Insights into neutralization of animal viruses gained from study of influenza virus

It has long been known that the binding of antibodies to viruses can result in a loss of infectivity, or neutralization, but little is understood of the mechanism or mechanisms of this process. This is probably because neutralization is a multifactorial phenomenon depending upon the nature of the virus itself, the particular antigenic site involved, the isotype of immunoglobulin and the ratio of virus to immunoglobulin (see below). Thus not only is it likely that neutralization of one virus will differ from another but that changing the circumstances of neutralization can change the mechanism itself. To give coherence to the topic we are concentrating this review on one virus, influenza type A which is itself well studied and reasonably well understood [1–3]. Reviews of the older literature can be found in references 4 to 7

The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Potentially Diagnostic Electron Paramagnetic Resonance Spectra Elucidate the Underlying Mechanism of Mitochondrial Dysfunction in the Deoxyguanosine Kinase Deficient Rat Model of a Genetic Mitochondrial DNA Depletion Syndrome

A novel rat model for a well-characterized human mitochondrial disease, mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase (DGUOK) deficiency, is described. The rat model recapitulates the pathologic and biochemical signatures of the human disease. The application of electron paramagnetic (spin) resonance (EPR) spectroscopy to the identification and characterization of respiratory chain abnormalities in the mitochondria from freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR is shown to be a sensitive technique for detecting mitochondrial functional abnormalities in situ and, here, is particularly useful in characterizing the redox state changes and oxidative stress that can result from depressed expression and/or diminished specific activity of the distinct respiratory chain complexes. As EPR requires no sample preparation or non-physiological reagents, it provides information on the status of the mitochondrion as it was in the functioning state. On its own, this information is of use in identifying respiratory chain dysfunction; in conjunction with other techniques, the information from EPR shows how the respiratory chain is affected at the molecular level by the dysfunction. It is proposed that EPR has a role in mechanistic pathophysiological studies of mitochondrial disease and could be used to study the impact of new treatment modalities or as an additional diagnostic tool

Exploring efficacy in personal constraint negotiation: an ethnography of mountaineering tourists

Limited work has explored the relationship between efficacy and personal constraint negotiation for adventure tourists, yet efficacy is pivotal to successful activity participation as it influences people’s perceived ability to cope with constraints, and their decision to use negotiation strategies. This paper explores these themes with participants of a commercially organised mountaineering expedition. Phenomenology-based ethnography was adopted to appreciate the social and cultural mountaineering setting from an emic perspective. Ethnography is already being used to understand adventure participation, yet there is considerable scope to employ it further through researchers immersing themselves into the experience. The findings capture the interaction between the ethnographer and the group members, and provide an embodied account using their lived experiences. Findings reveal that personal mountaineering skills, personal fitness, altitude sickness and fatigue were the four key types of personal constraint. Self-efficacy, negotiation-efficacy and other factors, such as hardiness and motivation, influenced the effectiveness of negotiation strategies. Training, rest days, personal health, and positive self-talk were negotiation strategies. A conceptual model illustrates these results and demonstrates the interplay between efficacy and the personal constraint negotiation journey for led mountaineers

The Design and Cytotoxic Evaluation of Some 1-Aryl-3- isopropylamino-1-propanone Hydrochlorides towards Human Huh-7 Hepatoma Cells

Cataloged from PDF version of article.A series of 1-aryl-3-isopropylamino-1-propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth-inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally. X-ray crystallography of two representative compounds 1d and 1g were achieved. Over half of the compounds are more potent than 5-fluorouracil which is an established drug used in treating liver cancers. QSAR evaluations and molecular modeling studies were undertaken with a view to detecting some physicochemical parameters which govern cytotoxic potencies. A number of guidelines for amplification of the project have been formulated. A number of Mannich bases displayed greater potency than the reference drug 5-fluorouracil against human Huh-7 hepatoma cells. In particular, 1i emerged as a lead compound possessing 2.8 fold higher activity than that of the reference drug. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Evaluation of α,β-unsaturated ketones as antileishmanial agents

In this study, we assessed the antileishmanial activity of 126 α,β-unsaturated ketones. The compounds NC901, NC884, and NC2459 showed high leishmanicidal activity for both the extracellular (50% effective concentration [EC(50)], 456 nM, 1,122 nM, and 20 nM, respectively) and intracellular (EC(50), 1,870 nM, 937 nM, and 625 nM, respectively) forms of Leishmania major propagated in macrophages, with little or no toxicity to mammalian cells. Bioluminescent imaging of parasite replication showed that all three compounds reduced the parasite burden in the murine model, with no apparent toxicity

Topological crystalline insulator states in Pb(1-x)Sn(x)Se

Topological insulators are a novel class of quantum materials in which time-reversal symmetry, relativistic (spin-orbit) effects and an inverted band structure result in electronic metallic states on the surfaces of bulk crystals. These helical states exhibit a Dirac-like energy dispersion across the bulk bandgap, and they are topologically protected. Recent theoretical proposals have suggested the existence of topological crystalline insulators, a novel class of topological insulators in which crystalline symmetry replaces the role of time-reversal symmetry in topological protection [1,2]. In this study, we show that the narrow-gap semiconductor Pb(1-x)Sn(x)Se is a topological crystalline insulator for x=0.23. Temperature-dependent magnetotransport measurements and angle-resolved photoelectron spectroscopy demonstrate that the material undergoes a temperature-driven topological phase transition from a trivial insulator to a topological crystalline insulator. These experimental findings add a new class to the family of topological insulators. We expect these results to be the beginning of both a considerable body of additional research on topological crystalline insulators as well as detailed studies of topological phase transitions.Comment: v2: published revised manuscript (6 pages, 3 figures) and supplementary information (5 pages, 8 figures

Spontaneous emission from large quantum dots in nanostructures: exciton-photon interaction beyond the dipole approximation

We derive a rigorous theory of the interaction between photons and spatially extended excitons confined in quantum dots in inhomogeneous photonic materials. We show that, beyond the dipole approximation, the radiative decay rate is proportional to a non-local interaction function, which describes the interaction between light and spatially extended excitons. In this regime, light and matter degrees of freedom cannot be separated and a complex interplay between the nanostructured optical environment and the exciton envelope function emerges. We illustrate this by specific examples and derive a series of important analytical relations, which are useful for applying the formalism to practical problems. In the dipole limit, the decay rate is proportional to the projected local density of optical states and we obtain the strong and weak confinement regimes as special cases.Comment: 14 pages, 4 figure

Magnetosheath control of solar wind-magnetosphere coupling efficiency

We examine the role of the magnetosheath in solar wind-magnetosphere-ionosphere coupling using the Time History of Events and Macroscale Interactions during Substorms plasma and magnetic field observations in the magnetosheath together with OMNI solar wind data and auroral electrojet recordings from the International Monitor for Auroral Geomagnetic Effects (IMAGE) magnetometer chain. We demonstrate that the electric field and Poynting flux reaching the magnetopause are not linear functions of the electric field and Poynting flux observed in the solar wind: the electric field and Poynting flux at the magnetopause during higher driving conditions are lower than those predicted from a linear function. We also show that the Poynting flux normal to the magnetopause is linearly correlated with the directly driven part of the auroral electrojets in the ionosphere. This indicates that the energy entering the magnetosphere in the form of the Poynting flux is directly responsible for driving the electrojets. Furthermore, we argue that the polar cap potential saturation discussed in the literature is associated with the way solar wind plasma gets processed during the bow shock crossing and motion within the magnetosheath.Peer reviewe

Excitonic effects on the two-color coherent control of interband transitions in bulk semiconductors

Quantum interference between one- and two-photon absorption pathways allows coherent control of interband transitions in unbiased bulk semiconductors; carrier population, carrier spin polarization, photocurrent injection, and spin current injection may all be controlled. We extend the theory of these processes to include the electron-hole interaction. Our focus is on photon energies that excite carriers above the band edge, but close enough to it so that transition amplitudes based on low order expansions in $\mathbf{k}$ are applicable; both allowed-allowed and allowed-forbidden two-photon transition amplitudes are included. Analytic solutions are obtained using the effective mass theory of Wannier excitons; degenerate bands are accounted for, but envelope-hole coupling is neglected. We find a Coulomb enhancement of two-color coherent control process, and relate it to the Coulomb enhancements of one- and two-photon absorption. In addition, we find a frequency dependent phase shift in the dependence of photocurrent and spin current on the optical phases. The phase shift decreases monotonically from $\pi /2$ at the band edge to 0 over an energy range governed by the exciton binding energy. It is the difference between the partial wave phase shifts of the electron-hole envelope function reached by one- and two-photon pathways.Comment: 31 pages, 4 figures, to be published in Phys. Rev.