Codeine, tramadol, and hydrocodone have been associated with morbidity and death in children, secondary to respiratory depression. The aim of this paper is to increase awareness of this issue and to ...encourage clinicians to prescribe safer alternatives such as morphine, ibuprofen, or paracetamol.
Defining the structural features of a transition state is important in understanding a folding reaction. Here, we use Φ-value and double mutant analyses to probe the folding transition state of the ...membrane protein bacteriorhodopsin. We focus on the final C-terminal helix, helix G, of this seven transmembrane helical protein. Φ-values could be derived for 12 amino acid residues in helix G, most of which have low or intermediate values, suggesting that native structure is disrupted at these amino acid positions in the transition state. Notably, a cluster of residues between E204 and M209 all have Φ-values close to zero. Disruption of helix G is further confirmed by a low Φ-value of 0.2 between residues T170 on helix F and S226 on helix G, suggesting the absence of a native hydrogen bond between helices F and G. Φ-values for paired mutations involved in four interhelical hydrogen bonds revealed that all but one of these bonds is absent in the transition state. The unstructured helix G contrasts with Φ-values along helix B that are generally high, implying native structure in helix B in the transition state. Thus helix B seems to constitute part of a stable folding nucleus while the consolidation of helix G is a relatively late folding event. Polarization of secondary structure correlates with sequence position, with a structured helix B near the N terminus contrasting with an unstructured C-terminal helix G.
The issue of soft errors is an important emerging concern in the design and implementation of future microprocessors. The authors examine the impact of soft errors on two different ...microarchitectures: a DLX processor for embedded applications and a high-performance alpha processor. The results contrast impact of soft errors on combinational and sequential logic, identify the most vulnerable units, and assess soft error impact on the application.
Intra-uterine metabolic environment predicts newborns’ cardiac morphology, metabolism and future health. In adults, gut microbiota composition relates to altered cardiac structure and metabolism. We ...investigated the relationship between gut microbiota colonization and fetal cardiac growth.
Bacterial composition in meconium samples of 26 healthy, full-term newborns was assessed by 16S rDNA gene sequencing. Its relationship with birth echocardiographic parameters, and the interaction with cord blood levels of inflammatory markers were investigated. Correlative and cluster analysis, linear discriminant analysis effect size and predictive functional analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were applied. Fetal left ventricle growth was related to gut microbiota composition at birth. Specifically, left ventricle posterior wall thickness (LVPW) greater than 4 mm was associated with lower microbiota beta and alpha diversity, depletion (LDA score > 3) of several bacteria at each taxonomic level, including Lactobacillales, and enrichment (LDA score > 5) in Enterobacteriales and Enterobacteriaceae. The latter was significantly related to cord blood gamma-glutamyltransferase levels (r = 0.58, p = 0.0057). Functionally, a thicker LVPW was related to up-regulation of pathways involved in lipopolysaccharide biosynthesis (+50%, p = 0.045 in correlative analysis) and energy metabolism (+12%, p = 0.028), and down-regulation of pathways involved in xenobiotic biodegradation (−21 to −53%, p = 0.0063–0.039), PPAR signaling (−24%, p = 0.021) and cardiac muscle contraction (−100%, p = 0.049).
Fetal cardiac growth and gut colonization are associated. Greater neonatal LVPW thickness is related to lower diversity of the gut microbiota community, depletion of bacteria having anti-remodeling effects, and enrichment in bacteria functionally linked to inflammation.
•Parameters of LV hypertrophy at birth may signal the presence of gut dysbiosis.•Thicker birth LVPW is related to depletion in bacteria with anti-remodeling effects.•Thicker birth LVPW is related to enrichment in bacteria linked to inflammation.
This article describes a design of an field-programmable gate array (FPGA) implementation of a clock and data recovery (CDR) system. The core will be integrated in the FPGA configuration for the ...front-end electronics (FEE) board of the Jiangmen underground neutrino observatory (JUNO) experiment. The front-end will be placed on the main detector, underground and underwater, making the electronics not accessible after installation. The timing and trigger system relies on a synchronous link connection over CAT5e cable (up to 100 m long) between the front-end and the back-end electronics (BEE), where a twisted-pair is dedicated to clock-forwarding. The robustness of the recovery clock system is essential for the stability of the FPGA firmware. The proposed project is intended to improve the clock recovery operation by increasing the immunity of the link to sudden electromagnetic interference (EMI). On top of this, the core allows to free a twisted-pair in the link, since the clock can be recovered from the data and there is no more need for a clock-dedicated transmission. This will optimize the link granting the possibility to implement other features. The design is based on two components: a numerically-controlled oscillator (NCO), in order to create a controlled frequency clock signal, and a digital phase detector (PD) to match the clock frequency with the data rate. NCOs are often coupled with a digital-to-analog converter (DAC) to create direct digital synthesizers (DDSs), which are able to produce analog waveforms of any desired frequency. In the presented case instead, the NCO generates a digital clock signal of an arbitrary frequency, while the PD manages this frequency by intercepting any shifting on the relative phase between the clock and the data. A phase aligner (PA) module guarantees that data are sampled in the middle of the eye pattern, which represents the optimal sampling point. The article presents an overview of the NCO-based CDR design and implementation, together with some tests and results in order to verify the CDR reliability. Moreover, in the last section, some other possible applications of the core are illustrated.