharyngeal structure augmentation are administered while observing the injection points directly, also enabling adjustment of the amount of material injected. A case series of five patients aged 8–16 years who underwent endoscopic soft palate augmentation under general anaesthesia is reported. Autologous fat tissue was injected into the nasal mucosa of the soft palate using a needle-type device of an endoscope, and the effects of the treatment were evaluated. The injections were performed successfully, and the velopharyngeal function was improved. This new technique of endoscopy-assisted augmentation was useful for the treatment of velopharyngeal insufficiency.Isomura E.T., Matsukawa M., Yokota Y., et al. Clinical application of endoscopic soft palate augmentation in the treatment of velopharyngeal insufficiency. International Journal of Oral and Maxillofacial Surgery, (2023); https://doi.org/10.1016/j.ijom.2023.01.003

The Human Cytomegalovirus UL76 Gene Regulates the Level of Expression of the UL77 Gene

Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein.To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth.While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV- infected cells

A Molecular Platinum Cluster Junction: A Single-Molecule Switch

We present a theoretical study of the electronic transport through single-molecule junctions incorporating a Pt6 metal cluster bound within an organic framework. We show that the insertion of this molecule between a pair of electrodes leads to a fully atomically engineered nano-metallic device with high conductance at the Fermi level and two sequential high on/off switching states. The origin of this property can be traced back to the existence of a HOMO which consists of two degenerate and asymmetric orbitals, lying close in energy to the Fermi level of the metallic leads. Their degeneracy is broken when the molecule is contacted to the leads, giving rise to two resonances which become pinned close to the Fermi level and display destructive interference.Comment: 4 pages, 4 figures. Reprinted (adapted) with permission from J. Am. Chem. Soc., 2013, 135 (6), 2052. Copyright 2013 American Chemical Societ

CuInSe2 thin films produced by rf sputtering in Ar/H2 atmospheres

Structural, compositional, optical, and electrical properties of CuInSe2thin filmsgrown by rf reactive sputtering from a Se excess target in Ar/H2 atmospheres are presented. The addition of H2 to the sputtering atmospheres allows the control of stoichiometry of films giving rise to remarkable changes in the film properties. Variation of substrate temperature causes changes in film composition because of the variation of hydrogen reactivity at the substrate. Measurements of resistivity at variable temperatures indicate a hopping conduction mechanism through gap states for films grown at low temperature (100–250 °C), the existence of three acceptor levels at about 0.046, 0.098, and 0.144 eV above valence band for films grown at intermediate temperature (250–350 °C), and a pseudometallic behavior for film grown at high temperatures (350–450 °C). Chalcopyrite polycrystalline thin films of CuInSe2 with an average grain size of 1 μm, an optical gap of 1.01 eV, and resistivities from 10− 1 to 103 Ω cm can be obtained by adding 1.5% of H2 to the sputtering atmosphere and by varying the substrate temperature from 300 to 400 °C

Power-Law Inter-Spike Interval Distributions Infer a Conditional Maximization of Entropy in Cortical Neurons

The brain is considered to use a relatively small amount of energy for its efficient information processing. Under a severe restriction on the energy consumption, the maximization of mutual information (MMI), which is adequate for designing artificial processing machines, may not suit for the brain. The MMI attempts to send information as accurate as possible and this usually requires a sufficient energy supply for establishing clearly discretized communication bands. Here, we derive an alternative hypothesis for neural code from the neuronal activities recorded juxtacellularly in the sensorimotor cortex of behaving rats. Our hypothesis states that in vivo cortical neurons maximize the entropy of neuronal firing under two constraints, one limiting the energy consumption (as assumed previously) and one restricting the uncertainty in output spike sequences at given firing rate. Thus, the conditional maximization of firing-rate entropy (CMFE) solves a tradeoff between the energy cost and noise in neuronal response. In short, the CMFE sends a rich variety of information through broader communication bands (i.e., widely distributed firing rates) at the cost of accuracy. We demonstrate that the CMFE is reflected in the long-tailed, typically power law, distributions of inter-spike intervals obtained for the majority of recorded neurons. In other words, the power-law tails are more consistent with the CMFE rather than the MMI. Thus, we propose the mathematical principle by which cortical neurons may represent information about synaptic input into their output spike trains

Measles vaccine coverage and factors related to uncompleted vaccination among 18-month-old and 36-month-old children in Kyoto, Japan

BACKGROUND: Due to low vaccine coverage, Japan has not only experienced outbreaks of measles but has also been exporting it overseas. This study aims to survey measles vaccine coverage and the factors uncompleted vaccination among community-living children. METHODS: Subjects were the parents whose children had undergone either an 18-month or a 36-month checkup publicly provided by Kyoto City during November 2001 to January 2002. An anonymous self-administered questionnaire survey was conducted. RESULTS: The coverage was 73.2% among the 18-month-old children (n = 2707) and 88.9% among the 36-month-old children (n = 2340), respectively. The following characteristics of mothers were related to uncompleted measles vaccination: aged below 30, working, concerned about the adverse events of the vaccine, and had insufficient knowledge. Similarly, the following characteristics among children were related to uncompleted measles vaccination: not the first-born child, interacting with other children in group settings. The coverage was the lowest among the children whose mothers were concerned about the adverse events of the vaccine without proper knowledge of measles and its vaccination. CONCLUSION: To increase vaccine coverage among children, parents' awareness about measles and vaccination against it should be promoted, especially for working mothers. Efforts to enhance access to vaccination services and to communicate with parents about changing vaccination schedules are necessary

Consensus on the assessment of systemic sclerosis–associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment

INTRODUCTION: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. METHODS: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. RESULTS: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. CONCLUSION: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice