Controlling the crystal polymorph by exploiting the time dependence of nucleation rates

Most substances can crystallise into two or more different crystal lattices, called polymorphs. Despite this, there are no systems in which we can quantitatively predict the probability of one competing polymorph forming, instead of the other. We address this problem using large scale (hundreds of events) studies of the competing nucleation of the alpha and gamma polymorphs of glycine. In situ Raman spectroscopy is used to identify the polymorph of each crystal. We find that the nucleation kinetics of the two polymorphs is very different. Nucleation of the alpha polymorph starts off slowly but accelerates, while nucleation of the gamma polymorph starts off fast but then slows. We exploit this difference to increase the purity with which we obtain the gamma polymorph by a factor of ten. The statistics of the nucleation of crystals is analogous to that of human mortality, and using a result from medical statistics we show that conventional nucleation data can say nothing about what, if any, are the correlations between competing nucleation processes. Thus we can show that, with data of our form, it is impossible to disentangle the competing nucleation processes. We also find that the growth rate and the shape of a crystal depends on when it nucleated. This is new evidence that nucleation and growth are linked.Comment: 8 pages, plus 17 pages of supplementary materia

Price Indexes for Medical Care Goods and Services: An Overview of Measurement Issues

We review in considerable detail the conceptual and measurement issues that underlie construction of medical care price indexes in the U.S., particularly the medical care consumer price indexes (MCPIs) and medical-related producer price indexes (MPPIs). We outline salient features of the medical care marketplace, including the impacts of insurance, moral hazard, principal-agent relationships, technological progress and organizational changes. Since observed data are unlikely to correspond with efficient outcomes, we discuss implications of the failure of transactions data in this market to reveal reliable marginal valuations, and the consequent need to augment traditional transactions data with information based on cost-effectiveness and outcomes studies. We describe procedures currently used by the BLS in constructing MCPIs and MPPIs, including recent revisions, and then consider alternative notions of medical care output pricing that involve the price or cost of an episode of treatment, rather than prices of fixed bundles of inputs. We outline features of a proposed new experimental price index -- a medical care expenditure price index -- that is more suitable for evaluation and analyses of medical care cost changes, than are the current MCPIs and MPPIs. We conclude by suggesting future research and measurement issues that are most likely to be fruitful.

ACTH4 -10, Substance P, and Dizolcipine (Mk-801) Accelerate Functional Recovery After Hemilabyrinthectomy in Goldfish

In this study, we evaluated the goldfish model of hemilabyrinthectomy for investigating potential recovery-promoting drugs. In this lesion model, the unilateral removal of the labyrinth induces a postural imbalance in response to light (Dorsal Light Reflex), from which the animals can recover over time. The behavioral effects of two neuropeptides were tested–namely, of substance P and ACTH4-10, both of which are known to promote functional recovery in several other lesion models. Furthermore, the effect of MK- 801, an antagonist of the glutamatergic NMDAreceptor subtype, was tested because this substance has also been shown to exert a neuroprotective effect. After lesion of the right labyrinth, the animals (n=12) were treated intraperitoneally daily either with vehicle (n=12), substance P (n=11) , ACTH4-10 (n=12) , or MK- 801 (n=12) . Another group(n=11) , which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. The lesion group, treated post-operatively with vehicle, did not recover from the postural deviation over the 24-d testing period. In contrast, all three test substances accelerated the functional recovery after unilateral labyrinthectomy. The decrease of the dorsal light reflex persisted even after cessation of drug treatment after 20d. The results indicate that using the dorsal light reflex in the model of hemilabyrinthectomy in goldfish provides a useful approach to studying the ability of potential new neurotrophic or neuroprotective drugs to promote functional recovery

Strontium is required for statolith development and thus normal swimming behaviour of hatchling cephalopods

When cephalopod eggs were incubated in artificial sea water it was found that they sometimes resulted in hatchlings with defects of the statocyst suprastructure, leading to the severe behavioural defect of uncontrolled swimming. Experiments in defined media (seven basic salts mixed in deionized water) with seven species of cephalopods demonstrated clearly that there is 100% normal development of the aragonite statoliths when strontium levels were 8 mg l-1. Conversely, statoliths did not develop when strontium was absent. In cuttlefish, the growth of the cuttlebone was also affected adversely when strontium was absent. In mariculture production tanks, supplementing commercial artificial sea water with strontium to normal levels of 8 mg l-1 almost eliminated the occurrence of abnormal hatchlings. Circumstantial evidence indicates that there is a critical window in development during which strontium is required for normal development. The role of strontium in biomineralization during embryogenesis is unknown, but it appears to be important in the Mollusca

A One Chip Hardened Solution for High Speed SpaceWire System Implementations. Session: Components

An Application Specific Integrated Circuit (ASIC) that implements the SpaceWire protocol has been developed in a radiation hardened 0.25 micron CMOS technology. This effort began in March 2003 as a joint development between the NASA Goddard Space Flight Center (GSFC) and BAE Systems. The BAE Systems SpaceWire ASIC is comprised entirely of reusable core elements, many of which are already flight-proven. It incorporates a router with 4 SpaceWire ports and two local ports, dual PC1 bus interfaces, a microcontroller, 32KB of internal memory, and a memory controller for additional external memory use. The SpaceWire cores are also reused in other ASICs under development. The SpaceWire ASIC is planned for use on the Geostationary Operational Environmental Satellites (GOES)-R, the Lunar Reconnaissance Orbiter (LRO) and other missions. Engineering and flight parts have been delivered to programs and users. This paper reviews the SpaceWire protocol and those elements of it that have been built into the current and next SpaceWire reusable cores and features within the core that go beyond the current standard and can be enabled or disabled by the user. The adaptation of SpaceWire to BAE Systems' On Chip Bus (OCB) for compatibility with the other reusable cores will be reviewed and highlighted. Optional configurations within user systems and test boards will be shown. The physical implementation of the design will be described and test results from the hardware will be discussed. Application of this ASIC and other ASICs containing the SpaceWire cores and embedded microcontroller to Plug and Play and reconfigurable implementations will be described. Finally, the BAE Systems roadmap for SpaceWire developments will be updated, including some products already in design as well as longer term plans

Circadian Variation of Brain Histamine in Goldfish

Teleosts may make an excellent model to study brain histamine function. Fishes are phylogenetically closer to the basic vertebrate blueprint than higher vertebrates. They appear to have a simpler histaminergic system in terms of central nervous system distribution and, contrary to higher vertebrates, brain histamine appears to be strictly neuronal. In this preliminary study, we examined circadian variation of brain histamine in goldfish, Carassius auratus, as this neurotransmitter correlates with circadian behavior of some mammals. Two groups of juvenile goldfish were held in 24 60L aquaria, six fish per aquarium, on reversed photoperiods; L:D 12:12 with light onset either at 0700 or 1900 h. Fish were sampled every 4 h. At a sampling time, all the fish in a tank were taken; each sampling, for both groups, was done in replicate. Brain histamine was determined by immunoassay. There was a significant circadian variation in histamine on both photoperiod regimes with the highest levels during the photophase. These results support the hypothesis of an early phylogenic role for histamine in vertebrate circadian physiology