Discovery in space of ethanolamine, the simplest phospholipid head group.

Cell membranes are a key element of life because they keep the genetic material and metabolic machinery together. All present cell membranes are made of phospholipids, yet the nature of the first membranes and the origin of phospholipids are still under debate. We report here the presence of ethanolamine in space, [Formula: see text]OH, which forms the hydrophilic head of the simplest and second-most-abundant phospholipid in membranes. The molecular column density of ethanolamine in interstellar space is N = (1.51[Formula: see text]0.07)[Formula: see text], implying a molecular abundance with respect to [Formula: see text] of [Formula: see text] Previous studies reported its presence in meteoritic material, but they suggested that it is synthesized in the meteorite itself by decomposition of amino acids. However, we find that the proportion of the molecule with respect to water in the interstellar medium is similar to the one found in the meteorite ([Formula: see text]). These results indicate that ethanolamine forms efficiently in space and, if delivered onto early Earth, could have contributed to the assembling and early evolution of primitive membranes.

Emergency Floor Plan Digitization Using Machine Learning.

An increasing number of special-use and high-rise buildings have presented challenges for efficient evacuations, particularly in fire emergencies. At the same time, however, the use of autonomous vehicles within indoor environments has received only limited attention for emergency scenarios. To address these issues, we developed a method that classifies emergency symbols and determines their location on emergency floor plans. The method incorporates color filtering, clustering and object detection techniques to extract walls, which were used in combination to generate clean, digitized plans. By integrating the geometric and semantic data digitized with our method, existing building information modeling (BIM) based evacuation tools can be enhanced, improving their capabilities for path planning and decision making. We collected a dataset of 403 German emergency floor plans and created a synthetic dataset comprising 5000 plans. Both datasets were used to train two distinct faster region-based convolutional neural networks (Faster R-CNNs). The models were evaluated and compared using 83 floor plan images. The results show that the synthetic model outperformed the standard model for rare symbols, correctly identifying symbol classes that were not detected by the standard model. The presented framework offers a valuable tool for digitizing emergency floor plans and enhancing digital evacuation applications.

Interpretable Classification of Tauopathies with a Convolutional Neural Network Pipeline Using Transfer Learning and Validation against Post-Mortem Clinical Cases of Alzheimer's Disease and Progressive Supranuclear Palsy.

Neurodegenerative diseases, tauopathies, constitute a serious global health problem. The etiology of these diseases is unclear and an increase in their incidence has been projected in the next 30 years. Therefore, the study of the molecular mechanisms that might stop these neurodegenerative processes is very relevant. Classification of neurodegenerative diseases using Machine and Deep Learning algorithms has been widely studied for medical imaging such as Magnetic Resonance Imaging. However, post-mortem immunofluorescence imaging studies of the brains of patients have not yet been used for this purpose. These studies may represent a valuable tool for monitoring aberrant chemical changes or pathological post-translational modifications of the Tau polypeptide. We propose a Convolutional Neural Network pipeline for the classification of Tau pathology of Alzheimer's disease and Progressive Supranuclear Palsy by analyzing post-mortem immunofluorescence images with different Tau biomarkers performed with models generated with the architecture ResNet-IFT using Transfer Learning. These models' outputs were interpreted with interpretability algorithms such as Guided Grad-CAM and Occlusion Analysis. To determine the best classifier, four different architectures were tested. We demonstrated that our design was able to classify diseases with an accuracy of 98.41% on average whilst providing an interpretation concerning the proper classification involving different structural patterns in the immunoreactivity of the Tau protein in NFTs present in the brains of patients with Progressive Supranuclear Palsy and Alzheimer's disease.

Application of a Control Scheme Based on Predictive and Linear Strategy for Improved Transient State and Steady-State Performance in a Single-Phase Quasi-Z-Source Inverter.

Z and quasi-Z-source inverters (Z/qZSI) have a nonlinear impedance network on their dc side, which allows the system to behave as a buck-boost converter in their outputs. The challenges derived from the qZSI topology include (a) the control of the voltage and current on its nonlinear impedance network, (b) the dynamic coupling between the ac and dc variables, and (c) the fact that a unique set of switches are used to manage the power at dc and ac side of the system. In this work, a control scheme that combines a PWM linear control strategy and a strategy based on finite control state model predictive control (FCS-MPC) is proposed. The linear approach works during steady state, while the FCS-MPC works during transient states, either in the start-up of the converter or during sudden reference changes. This work aims to show that the performance of this control proposal retains the best characteristics of both schemes, which allows it to achieve high-quality waveforms and error-free steady state, as well as a quick dynamic response during transients. The feasibility of the proposal is validated through experimental results.

Structure-function studies of tetrahydroprotoberberine N-methyltransferase reveal the molecular basis of stereoselective substrate recognition.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse class of plant-specialized metabolites that have been particularly well-studied in the order Ranunculales. The N-methyltransferases (NMTs) in BIA biosynthesis can be divided into three groups according to substrate specificity and amino acid sequence. Here, we report the first crystal structures of enzyme complexes from the tetrahydroprotoberberine NMT (TNMT) subclass, specifically for GfTNMT from the yellow horned poppy (Glaucium flavum). GfTNMT was co-crystallized with the cofactor S-adenosyl-l-methionine (dmin = 1.6 Å), the product S-adenosyl-l-homocysteine (dmin = 1.8 Å), or in complex with S-adenosyl-l-homocysteine and (S)-cis-N-methylstylopine (dmin = 1.8 Å). These structures reveal for the first time how a mostly hydrophobic L-shaped substrate recognition pocket selects for the (S)-cis configuration of the two central six-membered rings in protoberberine BIA compounds. Mutagenesis studies confirm and functionally define the roles of several highly-conserved residues within and near the GfTNMT-active site. The substrate specificity of TNMT enzymes appears to arise from the arrangement of subgroup-specific stereospecific recognition elements relative to catalytic elements that are more widely-conserved among all BIA NMTs. The binding mode of protoberberine compounds to GfTNMT appears to be similar to coclaurine NMT, with the isoquinoline rings buried deepest in the binding pocket. This binding mode differs from that of pavine NMT, in which the benzyl ring is bound more deeply than the isoquinoline rings. The insights into substrate recognition and catalysis provided here form a sound basis for the rational engineering of NMT enzymes for chemoenzymatic synthesis and metabolic engineering.

Codeinone reductase isoforms with differential stability, efficiency and product selectivity in opium poppy.

Codeinone reductase (COR) catalyzes the reversible NADPH-dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (Papaver somniferum). It also irreversibly reduces neopinone, which forms by spontaneous isomerization in aqueous solution from codeinone, to neopine. In a parallel pathway involving 3-O-demethylated analogs, COR converts morphinone to morphine, and neomorphinone to neomorphine. Similar to neopine, the formation of neomorphine by COR is irreversible. Neopine is a minor substrate for codeine O-demethylase (CODM), yielding morphine. In the plant, neopine levels are low and neomorphine has not been detected. Silencing of CODM leads to accumulation of upstream metabolites, such as codeine and thebaine, but does not result in a shift towards higher relative concentrations of neopine, suggesting a mechanism in the plant for limiting neopine production. In yeast (Saccharomyces cerevisiae) engineered to produce opiate alkaloids, the catalytic properties of COR lead to accumulation of neopine and neomorphine as major products. An isoform (COR-B) was isolated from opium poppy chemotype Bea's Choice that showed higher catalytic activity than previously characterized CORs, and it yielded mostly neopine in vitro and in engineered yeast. Five catalytically distinct COR isoforms (COR1.1-1.4 and COR-B) were used to determine sequence-function relationships that influence product selectivity. Biochemical characterization and site-directed mutagenesis of native COR isoforms identified four residues (V25, K41, F129 and W279) that affected protein stability, reaction velocity, and product selectivity and output. Improvement of COR performance coupled with an ability to guide pathway flux is necessary to facilitate commercial production of opiate alkaloids in engineered microorganisms.

Structural and Functional Studies of Pavine N-Methyltransferase from Thalictrum flavum Reveal Novel Insights into Substrate Recognition and Catalytic Mechanism.

Benzylisoquinoline alkaloids (BIAs) are produced in a wide variety of plants and include many common analgesic, antitussive, and anticancer compounds. Several members of a distinct family of S-adenosylmethionine (SAM)-dependent N-methyltransferases (NMTs) play critical roles in BIA biosynthesis, but the molecular basis of substrate recognition and catalysis is not known for NMTs involved in BIA metabolism. To address this issue, the crystal structure of pavine NMT from Thalictrum flavum was solved using selenomethionine-substituted protein (dmin = 2.8 Å). Additional structures were determined for the native protein (dmin = 2.0 Å) as well as binary complexes with SAM (dmin = 2.3 Å) or the reaction product S-adenosylhomocysteine (dmin = 1.6 Å). The structure of a complex with S-adenosylhomocysteine and two molecules of tetrahydropapaverine (THP; one as the S conformer and a second in the R configuration) (dmin = 1.8 Å) revealed key features of substrate recognition. Pavine NMT converted racemic THP to laudanosine, but the enzyme showed a preference for (±)-pavine and (S)-reticuline as substrates. These structures suggest the involvement of highly conserved residues at the active site. Mutagenesis of three residues near the methyl group of SAM and the nitrogen atom of the alkaloid acceptor decreased enzyme activity without disrupting the structure of the protein. The binding site for THP provides a framework for understanding substrate specificity among numerous NMTs involved in the biosynthesis of BIAs and other specialized metabolites. This information will facilitate metabolic engineering efforts aimed at producing medicinally important compounds in heterologous systems, such as yeast.

Effects of backscattering in high-Q, large-area silicon-on-insulator ring resonators.

We demonstrate large-area silicon-on-insulator ring resonators with Q values of about 2×106 at critical coupling and 3.6×106 for heavily undercoupled conditions. A model has been developed to understand the impact of waveguide backscattering and subcomponent imperfections on the spectral response of our devices. The model predicts the appearance of signals at ports that would not have them under backscattering-free, ideal-power-splitting conditions. The predictions of our model are shown to match the phenomena observed in our measurements.

Detection of hepatitis C virus RNA in saliva of patients with active infection not associated with periodontal or liver disease severity.

BACKGROUND: Hepatitis C virus (HCV) is mainly transmitted by parenteral route, being blood transfusion and intravenous drug use the most frequent risk factors. However, it has been suggested that there are other routes of transmission. There are several studies where HCV RNA has been detected in saliva of patients infected with HCV, and epidemiological studies have proposed the dental treatments as possible risk factors for HCV transmission. The purpose of this study was to detect the presence of HCV RNA in saliva of patients with active infection and associating with periodontal or liver disease. METHODS: Patients with quantifiable HCV-RNA in serum were enrolled in the study. Periodontal disease was assessed using the modified gingival index (MGI). Presence of dental plaque was assessed with the use of disclosing tablets. Patients were clinically and laboratory evaluated to identify the stage of liver disease, the HCV RNA was determinate in saliva by nested RT-PCR. To determine associations between different parameters univariate and multivariate analysis were used. RESULTS: A total of 45 patients were included. Of these patients, 21 (46.6%) had hepatitis, 23 (51.1%) had cirrhosis and one patient (2.4%) presented hepatocellular carcinoma (HCC). Viral loads in serum ranged from 2.31-6.68 log IU/ml with a mean of 5.46 log IU/ml (95% CI 5.23-5.70). HCV RNA was positive in saliva of 29 patients (64.4%) and was not detected in 16 (35.6%). For univariate analysis three independent variables were associated with the detection of HCV-RNA in saliva: gender, viral load and dental plaque and multivariate analysis only one independent variable viral load >5.17 log IU/mL remained significantly associated with the detection of HCV in saliva (p = 0.0002). A statistical difference was observed when viral load was analyzed, log 5.85 IU/mL (95% CI 5.67-6.02) for patients with HCV in saliva vs. log 4.77 IU/mL (95% CI 4.35-5.19) for patients without HCV in saliva (p = 0.0001). The detection of HCV-RNA in saliva was more frequent in patients with relatively high serum viral loads. CONCLUSION: HCV-RNA in saliva was associated with the level of serum viral load but not with periodontal or liver disease severity.

Gold-Catalyzed "Back-to-Front" Synthesis of 4-Silyloxyindoles.

A series of pyrrol-yn-glycol derivatives were easily prepared from simple pyrroles through a three-step sequence involving hydroxyalkylation-alkynylation-O-silylation. Their reaction with IPrAuNTf2 triggers a C2-pyrrole attack onto the activated alkyne and subsequent highly selective 1,2-migration of the oxyalkyl group in the intermediate spirocycle. This approach enables the efficient synthesis of a wide selection of regioselectively functionalized 4-hydroxyindoles, which represent important yet challenging indole scaffolds, in high yields.

Detection Capability of 89Sr and 90Sr Using Liquid Scintillation Counting.

ABSTRACT: We developed a new method for simultaneous determination of 89Sr and 90Sr with an emphasis on detectability. The samples were digested, and Sr was chemically purified followed by a single count on a liquid scintillation counter in three windows overlapping the 90Sr, 89Sr, and 90Y peaks. Gamma spectrometry was used to measure 85Sr, added for chemical recovery. The method was tested on 18 water samples spiked at levels from 9 to 242 Bq of 89Sr and 90Sr, with either single radionuclides or their mixtures. In addition, eight method blanks were measured. The data were analyzed numerically by solving a system of linear equations for 89Sr and 90Sr activities as analytes and 90Y activity as a participating component. The total uncertainties of the results were calculated numerically using variances and covariances. The average bias from the known activities was -0.3% (range from -3.6 to 3.1%) for 90Sr and - 1.5% (range from -10.1 to 5.1%) for 89Sr. The En-scores were within -1.0 and 1.0 at 95% confidence level. The detection capabilities of this method were determined by means of the decision threshold LC and the limit of detection referred to as the minimum detectable activity. All relevant uncertainties were propagated into the LC and minimum detectable activity. In addition, detection limits were calculated for the purpose of Safe Drinking Water Act monitoring. The detection capabilities were compared with the regulatory requirements in the US and EU for food and water. For samples spiked with either pure 89Sr or 90Sr, false positives were observed for the opposite radionuclide exceeding the above LC values. This was attributed to interference by the spiked activity. A new method was developed to calculate decision and detectability curves in the presence of interference.

Catalyst- and Substrate-Controlled Regiodivergent Synthesis of Carbazoles through Gold-Catalyzed Cyclizations of Indole-Functionalized Alkynols.

A wide variety of regioselectively substituted carbazole derivatives can be synthesized by the gold-catalyzed cyclization of alkynols bearing an indol-3-yl and an additional group at the homopropargylic positions. The regioselectivity of the process can be controlled by both the oxidation state of the gold catalyst and the electronic nature of the substituents of the alkynol moiety. The 1,2-alkyl migration in the spiroindoleninium intermediate, generated after indole attack to the activated alkyne, is favored with gold(I) complexes and for electron-rich aromatic substituents at the homopropargylic position, whereas the 1,2-alkenyl shift is preferred when using gold(III) salts and for alkyl or non-electron-rich aromatic groups.

Gamma Radioactivity Detection Limits and Associated Radionuclide Intakes Study in Artificial Human Urine Using Sodium-iodide and High-purity Germanium Detectors.

ABSTRACT: The performance of several gamma detectors was investigated for emergency urine bioassay screening of two radionuclides of concern: 131 I and 137 Cs. Unspiked artificial urine samples were measured for 10 min each on four different gamma detectors: 80% relative efficiency high-purity Ge detector in standard shielding, 102% low-background high-purity Ge detector equipped with top muon shield, 78% high-purity Ge well detector in standard shielding, and 4″ × 4″ NaI well detector in standard shielding. The measured gamma spectra were analyzed in two ways: (1) for the 364-keV peak region of 131 I and 662-keV peak region of 137 Cs and (2) for the total counts in the full energy spectrum (50-2,048 keV). The results were analyzed using the principles of signal detection theory according to the Currie's formalism extended by a complete uncertainty propagation. This enabled calculation of the detection capability in terms of detection limit (Bq L -1 ) of urine, the latter referred to as minimum detectable activity. The NaI well detector had the lowest minimum detectable activities for total spectra, whereas the high-purity Ge well detector had the lowest peak minimum detectable activity values. Minimum detectable inhalation and ingestion intakes from urine bioassay were calculated from the minimum detectable activity values for urine collection 1 d, 1 wk, and 1 mo past the initial intake. The calculated intakes were compared with annual limits on intake. The results are interpreted with respect to a large-scale radiological emergency response.

A cosmic stream of atomic carbon gas connected to a massive radio galaxy at redshift 3.8.

The growth of galaxies in the early Universe is driven by accretion of circum- and intergalactic gas. Simulations have predicted that steady streams of cold gas penetrate the dark matter halos of galaxies and provide the raw material necessary to sustain star formation. We report a filamentary stream of gas that extends for 100 kiloparsecs and connects to the massive radio galaxy 4C 41.17. We detected the stream using submillimeter observations of the 3P1 to 3P0 emission from the [C i] line of atomic carbon, a tracer of neutral atomic or molecular hydrogen gas. The galaxy contains a central gas reservoir that is fueling a vigorous starburst. Our results show that the raw material for star formation can be present in cosmic streams outside galaxies.

A Novel Automatic Quantification Protocol for Biomarkers of Tauopathies in the Hippocampus and Entorhinal Cortex of Post-Mortem Samples Using an Extended Semi-Siamese U-Net.

Efforts have been made to diagnose and predict the course of different neurodegenerative diseases through various imaging techniques. Particularly tauopathies, where the tau polypeptide is a key participant in molecular pathogenesis, have significantly increased their morbidity and mortality in the human population over the years. However, the standard approach to exploring the phenomenon of neurodegeneration in tauopathies has not been directed at understanding the molecular mechanism that causes the aberrant polymeric and fibrillar behavior of the tau protein, which forms neurofibrillary tangles that replace neuronal populations in the hippocampal and cortical regions. The main objective of this work is to implement a novel quantification protocol for different biomarkers based on pathological post-translational modifications undergone by tau in the brains of patients with tauopathies. The quantification protocol consists of an adaptation of the U-Net neural network architecture. We used the resulting segmentation masks for the quantification of combined fluorescent signals of the different molecular changes tau underwent in neurofibrillary tangles. The quantification considers the neurofibrillary tangles as an individual study structure separated from the rest of the quadrant present in the images. This allows us to detect unconventional interaction signals between the different biomarkers. Our algorithm provides information that will be fundamental to understanding the pathogenesis of dementias with another computational analysis approach in subsequent studies.

Variability of plasma homovanillic acid over 13 months in patients with schizophrenia; relationship with the clinical response and the Wisconsin card sort test.

In the present study we have measured, on a monthly basis, the concentration of plasma homovanillic acid (pHVA) in schizophrenic patients during 13 months of their pharmacological treatment. The average pHVA values of each patient were within the range of 7.30-17.70 ng/ml and the coefficients of variation for each patient (CV %) were within the range of 13-33%. Half of the patients that showed higher pHVA CV% values also showed higher scores on the Brief Psychiatric Rating Scale at the beginning of the study, and improved more after 6 months, when compared to the remaining 50% with lower CV% values. There was no significant relationship between the scores of the Wisconsin Card Sort Test and the concentration or the CV% of the pHVA of each patient. A greater variability in the pHVA may be associated with a greater plasticity of the dopaminergic system and a better clinical response.

The opinion of psychiatric residents on the training they receive.

The results of a survey carried out by the Spanish National Board for Psychiatric Training among psychiatric trainees in their third and fourth year of training are presented and discussed. The aim of the survey was to know the resident's opinion and level of satisfaction on the training they had received. The results indicate that the majority of residents had complied with the National Program for Psychiatric Training requirements and that their level of satisfaction was fair. However a small but substantial percentage did not comply adequately with the program, particularly in relation with the training in psychotherapy, research methodology, old age psychiatry, neurology and general medicine. Based on these results the National Board puts forward some recommendations meant for those involved in the training of psychiatrists in Spain.

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis.

BACKGROUND: To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). METHODS: A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. RESULTS: One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. CONCLUSIONS: Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.

Thiols in the ISM: first detection of HC(O)SH and confirmation of C2H5SH.

The chemical compounds carrying the thiol group (-SH) have been considered essential in recent prebiotic studies regarding the polymerization of amino acids. We have searched for this kind of compounds toward the Galactic Centre quiescent cloud G+0.693-0.027. We report the first detection in the interstellar space of the trans-isomer of monothioformic acid (t-HC(O)SH) with an abundance of ~ 1 × 10-10. Additionally, we provide a solid confirmation of the gauche isomer of ethyl mercaptan (g-C2H5SH) with an abundance of ~ 3 × 10-10, and we also detect methyl mercaptan (CH3SH) with an abundance of ~ 5 × 10-9. Abundance ratios were calculated for the three SH-bearing species and their OH-analogues, revealing similar trends between alcohols and thiols with increasing complexity. Possible chemical routes for the interstellar synthesis of t-HC(O)SH, CH3SH and C2H5SH are discussed, as well as the relevance of these compounds in the synthesis of prebiotic proteins in the primitive Earth.

Ultra-Short Term Evaluation of Coronary Vessel Wall Changes in Reference Segments Adjacent to Culprit Lesions in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Culprit lesions of ST-segment elevation myocardial infarction (STEMI) patients are friable, soft, and prone to disruption during primary percutaneous coronary intervention (pPCI). The presence of dissections in reference vessel segments (RVSs), adjacent to stented culprit lesions, and dynamic luminal changes in proximal or distal RVSs have not yet been investigated. We therefore sought to assess the healing patterns of edge dissections and the changes of lumen area at RVSs within 1 week post stent implantation in patients with STEMI. METHODS: In the MATRIX trial (ClinicalTrials.gov NCT01433627), optical coherence tomography (OCT) was performed at the end of pPCI and within 1 week during staged PCI. The RVS dissection was defined as: type 1 = flap; type 2 = cavity; type 3 = double barrel; and type 4 = fissure. We compared separately the fate of residual dissection and luminal area/dimension by OCT in the target vessel between pPCI and staged PCI, including 1-year clinical outcomes. RESULTS: Out of 151 patients, 46 patients had dissections in 50 RVSs and did not experience worse clinical outcome. Dissections were 44% type 1, 28% type 2, 12% type 3, and 16% type 4. Overall, 18% of the dissections healed. The mean lumen area of the RVS enlarged in 82 patients (59%) from pPCI to staged PCI. Compared with the proximal RVS, there was a significant increase in the lumen diameter at the distal RVS (0.06 ± 0.25 mm vs -0.01 ± 0.21 mm; P=.01). CONCLUSION: Dissections occur frequently after pPCI. One-fifth of them heal within 1 week and do not seem to negatively impact clinical outcomes. Distal RVS lumen area increased compared with proximal RVS, likely reflecting a different vasoconstriction pattern over time.