Antiviral Strategies for Pandemic and Seasonal Influenza

While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein

Characterisation of spatial network-like patterns from junctions' geometry

We propose a new method for quantitative characterization of spatial network-like patterns with loops, such as surface fracture patterns, leaf vein networks and patterns of urban streets. Such patterns are not well characterized by purely topological estimators: also patterns that both look different and result from different morphogenetic processes can have similar topology. A local geometric cue -the angles formed by the different branches at junctions- can complement topological information and allow to quantify the large scale spatial coherence of the pattern. For patterns that grow over time, such as fracture lines on the surface of ceramics, the rank assigned by our method to each individual segment of the pattern approximates the order of appearance of that segment. We apply the method to various network-like patterns and we find a continuous but sharp dichotomy between two classes of spatial networks: hierarchical and homogeneous. The first class results from a sequential growth process and presents large scale organization, the latter presents local, but not global organization.Comment: version 2, 14 page

Interplay between magnetism and short-range order in medium- and high-entropy alloys: CrCoNi, CrFeCoNi, and CrMnFeCoNi

The impact of magnetism on predicted atomic short-range order in three medium- and high-entropy alloys is studied using a first-principles, all-electron, Landau-type linear response theory, coupled with lattice-based atomistic modelling. We perform two sets of linear-response calculations: one in which the paramagnetic state is modelled within the disordered local moment picture, and one in which systems are modelled in a magnetically ordered state, which is ferrimagnetic for the alloys considered in this work. We show that the treatment of magnetism can have significant impact both on the predicted temperature of atomic ordering and also the nature of atomic order itself. In CrCoNi, we find that the nature of atomic order changes from being $\mathrm{L}1_2$-like when modelled in the paramagnetic state to MoPt$_2$-like when modelled assuming the system has magnetically ordered. In CrFeCoNi, atomic correlations between Fe and the other elements present are dramatically strengthened when we switch from treating the system as magnetically disordered to magnetically ordered. Our results show it is necessary to consider the magnetic state when modelling multicomponent alloys containing mid- to late-$3d$ elements. Further, we suggest that there may be high-entropy alloy compositions containing $3d$ transition metals that will exhibit specific atomic short-range order when thermally treated in an applied magnetic field. This has the potential to provide a route for tuning physical and mechanical properties in this class of materials.Comment: 26 pages, 4 figures, 2 table

Survey of Glycerol Dialkyl Glycerol Tetraethers (GDGTs) in Nevada and California Hot Springs and Selected T thermophiles

Glycerol dialkyl glycerol tetraethers (GDGTs) are core membrane lipids of many Archaea and some Bacteria found ubiquitously in soils and in many aqueous environments. Here, we examined the GDGT concentration in forty sediment samples from geothermal hot springs in the Great Basin (USA). Sediment samples were collected in tandem with extensive geochemical and site characterization. Hot spring temperatures ranged from 31 to 95°C and pH values from 6.8 to 10.7. Parametric Pearson\u27s correlation coefficients and nonparametric Spearman\u27s rho values were calculated to identify significant correlations between GDGT profiles and geochemical analytes. Isoprenoidal GDGTs (iGDGTs) negatively correlated with pH and positively correlated with temperature, Cr, and Cu, which is consistent with the importance of iGDGTs in the maintenance of membrane integrity at high temperature spring sources. In contrast, branched GDGTs (bGDGTs) displayed a negative relationship with temperature and a positive correlation with nitrate, nitrite and dissolved oxygen, demonstrating a niche for bGDGT-producing organisms in cooler, more oxidized springs away from the hottest geothermal sources. In addition, a collection of eleven thermophilic bacterial strains hypothesized to synthesize bGDGTs were tested; however, none synthesized GDGTs under the tested conditions. Our data provides insight into the environmental conditions under which archaeal and bacterial GDGTs are produced, which may improve the use of GDGTs as environmental proxies for understanding climates and conditions of the past and the future

Repetitions in beta-integers

Classical crystals are solid materials containing arbitrarily long periodic repetitions of a single motif. In this paper, we study the maximal possible repetition of the same motif occurring in beta-integers -- one dimensional models of quasicrystals. We are interested in beta-integers realizing only a finite number of distinct distances between neighboring elements. In such a case, the problem may be reformulated in terms of combinatorics on words as a study of the index of infinite words coding beta-integers. We will solve a particular case for beta being a quadratic non-simple Parry number.Comment: 11 page

Implementation of Continuous Capnography Is Associated With a Decreased Utilization of Blood Gases

Background Capnography provides a continuous, non-invasive monitoring of the CO2 to assess adequacy of ventilation and provide added safety features in mechanically ventilated patients by allowing for quick identification of unplanned extubation. These monitors may allow for decreased utilization of blood gases. The objective was to determine if implementation of continuous capnography monitoring decreases the utilization of blood gases resulting in decreased charges. Methods This is a retrospective review of a quality improvement project that compares the utilization of blood gases before and after the implementation of standard continuous capnography. The time period of April 2010 to September 2010 was compared to April 2011 to September 2011. Parameters collected included total number of blood gases analyzed, cost of blood gas analysis, ventilator and patient days. Results The total number of blood gases after the institution of end tidal CO2 monitoring decreased from 12,937 in 2009 and 13,171 in 2010 to 8,070 in 2011. The average number of blood gases per encounter decreased from 20.8 in 2009 and 21.6 in 2010 to 13.8 post intervention. The blood gases per ventilator day decreased from 4.94 in 2009 and 4.76 in 2010 to 3.30 post intervention. The total charge savings over a 6-month period was $880,496. Conclusions Continuous capnography resulted in a significant savings over a 6-month period by decreasing the utilization of blood gas measurements

Noise Effects on the Complex Patterns of Abnormal Heartbeats

Patients at high risk for sudden death often exhibit complex heart rhythms in which abnormal heartbeats are interspersed with normal heartbeats. We analyze such a complex rhythm in a single patient over a 12-hour period and show that the rhythm can be described by a theoretical model consisting of two interacting oscillators with stochastic elements. By varying the magnitude of the noise, we show that for an intermediate level of noise, the model gives best agreement with key statistical features of the dynamics.Comment: 4 pages, 4 figures, RevTe

Conservation Laws in Cellular Automata

If X is a discrete abelian group and B a finite set, then a cellular automaton (CA) is a continuous map F:B^X-->B^X that commutes with all X-shifts. If g is a real-valued function on B, then, for any b in B^X, we define G(b) to be the sum over all x in X of g(b_x) (if finite). We say g is `conserved' by F if G is constant under the action of F. We characterize such `conservation laws' in several ways, deriving both theoretical consequences and practical tests, and provide a method for constructing all one-dimensional CA exhibiting a given conservation law.Comment: 19 pages, LaTeX 2E with one (1) Encapsulated PostScript figure. To appear in Nonlinearity. (v2) minor changes/corrections; new references added to bibliograph

The 5-HT7 receptor as a potential target for treating drug and alcohol abuse

Alcohol and drug abuse take a large toll on society and affected individuals. However, very few effective treatments are currently available to treat alcohol and drug addiction. Basic and clinical research has begun to provide some insights into the underlying neurobiological systems involved in the addiction process. Several neurotransmitter pathways have been implicated and distinct reward neurocircuitry have been proposed—including the mesocorticolimbic dopamine (MCL-DA) system and the extended amygdala. The serotonin (5-HT) neurotransmitter system is of particular interest and multiple 5-HT receptors are thought to play significant roles in alcohol and drug self-administration and the development of drug dependence. Among the 5-HT receptors, the 5-HT7 receptor is currently undergoing characterization as a potential target for the treatment of several psychiatric disorders. Although this receptor has received only limited research regarding addictive behaviors, aspects of its neuroanatomical, biochemical, physiological, pharmacological, and behavioral profiles suggest that it could play a key role in the addiction process. For instance, genomic studies in humans have suggested a link between variants in the gene encoding the 5-HT7 receptor and alcoholism. Recent behavioral testing using high-affinity antagonists in mice and preliminary tests with alcohol-preferring rats suggest that this receptor could mediate alcohol consumption and/or reinforcement and play a role in seeking/craving behavior. Interest in the development of new and more selective pharmacological agents for this receptor will aid in examining the 5-HT7 receptor as a novel target for treating addiction