Optimizing the Allocation of Vaccines in the Presence of Multiple Strains of the Influenza Virus

During the annual flu season, multiple strains of the influenza virus are often present within a population. It is a significant challenge for health care administrators to determine the most effective allocation of two different vaccines to combat the various strains when treating the public. We employ a mathematical model, a system of differential equations, to find a strategy for vaccinating a population in order to minimize the number of infected individuals. We consider various strengths of transmission of the disease, availability of vaccine doses, vaccination rates, and other model parameters. This research may lead to more effective health care policies for vaccine administration

Sidestepping Copyright: British Fairy Tale Anthologies of the 19th Century

One question is how in the golden period of fairy tale anthologising the work of the anthologists escaped the complete influence of copyright law with its paradigm of the individually authored work. The answer, it is suggested, lies, in part, in the early anthologists who formed a folklore society, saw themselves as anthropologists of folk culture, and treated copyright as largely irrelevant for the sake of their perception of the common good, and, in part, in the structure of copyright law itself which does not mandate but simply permits proprietary rights to be asserted

Optimizing the Allocation of Vaccines in the Presence of Multiple Strains of the Influenza Virus

During the annual flu season, multiple strains of the influenza virus are often present within a population. It is a significant challenge for health care administrators to determine the most effective allocation of multiple different vaccines to combat the various strains when protecting the public. We employ a mathematical model, a system of differential equations, to find a strategy for vaccinating a population to minimize the number of infected individuals. We consider various strengths of transmission of the disease, availability of vaccine doses, vaccination rates, and other model parameters. This research may lead to more effective health care policies for vaccine administration

Formation of Kuiper Belt Binaries by Gravitational Collapse

A large fraction of 100-km-class low-inclination objects in the classical Kuiper Belt (KB) are binaries with comparable mass and wide separation of components. A favored model for their formation was capture during the coagulation growth of bodies in the early KB. Instead, recent studies suggested that large objects can rapidly form in the protoplanetary disks when swarms of locally concentrated solids collapse under their own gravity. Here we examine the possibility that KB binaries formed during gravitational collapse when the excess of angular momentum prevented the agglomeration of available mass into a solitary object. We find that this new mechanism provides a robust path toward the formation of KB binaries with observed properties, and can explain wide systems such as 2001 QW322 and multiples such as (47171) 1999 TC36. Notably, the gravitational collapse is capable of producing 100% binary fraction for a wide range of the swarm's initial angular momentum values. The binary components have similar masses (80% have the secondary-over-primary radius ratio >0.7) and their separation ranges from ~1,000 to ~100,000 km. The binary orbits have eccentricities from e=0 to ~1, with the majority having e<0.6. The binary orbit inclinations with respect to the initial angular momentum of the swarm range from i=0 to ~90 deg, with most cases having i<50 deg. Our binary formation mechanism implies that the primary and secondary components in each binary pair should have identical bulk composition, which is consistent with the current photometric data. We discuss the applicability of our results to the Pluto-Charon, Orcus-Vanth, (617) Patroclus-Menoetius and (90) Antiope binary systems.Comment: Astronomical Journal, in pres

The angular momentum of two collided rarefied preplanetesimals and the formation of binaries

This paper studies the mean angular momentum associated with the collision of two celestial objects in the earliest stages of planet formation. Of primary concern is the scenario of two rarefied preplanetesimals (RPPs) in circular heliocentric orbits. The theoretical results are used to develop models of binary or multiple system formation from RPPs, and explain the observation that a greater fraction of binaries originated farther from the Sun. At the stage of RPPs, small-body satellites can form in two ways: a merger between RPPs can have two centers of contraction, or the formation of satellites from a disc around the primary or the secondary. Formation of the disc can be caused by that the angular momentum of the RPP formed by the merger is greater than the critical angular momentum for a solid body. One or several satellites of the primary (moving mainly in low-eccentricity orbits) can be formed from this disc at any separation less than the Hill radius. The first scenario can explain a system such as 2001 QW322 where the two components have similar masses but are separated by a great distance. In general, any values for the eccentricity and inclination of the mutual orbit are possible. Among discovered binaries, the observed angular momenta are smaller than the typical angular momenta expected for identical RPPs having the same total mass as the discovered binary and encountering each other in circular heliocentric orbits. This suggests that the population of RPPs underwent some contraction before mergers became common.Comment: 12 pages, Monthly Notices of Royal Astron. Society, in pres

2D growth processes: SLE and Loewner chains

This review provides an introduction to two dimensional growth processes. Although it covers a variety processes such as diffusion limited aggregation, it is mostly devoted to a detailed presentation of stochastic Schramm-Loewner evolutions (SLE) which are Markov processes describing interfaces in 2D critical systems. It starts with an informal discussion, using numerical simulations, of various examples of 2D growth processes and their connections with statistical mechanics. SLE is then introduced and Schramm's argument mapping conformally invariant interfaces to SLE is explained. A substantial part of the review is devoted to reveal the deep connections between statistical mechanics and processes, and more specifically to the present context, between 2D critical systems and SLE. Some of the SLE remarkable properties are explained, as well as the tools for computing with SLE. This review has been written with the aim of filling the gap between the mathematical and the physical literatures on the subject.Comment: A review on Stochastic Loewner evolutions for Physics Reports, 172 pages, low quality figures, better quality figures upon request to the authors, comments welcom

d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical transducer (MET) channels located at the tips of the hair cell’s stereocilia. d-Tubocurarine (dTC) is a MET channel blocker that reduces the loading of gentamicin-Texas Red (GTTR) into rat cochlear hair cells and protects them from gentamicin treatment. Berbamine is a structurally related alkaloid that reduces GTTR labeling of zebrafish lateral-line hair cells and protects them from aminoglycoside-induced cell death. Both compounds are thought to reduce aminoglycoside entry into hair cells through the MET channels. Here we show that dTC (≥6.25 µM) or berbamine (≥1.55 µM) protect zebrafish hair cells in vivo from neomycin (6.25 µM, 1 h). Protection of zebrafish hair cells against gentamicin (10 µM, 6 h) was provided by ≥25 µM dTC or ≥12.5 µM berbamine. Hair cells in mouse cochlear cultures are protected from longer-term exposure to gentamicin (5 µM, 48 h) by 20 µM berbamine or 25 µM dTC. Berbamine is, however, highly toxic to mouse cochlear hair cells at higher concentrations (≥30 µM) whilst dTC is not. The absence of toxicity in the zebrafish assays prompts caution in extrapolating results from zebrafish neuromasts to mammalian cochlear hair cells. MET current recordings from mouse outer hair cells (OHCs) show that both compounds are permeant open-channel blockers, rapidly and reversibly blocking the MET channel with half-blocking concentrations of 2.2 µM (dTC) and 2.8 µM (berbamine) in the presence of 1.3 mM Ca2+ at −104 mV. Berbamine, but not dTC, also blocks the hair cell’s basolateral K + current, IK,neo, and modeling studies indicate that berbamine permeates the MET channel more readily than dTC. These studies reveal key properties of MET-channel blockers required for the future design of successful otoprotectants

Design, synthesis and biological evaluation of a new series of carvedilol derivatives that protect sensory hair cells from aminoglycoside-induced damage by blocking the mechanoelectrical transducer channel

Aminoglycosides (AGs) are broad-spectrum antibiotics used for the treatment of serious bacterial infections but have use-limiting side effects including irreversible hearing loss. Here, we assessed the otoprotective profile of carvedilol in mouse cochlear cultures and in vivo zebrafish assays and investigated its mechanism of protection which, we found, may be mediated by a block of the hair cell’s mechanoelectrical transducer (MET) channel, the major entry route for the AGs. To understand the full otoprotective potential of carvedilol, a series of 18 analogues were prepared and evaluated for their effect against AG-induced damage as well as their affinity for the MET channel. One derivative was found to confer greater protection than carvedilol itself in cochlear cultures and also to bind more tightly to the MET channel. At higher concentrations, both carvedilol and this derivative were toxic in cochlear cultures but not in zebrafish, suggesting a good therapeutic window under in vivo conditions

SPICA infrared coronagraph for the direct observation of exo-planets

We present a MIR coronagraph to target the direct observation of extrasolar planets for SPICA, in which a coronagraph is currently regarded as an option of the focal plane instruments. The primary target of the SPICA coronagraph is the direct observation of Jovian exo-planets. A strategy of the baseline survey and the specifications for the coronagraph instrument for the survey are introduced together. The main wavelengths and the contrast required for the observations are 3.5-27um, and 10^{-6}, respectively.Laboratory experiments were performed with a visible laser to demonstrate the principles of the coronagraphs. In an experiment using binary-shaped pupil coronagraphs, a contrast of 6.7x10^{-8} was achieved, as derived from the linear average in the dark region and the core of the PSF. A coronagraph by a binary-shaped pupil mask is a baseline solution for SPICA because of its feasibility and robustness. On the other hand, a laboratory experiment of the phase induced amplitude apodization/binary-mask hybrid coronagraph has been executed to obtain an option of higher performance, and a contrast of 6.5x10^{-7} was achieved with active wavefront control.Potentially important by-product of the instrument, transit monitoring for characteization of exo-planets, is also described. We also present recent progress of technology on a design of a binary-shaped pupil mask for the actual pupil of SPICA, PSF subtraction, the development of free-standing binary masks, a vacuum chamber, and a cryogenic deformable mirror. Considering SPICA to be an essential platform for coronagraphs and the progress of key technologies, we propose to develop a mid-infrared coronagraph instrument for SPICA and to perform the direct observation of exo-planets with it.Comment: 37th COSPAR Scientific Assembly; Montreal, Canada 13-20 July 2008/Submitted to AS

MDL‐1, a growth‐ and tumor‐suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans

In C. elegans, increased lifespan in daf‐2 insulin/IGF‐1 receptor mutants is accompanied by up‐regulation of the MDL‐1 Mad basic helix‐loop‐helix leucine zipper transcription factor. Here we describe the role of mdl‐1 in C. elegans germline proliferation and aging. The deletion allele mdl‐1(tm311) shortened lifespan, and did so significantly more so in long‐lived daf‐2 mutants implying that mdl‐1(+) contributes to effects of daf‐2 on lifespan. mdl‐1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl‐1(tm311). Opposite phenotypes were seen in daf‐2 mutants, i.e. mdl‐1 and daf‐2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL‐1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age‐related pathology in C. elegans (uterine tumors). In addition, intestine‐limited rescue of mdl‐1 increased lifespan but not to wild type levels. Thus, mdl‐1 likely acts both in the intestine and the germline to influence age‐related mortality