1,508 research outputs found
Computational prediction of splicing regulatory elements shared by Tetrapoda organisms
No full textBackground: auxiliary splicing sequences play an important role in ensuring accurate and efficient splicing by promoting or repressing recognition of authentic splice sites. These cis-acting motifs have been termed splicing enhancers and silencers and are located both in introns and exons. They co-evolved into an intricate splicing code together with additional functional constraints, such as tissue-specific and alternative splicing patterns. We used orthologous exons extracted from the University of California Santa Cruz multiple genome alignments of human and 22 Tetrapoda organisms to predict candidate enhancers and silencers that have reproducible and statistically significant bias towards annotated exonic boundaries.Results: a total of 2,546 Tetrapoda enhancers and silencers were clustered into 15 putative core motifs based on their Markov properties. Most of these elements have been identified previously, but 118 putative silencers and 260 enhancers (~15%) were novel. Examination of previously published experimental data for the presence of predicted elements showed that their mutations in 21/23 (91.3%) cases altered the splicing pattern as expected. Predicted intronic motifs flanking 3' and 5' splice sites had higher evolutionary conservation than other sequences within intronic flanks and the intronic enhancers were markedly differed between 3' and 5' intronic flanks.Conclusion: difference in intronic enhancers supporting 5' and 3' splice sites suggests an independent splicing commitment for neighboring exons. Increased evolutionary conservation for ISEs/ISSs within intronic flanks and effect of modulation of predicted elements on splicing suggest functional significance of found elements in splicing regulation. Most of the elements identified were shown to have direct implications in human splicing and therefore could be useful for building computational splicing models in biomedical researc
Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.
No full textABSTRACT: BACKGROUND: Apolipoprotein B (APOB) is an integral component of the chylomicron and the atherogenic lipoproteins LDL and Lp(a). Exon 26 of the APOB pre-mRNA is unusually long at 7,572 nt and is constitutively spliced. It is also subject to RNA editing in the intestine, which generates a shortened isoform, APOB48, assembled exclusively into chylomicrons. Due to its length, exon 26 contains multiple pseudo splice sites which are not spliced, but which conform to the degenerate splice site consensus. RESULTS: We demonstrate that these pseudo splice sites are repressed by multiple, tandem splicing silencers distributed along the length of exon 26. The distribution of these elements appears to be heterogeneous, with a greater frequency in the middle 4,800 nt of the exon. CONCLUSION: Repression of these splice sites is key to maintaining the integrity of exon 26 during RNA splicing and therefore the correct expression of both isoforms of APOB
A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements
No full textBackground: polymorphic variants and mutations disrupting canonical splicing isoforms are among the
leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing
causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well
understood. We have developed a new tool (SpliceScan II) for predicting the effects of genetic
variants on splicing and cis-regulatory elements. The novel Bayesian non-canonical 5’GC splice site (SS)
sensor used in our tool allows inference on non-canonical exons. Result: our tool performed favorably when compared with the existing methods in the context of genes
linked to the Autism Spectrum Disorder (ASD). SpliceScan II was able to predict more aberrant
splicing isoforms triggered by the mutations, as documented in DBASS5 and DBASS3 aberrant splicing
databases, than other existing methods. Detrimental effects behind some of the polymorphic variations
previously associated with Alzheimer’s and breast cancer could be explained by changes in predicted
splicing patterns. Conclusions: we have developed SpliceScan II, an effective and sensitive tool for predicting the
detrimental effects of genomic variants on splicing leading to Mendelian and complex hereditary
disorders. The method could potentially be used to screen resequenced patient DNA to identify de novo
mutations and polymorphic variants that could contribute to a genetic disorde
A historical comment about the GVT in short interval
No full textIn this article, the author introduces the history, progress and method in the Goldbach-Vinogradov Theorem in short interval by which every sufficiently large odd integer could be expressed as the sum of three almost equal prime numbers.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000183488400018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701MathematicsCPCI-S(ISTP)
Investigation on the DC CB Performance during a Current Interruption Failure at First Current Zero
No full textThe vacuum interrupter is used as the key component of an active DCCB due to its excellent interruption and dielectric recovery characteristics after current zero. The vacuum interrupter can only interrupt the fault currents below the limitation of a critical di/dt and TIV, otherwise it causes a reignition and the interruption failure. In this paper, a detailed active injection DC CB model is developed, considering operation delay of switches, parasitic parameters of switches and thorough control logic. The limitation dielectric strength between the vacuum gap is defined by the cold break down voltage. Based on the numerical modelling, investigation will be performed to see the performance of DC CB with a failure interruption on the first current zero. The simulation results can help to optimize the injection circuit parameters when DC CB has a failure on the first current zero and has to interrupt in the next current zeros. This algorithm will consider predefined threshold of di/dt, chopping current and variable operation time in different scenarios.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Intelligent Electrical Power Grid
Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring
No full textBackground :miRNAs play important roles in the regulation of gene functions. Maternal dietary modifications during pregnancy and gestation have long-term effects on the offspring, but it is not known whether a maternal high fat (HF) diet during pregnancy and lactation alters expression of key miRNAs in the offspring.Results: We studied the effects of maternal HF diet on the adult offspring by feeding mice with either a HF or a chow diet prior to conception, during pregnancy and lactation, and all offspring were weaned onto the same chow diet until adulthood. Maternal HF fed offspring had markedly increased hepatic mRNA levels of peroxisome proliferator activated receptor-alpha (ppar-alpha) and carnitine palmitoyl transferase-1a (cpt-1a) as well as insulin like growth factor-2 (Igf2). A HF diet induced up-regulation of ppar-alpha and cpt-1a expression in the wild type but not in Igf2 knock out mice. Furthermore, hepatic expression of let-7c was also reduced in maternal HF fed offspring. Among 579 miRNAs measured with microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced expression of miR-709 (a highly expressed miRNA), miR-122, miR-192, miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483* (reduced by ~4.9 fold) was validated by qPCR. We found that methyl-CpG binding protein 2 was the common predicted target for miR-709, miR-let7s, miR-122, miR-194 and miR-26a using our own purpose-built computer program.Conclusion: Maternal HF feeding during pregnancy and lactation induced co-ordinated and long-lasting changes in expression of Igf2, fat metabolic genes and several important miRNAs in the offspring
Technical performance of different DC CB technologies for future HVDC Grids
No full textMultiterminal dc (MTDC) network is preferred due to its reliability, security of supply and flexibility. However, MTDC network also comes with the protection challenges resulting from dc faults. Hence, the dc circuit breaker (DC CB) is imperative in such a network. In these recent years, several DC CB technologies have been proposed and demonstrated by different manufacturers. Besides, these DC CB technologies differ from each other in terms of the speed of operation, interruption capability and costs. Hence, for the optimal performance of the MTDC network, a study of the co-ordinative operation of different DC CB technologies is required. In this thesis, two typical types of DC CBs are modelled in detail and implemented in a 4-terminal MTDC network in PSCAD environment, by considering operation time, interruption capability and interruption characteristics. The obtained results are used for DC CB’s selection optimization methodology for the future MTDC networks. Similarly, a scaled model of DC CB has to be analysed in terms of its interruption capability in MTDC network considering various scenarios. Therefore, in this master thesis, technical performance of DC CB technologies is conducted for a test and multiterminal dc network in EMT based software environment.The DC CB is the key to unlock the reliable operation of a Multi-terminal direct current network, whereas fast, effective and accurate models are frequently needed for system-level studies. Due to higher subsystem components in DC CB, a detailed DC CB model creates a bottleneck in the network analysis. This thesis also proposes and compares, an average model with a detailed model of Voltage source converter Assisted Resonant Current (VARC) and Mechanical DC CB in MTDC Network in terms of their performance and computation time for two typical simulation cases. The average and detailed model is modelled and simulated on the PSCAD/EMTDC electromagnetic transient platform. Decisively, this thesis concludes by presenting an accurate response of the average model during the fast transient event, showing additional computational advantage.<br/
The characteristics of the polish CB-language
No full textThe paper analyzes the language used by drivers on the Citizens’ Band radio (CB radio). The
users of the radio communicate only in speech, their communication is highly pragmatic and
based on partnership. The utterances alternate between formal and informal ones, which
determines the range and register of vocabulary. Drivers often use diminutives and polite
addresses thus creating the atmosphere of mutual respect and cordiality, which can be
comforting and reassuring for strangers who happen to establish a casual contact. The specific
language used on the CB radio fulfils two basic functions: it creates a sense of community
among drivers and protects the information passed on as warnings. At the end of the paper,
the author appends a comprehensive glossary of the CB language
Modelling of GO/PPy/CB and rGO/PPy/CB nanocomposite supercapacitors using an electrical equivalent circuit
No full textIn this study, supercapacitor device performances of graphene oxide (GO), reduced graphene oxide (rGO), polypyrrole (PPy), and ternary nanocomposites of GO, PPy, and carbon black (CB) as GO/PPy/CB and rGO/PPy/CB were firstly prepared using the in situ polymerization method. The obtained composite materials were characterized by scanning electron microscopy energy–dispersive X-ray (SEM–EDX), Fourier-transform infrared-attenuated transmission reflectance (FTIR-ATR), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), atomic force microscopy (AFM), Brunauer–Emmett–Teller (BET) surface area analysis, cyclic voltammetry (CV), galvanostatic charge–discharge (GCD), and electrochemical impedance spectroscopic (EIS) methods. The highest specific capacitance (Csp) of the rGO/PPy/CB nanocomposite was obtained as Csp = 39, 48, and 27.86 F × g?1 by three methods of CV, GCD, and EIS, respectively. Two equivalent circuit models of Rs(CdlRct) and LRs(QRct) were presented to compare equivalent circuit parameters. Theoretical and experimental values are compatible with each other. Graphical abstract: [Figure not available: see fulltext.]. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Trakya ÜniversitesiThis work is a part of the research project NKUBAP.01.?NAP.19.213 approved by the Scientific and Research Project Unit (Tekirdag Namik Kemal University). This research grant is gratefully acknowledged. We thank Prof. Dr. Murat Turkyilmaz and Ozan Yoruk (PhD student) for TGA and BET measurements (TUTAGEM, Trakya University, Turkey)
„Misiek z okularami na hulajnodze”, czyli o CB-polszczyźnie
No full textThe paper analyzes the language used by drivers on the Citizens’ Band radio (CB radio). The users of the radio communicate only in speech, their communication is highly pragmatic and based on partnership. The utterances alternate between formal and informal ones, which determines the range and register of vocabulary. Drivers often use diminutives and polite addresses thus creating the atmosphere of mutual respect and cordiality, which can be comforting and reassuring for strangers who happen to establish a casual contact. The specific language used on the CB radio fulfils two basic functions: it creates a sense of community among drivers and protects the information passed on as warnings. At the end of the paper, the author appends a comprehensive glossary of the CB language
- …
