General Tests of Latent Variable Models and Mean-Variance Spanning

The methods of Gibbons and Ferson (1985) are extended, relaxing the assumption that expected returns are linear functions of predetermined instruments. A model of conditional mean-variance spanning generalizes Huberman and Kandel (1987). The empirical results indicate that more than a single risk premium is needed to model expected stock and bond returns, but the number of common factors in the expected returns is small. However, when size-based common stock portfolios proxy for the risk factors, we reject the hypothesis that four of them describe the conditional expected returns of the other assets

Visual interaction with dimensionality reduction: a structured literature analysis

Dimensionality Reduction (DR) is a core building block in visualizing multidimensional data. For DR techniques to be useful in exploratory data analysis, they need to be adapted to human needs and domain-specific problems, ideally, interactively, and on-the-fly. Many visual analytics systems have already demonstrated the benefits of tightly integrating DR with interactive visualizations. Nevertheless, a general, structured understanding of this integration is missing. To address this, we systematically studied the visual analytics and visualization literature to investigate how analysts interact with automatic DR techniques. The results reveal seven common interaction scenarios that are amenable to interactive control such as specifying algorithmic constraints, selecting relevant features, or choosing among several DR algorithms. We investigate specific implementations of visual analysis systems integrating DR, and analyze ways that other machine learning methods have been combined with DR. Summarizing the results in a “human in the loop” process model provides a general lens for the evaluation of visual interactive DR systems. We apply the proposed model to study and classify several systems previously described in the literature, and to derive future research opportunities

A decade of plague in Mahajanga, Madagascar: insights into the global maritime spread of pandemic plague

A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62 years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (SNP) discovery on those strains, screened the discovered SNPs, and performed a high-resolution 43-locus multilocus variable-number tandem-repeat analysis of the isolate panel. Twenty-two new SNPs were identified and defined a new phylogenetic lineage among the Malagasy isolates. Phylogeographic analysis suggests that the Mahajanga lineage likely originated in the Ambositra district in the highlands, spread throughout the northern central highlands, and was then introduced into and became transiently established in Mahajanga. Although multiple transfers between the central highlands and Mahajanga occurred, there was a locally differentiating and dominant subpopulation that was primarily responsible for the 1991-to-1999 Mahajanga outbreaks. Phylotemporal analysis of this Mahajanga subpopulation revealed a cycling pattern of diversity generation and loss that occurred during and after each outbreak. This pattern is consistent with severe interseasonal genetic bottlenecks along with large seasonal population expansions. The ultimate extinction of plague pathogens in Mahajanga suggests that, in this environment, the plague pathogen niche is tenuous at best. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments. Maritime spread of plague led to the global dissemination of this disease and affected the course of human history. Multiple historical plague waves resulted in massive human mortalities in three classical plague pandemics: Justinian (6th and 7th centuries), Middle Ages (14th to 17th centuries), and third (mid-1800s to the present). Key to these events was the pathogen’s entry into new lands by “plague ships” via seaport cities. Although initial disease outbreaks in ports were common, they were almost never sustained for long and plague pathogens survived only if they could become established in ecologically suitable habitats. Although plague pathogens’ ability to invade port cities has been essential for intercontinental spread, these regions have not proven to be a suitable long-term niche. The disease dynamics in port cities such as Mahajanga are thus critical to plague pathogen amplification and dispersal into new suitable ecological niches for the observed global long-term maintenance of plague pathogens

Fabrication

What aspects of optical fabrication technology need to be developed so as to facilitate existing planned missions, or enable new ones? Throughout the submillimeter to UV wavelengths, the common goal is to push technology to the limits to make the largest possible apertures that are diffraction limited. At any one wavelength, the accuracy of the surface must be better than lambda/30 (rms error). The wavelength range is huge, covering four orders of magnitude from 1 mm to 100 nm. At the longer wavelengths, diffraction limited surfaces can be shaped with relatively crude techniques. The challenge in their fabrication is to make as large as possible a reflector, given the weight and volume constraints of the launch vehicle. The limited cargo diameter of the shuttle has led in the past to emphasis on deployable or erectable concepts such as the Large Deployable Reflector (LDR), which was studied by NASA for a submillimeter astrophysics mission. Replication techniques that can be used to produce light, low-cost reflecting panels are of great interest for this class of mission. At shorter wavelengths, in the optical and ultraviolet, optical fabrication will tax to the limit the most refined polishing methods. Methods of mechanical and thermal stabilization of the substrate will be severely stressed. In the thermal infrared, the need for large aperture is tempered by the even stronger need to control the telescope's thermal emission by cooled or cryogenic operation. Thus, the SIRTF mirror at 1 meter is not large and does not require unusually high accuracy, but the fabrication process must produce a mirror that is the right shape at a temperature of 4 K. Future large cooled mirrors will present more severe problems, especially if they must also be accurate enough to work at optical wavelengths. At the very shortest wavelengths accessible to reflecting optics, in the x-ray domain, the very low count fluxes of high energy photons place a premium on the collecting area. It is not necessary to reach or even approach the diffraction limit, which would demand subnanometer fabrication and figure control. Replication techniques that produce large very lightweight surfaces are of interest for x-ray optics just as they are for the submillimeter region. Optical fabrication requirements are examined in more detail for missions in each of the three spectral regions of interest in astrophysics

Molecular Basis of Rare Aminoglycoside Susceptibility and Pathogenesis of Burkholderia pseudomallei Clinical Isolates from Thailand

Burkholderia pseudomallei is the etiologic agent of melioidosis, an emerging tropical disease. Because of low infectious dose, broad-host-range infectivity, intrinsic antibiotic resistance and historic precedent as a bioweapon, B. pseudomallei was listed in the United States as a Select Agent and Priority Pathogen of biodefense concern by the US Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. The mechanisms governing antibiotic resistance and/or susceptibility and virulence in this bacterium are not well understood. Most clinical and environmental B. pseudomallei isolates are highly resistant to aminoglycosides, but susceptible variants do exist. The results of our studies with three such variants from Thailand reveal that lack of expression or deletion of an efflux pump is responsible for this susceptibility. The large deletion present in one strain not only removes an efflux pump but also several putative virulence genes, including an entire siderophore gene cluster. Despite this deletion, the strain is fully virulent in an acute mouse melioidosis model. In summary, our findings shed light on mechanisms of antibiotic resistance and pathogenesis. They also validate the previously advocated use of laboratory-constructed, aminoglycoside susceptible efflux pump mutants in genetic manipulation experiments

Historical Distribution and Molecular Diversity of Bacillus anthracis, Kazakhstan

This study provides useful baseline data for guiding future disease control programs

Phylogeography of Francisella tularensis subsp. holarctica, Europe

Francisella tularensis subsp. holarctica isolates from Austria, Germany, Hungary, Italy, and Romania were placed into an existing phylogeographic framework. Isolates from Italy were assigned to phylogenetic group B.FTNF002–00; the other isolates, to group B.13. Most F. tularensis subsp. holarctica isolates from Europe belong to these 2 geographically segregated groups