S6 kinases (S6Ks) are mechanistic target of rapamycin substrates that participate in cell growth control. S6Ks phosphorylate ribosomal protein S6 (rpS6) and additional proteins involved in the ...translational machinery, although the functional roles of these modifications remain elusive. Here we analyze the S6K-dependent transcriptional and translational regulation of gene expression by comparing whole-genome microarray of total and polysomal mouse liver RNA after feeding. We show that tissue lacking S6Ks 1 and 2 (S6K1 and S6K2), displays a defect in the ribosome biogenesis (RiBi) transcriptional program after feeding. Over 75% of RiBi factors are controlled by S6K, including Nop56, Nop14, Gar1, Rrp9, Rrp15, Rrp12 and Pwp2 nucleolar proteins. Importantly, the reduced activity of RiBi transcriptional promoters in S6K1;S6K2(-/-) cells is also observed in rpS6 knock-in mutants that cannot be phosphorylated. As ribosomal protein synthesis is not affected by these mutations, our data reveal a distinct and specific aspect of RiBi under the control of rpS6 kinase activity, that is, the RiBi transcriptional program.
ABSTRACT Macrospicules (MSs) are localized small-scale jet-like phenomena in the solar atmosphere, which have the potential to transport a considerable amount of momentum and energy from the lower ...solar atmospheric regions to the transition region and the low corona. A detailed statistical analysis of their temporal behavior and spatial properties is carried out in this work. Using state-of-the-art spatial and temporal resolution observations, yielded by the Atmospheric Imaging Assembly of Solar Dynamics Observatory, we constructed a database covering a 5.5 year long period, containing 301 macrospicules that occurred between 2010 June and 2015 December, detected at 30.4 nm wavelength. Here, we report the long-term variation of the height, length, average speed, and width of MS in coronal holes and Quiet Sun areas both in the northern and southern hemisphere of the Sun. This new database helps to refine our knowledge about the physical properties of MSs. Cross-correlation of these properties shows a relatively strong correlation, but not always a dominant one. However, a more detailed analysis indicates a wave-like signature in the behavior of MS properties in time. The periods of these long-term oscillatory behaviors are just under two years. Also, in terms of solar north/south hemispheres, a strong asymmetry was found in the spatial distribution of MS properties, which may be accounted for by the solar dynamo. This latter feature may then indicate a strong and rather intrinsic link between global internal and local atmospheric phenomena in the Sun.
The electrical parameters used for deep brain stimulation (DBS) in movement disorders have been relatively well studied, however for the newer indications of DBS for psychiatric indications these are ...less clear. Based on the movement disorder literature, use of the correct stimulation parameters should be crucial for clinical outcomes. This review examines the stimulation parameters used in DBS studies for treatment resistant depression (TRD) and their relevance to clinical outcome and brain targets.
We examined the published studies on DBS for TRD archived in major databases. Data on stimulus parameters (frequency, pulse width, amplitude), stimulation mode, brain target, efficacy, safety, and duration of follow up were extracted from 29 observational studies including case reports of patients with treatment resistant unipolar, bipolar, and co-morbid depression.
The algorithms commonly used to optimize efficacy were increasing amplitude followed by changing the electric contacts or increasing pulse width. High frequency stimulation (>100 Hz) was applied in most cases across brain targets. Keeping the high frequency stimulation constant, three different combinations of parameters were mainly used: (i) short pulse width (60-90 us) and low amplitude (0-4 V), (ii) short pulse width and high amplitude (5-10 V), (iii) long pulse width (120-450 us) and low amplitude. There were individual variations in clinical response to electrical dosing and also in the time of clinical recovery. There was no significant difference in mean stimulation parameters between responders and non-responders suggesting a role for stimulation unrelated factors in response.
Although limited by open trials and small sample size, three optimal stimulation parameter combinations emerged from this review. Studies are needed to assess the comparative efficacy and safety of these combinations, such as a registry of data from patients undergoing DBS for TRD with individual data on stimulation parameters.
Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective treatment for generalized dystonia. Its role in the management of other types of dystonia is uncertain. ...Therefore we performed a prospective, single-blind, multicentre study assessing the efficacy and safety of bilateral GPi-DBS in 10 patients with severe, chronic, medication-resistant cervical dystonia. Two blinded neurologists assessed patients before surgery and at 6 and 12 months post-operatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The primary outcome measure was the severity subscore (range 0–30, higher scores indicating greater impairment). Secondary outcomes included disability (0 to 30), pain (0 to 40) subscores and total scores of the TWSTRS, Short Form-36 and Beck depression inventory. Swallowing and neuropsychological assessment were also performed at baseline and 12 months. One-way repeated measures analysis of variance was used to analyse the data. The TWSTRS severity score improved from a mean (SD) of 14.7 (4.2) before surgery to 8.4 (4.4) at 12 months post-operatively (P = 0.003). The disability and pain scores improved from 14.9 (3.8) and 26.6 (3.6) before surgery, to 5.4 (7.0) and 9.2 (13.1) at 12 months, respectively (both P < 0.001). General health and physical functioning as well as depression scores improved significantly. Complications were mild and reversible in four patients. Some changes in neuropsychological tests were observed, although these did not impact daily life or employment. Our results support the efficacy and safety of GPi-DBS for the treatment of patients with severe and prolonged cervical dystonia who have failed medical management.
The transport sector is undergoing a major transformation, as battery electric vehicles (BEV) are gaining ground. Therefore, assessing the sustainability aspects of their use is crucial to obtaining ...a clear picture of the sector. This article aims to meet this requirement by using European Union (EU) data for the period 2011 to 2021 and focuses not only on EU-27 aggregates but also on each member state separately. For the evaluation, a well-to-wheel (WTW) method was used to calculate two parameters: energy-specific CO2 emissions (ε) and total efficiency of energy conversions, transmission, and battery (ηtotal). For these values, the annual electricity mixes of the countries were tracked in 5 + 1 categories (combined cycle gas turbine (CCGT), thermal power plant, biofuels, nuclear power plant (NPP), renewables, and imports). The calculated results were illustrated by sustainability matrices describing the former and current positions of the countries. The EU-27 aggregate achieved a 0.04 increase (from 0.37 to 0.41) in total efficiency and a 29 gCO2/MJmotion decrease (from 113 to 84 gCO2/MJmotion) during the period. This ε value for 2021 was around half the world average. However, very significant differences were identified between member states, which are also assessed in the article with special emphases on the five most populated EU countries (Germany, France, Italy, Spain, and Poland).
In iron-pnictide superconductivity, the interband interaction between the hole and electron Fermi surfaces (FSs) is believed to play an important role. However, KFe 2 As 2 has three zone-centered ...hole FSs and no electron FS but still exhibits superconductivity. Our ultrahigh-resolution laser angle-resolved photoemission spectroscopy unveils that KFe 2 As 2 is a nodal s-wave superconductor with highly unusual FS-selective multi-gap structure: a nodeless gap on the inner FS, an unconventional gap with "octet-line nodes" on the middle FS, and an almost-zero gap on the outer FS. This gap structure may arise from the frustration between competing pairing interactions on the hole FSs causing the eightfold sign reversal. Our results suggest that the A 1g superconducting symmetry is universal in iron-pnictides, in spite of the variety of gap functions.
We present a mesh-based Ewald summation method that is suitable for the calculation of the electrostatic interaction between Gaussian charge distributions, instead of point charges. As an ...application, we implemented the method in the Gromacs simulation package and tested it with a polarizable water model, showing that the interaction between Gaussian charge distributions can be computed with a small (10%) additional computational cost with respect to the point charge case. In addition, since the performance of polarizable models is strongly influenced by the number of iterations required for the self-consistent field solution, we tested also the Always Stable Predictor-Corrector (ASPC) method of Kolafa (Kolafa, J. J. Comp. Chem. 2003, 25, 335) as an alternative to the steepest descent (SD) based algorithm with predictor implemented in the Gromacs, and found that it speeds up the integration of the equations of motion by a factor of 1.6–2.0, depending on the target model.
This study aims to provide further evidence for the potential influence of the global solar magnetic field on localized chromospheric jets, the macrospicules (MS). To find a connection between the ...long-term variation of properties of MS and other solar activity proxies, including, e.g., the temporal variation of the frequency shift of solar global oscillations, sunspot area, etc., a database overarching seven years of observations was compiled. This database contains 362 MS, based on observations at the 30.4 nm of the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory. Three of the five investigated physical properties of MS show a clear long-term temporal variation after smoothing the raw data. Wavelet analysis of the temporal variation of maximum length, maximum area, and average velocity is carried out. The results reveal a strong pattern of periodicities at around 2 years (also referred to as quasi-biennial oscillations-QBOs). A comparison with solar activity proxies that also possess the properties of QBOs provides some interesting features: the minima and maxima of QBOs of MS properties occur at around the same epoch as the minima and maxima of these activity proxies. For most of the time span investigated, the oscillations are out of phase. This out-of-phase behavior was also corroborated by a cross-correlation analysis. These results suggest that the physical processes that generate and drive the long-term evolution of the global solar activity proxies may be coupled to the short-term local physical processes driving the macrospicules, and, therefore modulate the properties of local dynamics.
We have succeeded in detecting local obstacles automatically in a 200-m-long RE-123 coated conductor (CC) by introducing deep-learning based image recognition in reel-to-reel scanning Hall probe ...microscopy (RTR-SHPM). Longitudinal critical current ( I c ) homogeneity in CCs is one of the most important requirements for practical applications. Usually, such properties as I c variation as a function of longitudinal coordinate is characterized by magnetization measurements adopting Hall probe array as a de facto standard characterization method for ensuring uniformity in long CCs. In this measurement, local I c drop indicates the existence of current blocking obstacles. The group of authors also developed a magnetic microscopy applicable to reel-to-reel continuous measurements, RTR-SHPM, which makes it possible to visualize two-dimensional critical current density ( J c ) in the tape plane because of its high-resolution imaging along the tape width. As a result, more elaborate defect detection has been enabled. However, in the conventional technique, the observation depends on the human eye in order for characterizing detailed features of the obstacles such as shape and size especially in case with a small I c drop, therefore, there was a limit to analyze the J c mapping with such detailed information extending to thousands of images in the long tape of several 100 of meters. In this study, the image classification based on the deep learning method was introduced in our magnetic microscopy. The analytical model classifies the input image into the defect position and the normal position, respectively, together with a heat map and a score of confidence in the recognition. As a result, we have succeeded in detecting obstacles automatically from more than 4,000 of J c images with a high accuracy of 98.5%. Furthermore, we revealed the existence of the obstacles which were not distinguishable by the local I c criterion. This method allows us to clarify the origin of the instability of long CC wire and will have a strong impact as an evaluation technique for dramatically improving the reliability of the CCs.
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