Objective is a joint primary and secondary code (SC) acquisition estimator of tiered Global Navigation Satellite Systems (GNSS) signals. The estimator is based on the Parallel Code Search algorithm (PCS) combined with the Single-Block-Zero-Padding (SBZP) and the Pre-correlation Coherent Accumulation (PCA). The PCA realizes the extension of the coherent integration time in front of the PCS. However, the PCS with the SBZP and the PCA is affected by a navigation/SC bit transition problem due to its cyclic property of a computed Cross-Ambiguity Function (CAF). This CAF is degraded by diverse parasitic fragments and is not directly applicable for an acquisition. A novel analysis of this mechanism and its impact is presented. Then, the proposed modified SBZP (mSBZP) modified PCA (mPCA) PCS estimator is constructed, which does not degrade the CAF. The mSBZP allows the use of the PCS algorithm in the presence of SC bit transition, while the mPCA decreases the number of PCS algorithm calculations by a factor of SC chip count due to SC pre-correlation processing. The algorithm has the same detection performance in comparison with conventional Double-Block-Zero-Padding (DBZP). However, it allows using the PCS of half-length with longer latency up to a factor of SC chip count.

• Keywords
• GNSS signal acquisition, block signal processing, parallel code search algorithm, pre-correlation coherent accumulation, secondary code, single block zero-padding,
• Publication type
• Journal Article MeSH

Recent advances in protein 3D structure prediction using deep learning have focused on the importance of amino acid residue-residue connections (i.e., pairwise atomic contacts) for accuracy at the expense of mechanistic interpretability. Therefore, we decided to perform a series of analyses based on an alternative framework of residue-residue connections making primary use of the TOP2018 dataset. This framework of residue-residue connections is derived from amino acid residue pairing models both historic and new, all based on genetic principles complemented by relevant biophysical principles. Of these pairing models, three new models (named the GU, Transmuted and Shift pairing models) exhibit the highest observed-over-expected ratios and highest correlations in statistical analyses with various intra- and inter-chain datasets, in comparison to the remaining models. In addition, these new pairing models are universally frequent across different connection ranges, secondary structure connections, and protein sizes. Accordingly, following further statistical and other analyses described herein, we have come to a major conclusion that all three pairing models together could represent the basis of a universal proteomic code (second genetic code) sufficient, in and of itself, to "encode" for both protein folding mechanisms and protein-protein interactions.

• Keywords
• Contact map, Protein 3D structure, Protein folding, Protein-protein interactions, Proteomic code, Sense-antisense,
• MeSH
• Amino Acids * chemistry   genetics   MeSH
• Databases, Protein MeSH
• Humans MeSH
• Models, Molecular * MeSH
• Proteins * chemistry   genetics   metabolism   MeSH
• Proteomics * MeSH
• Protein Folding * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amino Acids * MeSH
• Proteins * MeSH

SUMMARY: We present the cpPredictor webserver that implements a novel template-based method for prediction of secondary structure of RNA. The method outperforms available prediction methods as it uses RNA structures of related molecules, either predicted or experimentally identified, as structural templates. The server aims at three major tasks: i) prediction of RNA secondary structures that are difficult to predict by available methods, ii) characterization of uncharacterized RNAs as compatible or incompatible with a chosen template structure and iii) an identification of the most relevant structure among different candidate structures of a single RNA ambiguously predicted by available methods. The web server is accompanied with a comprehensive documentation. AVAILABILITY AND IMPLEMENTATION: The web server is freely available at http://cppredictor.elixir-czech.cz/. The source code of the cpPredictor algorithm is freely available from the webserver under the Apache License, Version 2.0.

• MeSH
• Algorithms MeSH
• Internet MeSH
• Nucleic Acid Conformation * MeSH
• RNA MeSH
• Protein Structure, Secondary MeSH
• Sequence Analysis, RNA MeSH
• Software * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA MeSH

Methods of artificial evolution such as SELEX and in vitro selection have made it possible to isolate RNA and DNA motifs with a wide range of functions from large random sequence libraries. Once the primary sequence of a functional motif is known, the sequence space around it can be comprehensively explored using a combination of random mutagenesis and selection. However, methods to explore the sequence space of a secondary structure are not as well characterized. Here we address this question by describing a method to construct libraries in a single synthesis which are enriched for sequences with the potential to form a specific secondary structure, such as that of an aptamer, ribozyme, or deoxyribozyme. Although interactions such as base pairs cannot be encoded in a library using conventional DNA synthesizers, it is possible to modulate the probability that two positions will have the potential to pair by biasing the nucleotide composition at these positions. Here we show how to maximize this probability for each of the possible ways to encode a pair (in this study defined as A-U or U-A or C-G or G-C or G.U or U.G). We then use these optimized coding schemes to calculate the number of different variants of model stems and secondary structures expected to occur in a library for a series of structures in which the number of pairs and the extent of conservation of unpaired positions is systematically varied. Our calculations reveal a tradeoff between maximizing the probability of forming a pair and maximizing the number of possible variants of a desired secondary structure that can occur in the library. They also indicate that the optimal coding strategy for a library depends on the complexity of the motif being characterized. Because this approach provides a simple way to generate libraries enriched for sequences with the potential to form a specific secondary structure, we anticipate that it should be useful for the optimization and structural characterization of functional nucleic acid motifs.

• Keywords
• DNA, RNA, SELEX, aptamer, artificial evolution, deoxyribozyme, in vitro selection, nucleic acids, ribozyme, secondary structure, synthetic biology,
• MeSH
• Aptamers, Nucleotide genetics   MeSH
• DNA, Catalytic genetics   MeSH
• Gene Library * MeSH
• Nucleic Acid Conformation MeSH
• Mutagenesis MeSH
• Nucleotide Motifs genetics   MeSH
• Inverted Repeat Sequences genetics   MeSH
• Base Pairing MeSH
• Probability MeSH
• Directed Molecular Evolution methods   MeSH
• RNA, Catalytic genetics   MeSH
• Synthetic Biology methods   MeSH
• In Vitro Techniques MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Aptamers, Nucleotide MeSH
• DNA, Catalytic MeSH
• RNA, Catalytic MeSH

Biotic stresses threaten to destabilize global food security and cause major losses to crop yield worldwide. In response to pest and pathogen attacks, plants trigger many adaptive cellular, morphological, physiological, and metabolic changes. One of the crucial stress-induced adaptive responses is the synthesis and accumulation of plant secondary metabolites (PSMs). PSMs mitigate the adverse effects of stress by maintaining the normal physiological and metabolic functioning of the plants, thereby providing stress tolerance. This differential production of PSMs is tightly orchestrated by master regulatory elements, Transcription factors (TFs) express differentially or undergo transcriptional and translational modifications during stress conditions and influence the production of PSMs. Amongst others, microRNAs, a class of small, non-coding RNA molecules that regulate gene expression post-transcriptionally, also play a vital role in controlling the expression of many such TFs. The present review summarizes the role of stress-inducible TFs in synthesizing and accumulating secondary metabolites and also highlights how miRNAs fine-tune the differential expression of various stress-responsive transcription factors during biotic stress.

• Keywords
• miRNAs, pathogen infection, pest attack, plant specialized/secondary metabolites, transcription factors,
• Publication type
• Journal Article MeSH
• Review MeSH

Non-coding RNAs (ncRNA) are essential for all life, and their functions often depend on their secondary (2D) and tertiary structure. Despite the abundance of software for the visualisation of ncRNAs, few automatically generate consistent and recognisable 2D layouts, which makes it challenging for users to construct, compare and analyse structures. Here, we present R2DT, a method for predicting and visualising a wide range of RNA structures in standardised layouts. R2DT is based on a library of 3,647 templates representing the majority of known structured RNAs. R2DT has been applied to ncRNA sequences from the RNAcentral database and produced >13 million diagrams, creating the world's largest RNA 2D structure dataset. The software is amenable to community expansion, and is freely available at https://github.com/rnacentral/R2DT and a web server is found at https://rnacentral.org/r2dt .

• MeSH
• Databases, Nucleic Acid MeSH
• Nucleic Acid Conformation MeSH
• RNA, Untranslated chemistry   MeSH
• Reproducibility of Results MeSH
• RNA chemistry   MeSH
• Sequence Analysis, RNA MeSH
• Software MeSH
• Computational Biology methods   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Names of Substances
• RNA, Untranslated MeSH
• RNA MeSH

BACKGROUND: The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia. METHODS: Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0-3. Time-to-death and the occurrence of adverse events were also reported. RESULTS: From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%-OR 1.49, 95% CI 1.05-2.14; p = 0.026). CONCLUSIONS: In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.

• Keywords
• Cardiac arrest, Hypothermia, Outcome, Shockable rhythm,
• MeSH
• Cardiopulmonary Resuscitation methods   statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Hypothermia, Induced * methods   statistics & numerical data   MeSH
• Treatment Outcome MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear. METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6. RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 % Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods. CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.

• Keywords
• Cardiac arrest, Functional outcome, Oxygen radicals, Oxygenation, Timing,
• MeSH
• Time Factors MeSH
• Hyperoxia * etiology   complications   blood   MeSH
• Intensive Care Units MeSH
• Cardiopulmonary Resuscitation * methods   adverse effects   MeSH
• Oxygen * blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Hypothermia, Induced * methods   MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   complications   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Oxygen * MeSH

BACKGROUND: Survival rates in refractory out-of-hospital cardiac arrest (OHCA) remain low with conventional advanced cardiac life support (ACLS). Extracorporeal life support (ECLS) implantation during ongoing resuscitation, a method called extracorporeal cardiopulmonary resuscitation (ECPR), may increase survival. This study examined whether ECPR is associated with improved outcomes. METHODS: Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this secondary analysis, the effect of ECPR on 180-day survival using Kaplan-Meier estimates and Cox proportional hazard model was examined. RESULTS: Among 256 patients (median age 58 years, 83% male) with median duration of resuscitation 52.5 min (36.5-68), 83 (32%) patients achieved prehospital ROSC during ongoing conventional ACLS prehospitally, 81 (32%) patients did not achieve prehospital ROSC with prolonged conventional ACLS, and 92 (36%) patients did not achieve prehospital ROSC and received ECPR. The overall 180-day survival was 51/83 (61.5%) in patients with prehospital ROSC, 1/81 (1.2%) in patients without prehospital ROSC treated with conventional ACLS and 22/92 (23.9%) in patients without prehospital ROSC treated with ECPR (log-rank p < 0.001). After adjustment for covariates (age, sex, initial rhythm, prehospital ROSC status, time of emergency medical service arrival, resuscitation time, place of cardiac arrest, percutaneous coronary intervention status), ECPR was associated with a lower risk of 180-day death (HR 0.21, 95% CI 0.14-0.31; P < 0.001). CONCLUSIONS: In this secondary analysis of the randomized refractory OHCA trial, ECPR was associated with improved 180-day survival in patients without prehospital ROSC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

• Keywords
• Extracorporeal cardiopulmonary resuscitation, Extracorporeal life support, Extracorporeal membrane oxygenation, Out-of-hospital cardiac arrest, Return of spontaneous circulation,
• MeSH
• Adult MeSH
• Cardiopulmonary Resuscitation * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * methods   MeSH
• Advanced Cardiac Life Support MeSH
• Emergency Medical Services * methods   MeSH
• Out-of-Hospital Cardiac Arrest * therapy   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: It is unclear how invasive resuscitative protocols may impact the time-dependent prognosis of out-of-hospital cardiac arrest (OHCA) resuscitations, or the relationship between intra-arrest transport and outcomes. METHODS: We performed a secondary analysis of the Prague OHCA Study, which randomized refractory OHCAs to "invasive" (intra-arrest transport for possible ECPR initiation) vs. "standard" resuscitation strategies (predominantly performed on-scene). Between groups, we compared outcomes of the initial resuscitation and 180- and 30-day favourable neurological outcomes (CPC 1-2), and within categories based on resuscitation duration (collapse-to-ROSC/ECPR interval). We plotted the dynamic probability of favourable outcomes with increasing durations of unsuccessful resuscitation. RESULTS: Among invasive and standard groups, respectively: 34/124 (27%) vs. 58/132 (44%) had sustained ROSC (difference -17%, 95%CI -5.0, -28); 38/124 (31%) vs. 24/132 (18%) had 30-day favourable neurological outcomes (difference 12%; 95%CI 2.0, 23); and 39/124 (31%) vs. 29/132 (22%) had 180-day favourable neurological outcomes (difference 9.5%; 95%CI -1.3, 20). For favourable outcome cases: standard group resuscitation durations were right-skewed within the first 60 min; for the invasive group the distribution was bimodal, extending to 77 min. For invasive- and standard-treated cases, the probability of favourable outcomes among those in refractory arrest at 30 min was 28% and 7.6%, respectively; declining to 0% at 77 and 60 min. CONCLUSION: In comparison to standard resuscitation, invasive strategy cases had fewer achieve sustained ROSC, however improved overall 30-day favourable neurological outcomes. While standard resuscitation yield was limited to < 60 min, invasive protocols offer a second extended window of potential successful resuscitation.

• Keywords
• Cardiopulmonary resuscitation, Extracorporeal membrane oxygenation, Heart arrest, Out-of-Hospital Cardiac Arrest,
• MeSH
• Time Factors MeSH
• Cardiopulmonary Resuscitation * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Emergency Medical Services methods   MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH