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Contains fulltext : 228246.pdf (Publisher’s version ) (Closed access) This eye-tracking study explored how phonological encoding and speech production planning for successive words are coordinated in adult readers with dyslexia (N = 22) and control readers (N = 25) during rapid automatized naming (RAN). Using an object-RAN task, we orthogonally manipulated the word-form frequency and phonological neighborhood density of the object names and assessed the effects on speech and eye movements and their temporal coordination. In both groups, there was a significant interaction between word frequency and neighborhood density: shorter fixations for dense than for sparse neighborhoods were observed for low- but not for high-frequency words. This finding does not suggest a specific difficulty in lexical phonological access in dyslexia. However, in readers with dyslexia only, these lexical effects percolated to the late processing stages, indicated by longer offset eye-speech lags. We close by discussing potential reasons for this finding, including suboptimal specification of phonological representations and deficits in attention control or in multi-item coordination. 16 p.

The author of the book has made a significant contribution to the development of such a genre of historical literature as political biography. The quality of the Russian language used in the monograph is highly appreciated. Though a number of summary assessments which the author applies to characterize the personality of the central figure of the book involve some criticism

The fundamental work offered for consideration presents the results of fortyyear sociological research of the phenomenon of youth, one of the main goals ofwhich was to justify an effective youth policy. It is argued that overall the domestic version of sociology of youth, it being a sub-discipline of sociology, has a century of history and in a number of aspects is superior to its foreign counterpart. The book highlights how important it is in regards to socio-economic development and political progress for Russian youth to possess such qualities as morality, national orientation, a high level of culture, innovativeness, entrepreneurial spirit, health, all of which imply their active inclusion into social practices. To this end, it is necessary to modernize the system of youth policy management, strengthening the possibilities of effective interaction between the state, the youth community, social institutions and civil society.

Extensive structural and functional studies have been carried out in the field of nucleocytoplasmic transport. Nuclear transport factors, such as Importin-α/-β, recognize nuclear localization signals (NLSs) on cargo, and together with the small GTPase Ran, facilitate their nuclear localization. However, it is now emerging that binding of nuclear transport factors to NLSs not only mediates nuclear transport but also contributes to a variety of cellular functions in eukaryotes. Here, we describe recent advances that reveal how NLSs facilitate diverse cellular functions beyond nuclear transport activity. We review separately NLS-mediated regulatory mechanisms at different levels of biological organization, including: (1) assembly of higher-order structures; (2) cellular organelle dynamics; and (3) modulation of cellular stress responses and viral infections. Finally, we provide mechanistic insights into how NLSs can regulate such a broad range of functions via their structural and biochemical properties.

Network slicing in 5G RAN enables building logical networks on top of physical infrastructure. In case of RAN spectrum resources are divided into small bandwidth parts then, the network function in core network, namely Network Slice Admission Control Function (NSACF) enables to limit the count of user equipments (UE) and packet data unit (PDU) sessions in a slice. This paper presents negative results and a practical analysis of how many UEs and PDU sessions can be allowed to use if available bandwidth is fixed and tries to evaluate the optimal count of subslices at this bandwidth. In case of slice resource overutilization there are 2 options: increase resources or move UEs to another slice. In this paper, the feasibility of the other option is evaluated in case of fixed overall bandwidth where resource increase is not possible. Results show that infrastructure can afford as few slices as possible and slicing does not help if theoretical capacity is exceeded.

Before diving into the details of NG‐Radio Access Network (RAN) architecture, it is important to have at least a high‐level understanding of the whole 5G System (5GS). To provide such a high‐level picture, this chapter describes the functionalities of the physical layer, the protocol stack, the NG‐RAN, and the 5G Core (5GC) network. It provides an overview of all the components of 5GS, with emphasis on what is new compared with 4G. 5GS architecture is functionally split into 5GC and RAN (NR) functionalities similar to older cellular technologies. 5GC functionality is responsible for the overall user registrations and session management functions, while NR provides the radio access‐related functionalities. The chapter also describes the subset of the most commonly used NG‐Application Protocol procedures and the New Radio physical layer, focusing on differences compared with Long‐Term Evolution.

Despite the widespread use of rapid automatized naming (RAN) tasks in reading and mathematics research, little is known about the direction of their relation. Thus, in this longitudinal study, we examined the direction of the relation between RAN and reading/mathematics accuracy and fluency. One-hundred and eighty-three Grade 1 Chinese children from Shanghai (84 girls and 99 boys; Mage = 85.98 months, SD = 3.76) were followed until Grade 5 and were assessed annually on RAN, reading, and mathematics. The results of standard cross-lagged analyses indicated that the effects were unidirectional (earlier RAN predicted future reading and mathematics fluency), specific (earlier RAN predicted further growth only in fluency outcomes), and consistent (with one exception, earlier RAN predicted every subsequent reading and mathematics fluency). Theoretical implications of these findings are discussed in light of the language in which the study was conducted and the developmental span covered. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

Why do social movement participants turn to elections to advance their goals? Little scholarship has examined movement–election connections at the micro level, and cases from nondemocratic settings are few. After the 2014 Umbrella Movement in Hong Kong failed to achieve substantive results, very few occupiers ran as candidates in the next two general elections. Drawing on interviews with Umbrella candidates and campaign assistants, I argue that after being politicized by the occupation, those candidates used the authoritarian elections to prolong their challenge. They ran to prove that the occupation, though it had failed, did enjoy popular support, thus turning the elections into electoral “moments”: eruptions of civic energy. Their campaigns were also direct challenges to the existing parties. However, they were constrained by electoral logic. Candidates therefore devised various tactics to justify their decision, and to differentiate themselves from conventional candidates.

This study processes and analyses the documentation about Thai, of which, the most important one is the material in the field. Thereby, the popularity of the rong-tien legend has been shown to exist in Thai communities, including North-West Thai and Thai in the Thanh hoa - Nghe an highland. Since then, the research gives conclusion about the universality of the rong-tien legend in the multi-ethnic Vietnamese nation.

The importin α/β transport machinery mediates the nuclear import of cargo proteins that bear a classical nuclear localization sequence (cNLS). These cargo proteins are linked to the major nuclear protein import factor, importin‐β, by the importin‐α adapter, after which cargo/carrier complexes enter the nucleus through nuclear pores. In the nucleus, cargo is released by the action of RanGTP and the nuclear pore protein Nup2, after which the importins are recycled to the cytoplasm for further transport cycles. The nuclear export of importin‐α is mediated by Cse1/CAS. Here, we exploit structures of functionally important complexes to identify residues that are critical for these interactions and provide insight into how cycles of protein import and recycling of importin‐α occur in vivo using a Saccharomyces cerevisiae model. We examine how these molecular interactions impact protein localization, cargo import, function and complex formation. We show that reversing the charge of key residues in importin‐α (Arg44) or Cse1 (Asp220) results in loss of function of the respective proteins and impairs complex formation both in vitro and in vivo. To extend these results, we show that basic residues in the Nup2 N‐terminus are required for both Nup2 interaction with importin‐α and Nup2 function. These results provide a more comprehensive mechanistic model of how Cse1, RanGTP and Nup2 function in concert to mediate cNLS‐cargo release in the nucleus., Directional transport of cargoes between the nucleus and cytoplasm is mediated by receptors that bind cargo in one compartment and release cargo into a destination compartment. Cargoes that contain a cNLS are recognized by importin‐α in the cytoplasm. Release factors including the importin‐α export receptor, Cse1, and a nuclear pore complex protein, Nup2, ensure efficient cargo delivery into the nucleus. Interactions defined by previous structural studies are required for productive interactions between importin‐α, Cse1, and Nup2 to occur in vivo.

According to structural and functional similarities, small GTP-binding proteins can be divided into five distinct families, in which, Ras-related nuclear protein (Ran) GTPases regulates proteins an...

Rapid Automatized Naming (RAN), a task in which participants must name a series of items as rapidly as possible, has been very useful as a measure of cognitive abilities that predict reading skill both in children and in young adults. This study examined RAN performance of 100 younger adults (YAs) and 80 cognitively healthy older adults (OAs) in order to provide evidence about how performance on the task is influenced by cognitive aging. RAN performance was highly reliable, both for YAs and OAs, but showed only a few weak correlations to other measures of individual differences used to study cognitive aging. RAN performance did not differ significantly by age group for symbolic (letter and digit) RANs but was significantly slower for OAs than YAs for non-symbolic (color and object) RANs, consistent with results showing OAs had less overlap than YAs in the factors associated with performance on these two types of RANs. This pattern suggests that healthy aging is associated with little to no decline in the ability to sustain overlapping encoding and production of a sequence of items when it involves the form-to-form mapping required by symbolic RANs but with measurable decline in that ability when it involves the concept-to-form mapping required by non-symbolic RANs.

Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.

Significance Repeat-associated non-AUG (RAN) proteins accumulate in patient brains and contribute to a growing number of neurodegenerative diseases. There is an urgent need to understand why expression of these proteins does not require canonical or near-cognate AUG start codons and to develop ways to block RAN protein production. We show several types of repeat-expansion RNAs activate the double-stranded RNA-dependent protein kinase (PKR) pathway and that blocking PKR reduces RAN protein levels in cells. PKR is activated in C9orf72 ALS/FTD human and mouse brains and PKR inhibition using AAV-PKR-K296R or the FDA-approved drug metformin decreases RAN protein levels and improves disease in ALS/FTD mice. Targeting PKR using gene therapy or metformin are promising therapeutic approaches for C9orf72 ALS/FTD and other expansion diseases.

Segregation Distorter (SD) is an autosomal meiotic drive system found worldwide in natural populations of Drosophila melanogaster. This gene complex induces the preferential and nearly exclusive transmission of the SD chromosome in SD/SD+ males. This selfish propagation occurs through the interplay of the Sd locus, its enhancers and the Rsps locus during spermatid development. The key distorter locus, Sd, encodes a truncated but enzymatically active RanGAP (RanGTPase-activating protein), a key nuclear transport factor in the Ran signaling pathway. When encoded by Sd, RanGAP is mislocalized to the nucleus interior, which then traps Ran inside the nucleus and disrupts nuclear import. As a result of this aberrant nuclear transport, a process known as the histone-to-protamine transition that is required for proper spermatid condensation fails to occur in SD/SD+ males. In this process, sperm-specific protamine proteins enter the spermatid nucleus and replace the formerly chromatin-complexed histones. Previously, we have shown that mutations affecting nuclear import and export can enhance distortion in an SD background, thus verifying that a defect in nuclear transport is responsible for the unequal transmission of chromosomes. Herein, we show that specifically reducing protamines induces distortion in an SD background, verifying that protamines are transported via the RanGAP/GEF pathway and indicating that E(SD) plays a significant and unique role in the process of distortion.

Despite its popularity, chromatin immunoprecipitation followed by sequencing (ChIP-seq) remains a tedious (>2 d), manually intensive, low-sensitivity and low-throughput approach. Here, we combine principles of microengineering, surface chemistry, and molecular biology to address the major limitations of standard ChIP-seq. The resulting technology, FloChIP, automates and miniaturizes ChIP in a beadless fashion while facilitating the downstream library preparation process through on-chip chromatin tagmentation. FloChIP is fast (6 to 500 cells), is scalable and parallelized, and supports antibody- or sample-multiplexed ChIP on both histone marks and transcription factors. In addition, FloChIP’s interconnected design allows for straightforward chromatin reimmunoprecipitation, which allows this technology to also act as a microfluidic sequential ChIP-seq system. Finally, we ran FloChIP for the transcription factor MEF2A in 32 distinct human lymphoblastoid cell lines, providing insights into the main factors driving collaborative DNA binding of MEF2A and into its role in B cell-specific gene regulation. Together, our results validate FloChIP as a flexible and reproducible automated solution for individual or sequential ChIP-seq.

Neljäs kirjoittaja Doris Kofler, Free University of Bozen-Bolzano We investigated the predictive power of cognitive skills and background variables of 769 first and second grade children learning to read two orthographically different languages Finnish and German in three countries Finland, Germany and Italy. Main results from stepwise regression models showed that in all countries word reading at first grade was best predicted by letter-sound-connection, as found in other transparent orthographies. In Italy and Finland also phoneme blending, a demanding phoneme awareness skill, was a good predictor. Surprisingly, in Germany initial phoneme identification which is a basic phone awareness skill, and mother's occupation predicted first grade reading. At second grade in Finland and Germany the strongest predictors of word reading were rapid naming, in Finland also short-term-memory and in Germany and Italy reading level at the first grade. Results indicate that both orthographical and educational differences in the three countries can account for different predictors in reading.

Background: Ranitidine (RAN) is one of the common drugs associated with idiosyncratic adverse drug reactions (IADRs) in humans. It was found to be associated with severe adverse drug reactions due to the presence of contaminants such as N-Nitrosodimethylamine (NDMA) which is claimed to be carcinogenic. As a consequence, on April 1, 2020, United States Food and Drug Administration (USFDA) had decided to call off all the RAN products from the market. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. Purpose: To summarize and analyze the reason behind the withdrawal of RAN products from the market and whether ranitidine will be available again in future or will FDA withdraw approvals of ranitidine National Drug Authority (NDA) and an abbreviated new drug application (ANDA)? Methods: We performed a systematic PubMed/MEDLINE search of studies investigating the reason behind the withdrawal of RAN products and explored the possible mechanism associated with RAN induced hepatotoxicity.Conclusion: RAN induced liver injury is difficult to diagnose and study because of its relative rarity and unpredictive occurrence. Recent studies suggest that most of the RAN associated idiosyncratic reactions may lead to hepatocyte damage, followed by a series of events, such as activation of specific T- and B-cells, release of proinflammatory mediators like TNFα, interleukins, various cytokines and chemokines. The exact cause of RAN associated idiosyncratic hepatotoxicity is not clear yet. More studies must be carried out on this to know about the exact reason behind RAN associated hepatotoxicity.

The article discusses the current problems of implementing 5G networks in the existing infrastructure of urban networks. A general overview of development options for the transport network operators in various data transmission areas has been given. The possibilities of applying new standards and technologies for building high-performance fifth-generation networks have been considered. The increased requirements for speed performance of new transport networks dictate new rules for the design of linear-cable structures and the choice of equipment at intermediate communication nodes. Greater investments at the initial stage of launching a new network are the key to successful servicing thousands of new subscribers and IoT devices.

Background: Genetic factors could account for recurrent pregnancy loss (RPL). The RAN gene is a member of the ”large RAS family” and a small GTPase that is essential for the translocation of Ribonucleic acid (RNA) and proteins through the nuclear pore. Mutation in the RAN constitutive gene could stop DNA synthesis and alter the expression of genes in the uterus, likely playing a role in recurrent miscarriage. Objective: The aim was to investigate the frequency of RAN (rs 14035) polymorphism in women with RPL compared with women without abortion history. Materials and Methods: In this case-control study, 100 women with at least two consecutive miscarriages before the 20th wk of gestation and having spouses with karyotype and normal sperm parameters as the case group and 100 women with no history of abortion and having at least one successful pregnancy and normal delivery as the control group. The groups were age matched (20-40 yr). The rs 14035 polymorphism of RAN gene was investigated by Polymerase Chain Reaction- Restriction Fragment Length poly morphism technique and the frequency of which was compared between the two groups. Results: The frequency of TT, TC, and CC genotypes of RAN gene polymorphism in the case group were 9%, 40%, and 51%, respectively, and in the control group were 11%, 38%, and 51%, respectively. There was no significant difference in the genotypes between two groups (p = 0.882). Conclusion: According to our results, it seems that RAN polymorphism (rs 14035) is not associated with the risk of RPL in this study population. Key words: RAN gene, Repeated abortion, Polymorphism, PCR-RFLP.

Small GTP-binding proteins represent a highly conserved signaling module in eukaryotes that regulates diverse cellular processes such as signal transduction, cytoskeletal organization and cell polarity, cell proliferation and differentiation, intracellular membrane trafficking and transport vesicle formation, and nucleocytoplasmic transport. These proteins function as molecular switches that cycle between active and inactive states, and this cycle is linked to GTP binding and hydrolysis. In this review, the roles of the plant complement of small GTP-binding proteins in these cellular processes are described, as well as accessory proteins that control their activity, and current understanding of the functions of individual members of these families in plants—with a focus on the model organism Arabidopsis—is presented. Some potential novel roles of these GTPases in plants, relative to their established roles in yeast and/or animal systems, are also discussed.

As an indispensable structure protein, the herpes simplex virus 1 (HSV-1) UL6 has been described to exert numerous roles in viral proliferation. However, its exact subcellular localization and subcellular transport mechanism is not well known. In the present study, by utilizing confocal fluorescent microscopy, UL6 was shown to mainly locate in the nucleus in enhanced yellow fluorescent protein or Flag tag fused expression plasmid-transfected cells or HSV-1-infected cells, whereas its predicted nuclear localization signal was nonfunctional. In addition, by exploiting dominant negative mutant and inhibitor of different nuclear import receptors, as well as co-immunoprecipitation and RNA interference assays, UL6 was established to interact with importin α1, importin α7 and transportin-1 to mediate its nuclear translocation under the help of Ran-mediated GTP hydrolysis. Accordingly, these results will advance the knowledge of UL6-mediated biological significances in HSV-1 infection cycle.

Background: To complete its replication cycle, HIV-1 requires the nucleocytoplasmic export of intron-containing viral mRNAs. This process is ordinarily restricted by the cell, but HIV overcomes the block by means of a viral protein, Rev, and an RNA secondary structure found in all unspliced and incompletely spliced viral mRNAs called the Rev Response Element (RRE). In vivo activity of the Rev-RRE axis requires Rev binding to the RRE, oligomerization of Rev to form a competent ribonucleoprotein complex, and recruitment of cellular factors including Crm1 and RanGTP in order to export the targeted transcript. Sequence variability is observed among primary isolates in both Rev and the RRE, and the activity of both can be modulated through relatively small sequence changes. Primary isolates show differences in Rev-RRE activity and a few studies have found a correlation between lower Rev-RRE activity and slower progression of clinical disease. Lower Rev-RRE activity has also been associated with the evasion of cytotoxic T lymphocyte mediated killing. Conclusions: The HIV-1 Rev-RRE regulatory axis is an understudied mechanism by which viral adaptation to diverse immune milieus may take place. There is evidence that this adaptation plays a role in HIV pathogenesis, particularly in immune evasion and latency, but further studies with larger sample sizes are warranted.

Perceivable objects are customarily termed as concepts and their representations (localist-distributed, modality-specific, or experience-dependent) are ingrained in our lives. Despite a considerable amount of computational modeling research focuses on concrete concepts, no comprehensible method for abstract concepts has hitherto been considered. Abstract concepts can be viewed as a blend of concrete concepts. We use this view in our proposed model, Regulated Activation Network (RAN), by learning representations of non-convex abstract concepts without supervision via a hybrid model that has an evolving topology. First, we describe the RAN’s modeling process through a Toy-data problem yielding a performance of 98.5%(ca.) in a classification task. Second, RAN’s model is used to infer psychological and physiological biomarkers from students’ active and inactive states using sleep-detection data. The RAN’s capability of performing classification is shown using five UCI benchmarks, with the best outcome of 96.5% (ca.) for Human Activity recognition data. We empirically demonstrate the proposed model using standard performance measures for classification and establish RAN’s competency with five classifiers. We show that the RAN adeptly performs classification with a small amount of data and simulate cognitive functions like activation propagation and learning.

Purpose Colorectal cancer is one of the most malignant tumors in the world, and the incidence is increasing every year. MicroRNAs (miRNA) are small non-coding RNAs that are involved in a variety of physiological or pathological processes. Abnormal expression of microRNA-802 (miR-802) has been demonstrated in various types of cancer. However, the expression and biological role of miR-802 in human colorectal cancer remain largely unknown. Methods Here, we used quantitative real-time PCR (qRT-PCR) to measure miR-802 expression levels in colorectal cancer tissues and cell lines. Cell Counting Kit-8 (CCK-8) was used to assess the effect of miR-802 on colorectal cancer cell viability. Migration and invasion assays were performed to determine the effect of miR-802 on metastasis of colon tumor cells by transwell analysis. Luciferase activity assays were used to confirm the target of miR-802. Results The results show that miR-802 is significantly downregulated in colorectal cancer tissues and cell lines. Overexpression of miR-802 profoundly inhibited viability, migration and invasion of colorectal cancer cells. In addition, we have newly discovered that the Ras-associated nucleus (RAN) is a direct target of miR-802 which could reverse the effects induced by miR-802 overexpression in colorectal cancer cells. Conclusion In conclusion, our study shows that miR-802 is downregulated in colorectal cancer, and overexpression of miR-802 inhibits colorectal cancer cell viability, migration and invasion by directly targeting RAN.

The inactive state has become the main status of user equipments (UEs) in 5G networks due to its low power consumption and energy saving features. To deal with the massive paging and location update signaling overhead from the movement of inactive UEs, in this article, we propose a UE assisted dynamic Radio Access Network (RAN) notification area (RNA) configuration scheme to effectively reduce the latency and minimize the total number of paging and RNA update overhead of inactive UEs. The delay sensitivity factor is designed in the dynamic RNA configuration scheme to classify UEs into two categories: delay-sensitive and delay-tolerant. In order to satisfy the delay requirement for various UEs, the parallel and the sequential paging schemes are adopted to the delay-sensitive and the delay-tolerant UEs respectively. The proposed dynamic RNA configuration scheme consists of two steps: online decision making and offline RNA optimization. In the online decision making step, the optimal RNA list will be assigned to UEs according to the activities of UEs while in the offline RNA optimization step, the optimal RNA list is generated to minimize the overall signaling messages. Additionally, we further extensively investigate the dynamic RNA configuration update process in both the theoretical and the practical manner. The performance of the proposed scheme is evaluated and the results demonstrate the efficiency in achieving the design goals, which could obtain a considerable performance improvement compared to the related schemes in previous literatures.

Background The small GTPase Ran is upregulated in multiple cancers and fundamental for cancer cell survival and progression, but its significance and molecular mechanisms in colorectal cancer (CRC) remain elusive. Methods Ran expression was detected in CRC cell lines and tumour tissues. In vitro and in vivo functional assays were performed to examine the effects of Ran on cell proliferation and metastasis. The pathways and effectors regulated by Ran were explored by an unbiased screening. Bioinformatics prediction and experimental validation were used to identify the miRNA regulator for Ran. Results Ran expression was frequently increased in metastatic CRC cells and tissues, especially in metastatic tissues. The upregulation of Ran correlated with poor CRC patient prognosis. Ran silencing reduced proliferation and metastasis of CRC cells both in vitro and in vivo. Ran regulated the expression of EGFR and activation of ERK and AKT signalling pathways. miR-802 was identified as an upstream regulator of Ran and miR-802 overexpression resulted in antiproliferative and antimetastatic activities. Conclusion Our study demonstrates the oncogenic roles and underlying mechanisms of Ran in CRC and the novel miR-802/Ran/EGFR regulatory axis may provide potential biomarkers for the treatment of CRC.