Asbestos in potable water

Several published reports indicate that asbestos is found in public drinking water supplies. In order to determine the health effects of ingested asbestos, relevant animal and human studies were reviewed. From these studies, it was not possible to predict potential health hazards associated with ingestion of the levels of asbestos found in drinking water. Detailed examinations of Water samples were carried out by electron microscopy in order to determine the precision of analysis for waterborne asbestos. Asbestos-cement pipes, used to transmit drinking water, were studied under field conditions. No significant release of asbestos was observed. Preliminary work suggests that asbestos is present in Lake Michigan. An investigation of possible sources of asbestos into Lake Michigan indicated that wet deposition of asbestos may be a principal pathway of asbestos contamination of Lake Michigan. A feasibility study was carried out to determine if asbestos is present in rainwater collected in the Chicago area. Chrysotile asbestos was found in Chicago rainwater at a level of 10⁵ to 10⁶ fibers per liter. This finding demonstrates that precipitation scavenges airborne chrysotile asbestos which may result in the contamination of surface waters.U.S. Department of the InteriorU.S. Geological SurveyOpe

Structural analysis of the synthetic Duffy Binding Protein (DBP) antigen DEKnull relevant for Plasmodium vivax malaria vaccine design

The Plasmodium vivax vaccine candidate Duffy Binding Protein (DBP) is a protein necessary for P. vivax invasion of reticulocytes. The polymorphic nature of DBP induces strain-specific immune responses that pose unique challenges for vaccine development. DEKnull is a synthetic DBP based antigen that has been engineered through mutation to enhance induction of blocking inhibitory antibodies. We determined the x-ray crystal structure of DEKnull to identify if any conformational changes had occurred upon mutation. Computational and experimental analyses assessed immunogenicity differences between DBP and DEKnull epitopes. Functional binding assays with monoclonal antibodies were used to interrogate the available epitopes in DEKnull. We demonstrate that DEKnull is structurally similar to the parental Sal1 DBP. The DEKnull mutations do not cause peptide backbone shifts within the polymorphic loop, or at either the DBP dimerization interface or DARC receptor binding pockets, two important structurally conserved protective epitope motifs. All B-cell epitopes, except for the mutated DEK motif, are conserved between DEKnull and DBP. The DEKnull protein retains binding to conformationally dependent inhibitory antibodies. DEKnull is an iterative improvement of DBP as a vaccine candidate. DEKnull has reduced immunogenicity to polymorphic regions responsible for strain-specific immunity while retaining conserved protein folds necessary for induction of strain-transcending blocking inhibitory antibodies

Structural and functional basis for inhibition of erythrocyte invasion by antibodies that target Plasmodium falciparum EBA-175

Disrupting erythrocyte invasion by Plasmodium falciparum is an attractive approach to combat malaria. P. falciparum EBA-175 (PfEBA-175) engages the host receptor Glycophorin A (GpA) during invasion and is a leading vaccine candidate. Antibodies that recognize PfEBA-175 can prevent parasite growth, although not all antibodies are inhibitory. Here, using x-ray crystallography, small-angle x-ray scattering and functional studies, we report the structural basis and mechanism for inhibition by two PfEBA-175 antibodies. Structures of each antibody in complex with the PfEBA-175 receptor binding domain reveal that the most potent inhibitory antibody, R217, engages critical GpA binding residues and the proposed dimer interface of PfEBA-175. A second weakly inhibitory antibody, R218, binds to an asparagine-rich surface loop. We show that the epitopes identified by structural studies are critical for antibody binding. Together, the structural and mapping studies reveal distinct mechanisms of action, with R217 directly preventing receptor binding while R218 allows for receptor binding. Using a direct receptor binding assay we show R217 directly blocks GpA engagement while R218 does not. Our studies elaborate on the complex interaction between PfEBA-175 and GpA and highlight new approaches to targeting the molecular mechanism of P. falciparum invasion of erythrocytes. The results suggest studies aiming to improve the efficacy of blood-stage vaccines, either by selecting single or combining multiple parasite antigens, should assess the antibody response to defined inhibitory epitopes as well as the response to the whole protein antigen. Finally, this work demonstrates the importance of identifying inhibitory-epitopes and avoiding decoy-epitopes in antibody-based therapies, vaccines and diagnostics

Prognostic Factors in Dedifferentiated Chondrosarcoma: A Retrospective Analysis of a Large Series Treated at a Single Institution.

Background:Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. Methods:In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors. Results:Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis. Conclusions:The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients

Crystallization and preliminary crystallographic analysis of the central domain of Drosophila Dribble, a protein that is essential for ribosome biogenesis. Addendum

An addition to the paper by Cheng et al. [(2010), Acta Cryst. F66, 546–548]

Streamer Wave Events Observed in Solar Cycle 23

In this paper we conduct a data survey searching for well-defined streamer wave events observed by the Large Angle and Spectrometric Coronagraph (LASCO) on-board the Solar and Heliospheric Observatory (SOHO) throughout Solar Cycle 23. As a result, 8 candidate events are found and presented here. We compare different events and find that in most of them the driving CMEs ejecta are characterized by a high speed and a wide angular span, and the CME-streamer interactions occur generally along the flank of the streamer structure at an altitude no higher than the bottom of the field of view of LASCO C2. In addition, all front-side CMEs have accompanying flares. These common observational features shed light on the excitation conditions of streamer wave events. We also conduct a further analysis on one specific streamer wave event on 5 June 2003. The heliocentric distances of 4 wave troughs/crests at various exposure times are determined; they are then used to deduce the wave properties like period, wavelength, and phase speeds. It is found that both the period and wavelength increase gradually with the wave propagation along the streamer plasma sheet, and the phase speed of the preceding wave is generally faster than that of the trailing ones. The associated coronal seismological study yields the radial profiles of the Alfv\'en speed and magnetic field strength in the region surrounding the streamer plasma sheet. Both quantities show a general declining trend with time. This is interpreted as an observational manifestation of the recovering process of the CME-disturbed corona. It is also found that the Alfv\'enic critical point is at about 10 R$_\odot$ where the flow speed, which equals the Alfv\'en speed, is $\sim$ 200 km s$^{-1}$