Inapparent infections and cholera dynamics

In many infectious diseases, an unknown fraction of infections produce symptoms mild enough to go unrecorded, a fact that can seriously compromise the interpretation of epidemiological records. This is true for cholera, a pandemic bacterial disease, where estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100 (refs 1-5). In the absence of direct evidence, understanding of fundamental aspects of cholera transmission, immunology and control has been based on assumptions about this ratio and about the immunological consequences of inapparent infections. Here we show that a model incorporating high asymptomatic ratio and rapidly waning immunity, with infection both from human and environmental sources, explains 50 yr of mortality data from 26 districts of Bengal, the pathogen's endemic home. We find that the asymptomatic ratio in cholera is far higher than had been previously supposed and that the immunity derived from mild infections wanes much more rapidly than earlier analyses have indicated. We find, too, that the environmental reservoir (free-living pathogen) is directly responsible for relatively few infections but that it may be critical to the disease's endemicity. Our results demonstrate that inapparent infections can hold the key to interpreting the patterns of disease outbreaks. New statistical methods, which allow rigorous maximum likelihood inference based on dynamical models incorporating multiple sources and outcomes of infection, seasonality, process noise, hidden variables and measurement error, make it possible to test more precise hypotheses and obtain unexpected results. Our experience suggests that the confrontation of time-series data with mechanistic models is likely to revise our understanding of the ecology of many infectious diseases.     

L 1 Optimization under Linear Inequality Constraints

1 optimization under linear inequality constraints based upon iteratively reweighted iterative projection (or IRIP). IRIP is compared to a linear programming (LP) strategy for L₁ minimization (Sp?th 1987, Chapter 5.3) using the ultrametric condition as an exemlar class of constraints to be fitted. Coded for general constraints, the LP approach proves to be faster. Both methods, however, suffer from a serious limitation in being unable to process reasonably-sized data sets because of storage requirements for the constraints. When the simplicity of vector projections is used to allow IRIP to be coded for specific (in this case, ultrametric) constraints, we obtain a fast and efficient algorithm capable of handling large data sets. It is also possible to extend IRIP to operate as a heuristic search strategy that simultaneously identifies both a reasonable set of constraints to impose and the optimally-estimated parameters satisfying these constraints. A few noteworthy characteristics of L₁ optimal ultrametrics are discussed, including other strategies for reformulating the ultrametric optimization problem.     

Chimaeric sounds reveal dichotomies in auditory perception

By Fourier's theorem, signals can be decomposed into a sum of sinusoids of different frequencies. This is especially relevant for hearing, because the inner ear performs a form of mechanical Fourier transform by mapping frequencies along the length of the cochlear partition. An alternative signal decomposition, originated by Hilbert, is to factor a signal into the product of a slowly varying envelope and a rapidly varying fine time structure. Neurons in the auditory brainstem sensitive to these features have been found in mammalian physiological studies. To investigate the relative perceptual importance of envelope and fine structure, we synthesized stimuli that we call 'auditory chimaeras', which have the envelope of one sound and the fine structure of another. Here we show that the envelope is most important for speech reception, and the fine structure is most important for pitch perception and sound localization. When the two features are in conflict, the sound of speech is heard at a location determined by the fine structure, but the words are identified according to the envelope. This finding reveals a possible acoustic basis for the hypothesized 'what' and 'where' pathways in the auditory cortex.     

Size-dependent optical properties of Au nanorods

In the fast evolving field of nanoscience and nanotechnology,where size and shape are crucial in deciding the optoelectronic properties of nanomaterials,the understanding of size and shape dependent behavior is of direct relevance to device applications.Present study reports the synthesis of Au nanorods with well controlled aspect ratios,and the influence of the aspect ratio on the surface enhanced Raman scattering(SERS) activity using crystal violet(CV) as the probe molecule.The influence of pH and the concentrations of reducing agent and Ag ions in controlling the aspect ratio of gold nanorods are also investigated.The structural and optical properties of the synthesized samples have been characterized by transmission electron microscopy(TEM) and UV-visible absorption spectroscopy.The nonlinear optical(NLO) transmission of the Au nanorods investigated using the open aperture Z-scan technique revealed the absorption saturation followed by an optical limiting behavior,which may find potential applications in optoelectronic nanodevices.     

Algae acquire vitamin B12 through a symbiotic relationship with bacteria

Vitamin B12 (cobalamin) was identified nearly 80 years ago as the anti-pernicious anaemia factor in liver, and its importance in human health and disease has resulted in much work on its uptake, cellular transport and utilization. Plants do not contain cobalamin because they have no cobalamin-dependent enzymes. Deficiencies are therefore common in strict vegetarians, and in the elderly, who are susceptible to an autoimmune disorder that prevents its efficient uptake. In contrast, many algae are rich in vitamin B12, with some species, such as Porphyra yezoensis (Nori), containing as much cobalamin as liver. Despite this, the role of the cofactor in algal metabolism remains unknown, as does the source of the vitamin for these organisms. A survey of 326 algal species revealed that 171 species require exogenous vitamin B12 for growth, implying that more than half of the algal kingdom are cobalamin auxotrophs. Here we show that the role of vitamin B12 in algal metabolism is primarily as a cofactor for vitamin B12-dependent methionine synthase, and that cobalamin auxotrophy has arisen numerous times throughout evolution, probably owing to the loss of the vitamin B12-independent form of the enzyme. The source of cobalamin seems to be bacteria, indicating an important and unsuspected symbiosis.     

Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus

The 9,213-nucleotide structure of the AIDS/lymphadenopathy virus has been determined from molecular clones representing the integrated provirus and viral RNA. The sequence reveals that the virus is highly polymorphic and lacks significant nucleotide homology with type C retroviruses characterized previously. Together with an analysis of the two major viral subgenomic RNAs, these studies establish the coding frames for the gag, pol and env genes and predict the expression of a novel gene at the 3' end of the genome unrelated to the X genes of HTLV-1 and -II.     

A new selective insecticidal uncoupler of oxidative phosphorylation

Summary A new aryl hydrazone structure with high insecticidal activity against the Australian sheep blowfly,Lucilia cuprina, was shown to have a higher activity as an uncoupler of oxidative phosphorylation in insect compared to mammalian mitochondrial preparations. This compound possesses the requirements of other uncouplers in its measured pKa and lipid solubility. However, when compared to a closely related structure with similar physicochemical properties, its insecticidal and insect mitochondrial uncoupling activities are greater and it exhibits decreased mammalian toxicity corresponding to this differential biochemical selectivity.Acknowledgment. We thank Mr K. Rihs for preparation of the hydrazones and Prof. Dr K.H. Büchel for supply of hydrazone III.