Nonlinear Waves on a String with Inhomogeneous Properties

Nonlinear waves on an infinite string with a rapid change in properties at one location are treated. The string is an idealized version of more complex configurations in both fluids and solids. This idealized version treats the property change as an interface with a discontinuity in properties. Packets of waves are then considered with a reduced model, here a set of nonlinear Schr¨odinger (NLS) equations. The stress and the displacement must both be matched at the interface, resulting in dynamic and kinematic interfacial conditions. The dynamic condition produces an inhomogeneous effect that cannot be treated successfully with separation-of-variables. This inhomogeneity is treated here with a time-evolution approach using Laplace transforms. The results show that this inhomogeneity creates a mean longitudinal displacement on both sides of the interface and a shift in the position of the interface as the waves transit the interface. This mean longitudinal displacement corresponds to a sustained strain in the string. The mean longitudinal displacement develops three distinct features. One feature has a length scale that is half the wave-length of the incident waves, while the lengths of the other two features have the same order as the length of the wave packet. The position of maximum strain as a result of this mean is often at the interface, depending on parameter values. These results apply to a variety of applications, such as waves in ocean ice, Rayleigh waves caused by earthquakes, internal waves in the oceans and atmosphere, as well as waves in stretched cables

Cloning and expression analysis of hemoglobin genes from maize (\u3ci\u3eZea mays\u3c/i\u3e ssp. \u3ci\u3emays\u3c/i\u3e) and teosinte (\u3ci\u3eZea mays\u3c/i\u3e ssp. \u3ci\u3eparviglumis\u3c/i\u3e)

With the exception of barley and rice, little is known about the existence of hemoglobins (Hbs) in cereals. This work reports the cloning and analysis of hb genes from maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis). Coding sequences of maize and teosinte hb genes (hbm and hbt, respectively) are highly similar to each other and are interrupted by three introns located at identical positions as other plant hb genes. Sequences of predicted Hbm and Hbt proteins are identical. The hydropathic profile of Hbm and Hbt is highly similar to that of rice Hb1, suggesting that Hbm, Hbt and Hb1 have the same tertiary structure and biochemical properties. Expression analysis showed that low levels of Hb transcripts, but considerable levels of Hb proteins exist in maize embryonic organs. No Hb transcripts and proteins were detected in teosinte embryonic organs. Low levels of Hb proteins, but no Hb transcripts, were detected in maize and teosinte vegetative organs. These observations suggest that the regulation of hb genes is different in maize and teosinte embryonic organs, and that the expression of hb genes is down- or up-regulated in maize and teosinte, respectively, from germination to vegetative growing

Cloning and expression analysis of hemoglobin genes from maize (\u3ci\u3eZea mays\u3c/i\u3e ssp. \u3ci\u3emays\u3c/i\u3e) and teosinte (\u3ci\u3eZea mays\u3c/i\u3e ssp. \u3ci\u3eparviglumis\u3c/i\u3e)

With the exception of barley and rice, little is known about the existence of hemoglobins (Hbs) in cereals. This work reports the cloning and analysis of hb genes from maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis). Coding sequences of maize and teosinte hb genes (hbm and hbt, respectively) are highly similar to each other and are interrupted by three introns located at identical positions as other plant hb genes. Sequences of predicted Hbm and Hbt proteins are identical. The hydropathic profile of Hbm and Hbt is highly similar to that of rice Hb1, suggesting that Hbm, Hbt and Hb1 have the same tertiary structure and biochemical properties. Expression analysis showed that low levels of Hb transcripts, but considerable levels of Hb proteins exist in maize embryonic organs. No Hb transcripts and proteins were detected in teosinte embryonic organs. Low levels of Hb proteins, but no Hb transcripts, were detected in maize and teosinte vegetative organs. These observations suggest that the regulation of hb genes is different in maize and teosinte embryonic organs, and that the expression of hb genes is down- or up-regulated in maize and teosinte, respectively, from germination to vegetative growing

Mutations in MUSK causing congenital myasthenic syndrome impair MuSK–Dok-7 interaction

We describe a severe congenital myasthenic syndrome (CMS) caused by two missense mutations in the gene encoding the muscle specific receptor tyrosine kinase (MUSK). The identified MUSK mutations M605I and A727V are both located in the kinase domain of MuSK. Intracellular microelectrode recordings and microscopy studies of the neuromuscular junction conducted in an anconeus muscle biopsy revealed decreased miniature endplate potential amplitudes, reduced endplate size and simplification of secondary synaptic folds, which were consistent with postsynaptic deficit. The study also showed a striking reduction of the endplate potential quantal content, consistent with additional presynaptic failure. Expression studies in MuSK deficient myotubes revealed that A727V, which is located within the catalytic loop of the enzyme, caused severe impairment of agrin-dependent MuSK phosphorylation, aggregation of acetylcholine receptors (AChRs) and interaction of MuSK with Dok-7, an essential intracellular binding protein of MuSK. In contrast, M605I, resulted in only moderate impairment of agrin-dependent MuSK phosphorylation, aggregation of AChRs and interaction of MuSK with Dok-7. There was no impairment of interaction of mutants with either the low-density lipoprotein receptor-related protein, Lrp4 (a co-receptor of agrin) or with the mammalian homolog of the Drosophila tumorous imaginal discs (Tid1). Our findings demonstrate that missense mutations in MUSK can result in a severe form of CMS and indicate that the inability of MuSK mutants to interact with Dok-7, but not with Lrp4 or Tid1, is a major determinant of the pathogenesis of the CMS caused by MUSK mutations

Crystal Structure of a Nonsymbiotic Plant Hemoglobin

Background: Nonsymbiotic hemoglobins (nsHbs) form a new class of plant proteins that is distinct genetically and structurally from leghemoglobins. They are found ubiquitously in plants and are expressed in low concentrations in a variety of tissues including roots and leaves. Their function involves a biochemical response to growth under limited O2 conditions. Results: The first X-ray crystal structure of a member of this class of proteins, riceHb1, has been determined to 2.4 Å resolution using a combination of phasing techniques. The active site of ferric riceHb1 differs significantly from those of traditional hemoglobins and myoglobins. The proximal and distal histidine sidechains coordinate directly to the heme iron, forming a hemichrome with spectral properties similar to those of cytochrome b5. The crystal structure also shows that riceHb1 is a dimer with a novel interface formed by close contacts between the G helix and the region between the B and C helices of the partner subunit. Conclusions: The bis-histidyl heme coordination found in riceHb1 is unusual for a protein that binds O2 reversibly. However, the distal His73 is rapidly displaced by ferrous ligands, and the overall O2 affinity is ultra-high (KD ≈ 1 nM). Our crystallographic model suggests that ligand binding occurs by an upward and outward movement of the E helix, concomitant dissociation of the distal histidine, possible repacking of the CD corner and folding of the D helix. Although the functional relevance of quaternary structure in nsHbs is unclear, the role of two conserved residues in stabilizing the dimer interface has been identified

Transmisión del virus del dengue y su relación con factores climáticos durante los períodos intra e interepidémicos en Santo Domingo, República Dominicana

Antecedentes: Aedes spp. y la dinámica del virus del dengue está altamente influenciada por factores ambientales. Una relación detallada entre el clima y la enfermedad en los períodos inter e intra-epidémicos podrían beneficiar la vigilancia del dengue para optimizar la preparación y las políticas adecuadas de control de vectores. Métodos: se analizaron los informes de casos de dengue y las variables climáticas en Santo Domingo, República Dominicana, para determinar la correlación del período 2012-2018 y los diferentes tiempos de retraso. Se llevó a cabo un análisis de regresión de dichas variables para comprender mejor las relaciones entre las tasas de incidencia del dengue y los cambios climáticos. Resultados: durante los brotes epidémicos, la temperatura (r = 0.73, p <0.001) y la humedad relativa (r = -0.22, p = 0.009) se correlacionan significativamente con la incidencia del dengue con un retraso de 9 semanas, el análisis de regresión muestra que la temperatura media (b = 62.401, p < 0.001), precipitación (b = 2.810, p <0.001) y humedad relativa (b = -5.462, p = 0.025) fueron predictores significativos. Durante los períodos inter-epidémico, la temperatura (r = 0.23, p <0.001) tuvo una correlación significativa con la incidencia del dengue con un retraso de 7 semanas, la humedad relativa (b = 1.454, p <0.05) y la temperatura media (b = 5.14, p <0.01) son predictores significativos de la cantidad de casos de dengue. La precipitación no se correlacionó significativamente con la incidencia del dengue. Conclusiones: existe una relación no lineal entre los factores climáticos y la incidencia del dengue. La infección por dengue depende del clima, y la temperatura parece jugar un papel importante en los factores climáticos

Structural evidence of quercetin multi-target bioactivity:A reverse virtual screening strategy

The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways. Even though there are a number of well-established protein targets such as phosphatidylinositol 3 kinase and xanthine oxidase, there remains a lack of a comprehensive knowledge of the potential mechanisms of action of quercetin and its target space. In the present work we adopted a reverse screening strategy based on ligand similarity (SHAFTS) and target structure (idTarget, LIBRA) resulting in a set of predicted protein target candidates. Furthermore, using this method we corroborated a broad array of previously experimentally tested candidates among the predicted targets, supporting the suitability of this screening approach. Notably, all of the predicted target candidates belonged to two main protein families, protein kinases and poly [ADP-ribose] polymerases. They also included key proteins involved at different points within the same signaling pathways or within interconnected signaling pathways, supporting a pleiotropic, multilevel and potentially synergistic mechanism of action of quercetin. In this context we highlight the value of quercetin's broad target profile for its therapeutic potential in diseases like inflammation, neurodegeneration and cancer

A two-directional approach to pyrrolizidines: total syntheses and biological evaluation of alkaloid cis-223B and (+/-)-xenovenine

Total syntheses of alkaloid cis-223B and xenovenine are reported in 3 and 4 steps respectively using a two-directional synthesis/triple reductive amination strategy, and their neurotoxic properties assessed

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography