On the feasibility of nanocrystal imaging using intense and ultrashort X-ray pulses.

Structural studies of biological macromolecules are severely limited by radiation damage. Traditional crystallography curbs the effects of damage by spreading damage over many copies of the molecule of interest in the crystal. X-ray lasers offer an additional opportunity for limiting damage by out-running damage processes with ultrashort and very intense X-ray pulses.

Feasibility of imaging living cells at subnanometer resolutions by ultrafast X-ray diffraction.

Detailed structural investigations on living cells are problematic because existing structural methods cannot reach high resolutions on non-reproducible objects. Illumination with an ultrashort and extremely bright X-ray pulse can outrun key damage processes over a very short period. This can be exploited to extend the diffraction signal to the highest possible resolution in flash diffraction experiments.

Femtosecond time-delay X-ray holography.

Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics.

Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb.

The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs.

Pulse requirements for x-ray diffraction imaging of single biological molecules.

In this paper we estimate the required pulse parameters for the future application of x-ray free electron lasers to imaging single biological molecules. The parameters are determined by a tradeoff between minimizing image degradation due to damage and maximizing the image signal-to-noise ratio. We discuss several means to alleviate the pulse requirements, and compare the requirements with parameters of two planned x-ray lasers.

Clocking femtosecond X rays.

Linear-accelerator-based sources will revolutionize ultrafast x-ray science due to their unprecedented brightness and short pulse duration. However, time-resolved studies at the resolution of the x-ray pulse duration are hampered by the inability to precisely synchronize an external laser to the accelerator. At the Sub-Picosecond Pulse Source at the Stanford Linear-Accelerator Center we solved this problem by measuring the arrival time of each high energy electron bunch with electro-optic sampling.

Atomic-scale visualization of inertial dynamics.

The motion of atoms on interatomic potential energy surfaces is fundamental to the dynamics of liquids and solids. An accelerator-based source of femtosecond x-ray pulses allowed us to follow directly atomic displacements on an optically modified energy landscape, leading eventually to the transition from crystalline solid to disordered liquid. We show that, to first order in time, the dynamics are inertial, and we place constraints on the shape and curvature of the transition-state potential energy surface.

Diffraction imaging of single particles and biomolecules.

Theory predicts that with a very short and very intense X-ray pulse, the image of a single diffraction pattern may be recorded from a large macromolecule, a virus, or a nanocluster of proteins without the need for a crystal. A three-dimensional data set can be assembled from such images when many copies of the molecule are exposed to the beam one by one in random orientations. We outline a method for structure reconstruction from such a data set in which no independent information is available about the orientation of the images.

Visceral leishmaniasis in Somalia. Significance of IgG subclasses and of IgE response.

We have determined the levels of IgG subclasses and IgE as well as specific antibodies of these isotypes in sera from 22 patients with clinical visceral leishmaniasis (VL) from Somalia. The results are compared with those obtained from 30 Somali and 23 Swedish controls. We found markedly increased concentrations of IgG1 in the VL sera, indicating that the pronounced increase in IgG in VL which is generally considered to be due to polyclonal B-cell activation is mainly restricted to this subclass.

Visceral leishmaniasis in Somalia: prevalence of markers of infection and disease manifestations in a village in an endemic area.

Prevalence and disease manifestations of visceral leishmaniasis (VL) were studied in a Somali village in an area which has long been known to be endemic for VL. Demographic data were collected from 102 households, comprising 438 inhabitants. Clinical examination was performed of 306 individuals, 72% of the 426 eligible persons.

An epidemic of Plasmodium falciparum malaria in Balcad, Somalia, and its causation.

The causative factors of an epidemic of falciparum malaria were investigated in Balcad, Somalia, a town with previously low malaria transmission, where malaria incidence rose more than twenty-fold between 1986 and 1988. The emergence of chloroquine resistance, accelerated by high drug pressure, low herd immunity and favourable meteorological conditions were identified as major causes of the epidemic. Chloroquine resistance of grades RII and RIII was first observed in Balcad in 1987 and rapidly increased to 72% of the Plasmodium falciparum infections in 1988.

Visceral leishmaniasis in Somalia. Circulating antibodies as measured by DAT, immunofluorescence and ELISA.

Sera from patients with visceral leishmaniasis (VL) (n = 26), healthy residents of Mogadishu (n = 157), inhabitants of a village in an endemic area (n = 276) and healthy Swedes (n = 60) were examined using the direct agglutination test (DAT), immunofluorescence (IF) and ELISA for antibodies against Leishmania donovani. The study was carried out in order to provide baseline data for antibody responses in visceral leishmaniasis as existing in Somalia and to explore which one of these methods would be most suitable for diagnosis of clinical cases as well as for epidemiological population studies in Somalia. All patients had high levels of circulating antibodies, however, lower values were recorded in the early stages of the disease.

Visceral leishmaniasis in Somalia: prevalence of leishmanin-positive and seropositive inhabitants in an endemic area.

In an endemic area of Somalia both humoral and cell mediated immunity against Leishmania donovani was demonstrated in 246 inhabitants. In a study of 14 patients with active visceral leishmaniasis, we found that antibodies appear early in infection and that they are then demonstrable for a limited period only. Leishmanin positivity develops later and persists longer, but does not seem to be lifelong.

Reference ranges for IgG, IgM and IgA in the serum of urban and rural Somalis.

In order to provide baseline data for an immuno-parasitological laboratory in Somalia, serum concentrations of IgG, IgM and IgA were determined in some key populations: healthy residents of Mogadishu (n = 157), inhabitants of the village of Daimo Samo (n = 276) and patients with malaria (n = 39) and visceral leishmaniasis (n = 26), both protozoan infections accompanied by hypergammaglobulinaemia and causing severe health problems in Somalia. Since the serum immunoglobulin concentrations in the Somali populations studied were not normally distributed, they were evaluated using medians and percentiles. Significantly higher values of IgG, IgM and IgA were demonstrated in healthy Mogadishu residents as compared to healthy Swedes.

Amebiasis in Nicaragua: class specific serum antibody responses.

With the aid of the indirect hemagglutination (IHA) test and IgG ELISA the antibody profile against E. histolytica in León, Nicaragua was investigated in 562 sera from individuals belonging to various age groups. The highest reactivity was invariably recorded in the age group 6-15 years where 48% were seropositive.

Antibody responses in schistosomiasis haematobium in Somalia. Relation to age and infection intensity.

Antibody responses in schistosomiasis haematobium were studied in relation to age and infection intensity in Somalia. The area is highly endemic for Schistosoma haematobium but free of S. mansoni.

Antibodies against Entamoeba histolytica antigens in sera from individuals with amoebiasis of different localization.

The over-all contents and relative component composition of Entamoeba histolytica antigens in abscess fluids and in extracts of cultured amoebae, strain NIH 200, were studied by antigen-catching EIA, counterimmunoelectrophoresis (CIE) and immunoblotting techniques. The antigen contents of liver abscess fluid were determined semiquantitatively by the antigen-catching EIA in four cases. In CIE against a standard "diagnostic" extract of cultured amoebae, sera from cases of acute amoebic liver abscess gave 4-5 precipitation lines while sera from cases of intestinal amoebiasis gave at most 3 lines.

Incidence of toxoplasmosis in pregnant women in the city of Malmö, Sweden.

The incidences of latent and primary Toxoplasma gondii infections in pregnant women were studied using stored sera from 4,351 women delivered in the city of Malmö, Sweden in 1982 and 1983. Infants born to mothers with signs of primary infection (seroconversion or specific IgM in sera collected during pregnancy) were studied with regard to serological evidence of congenital infection (specific IgM in cord serum). Sera were tested for specific IgG antibodies by direct agglutination test and enzyme-linked immunosorbent assay, and for specific IgM by immunosorbent assay.

Detection of giardia antigen in stool samples by a semi-quantitative enzyme immunoassay (EIA) test.

A semi-quantitative enzyme immunoassay (EIA) test for the detection of Giardia intestinalis antigen in faeces was developed. In order to avoid unspecific reactions due to anticalf serum activity, IgG fractions of anti-giardia rabbit and sheep sera were purified from antibovine antibodies by immunoadsorption. Faecal specimens tested in the assay were mixed with normal horse serum to avoid unspecific and proteolytic effects of stool components.

Human toxoplasmosis in Somalia. Prevalence of Toxoplasma antibodies in a village in the lower Scebelli region and in Mogadishu.

The acquisition of Toxoplasma antibodies in various age groups was studied in 2 populations in Somalia, inhabitants of a village in the southern part of the country and residents in Mogadishu. The overall prevalence of antibodies was 56% in the village and 40% in Mogadishu. In both populations, antibodies were acquired early in life.

The prevalence of Entamoeba histolytica in lactating women and in their infants in Bangladesh.

Entamoeba histolytica was studied in 33 lactating women and their infants in a periurban village in Bangladesh. Infant-mother pairs were followed for a period of 10-15 months: 67% of mothers excreted E. histolytica during the observation period, the majority for 3 months or more.

Cerebral schistosomiasis presenting as a brain tumor.

A patient with cerebral Schistosoma mansoni schistosomiasis is described. The infection presented as a cerebral tumor, and the patient did not have the usual hepatic or intestinal symptoms of this disease. The computed tomography (CT) findings in histologically proven cerebral schistosomiasis are reported.

Amoebicidal activity of the antifungal antibiotic sinefungin against Entamoeba histolytica.

The antifungal antibiotic sinefungin, a potent inhibitor of methyl transferases and a potential inhibitor of polyamine biosynthesis, exhibited marked cytolytic activity against Entamoeba histolytica in vitro with respect to all the amoeba strains tested. Strains of high and low virulence displayed equal sensitivity to the antibiotic. Minimal Amoebicidal Concentration was 5 to 10 micrograms/ml.