Transitions among crystal, glass, and liquid in a binary mixture with changing particle size ratio and temperature

Using molecular dynamics simulation we examine changeovers among crystal, glass, and liquid at high density in a two dimensional binary mixture. We change the ratio between the diameters of the two components and the temperature. The transitions from crystal to glass or liquid occur with proliferation of defects. We visualize the defects in terms of a disorder variable "D_j(t)" representing a deviation from the hexagonal order for particle j. The defect structures are heterogeneous and are particularly extended in polycrystal states. They look similar at the crystal-glass crossover and at the melting. Taking the average of "D_j(t)" over the particles, we define a disorder parameter "D(t)", which conveniently measures the degree of overall disorder. Its relaxation after quenching becomes slow at low temperature in the presence of size dispersity. Its steady state average is small in crystal and large in glass and liquid.Comment: 7 pages, 10 figure

Ferrofluids as thermal ratchets

Colloidal suspensions of ferromagnetic nano-particles, so-called ferrofluids, are shown to be suitable systems to demonstrate and investigate thermal ratchet behavior: By rectifying thermal fluctuations, angular momentum is transferred to a resting ferrofluid from an oscillating magnetic field without net rotating component. Via viscous coupling the noise driven rotation of the microscopic ferromagnetic grains is transmitted to the carrier liquid to yield a macroscopic torque. For a simple setup we analyze the rotation of the ferrofluid theoretically and show that the results are compatible with the outcome of a simple demonstration experiment.Comment: 4 pages, 3 figures, corrected version, improved figures, to be published in Phys. Rev. Let

Structural Analysis of Pathogenic Missense Mutations in GABRA2 and Identification of a Novel de Novo Variant in the Desensitization Gate

Background: Cys-loop receptors control neuronal excitability in the brain and their dysfunction results in numerous neurological disorders. Recently, six missense variants in GABRA2, a member of this family, have been associated with early infantile epileptic encephalopathy (EIEE). We identified a novel de novo missense variant in GABRA2 in a patient with EIEE and performed protein structural analysis of the seven variants. Methods: The novel variant was identified by trio whole-genome sequencing. We performed protein structural analysis of the seven variants, and compared them to previously reported pathogenic mutations at equivalent positions in other Cys-loop receptors. Additionally, we studied the distribution of disease-associated variants in the transmembrane helices of these proteins. Results: The seven variants are in the transmembrane domain, either close to the desensitization gate, the activation gate, or in inter-subunit interfaces. Six of them have pathogenic mutations at equivalent positions in other Cys-loop receptors, emphasizing the importance of these residues. Also, pathogenic mutations are more common in the pore-lining helix, consistent with this region being highly constrained for variation in control populations. Conclusion: Our study reports a novel pathogenic variant in GABRA2, characterizes the regions where pathogenic mutations are in the transmembrane helices, and underscores the value of considering sequence, evolutionary, and structural information as a strategy for variant interpretation of novel missense mutations.info:eu-repo/semantics/publishedVersio

GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

Comment on "Magnetoviscosity and relaxation in ferrofluids"

It is shown and discussed how the conventional system of hydrodynamic equations for ferrofluids was derived. The set consists of the equation of fluid motion, the Maxwell equations, and the magnetization equation. The latter was recently revised by Felderhof [Phys. Rev. E, v.62, p.3848 (2000)]. His phenomenological magnetization equation looks rather like corresponding Shliomis' equation, but leads to wrong consequences for the dependence of ferrofluid viscosity and magnetization relaxation time on magnetic field.Comment: 6 pages, 1 figure, Submitted to Phys. Rev.

Phenotypic Spectrum of Seizure Disorders in MBD5-Associated Neurodevelopmental Disorder

OBJECTIVE: To describe the phenotypic spectrum in patients with MBD5-associated neurodevelopmental disorder (MAND) and seizures; features of MAND include intellectual disability, epilepsy, psychiatric features of aggression and hyperactivity, and dysmorphic features including short stature and microcephaly, sleep disturbance, and ataxia. METHODS: We performed phenotyping on patients with MBD5 deletions, duplications, or point mutations and a history of seizures. RESULTS: Twenty-three patients with MAND and seizures were included. Median seizure onset age was 2.9 years (range 3 days–13 years). The most common seizure type was generalized tonic-clonic; focal, atypical absence, tonic, drop attacks, and myoclonic seizures occurred frequently. Seven children had convulsive status epilepticus and 3 nonconvulsive status epilepticus. Fever, viral illnesses, and hot weather provoked seizures. EEG studies in 17/21 patients were abnormal, typically showing slow generalized spike-wave and background slowing. Nine had drug-resistant epilepsy, although 3 eventually became seizure-free. All but one had moderate-to-severe developmental impairment. Epilepsy syndromes included Lennox-Gastaut syndrome, myoclonic-atonic epilepsy, and infantile spasms syndrome. Behavioral problems in 20/23 included aggression, self-injurious behavior, and sleep disturbance. CONCLUSION: MBD5 disruption may be associated with severe early childhood-onset developmental and epileptic encephalopathy. Because neuropsychiatric dysfunction is common and severe, it should be an important focus of clinical management

RARS2 mutations in a sibship with infantile spasms

Pontocerebellar hypoplasia is a group of heterogeneous neurodevelopmental disorders characterized by reduced volume of the brainstem and cerebellum. We report two male siblings who presented with early infantile clonic seizures, and then developed infantile spasms associated with prominent isolated cerebellar hypoplasia/atrophy on magnetic resonance imaging (MRI). Using whole exome sequencing techniques, both were found to be compound heterozygotes for one previously reported and one novel mutation in the gene encoding mitochondrial arginyl-tRNA synthetase 2 (RARS2). Mutations in this gene have been classically described in pontocerebellar hypoplasia type six (PCH6), a phenotype characterized by early (often intractable) seizures, profound developmental delay, and progressive pontocerebellar atrophy. The electroclinical spectrum of PCH6 is broad and includes a number of seizure types: myoclonic, generalized tonic-clonic, and focal clonic seizures. Our report expands the characterization of the PCH6 disease spectrum and presents infantile spasms as an associated electroclinical phenotype

Dissipation in ferrofluids: Mesoscopic versus hydrodynamic theory

Part of the field dependent dissipation in ferrofluids occurs due to the rotational motion of the ferromagnetic grains relative to the viscous flow of the carrier fluid. The classical theoretical description due to Shliomis uses a mesoscopic treatment of the particle motion to derive a relaxation equation for the non-equilibrium part of the magnetization. Complementary, the hydrodynamic approach of Liu involves only macroscopic quantities and results in dissipative Maxwell equations for the magnetic fields in the ferrofluid. Different stress tensors and constitutive equations lead to deviating theoretical predictions in those situations, where the magnetic relaxation processes cannot be considered instantaneous on the hydrodynamic time scale. We quantify these differences for two situations of experimental relevance namely a resting fluid in an oscillating oblique field and the damping of parametrically excited surface waves. The possibilities of an experimental differentiation between the two theoretical approaches is discussed.Comment: 14 pages, 2 figures, to appear in PR

Dispersity-Driven Melting Transition in Two Dimensional Solids

We perform extensive simulations of $10^4$ Lennard-Jones particles to study the effect of particle size dispersity on the thermodynamic stability of two-dimensional solids. We find a novel phase diagram in the dispersity-density parameter space. We observe that for large values of the density there is a threshold value of the size dispersity above which the solid melts to a liquid along a line of first order phase transitions. For smaller values of density, our results are consistent with the presence of an intermediate hexatic phase. Further, these findings support the possibility of a multicritical point in the dispersity-density parameter space.Comment: In revtex format, 4 pages, 6 postscript figures. Submitted to PR