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Abstract—Latest generation mobile networks aim to use multi-tier heterogeneous cellular networks integrated with cloud computing to provide users with low latency and energy-aware service. However, for high bandwidth and low latency services, edge/fog computing comes into the scenario. In edge/fog computing, the intermediate devices between end users and cloud participate in processing and storage of data as well as execution of applications. Mobile edge computing provides cloud computing services at the edge of mobile network, which facilitates the developers, service providers as well as the users. Internet of Things (IoT) has become a principal component to design smart technological solutions for our daily life. For low latency and high bandwidth services, edge computing assisted IoT has become the pillar for the development of smart home, smart health etc. This chapter will discuss the overview of mobile edge computing along with its real time applications.

Astrocytic calcium dynamics have been implicated in the encoding of sensory information, and modulating them has been shown to impact behavior. However, real-time calcium activity of astrocytes in the hippocampus of awake mice has never been investigated. We used 2-photon microscopy to chronically image CA1 astrocytes as mice ran in familiar or novel virtual environments and obtained water rewards. We found that astrocytes exhibit persistent ramping activity towards the reward location in a familiar environment, but not in a novel one. Using linear decoders, we could precisely predict the location of the mouse in a familiar environment from astrocyte activity alone. We could not do the same in the novel environment, suggesting astrocyte spatial activity is experience dependent. This is the first indication that astrocytes can encode location in spatial contexts, thereby extending their known computational capabilities, and their role in cognitive functions.

Visual attention span (VAS) has been shown to make a unique contribution to reading skills over and above phonological awareness and rapid automatized naming (RAN). In the current study, we examined the nature of this unique relationship. In particular, we tested whether VAS reflects the retrieval of a verbal code, serial processing, or parallel multi-element processing. To this end, we presented 180 third graders with tasks for VAS, discrete RAN, and serial RAN as well as serial and discrete reading of short words, pseudowords, and long words. VAS was found to correlate with serial RAN but not with discrete RAN. More important, similar relations were found for VAS with serial and discrete reading, which clearly differed from the format-specific relations between RAN and reading. Together, these findings suggest that VAS and serial RAN are related but are associated with reading for different reasons. Serial RAN appears to reflect serial interword reading processes, whereas the unique contribution of VAS mainly involves the parallel processing of orthographic units within words.

Summary: eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. In Drosophila, 5MP/Kra represses neuronal toxicity and enhances the lifespan in an FXTAS disease model. These results implicate 5MP in protecting cells from unwanted byproducts of non-AUG translation in neurodegeneration.

The MYC oncoprotein and its family members N-MYC and L-MYC are known to drive a wide variety of human cancers. Emerging evidence suggests that MYC has a bi-directional relationship with the molecular clock in cancer. The molecular clock is responsible for circadian (~24 h) rhythms in most eukaryotic cells and organisms, as a mechanism to adapt to light/dark cycles. Disruption of human circadian rhythms, such as through shift work, may serve as a risk factor for cancer, but connections with oncogenic drivers such as MYC were previously not well understood. In this review, we examine recent evidence that MYC in cancer cells can disrupt the molecular clock; and conversely, that molecular clock disruption in cancer can deregulate and elevate MYC. Since MYC and the molecular clock control many of the same processes, we then consider competition between MYC and the molecular clock in several select aspects of tumor biology, including chromatin state, global transcriptional profile, metabolic rewiring, and immune infiltrate in the tumor. Finally, we discuss how the molecular clock can be monitored or diagnosed in human tumors, and how MYC inhibition could potentially restore molecular clock function. Further study of the relationship between the molecular clock and MYC in cancer may reveal previously unsuspected vulnerabilities which could lead to new treatment strategies.

Review of: Nobody’s Girl Friday: The Women Who Ran Hollywood, J. E. Smyth (2018) New York: Oxford University Press, 328 pp., ISBN 978-0-19-084082-2, h/bk, $29.95

Dipeptide repeat proteins (DPRs) occur via repeat-associated non-AUG (RAN) translation. In this issue of Neuron, McEachin et al. (2020) show that the aggregation-prone poly(GA)-rich chimeric DPRs determine divergent poly(GP) mediated pathology between C9ALS/FTD and SCA36.

Repeat-associated non-AUG (RAN) translation is a noncanonical translation initiation event that occurs at nucleotide-repeat expansion mutations that are associated with several neurodegenerative diseases, including fragile X-associated tremor ataxia syndrome (FXTAS), ALS, and frontotemporal dementia (FTD). Translation of expanded repeats produces toxic proteins that accumulate in human brains and contribute to disease pathogenesis. Consequently, RAN translation constitutes a potentially important therapeutic target for managing multiple neurodegenerative disorders. Here, we adapted a previously developed RAN translation assay to a high-throughput format to screen 3,253 bioactive compounds for inhibition of RAN translation of expanded CGG repeats associated with FXTAS. We identified five diverse small molecules that dose-dependently inhibited CGG RAN translation, while relatively sparing canonical translation. All five compounds also inhibited RAN translation of expanded GGGGCC repeats associated with ALS and FTD. Using CD and native gel analyses, we found evidence that three of these compounds, BIX01294, CP-31398, and propidium iodide, bind directly to the repeat RNAs. These findings provide proof-of-principle supporting the development of selective small-molecule RAN translation inhibitors that act across multiple disease-causing repeats.

REV7, also termed mitotic arrest–deficient 2-like 2 (MAD2L2 or MAD2B), acts as an interaction module in a broad array of cellular pathways, including translesion DNA synthesis, cell cycle control, and nonhomologous end joining. Numerous REV7 binding partners have been identified, including the human small GTPase Ras-associated nuclear protein (RAN), which acts as a potential upstream regulator of REV7. Notably, the Shigella invasin IpaB hijacks REV7 to disrupt cell cycle control to prevent intestinal epithelial cell renewal and facilitate bacterial colonization. However, the structural details of the REV7–RAN and REV7–IpaB interactions are mostly unknown. Here, using fusion protein and rigid maltose-binding protein tagging strategies, we determined the crystal structures of these two complexes at 2.00–2.35 Å resolutions. The structures revealed that both RAN and IpaB fragments bind the “safety belt” region of REV7, inducing rearrangement of the C-terminal β-sheet region of REV7, conserved among REV7-related complexes. Of note, the REV7-binding motifs of RAN and IpaB each displayed some unique interactions with REV7 despite sharing consensus residues. Structural alignments revealed that REV7 has an adaptor region within the safety belt region that can rearrange secondary structures to fit a variety of different ligands. Our structural and biochemical results further indicated that REV7 preferentially binds GTP-bound RAN, implying that a GTP/GDP-bound transition of RAN may serve as the molecular switch that controls REV7's activity. These results provide insights into the regulatory mechanism of REV7 in cell cycle control, which may help with the development of small-molecule inhibitors that target REV7 activity.

Sirtuin 7 (SIRT7) is an NAD+-dependent lysine deacetylase that regulates diverse biological processes. We recently observed that SIRT7 deficiency suppresses the nuclear accumulation of p65, which is a component of nuclear factor kappa B. However, the underlying molecular mechanism remains elusive. In this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. The nuclear export of p65 was facilitated in SIRT7-deficient fibroblast cells, while the nuclear export was inhibited in SIRT7-deficient cells expressing K37R-Ran (deacetylation-mimicking mutant). Additionally, the nuclear export of p65 in wild-type fibroblast cells was promoted by K37Q-Ran (acetylation-mimicking mutant). K37Q-Ran exhibited an increased ability to bind to chromosome region maintenance 1 (CRM1), which is a major nuclear receptor that mediates the export of cargo proteins, and enhanced the binding between p65 and CRM1. These data suggest that SIRT7 is a lysine deacetylase that targets the K37 residue of Ran to suppress the nuclear export of p65.

Objective: The purpose of this research was to conduct an exploratory study of the performance of Brazilian children on the Rapid Automatic Naming (RAN) test, examining schooling effects of schooling and associations with reading speed, comprehension, and reading level for each of the RAN subtests of colour, numbers, letters, and objects. Methods: Participants were 97 children, aged 7–11 years, enrolled in the first to fifth grade of elementary public education. Results: The findings indicated a school-year effect on RAN performance, with recurrent differences in grades 1–4 and no effect in RAN Numbers. Correlations ranged from moderate to high for reading level, speed, and comprehension. In addition, multiple linear regression analysis indicated that RAN Letters could significantly predict performance in the three reading abilities studied. Conclusion: Thus, the study provided initial evidence of RAN’s performance in testing Brazilian children’s phonological processing as a form of predictive monitoring of reading development in school-age children as it relates to scholastic progress and reading speed, comprehension, and level.

Learning reading involves skills such as phonological awareness, alphabetic knowledge and naming speed. Different teaching methods have a different effect on their acquisition differently. This study analyses 1) the differential effect of analytic and synthetic phonological methods of acquiring reading skills, 2) whether the differences found, according to the method, followed the same pattern in the first four years of initial reading and 3) the effectiveness of the methods of teaching reading on reading performance in each one of the four years of initial reading studies. Therefore, cross-sectional study was conducted. Sample consisted of 614 children of kindergarten (aged 4 and 5), and first and second grade students (aged 6 and 7) from schools located in Valencia and Castellon. Instruments applied was RAN (Rapid Automatized Naming Test) and BIL (Initial Reading Program) (aged 4 and 5), and ACL (Reading Comprehension Test), DST-J (Dyslexia Screening Test) and a subtest of PROLEC-R (Battery for the Evaluation of Reading Processes revised) (aged 6 and 7). The analysis consisted of some t-tests to compare the effect of the two study methods at different developmental stages on the analyzed variables and two-factor (year and method) MANOVAs were used for each educational level. Results show the weight of the major reading skills involved vary throughout the process, so phonological awareness, naming speed or alphabetic knowledge have greater relevance during the early school years, while naming speed stands apart as the only variable at ages 6 and 7, when reading requirements change. The synthetic phonological method enhances the most important skills in learning to read in kindergarten, while in Primary Education, the global method provides more successful results in reading performance. The differential influence method has on reading performance also depends on the educational stage.

The study of the factors that influence the acquisition of reading facilitates the early detection of reading learning difficulties. Phonological awareness, alphabetic knowledge, naming speed has been highlighted as predictive skills. All of them are acquired throughout school but they do not have the same degree of involvement in the different phases of reading learning. This seems to depend, in part, on the teaching method of the reading used. The objectives of this study were to identify and analyze the skills involved in the beginning of reading and writing in Early Childhood Education that predict the level of reading comprehension in Primary Education and know the differential weight that phonological awareness, naming speed and other skills involved in the reading process have during the first years of instruction depending on the method used. Therefore, a longitudinal study was carried out in which 130 students enrolled in educational centres located in the provinces of Castellón and Valencia. 52% of them were studying according to the syntheticphonological method and 48% were following the analytic method. Instruments applied was RAN (Rapid Automatized Naming Test) and BIL (Initial Reading Program), and ACL (Reading Comprehension Test). The structural equation model has shown that in both methods the naming speed at 4 years has a significant effect on the variables related to the beginning of the reading at 5 years and these variables influence the reading comprehension of these children at 6 years. This indicates that naming speed constitutes the foundation of the phonological coding process on which the reader process is based.

Branching microtubule nucleation by its molecular mediators has never been directly observed in animal cells. By imaging augmin, γ-TuRC, and microtubules with high spatiotemporal resolution, Verma and Maresca quantitatively define the sequential steps of augmin-mediated branching microtubule nucleation in dividing Drosophila cells., Centrosome-mediated microtubule (MT) nucleation has been well characterized; however, numerous noncentrosomal MT nucleation mechanisms exist. The branching MT nucleation pathway envisages that the γ-tubulin ring complex (γ-TuRC) is recruited to MTs by the augmin complex to initiate nucleation of new MTs. While the pathway is well conserved at a molecular and functional level, branching MT nucleation by core constituents has never been directly observed in animal cells. Here, multicolor TIRF microscopy was applied to visualize and quantitatively define the entire process of branching MT nucleation in dividing Drosophila cells during anaphase. The steps of a stereotypical branching nucleation event entailed augmin binding to a mother MT and recruitment of γ-TuRC after 15 s, followed by nucleation 16 s later of a daughter MT at a 36° branch angle. Daughters typically remained attached throughout their ∼40-s lifetime unless the mother depolymerized past the branch point. Assembly of branched MT arrays, which did not require Drosophila TPX2, enhanced localized RhoA activation during cytokinesis.

Protein arginine deiminases (PADs) are calcium-dependent enzymes that mediate the post-translational conversion of arginine into citrulline. Dysregulated PAD activity is associated with numerous autoimmune disorders and cancers. In breast cancer, PAD2 citrullinates histone H3R26 and activates the transcription of estrogen receptor (ER) target genes. However, PAD2 lacks a canonical Nuclear Localization Sequence (NLS), and it is unclear how this enzyme is transported into the nucleus. Here, we show for the first time that PAD2 translocates into the nucleus in response to calcium signaling. Using BioID2, a proximity-dependent biotinylation method for identifying interacting proteins, we found that PAD2 preferentially associates with ANXA5 in the cytoplasm. Calcium binding to PAD2 weakens this cytoplasmic interaction, which generating a pool of calcium bound PAD2 that can interact with Ran. We hypothesize that this latter interaction promotes the translocation of PAD2 into nucleus. These findings highlight a critical role for ANXA5 in regulating PAD2 and identify an unusual mechanism whereby proteins translocate between the cytosol and nucleus.

China’s State Enterprises offers a nuanced and historically grounded analysis of China’s state-owned enterprises. The term “state enterprise” is specifically chosen to distinguish the state’s abili...

While computerized reading programs were found to enhance reading skills, less is known about their influence on reading self-concept (RSC). The current study aimed to examine short- and long-term effects of two versions of a computerized reading acceleration program (RAP) on reading skills and reading self-concept. One hundred thirty Hebrew-speaking second to third grade students completed 6 months of training with a computerized reading program. The results revealed significant short-term effects in both conditions for RSC. Furthermore, at the posttest, RSC of struggling readers was significantly higher in comparison to the RSC of second to third grade struggling readers from an age-matched normative sample that did not receive the reading training. Importantly, these gains remained evident 6 months after training was completed.

Reformation of a functional nucleus at the end of mitosis is crucial for normal cellular activity. Reconstitution approaches using artificial beads in frog egg extracts have clarified the molecules required for nuclear formation in vitro. However, the spatiotemporal regulation of these components, which is required for the formation of a functional nucleus in living embryos, remains unknown. Here we demonstrate that exogenous DNA introduced in the form of DNA-conjugated beads induces the assembly of an artificial nucleus in living mouse cleavage-stage embryos. Live-cell imaging and immunofluorescence studies revealed that core histones and regulator of chromosome condensation 1 (RCC1) assembled on the DNA, suggesting that nucleosomes were formed. Electron microscopy showed that double-membrane structures, partly extended from annulate lamellae, formed around the beads. Nuclear pore complex-like structures indistinguishable from those of native nuclei were also formed, suggesting that this membranous structure resembled the normal nuclear envelope (NE). However, the reconstituted NE had no nuclear import activity, probably because of the absence of Ras-related nuclear protein (Ran). Thus, DNA is necessary for NE reassembly in mouse embryos but is insufficient to form a functional nucleus. This approach provides a new tool to examine factors of interest and their spatiotemporal regulation in nuclear formation.

Former Nuclear Regulatory Commission (NRC) commissioner and chairman Gregory B. Jaczko is an outsider to the nuclear industry. But in this interview, he offers an inside view of a federal a...

Background/aims The rapid nuclear translocation of signaling proteins upon stimulation is important for the regulation of de-novo gene expression. However, the molecular mechanisms of this translocation is not well understood, although some studies suggest that much of this translocation may be mediated by beta-like importins (Imps). Here we undertook to study the stimulated nuclear shuttling of JNK and p38 MAPKs. Methods For this purpose, we used coimmunoprecipitation, proximity ligation assay, gel filtration and immunostaining to examine the mechanism of nuclear translocation of these proteins. Results We found that JNK and p38 MAPKs translocate into the nucleus in a Ran dependent, but NLS- or NTS-independent manner, unrelated to their catalytic activity. We show that this translocation involves three β-like Imps, 3, 7 and 9. Knockdown of these Imps inhibits the nuclear translocation of the MAPKs, and thereby, phosphorylation of their transcription factor targets. We further demonstrate that the translocation requires the stimulated formation of heterotrimers composed of Imp3/Imp7/MAPK or Imp3/Imp9/MAPK. JNK1/2 and p38α/β bind to either Imp7 or Imp9 upon stimulated post-translational modifications of the two Imps, while Imp3 joins the complex after its stimulation-induced phosphorylation. Once formed, these heterotrimers move to the nuclear envelope where Imp3 remains, while Imp7 or Imp9 escort the MAPKs into the nucleus. Conclusion These results suggest that β-like Imps are central mediators of stimulated nuclear translocation of signaling proteins, providing a central level of regulation of the induction of cellular processes such as transcription upon stimulation.

Fog radio access network (F‐RAN) architectures provide markedly improved performance compared to conventional approaches. In this paper, an efficient genetic algorithm‐based content distribution scheme is proposed that improves the throughput and reduces the transmission delay of a F‐RAN. First, an F‐RAN system model is presented that includes a certain number of randomly distributed fog access points (F‐APs) that cache popular content from cloud and other sources. Second, the problem of efficient content distribution in F‐RANs is described. Third, the details of the proposed optimal genetic algorithm‐based content distribution scheme are presented. Finally, simulation results are presented that show the performance of the proposed algorithm rapidly approaches the optimal throughput. When compared with the performance of existing random and exhaustive algorithms, that of the proposed method is demonstrably superior.

Radio access network (RAN) centralized processing and cell densification have been promising research and development focuses on the fifth generation (5G) network. The required centralized processing and complexity of an ultra-dense network can be effectively managed with the aids of cloud RAN (C-RAN). The focus on the C-RAN is due to its significant benefits concerning cost-effectiveness and performance optimization. However, the C-RAN mobile fronthaul (MFH) demands transport networks with very low-latency and very high-throughput. These requirements for the 5G use cases and deployment scenarios are stringent and uneconomical in the real-life scenarios. These growing requirements can be effectively lessened with the RAN functional split option (FunStiOn) techniques. This paper offers a comprehensive overview of the traditional C-RAN MFH and considers some viable RAN FunStiOn techniques that can help in relaxing the stringent requirements. The related trade-offs of the considered RAN FunStiOns are also presented. In addition, we offer and discuss a number of relevant cost-effective architectural variants that can relatively simplify the DU designs with low-footprints. The presented architectural variants can be employed to support different use cases of the emerging 5G networks depending on the deployment scenarios.

There is a bidirectional communication between the nucleus and the cytoplasm through highly regulated nucleocytoplasmic transport. This process allows the transport of proteins, RNAs, and ribonucleoproteins across the nuclear envelope via the nuclear pore complexes. The nuclear pore complexes are large macromolecular complexes composed of highly conserved proteins called nucleoporins (Nups). Proteins and RNAs are transported across the nuclear pore after binding of cargo transport receptors that interact with specific hydrophobic amino acid repeats of Nups that form a meshwork within the nuclear pore. These transporters include importins that recognize nuclear localization signals (NLS) in their cargo and mediate transport from the cytoplasm to the nucleoplasm and exportins that recognize nuclear export signals (NES) in their cargos and transport their cargo from the nucleus to the cytoplasm. Whereas nucleocytoplasmic transport largely involves protein–protein interactions between transport proteins and nuclear pore Nups, the directionality of transport is determined by a gradient of the small Ras-related nuclear protein (Ran) guanosine triphosphatase (Ran-GTPase). Whereas proteins and most RNA species are transported by these mechanisms, the transport of messenger RNA ribunucleoprotein particles (mRNPs) utilize an independent transport system. Overall, normal nucleocytoplasmic transport mechanisms ensure that transported cargos are retained in their respective compartments and prevent the passage of nonspecific macromolecules. Impaired nucleocytoplasmic transport is a major disease mechanism in neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Huntington disease (HD), and tauopathies. Studies in fly and mouse models, in patient-derived induced pluripotent stem cells (iPSCs), and in brain obtained from autopsy have elucidated pathogenic mechanisms that affect nucleocytoplasmic transport in these disorders. The mechanisms of nucleocytoplasmic transport and its involvement on neurodegenerative disorders have been reviewed recently.1–10

There is a need to rethink the architecture of RAN from a statically configured RAN to a dynamically self-configuring RAN based on the availability of spectrum (licensed/unlicensed), adjacent channel interference, co-channel interference etc. This will ensure that with configurable wide-band RF and programmable SDR and a Big Data Cloud Compute Server we should be able to operate in any usage scenario like eMBB (enhanced Mobile Broad Band), urLLC (ultra-reliable low latency communication) or mMTC (massive machine type communication) specified in IMT 2020 Vision document.

The nuclear pore is the gatekeeper of nucleocytoplasmic transport and signaling through which a vast flux of information is continuously exchanged between the nuclear and cytoplasmic compartments to maintain cellular homeostasis. A unifying and organizing principle has recently emerged that cements the notion that several forms of amyotrophic lateral sclerosis (ALS), and growing number of other neurodegenerative diseases, co-opt the dysregulation of nucleocytoplasmic transport and that this impairment is a pathogenic driver of neurodegeneration. The understanding of shared pathomechanisms that underpin neurodegenerative diseases with impairments in nucleocytoplasmic transport and how these interface with current concepts of nucleocytoplasmic transport is bound to illuminate this fundamental biological process in a yet more physiological context. Here, I summarize unresolved questions and evidence and extend basic and critical concepts and challenges of nucleocytoplasmic transport and its role in the pathogenesis of neurodegenerative diseases, such as ALS. These principles will help to appreciate the roles of nucleocytoplasmic transport in the pathogenesis of ALS and other neurodegenerative diseases, and generate a framework for new ideas of the susceptibility of motoneurons, and possibly other neurons, to degeneration by dysregulation of nucleocytoplasmic transport.

Semicrystalline polymers generally undergo polymorphic crystal transition and lamellae structural changes during stretching deformation. Such stretch-induced multilevel microstructural evolutions a...

Pure organic materials with circularly polarized luminescence (CPL) and delayed fluorescence have gained increasing interest from academic and technological areas. To enhance the solid-state emissi...

Proteins of the superfamily of small guanosine triphosphate hydrolase (GTPase) perform various functions: from the control of cell proliferation to the regulation of vesicular transport. The superfamily of small GTPase Ras includes more than 150 proteins, devided to 5 major families (Arf, Ran, Rho, Ras and Rab), and plays an important role in carcinogenesis. Compared to the other families, the Rab family was investigated by relatively small number studies, which does not equally reflect their role in malignant transformation processes. In our review we have focused on both the subfamily Rab3 and its poorly investigated member Rab3B. Recent findings allow to consider Rab3B not only as a promising diagnostic or prognostic marker for several types of neoplasms, but also is a potential target for antitumor therapy. Our analysis of publicly available transcriptional databases revealed that kidney, lung and liver cancer patients with low Rab3B gene expression demonstrate a better overall five-year survival.

The present study examined the contribution of working memory and Rapid Automatized Naming (RAN) to growth trajectories in number processing, measured using Curriculum-based Measurement (CBM). Participants were two groups of first grade children; one group were at risk of developing mathematics disabilities (MLD-at-risk, n = 32), and the other included typically developing (non-MLD, n = 32) children. Of all the cognitive measures, backward digit span (BDS) tasks and RAN-Letter made significant contributions to differentiating group performance. RAN-Letter provided differentiation of groups, and BDS provided differentiation of the growth rates of both groups in number processing skills. These results highlight the relevance of RAN and BDS for the development of number processing skills in first grade, especially for MLD-at-risk children. BDS is therefore a very important task to be measured during the early stages of mathematics instruction, because it predicts deficits in development of number skills.