Search

TAE Technologies’ fifth-generation fusion device, C-2W (also called ‘Norman’), is the world’s largest compact-toroid device and has made significant progress in field-reversed configuration (FRC) plasma performance. C-2W produces record breaking, macroscopically stable, high-temperature advanced beam-driven FRC plasmas, dominated by injected fast particles and sustained in steady state, which is primarily limited by neutral-beam (NB) pulse duration. The NB power supply system has recently been upgraded to extend the pulse length from 30 ms to 40 ms, which allows for a longer plasma lifetime and thus better characterization and further enhancement of FRC performance. An active plasma control system is routinely used in C-2W to produce consistent FRC performance as well as for reliable machine operations using magnet coils, edge-biasing electrodes, gas injection and tunable-energy NBs. Google’s machine learning framework for experimental optimization has also been routinely used to enhance plasma performance. Dedicated plasma optimization experimental campaigns, particularly focused on the external magnetic field profile and NB injection (NBI) optimizations, have produced a superior FRC plasma performance; for instance, achieving a total plasma energy of ∼13 kJ, a trapped poloidal magnetic flux of ∼16 mWb (based on the rigid-rotor model) and plasma sustainment in steady state up to ∼40 ms. Furthermore, under some operating conditions, the electron temperature of FRC plasmas at a quiescent phase has successfully reached up to ∼1 keV at the peak inside the FRC separatrix for the first time. The overall FRC performance is well correlated with the NB and edge-biasing systems, where higher total plasma energy is obtained with higher NBI power and applied voltage on biasing electrodes. C-2W operations have now reached a mature level where the machine can produce hot, stable, long-lived, and repeatable plasmas in a well-controlled manner.

Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human-based models of FXS, the roles of astrocytes, a type of glial cells in the brain, are largely unknown. Here, we generated a human-based FXS model via differentiation of astrocytes from human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) and characterized their development, function, and proteomic profiles. We identified shortened cell cycle, enhanced Ca2+ signaling, impaired sterol biosynthesis, and pervasive alterations in the proteome of FXS astrocytes. Our work identified astrocytic impairments that could contribute to the pathogenesis of FXS and highlight astrocytes as a novel therapeutic target for FXS treatment.

Motor skill learning induces changes in synaptic structure and function in the primary motor cortex (M1). In the fragile X syndrome (FXS) mouse model an impairment in motor skill learning and associated formation of new dendritic spines was previously reported. However, whether modulation of synaptic strength through trafficking of AMPA receptors (AMPARs) with motor skill training is impaired in FXS is not known. Here, we performed in vivo imaging of a tagged AMPA receptor subunit, GluA2, in layer (L)2/3 neurons in the primary motor cortex of wild-type (WT) and Fmr1 knock-out (KO) male mice at different stages of learning a single forelimb-reaching task. Surprisingly, in the Fmr1 KO mice, despite impairments in learning there was no deficit in motor skill training-induced spine formation. However, the gradual accumulation of GluA2 in WT stable spines, which persists after training is completed and past the phase of spine number normalization, is absent in the Fmr1 KO mouse. These results demonstrate that motor skill learning not only reorganizes circuits through formation of new synapses, but also strengthens existing synapses through accumulation of AMPA receptors and GluA2 changes are better associated with learning than new spine formation.

The article traces the origin of several generalized conformability bounds for split and splitless piston rings used in the automotive industry to troubleshoot and better design piston engines and compressors for lesser emissions and oil consumption by presenting an irregular power cylinder bore shape through individual Fourier waveforms of a different order. The work also elucidates the origin and capabilities of the prematurely forgotten specialized ring-bore contact models of the 1940s for single-order bore deformation (round and oval), according to which a ring-bore seal breach occurs only near the ring ends and emerges with any bore deformation. With the aid of this information, the report explains that the split ring generalized models' theoretically defined conformability bounds are largely conventional categories that become sufficiently compelling engineering tools only by adapting the models to the experimentally observed or analytically asserted ring-bore clearances near the ring ends and considering the ring and bore design and production deviations from the theoretical models. The study further demonstrates that different researchers' semiempirical versions of these bounds were spinoffs from the author's analytical model of 1990. The article's information helps engineers design piston rings and the associated components with better functional and tribological properties. [ABSTRACT FROM AUTHOR]

Tenebrio molitor is an important coleopteran model insect and agricultural pest from the Tenebrionidae family. We used RNA-Seq transcriptome data from T. molitor to annotate trypsin-like sequences from the chymotrypsin S1 family of serine peptidases, including sequences of active serine peptidases (SerP) and their inactive homologs (SerPH) in T. molitor transcriptomes. A total of 63 S1 family tryspin-like serine peptidase sequences were de novo assembled. Among the sequences, 58 were predicted to be active trypsins and five inactive SerPH. The length of preproenzyme and mature form of the predicted enzyme, position of signal peptide and proenzyme cleavage sites, molecular mass, active site and S1 substrate binding subsite residues, and transmembrane and regulatory domains were analyzed using bioinformatic tools. The data can be used for further physiological, biochemical, and phylogenetic study of tenebrionid pests and other animal systems.

The literature review describes history of views on catatonia from Kahlbaum to present time. Descripted as a discrete disease by Karl Kahlbaum, since Kraepelin’s and Bleuler’s works catatonia was associated with schizophrenia for many years. At the present time catatonia is classified as a nonspecific syndrome, which can be observed in many mental diseases. Despite of common view on catatonia as a rare disease, a lot of studies show that this state is very frequent. Catatonia remains an underdiagnosed syndrome. Prompt recognition of catatonia is important since this state is life-threatening and catatonic patients need correct treatment. This article describes some diagnostic scales, used to recognize catatonia in psychiatric patients.

Introduction: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation. Methods: We examined complement activation throughout Staphylococcus epidermidis (S. epidermidis) central nervous system (CNS) catheter infection. In addition, based on accumulating evidence that C3 plays a role in synaptic pruning in other neuroinflammatory states we determined if C3 and downstream C5 led to alterations in synaptic protein levels. Using our murine model of S. epidermidis catheter infection we quantified levels of the complement components C1q, Factor B, MASP2, C3, and C5 over the course of infection along with bacterial burdens. Results: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and the wealth of information regarding the emerging roles of C1q in the CNS, this suggests functions beyond pathogen elimination during S. epidermidis CNS catheter infection. To identify if C3 impacted synaptic protein levels we performed synaptosome isolation and quantified levels of VGLUT1 and PSD95 as well as pre-, post- and total synaptic puncta in cortical layer V of C3 knockout (KO) andwild typemice. We also used C5 KO andwild typemice to determine if therewas any difference in pre-, post- and total synaptic puncta. Discussion: Neither C3 nor C5 impacted synaptic protein abundance. These findings suggest that chronic elevations in C1q in the brain that persist once CNS catheter infection has resolved may be modulating disease sequalae. [ABSTRACT FROM AUTHOR]

New substrates with glutamine in the P1-position are introduced for the assay of peptidases from the C1 papain family, with a general formula of Glp-Phe-Gln-X, where Glp is pyroglutamyl and X is pNA (p-nitroanilide) or AMC (4-amino-7-methylcoumaride). The substrates have a simple structure, and C1 cysteine peptidases of various origins cleave them with high efficiency. The main advantage of the substrates is their selectivity for cysteine peptidases of the C1 family. Peptidases of other clans, including serine trypsin-like peptidases, do not cleave glutamine-containing substrates. We demonstrate that using Glp-Phe-Gln-pNA in combination with a commercially available substrate, Z-Arg-Arg-pNA, provided differential determination of cathepsins L and B. In terms of specific activity and kinetic parameters, the proposed substrates offer improvement over the previously described alanine-containing prototypes. The efficiency and selectivity of the substrates was demonstrated by the example of chromatographic and electrophoretic analysis of a multi-enzyme digestive complex of stored product pests from the Tenebrionidae family.