The evolution and future of influenza pandemic preparedness

The influenza virus is a global threat to human health causing unpredictable yet recurring pandemics, the last four emerging over the course of a hundred years. As our knowledge of influenza virus evolution, distribution, and transmission has increased, paths to pandemic preparedness have become apparent. In the 1950s, the World Health Organization (WHO) established a global influenza surveillance network that is now composed of institutions in 122 member states. This and other surveillance networks monitor circulating influenza strains in humans and animal reservoirs and are primed to detect influenza strains with pandemic potential. Both the United States Centers for Disease Control and Prevention and the WHO have also developed pandemic risk assessment tools that evaluate specific aspects of emerging influenza strains to develop a systematic process of determining research and funding priorities according to the risk of emergence and potential impact. Here, we review the history of influenza pandemic preparedness and the current state of preparedness, and we propose additional measures for improvement. We also comment on the intersection between the influenza pandemic preparedness network and the current SARS-CoV-2 crisis. We must continually evaluate and revise our risk assessment and pandemic preparedness plans and incorporate new information gathered from research and global crises.Subject terms: Influenza virus, Infectious diseases     

Assessment of the Formant Frequencies in Normal and Laryngectomized Individuals Using Linear Predictive Coding

The objective of this study was to assess the difference in voice quality as defined by acoustical analysis using sustained vowel in laryngectomized patients in comparison with normal volunteers. This was designed as a retrospective single center cohort study. An adult tertiary referral unit formed the setting of this study. Fifty patients (40 males) who underwent total laryngectomy and 31 normal volunteers (18 male) participated. Group comparisons with the first three formant frequencies (F1, F2, and F3) using linear predictive coding (LPC) (Laryngograph Ltd, London, UK) was performed. The existence of any significant difference of F1, F2, and F3 between the two groups using the sustained vowel /i/ and the effects of other factors namely, tumor stage (T), chemoradiotherapy, pharyngectomy, cricothyroid myotomy, closure of pharyngoesophageal segment, and postoperative complication were analyzed. Formant frequencies F1, F2, and F3 were significantly different in male laryngectomees compared to controls: F1 (P<0.001, Mann-Whitney U test), F2 (P<0.001, Student's t test), and F3 (P=0.008, Student's t test). There was no significant difference between females in both groups for all three formant frequencies. Chemoradiotherapy and postoperative complications (pharyngocutaneous fistula) caused a significantly lower formant F1 in men, but showed little effect in F2 and F3. Laryngectomized males produced significantly higher formant frequencies, F1, F2, and F3, compared to normal volunteers, and this is consistent with literature. Chemoradiotherapy and postoperative complications significantly influenced the formant scores in the laryngectomee population. This study shows that robust and reliable data could be obtained using electroglottography and LPC in normal volunteers and laryngectomees using a sustained vowel.     

Supramolecular fluorophores for biological studies: phenylene vinylene-amino acid amphiphiles

We report here on a family of self-assembling fluorescent organic amphiphiles with a biomolecular L-lysine hydrophile and a photonically active phenylene vinylene hydrophobe. Unlike conventional amphiphiles, these segmented dendrimers feature a rigid, branched hydrophobe, and have packing characteristics controlled by the ratio of cross-sectional areas of the hydrophobe and hydrophile. In dilute solution, the amphiphiles form supramolecular aggregates, which are easily taken in by cells through an endocytic pathway, and have no discernible effect on cell proliferation or morphology. An analogous pyrene-based amphiphile was cytotoxic, suggesting that cell survival may be linked either to the self-assembling nature of the amphiphiles, or to the specific properties of the phenylene vinylene segment. The combination of photonic and biological components in these amphiphiles provides great potential for applications in sensing or delivery of molecules to intracellular targets.     

Synthesis and absolute stereochemistry of roseophilin

The enantiospecific total synthesis of natural roseophilin has been completed in 7.0% overall yield over 15 steps by means of an asymmetric cyclopentannelation. This establishes the absolute configuration of the natural product as 22R,23R. Cyclopentenone (+)-12 was prepared in 78% yield and 86% ee in the key step.     

Total synthesis of (+)-amphidinolide A. Structure elucidation and completion of the synthesis

The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. The 20-membered ring of amphidinolide A was formed by a ruthenium-catalyzed alkene-alkyne coupling to forge the C15-C16 bond. Using the reported structure 1 as a starting point, a number of diastereomers of amphidinolide A were prepared. Deviations of the chemical shift of key protons in each isomer relative to the natural material were used as a guide to determine the locations of the errors in the relative stereochemistry. The spectroscopic data for the synthetic and natural material are in excellent agreement.     

Simplex optimisation of conditions for the determination of antimony in environmental samples by using electrothermal atomic absorption spectrometry

Analysis of the total antimony in plant material was unsuccessful using the electrothermal atomic absorption spectrometry (ETAAS) conditions recommended by the instrument manufacturer. For this reason, an optimisation procedure utilising the Plackett-Burman method, simplex optimisation and visualisation of the generated response surface via principal components analysis, was carried out. The Plackett-Burman method was used to eliminate four of the initial variables chosen. Four variables (atomisation temperature, atomisation time, ash temperature and modifier concentration) were subsequently optimised using the composite modified simplex method and the results were visualised as a contour diagram, after reduction to two principal components. The optimised conditions were used for the analysis of both an acid digested pine needle standard reference material (NIST 1575) and a pond weed sample, collected from a contaminated site at Yellowknife Bay, Yellowknife, NWT, Canada. The total concentration of antimony present in the pine needles was statistically indistinguishable from the non-certified value, as was the value for the pond weed sample, compared with a value determined by neutron activation analysis (NAA). The results for the analysis of the pond weed sample by ETAAS agreed with those obtained from a subsequent analysis by inductively coupled plasma-mass spectrometry.     

An activation mechanism for ATP cleavage in muscle.

Evidence for a proposed activation mechanism is summarized. The low rate of ATP cleavage in the resting state of muscle is considered to result from the formation of a stable ring structure involving the two essential sulfhydryl groups on each myosin head and MgATP. Activation is thought to occur by interaction of actin in the vicinity of one of the essential sulfhydryl groups. Thus opening the stable ring leading to rapid dissociation of split products. This idea is consistent with the kinetic scheme of ATP cleavage developed recently by other workers and allows a prediction of the shift in population of intermediate states with changes in solvent conditions. It is also supported by our recent studies on the spatial geometry of the ring. The possibility that other nucleophilic groups may replace the sulfhydryl groups in other contractile systems is considered. The relevance of the ring structure to the tension generating event is discussed on the basis of recent measurements of the rate of contraction of modified (SH1-blocked) actomyosin threads. Results indicate the ability to form the ring structure is an essential requirement of the contractile process in these systems, and, moreover, that single, modified heads of myosin can act independently to produce the same rate of contraction as native myosin. This latter finding suggests that the myosin duplex exhibits some type of negative cooperativity in the contractile process.     

Geometry and combinatorics of Julia sets of real quadratic maps

For real a correspondence is made between the Julia setB forz(z–)², in the hyperbolic case, and the set of-chains±(±(±..., with the aid of Cremer's theorem. It is shown how a number of features ofB can be understood in terms of-chains. The structure ofB is determined by certain equivalence classes of-chains, fixed by orders of visitation of certain real cycles; and the bifurcation history of a given cycle can be conveniently computed via the combinatorics of-chains. The functional equations obeyed by attractive cycles are investigated, and their relation to-chains is given. The first cascade of period-doubling bifurcations is described from the point of view of the associated Julia sets and-chains. Certain Julia sets associated with the Feigenbaum function and some theorems of Lanford are discussed.Supported by NSF grant No. MCS-8104862.Supported by NSF grant No. MCS-8203325.