Evaluating the Effects of Large Scale Health Interventions in Developing Countries: The Zambian Malaria Initiative

Since 2003, Zambia has been engaged in a large-scale, centrally coordinated national anti- Malaria campaign which has become a model in sub-Saharan Africa. This paper aims at quantifying the individual and macro level benefits of this campaign, which involved mass distribution of insecticide treated mosquito nets, intermittent preventive treatment for pregnant women, indoor residual spraying, rapid diagnostic tests, and artemisinin-based combination therapy. We discuss the timing and regional coverage of the program, and critically review the available health and program rollout data. To estimate the health benefits associated with the program rollout, we use both population based morbidity measures from the Demographic and Health Surveys and health facility based mortality data as reported in the national Health Management Information System. While we find rather robust correlations between the rollout of bed nets and subsequent improvements in our health measures, the link between regional spraying and individual level health appears rather weak in the data.

The hyaluronan-binding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin

The influence of the hyaluronanbinding protease (PHBSP), a plasma enzyme with FVII- and pro-urokinase-activating potency, on components of the contact phase (kallikrein/kinin) system was investigated. No activation or cleavage of the proenzymes involved in the contact phase system was observed. The procofactor high molecular weight kininogen (HK), however, was cleaved in vitro by PHBSP in the absence of any charged surface, releasing the activated cofactor and the vasoactive nonapeptide bradykinin. Glycosoaminoglycans strongly enhanced the reaction. The cleavage was comparable to that of plasma kallikrein, but clearly different from that of coagulation factor FXIa. Upon extended incubation with PHBSP, the light chain was further processed, partially removing about 60 amino acid residues from the Nterminus of domain D5 of the light chain. These cleavage site(s) were distinct from plasma kallikrein or FXIa cleavage sites. PHBSP and, more interestingly, also plasma kallikrein could cleave low molecular weight kininogen in vitro, indicating that domains D5(H) and D6(H) are no prerequisite for kininogen cleavage. PHBSP was also able to release bradykinin from HK in plasma where the pro-cofactor circulates predominantly in complex with plasma kallikrein or FXI. In conclusion, PHBSP represents a novel kininogen-cleaving and bradykinin-releasing enzyme in plasma that shares significant catalytic similarities with plasma kallikrein. Since they are structurally unrelated in their heavy chains (propeptide), their similar in vivo catalytic activities might be directed at distinct sites where PHBSP could induce processes that are related to the kallikrein/kinin system

ROSAT monitoring of persistent giant and rapid variability in the narrow-line Seyfert 1 galaxy IRAS 13224-3809

We report evidence for persistent giant and rapid X-ray variability in the radio-quiet, ultrasoft, strong Fe II, narrow-line Seyfert 1 galaxy IRAS 13224-3809. Within a 30 day ROSAT High Resolution Imager (HRI) monitoring observation at least five giant amplitude count rate variations are visible, with the maximum observed amplitude of variability being about a factor of 60. We detect a rise by a factor of about 57 in just two days. IRAS 13224-3809 appears to be the most X-ray variable Seyfert known, and its variability is probably nonlinear. We carefully check the identification of the highly variable X-ray source with the distant galaxy, and it appears to be secure. We examine possible explanations for the giant variability. Unusually strong relativistic effects and partial covering by occulting structures on an accretion disc can provide plausible explanations of the X-ray data, and we explore these two scenarios. Relativistic boosting effects may be relevant to understanding the strong X-ray variability of some steep spectrum Seyferts more generally.Comment: 14 pages, submitted to MNRA

Non-destructive imaging of an individual protein

The mode of action of proteins is to a large extent given by their ability to adopt different conformations. This is why imaging single biomolecules at atomic resolution is one of the ultimate goals of biophysics and structural biology. The existing protein database has emerged from X-ray crystallography, NMR or cryo-TEM investigations. However, these tools all require averaging over a large number of proteins and thus over different conformations. This of course results in the loss of structural information. Likewise it has been shown that even the emergent X-FEL technique will not get away without averaging over a large quantity of molecules. Here we report the first recordings of a protein at sub-nanometer resolution obtained from one individual ferritin by means of low-energy electron holography. One single protein could be imaged for an extended period of time without any sign of radiation damage. Since ferritin exhibits an iron core, the holographic reconstructions could also be cross-validated against TEM images of the very same molecule by imaging the iron cluster inside the molecule while the protein shell is decomposed

Matrix metalloproteinases-2,-3,-7,-9 and-10, but not MMP-11, are differentially expressed in normal, benign tumorigenic and malignant human keratinocyte cell lines

In order to investigate the correlations between constitutive proteinase expression and the degree of tumorigenicity of cancer cells we have studied a model system of three keratinocyte cell lines. RT-PCR studies showed that the cell lines express the genes of matrix metalloproteinase-2, -3, -7, -9, -10 and -11, indicating that they are able to synthesize the corresponding enzymes. Actual MMP synthesis was proven by zymography and Western blotting. In conditioned media gelatinolytic activities or immunoreactive forms of MMP-2, -3, -7, -9, -10 and -11 were detected. The signal intensities showed that MMP secretion increases in the order HaCaT < A5 less than or equal to II-4RT, whereas only MMP-11 is secreted by all cell lines in equal amounts, Intracellularly, enhanced levels of one or both of the tumorigenic variants were only found for MMP-3 -9 and -10, suggesting special functions of these intracellular MMP pools for the tumorigenic cell lines. For MMP-11 exclusive expression in stromal fibroblasts of tumor tissues is widely accepted; however, our results and three other recent reports demonstrate that this concept is not generally valid. In conclusion, the three keratinocyte cell lines investigated here represent an excellent model for studying constitutive expression and secretion of MMPs in correlation to the degree of in vivo tumorigenicity

Manifestation of spin-charge separation in the dynamic dielectric response of one--dimensional Sr2CuO3

We have determined the dynamical dielectric response of a one-dimensional, correlated insulator by carrying out electron energy-loss spectroscopy on Sr2CuO3 single crystals. The observed momentum and energy dependence of the low-energy features, which correspond to collective transitions across the gap, are well described by an extended one-band Hubbard model with moderate nearest neighbor Coulomb interaction strength. An exciton-like peak appears with increasing momentum transfer. These observations provide experimental evidence for spin-charge separation in the relevant excitations of this compound, as theoretically expected for the one-dimensional Hubbard model.Comment: RevTex, 4 pages+2 figures, to appear in PRL (July 13

Fabrication and characterization of low aberration micrometer-sized electron lenses

Intrinsic spherical aberrations of electron lenses have been the major resolution limiting factor in electron microscopes for several decades. While effective correctors have recently been implemented, an alternative to correct these aberrations is to circumvent them by scaling down lens dimensions by several orders of magnitude. We have fabricated electrostatic lenses exhibiting one micrometer diameter apertures and evaluated their beam forming properties against predictions from numerical ray tracing simulations. It turns out that it is routinely possible to shape a paraxial low-energy electron beam by such micron-sized lenses. Beam profiles have been measured both at a distant detector as well as in a plane close to the lens. It is shown that the lens can form a parallel beam extending no more than 800 nm from the optical axes at a distance of 200 microm beyond the lens exit. We believe that these findings constitute a prerequisite to derive novel tools for high resolution microscopy using low-energy electrons