A transition metal (TM)-free practical synthesis of biologically relevant benzoxazinones has been established via a selective oxidative decarbonylative cleavage of an unstrained C(sp 3)–C(sp 2) ...bond employing iodine, sodium bicarbonate, and t butyl hydroperoxide in DMSO at 95 °C. Control experiments and Density Functional Theory (DFT) calculations suggest that the reaction involves a 1,5H shift and extrusion of CO gas as the key steps. The extrusion of CO has also been established using PMA–PdCl2.
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IJS, KILJ, NUK, PNG, UL, UM
To compare quantitative EEG signal and test-retest reliability of medical grade and consumer EEG systems.
Resting state EEG was acquired by two medical grade (B-Alert, Enobio) and two consumer (Muse, ...Mindwave) EEG systems in five healthy subjects during two study visits. EEG patterns, power spectral densities (PSDs) and test/retest reliability in eyes closed and eyes open conditions were compared across the four systems, focusing on Fp1, the only common electrode. Fp1 PSDs were obtained using Welch's modified periodogram method and averaged for the five subjects for each visit. The test/retest results were calculated as a ratio of Visit 1/Visit 2 Fp1 channel PSD at each 1 s epoch.
B-Alert, Enobio, and Mindwave Fp1 power spectra were similar. Muse showed a broadband increase in power spectra and the highest relative variation across test-retest acquisitions. Consumer systems were more prone to artifact due to eye blinks and muscle movement in the frontal region.
EEG data can be successfully collected from all four systems tested. Although there was slightly more time required for application, medical systems offer clear advantages in data quality, reliability, and depth of analysis over the consumer systems.
This evaluation provides evidence for informed selection of EEG systemsappropriate for clinical trials.
Protocellular membranes are thought to be composed of mixtures of single chain amphiphiles, such as fatty acids and their derivatives, moieties that would have been part of the complex prebiotic ...chemical landscape. The composition and physico-chemical properties of these prebiological membranes would have been significantly affected and regulated by their environment. In this study, pertinent properties were systematically characterized, under early Earth conditions. Two different fatty acids were mixed with their respective alcohol and/or glycerol monoester derivatives to generate combinations of binary and tertiary membrane systems. Their properties were then evaluated as a function of multiple factors including their stability under varying pH, varying Mg
ion concentrations, dilution regimes, and their permeability to calcein. Our results demonstrate how environmental constraints would have acted as important prebiotic selection pressures to shape the evolution of prebiological membranes. The study also illustrates that compositionally diverse membrane systems are more stable and robust to multiple selection pressures, thereby making them more suitable for supporting protocellular life.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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•A database of closely related DNA-binding protein pairs with binding site mapping is developed.•Binding sites and amino acid substitutions in pairs are classified as conserved or ...transient.•Transient residues and their DNA-binding are analyzed structurally and sequence-based predictability.•Machine learning with single sequences clearly outperform PSSM in predicting transient DNA-binding residues.
Sequence-based prediction of DNA-binding residues in a protein is a widely studied problem for which machine learning methods with continuously improving predictive power have been developed. Concatenated rows within a sliding window of a Position Specific Substitution Matrix (PSSM) of the protein are currently used as the primary feature set in almost all the methods of predicting DNA-binding residues. Here we report that these evolutionary profiles are powerful, only for identifying conserved binding sites and fall short for the residue positions which undergo binding to non-binding transitions in closely related proteins. We created a database of highly similar protein pairs with known protein-DNA complexes and investigated differential predictability of conserved and transient binding residues within each pair. Retraining machine learning models uniformly, we compared the predictive powers of the models trained on PSSMs against similarly trained models on sparse-encoded single sequences. We found that the transient binding site predictions from evolutionary profiles are outperformed by single-sequence based models under controlled experiments by as much as 8 percentage points. Thus, we conclude that the PSSM-based models are inadequate to predict high-specificity DNA-binding residues. These findings are of critical significance for the design of mutant- and species-specific DNA ligands and for homology based modeling of protein-DNA complexes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Iron deficiency anaemia (IDA) is a major cause of morbidity and burden of disease worldwide. It can generally be diagnosed by blood testing and remedied by iron replacement therapy (IRT) using the ...oral or intravenous route. The many causes of iron deficiency include poor dietary intake and malabsorption of dietary iron, as well as a number of significant gastrointestinal (GI) pathologies. Because blood is iron-rich it can result from chronic blood loss, and this is a common mechanism underlying the development of IDA-for example, as a consequence of menstrual or GI blood loss.Approximately a third of men and postmenopausal women presenting with IDA have an underlying pathological abnormality, most commonly in the GI tract. Therefore optimal management of IDA requires IRT in combination with appropriate investigation to establish the underlying cause. Unexplained IDA in all at-risk individuals is an accepted indication for fast-track secondary care referral in the UK because GI malignancies can present in this way, often in the absence of specific symptoms. Bidirectional GI endoscopy is the standard diagnostic approach to examination of the upper and lower GI tract, though radiological scanning is an alternative in some situations for assessing the large bowel. In recurrent or refractory IDA, wireless capsule endoscopy plays an important role in assessment of the small bowel.IDA may present in primary care or across a range of specialties in secondary care, and because of this and the insidious nature of the condition it has not always been optimally managed despite the considerable burden of disease- with investigation sometimes being inappropriate, incorrectly timed or incomplete, and the role of IRT for symptom relief neglected. It is therefore important that contemporary guidelines for the management of IDA are available to all clinicians. This document is a revision of previous British Society of Gastroenterology guidelines, updated in the light of subsequent evidence and developments.
A metal and solvent free strategy to functionalize aryl methyl ethers through direct nucleophilic substitution of aryl C–OMe bond has been described. A wide range of O, S, N, and C-centered uncharged ...nucleophiles has been successfully employed. Using this protocol, functional derivatives of bisthiophene have been synthesized in a straightforward way. The reactions are highly atom-efficient and generate methanol as the only byproduct.
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The relationship between heart rate and blood pressure, as well as cardiorespiratory coupling, play a critical role in maintaining blood pressure and organ perfusion during conditions of blood loss. ...Traditional vital signs such as blood pressure, breathing rate, and oxygen saturation are poor markers of blood loss, making it difficult for medics to assess the severity of central hypovolemia. Monitoring hemorrhage is further complicated by the fact that some patients have a low tolerance to hemorrhage and would reach the point of cardiovascular collapse in less time than high tolerant individuals. Therefore, this study aimed to investigate the potential of the physiological interaction between heart rate and blood pressure, and cardiorespiratory coupling to track the progression of simulated hemorrhage, as well as distinguish individuals with low tolerance (LT) from the ones with high tolerance (HT) to hypovolemia. Nineteen subjects (age: 28 ± 6 years; height: 170 ± 7 cm; weight: 68 ± 10 kg) underwent a progressive lower body negative pressure (LBNP) protocol in which the participant was supine inside the chamber for 12 min (baseline) before 12 min of chamber decompression at -20, -30, -40, -50 and -60 mmHg followed by a 12 min recovery period. Twelve subjects reached presyncope before or during -60 mmHg LBNP stage and were considered low tolerant (LT, 12 participants), while the ones who completed -60 mmHg were considered high tolerant (HT, 7 participants). Continuous blood pressure (BP), respiration (RSP), and electrocardiogram (ECG) signals were acquired simultaneously during baseline and each LBNP stage. RR interval was calculated using ECG, while systolic blood pressure (SBP), and pulse pressure were derived from BP waveform. Wavelet transform coherence and convergent cross-mapping techniques were employed to study the physiological interdependence and the causal relationship between heart rate, blood pressure, and respiration. The interaction between blood pressure and heart rate in terms of gain, active gain, and fraction time active(SBP↔RR,PP↔RR)to maintain homeostasis was higher in the LT group during baseline, and LBNP simulated mild, moderate, and severe hemorrhage. The significant time of interaction between SBP and RSP, and the causal effect of blood pressure on respiration were higher in the HT group during baseline compared to the LT group. HT participants also had a higher causal effect of respiration on blood pressure(RSP→SBP,RSP→PP)during -30 and -40 mmHg compared to LT. Moreover, the HT group displayed a higher causal drive of respiratory-related changes in heart rate(RSP→RR)and heart rate mediated changes in respirationRR→RSPduring severe simulated hemorrhage (-40 mmHg) compared to the LT group. The calculated metrics to distinguish between individual LT from HT subjects achieved a sensitivity of 58%-83%, an accuracy of 63%-84%, and an area under the ROC curve of 74%-86%, while the overlap of LT individual responses with HT was 0%-33%. These results indicate the potential of cardiorespiratory coupling, and heart rate and blood pressure interaction toward tracking the progression of hemorrhage and distinguishing individuals with low tolerance to hypovolemia from those with high tolerance. Measurements of such interactions could improve clinical outcomes for patients with low tolerance to hypovolemia and therefore reduce morbidity and mortality through early implementation of life-saving interventions.
Basic vaccination is important to protect children from infectious diseases and illnesses. Adequate levels of vaccination coverage reduce the morbidity and mortality burden among children and promote ...their physical and mental development. This study aimed to assess the association between basic childhood vaccination and the cognitive and learning ability of school children in India. Nationally representative follow-up data on 6183 children from the Indian Human Development Surveys conducted in 2004-05 and 2011-12 (IHDS I & II) were analysed. Children aged 8-10 years who had received all basic vaccines by the age 12 months performed better in a maths test than partially vaccinated or unvaccinated children (OR: 1.87, 95% CI: 1.48, 2.35). Similarly, fully vaccinated children performed better in writing tasks than partially vaccinated or unvaccinated children (OR: 1.77, 95% CI: 1.44, 2.18). Likewise, fully vaccinated children had better reading skills than fully unvaccinated children (OR: 1.60, 95% CI: 1.23, 2.09). The results suggest that enhancing child vaccination coverage can have significant benefits beyond health and can potentially improve the long-term educational outcomes of children.
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