Imaging African trypanosomes

Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis (HAT), also known as sleeping sickness. In late-stage infection, trypanosomes cross the blood–brain barrier (BBB) and invade the central nervous system (CNS) invariably leading to coma and death if untreated. There is no available vaccine and current late-stage HAT chemotherapy consists of either melarsoprol, which is highly toxic causing up to 8% of deaths, or nifurtimox–eflornithine combination therapy (NECT), which is costly and difficult to administer. There is therefore an urgent need to identify new late-stage HAT drug candidates. Here, we review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to whole-animal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We also consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies

Measurement of Thermal Stress in Railroad Rails Using Ultrasonic SH Waves

The use of welded joints in railroad tracks has led to problems of rail buckling brought about by the development of large compressive stresses during hot days. On cold days, tensile stresses can actually fracture the rail. In order to prevent this source of derailments, it is desirable to develop an easily used instrument to measure the level of stress in an arbitrary section of track in the field. Ultrasonic birefringence, acoustic emission and certain magnetic phenomena have all been used to attack this problem but they all suffer from the necessity for calibrating the sensor under stress-free conditions in order to correct for metallurgical structure variations. A new ultrasonic technique based on using surface skimming shear horizontal ultrasonic waves generated and detected by EMATs was investigated here because it rigorously eliminates the effects of metallurgical texture as well as unreliable coupling of the transducer to the part. Tests on sections of rail mounted in a 200,000 pound testing machine at the University of New Mexico demonstrated that the theory for the basic phenomenon is correct and that the stress level can be measured in spite of the presence of considerable texture in the rail microstructure

Measuring aerosol active surface area by direct ultraviolet photoionization and charge capture in continuous flow

Direct ultraviolet photoionization electrically charges particles using a mechanism distinct from di usion charging. The purpose of this study is to evaluate aerosol photoemission theory as a function of aerosol particle size, concentration, material, and morphology. Particles are classi ed using an aerodynamic aerosol classi er (AAC) and subsequently measured with a scanning mobility particle sizer (SMPS) and photoionization measurement system in parallel. This con guration allows direct comparison of photo-emission from high concentrations of initially neutral, monodisperse aerosols with di erent morphologies or materials. Under all examined conditions, the overall photoelectric yields of particles of self-similar material (silver and unconditioned soot) and morphology (sintered spheres and agglomerates) are each linearly proportional to the second moment of the mobility-equivalent diameter distribution, even in the transition regime (mobility diameter 30 - 200 nm), with agglomerate silver particles resulting in 5 higher photoelectric yield than unconditioned soot from a propane ame. It is shown for the rst time that the photoelectric yield is signi cantly higher (2.6 ) for fractal-like agglomerate silver particles than sintered, close-packed spherical particles of the same material and mobility-equivalent diameter, which is inferred to be due to the larger material surface area exposed externally to the particle surroundings. It is demonstrated that photoelectric measurements of aerosols re ect the photoelectrically active surface area which depends on the particle morphology and therefore the state of sintering.Alphasense Natural Sciences and Engineering Research Council of Canada Cambustio

A probabilistic analysis of argument cogency

This paper offers a probabilistic treatment of the conditions for argument cogency as endorsed in informal logic: acceptability, relevance, and sufficiency. Treating a natural language argument as a reason-claim-complex, our analysis identifies content features of defeasible argument on which the RSA conditions depend, namely: change in the commitment to the reason, the reason’s sensitivity and selectivity to the claim, one’s prior commitment to the claim, and the contextually determined thresholds of acceptability for reasons and for claims. Results contrast with, and may indeed serve to correct, the informal understanding and applications of the RSA criteria concerning their conceptual dependence, their function as update-thresholds, and their status as obligatory rather than permissive norms, but also show how these formal and informal normative approachs can in fact align

Crime displacement: what we know, what we don't know, and what it means for crime reduction

Objectives If offending were simply displaced following (often spatially) focused crime reduction initiatives, the continued expenditure of resources on this approach to crime reduction would be pointless. The aims of this article were to: critically appraise the current body of displacement research; identify gaps in understanding; articulate an agenda for future research; and to consider the implications of the accumulated findings for practitioners, evaluators, and policy makers. Methods First, we review existing criminological theory regarding crime displacement and the alternative perspective—that crime prevention activity might generate a diffusion of crime control benefits. Second, we review the empirical research, focusing in particular on the findings of existing systematic reviews. Third, we consider the types of displacement that might occur and the methodological approaches employed to study them. Results Theoretical and empirical research suggests that displacement is far from inevitable and that a diffusion of crime control benefit is at least as likely. However, some forms of displacement have not been adequately studied. Conclusion Existing research suggests that successful crime reduction interventions often have a positive impact on crime that extends beyond the direct recipients of a particular project. However, current understanding of crime displacement and how benefits might diffuse remains incomplete. Consequently, to inform an agenda for future research, we derive a typology of methodological issues associated with studying displacement, along with suggestions as to how they might be addresse

Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial.

BackgroundRetinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%.PurposeThis randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN.MethodsAnalyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test.ResultsRA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible.ConclusionsA short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects.ImplicationsA derivative of vitamin A can reverse or suppress an epithelial preneoplasia, lending further support to the notion that chemoprevention of human cancer is feasible

Influenza transmission in a cohort of households with children: 2010-2011

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Evaluation of the fracture performance of different rubberised bitumens based on the essential work of fracture

The fracture performance of rubberised bitumen in addition to one pre-treated with a Warm Mix Additive (Sasobit®) was investigated using different test methods measuring different damage mechanisms. Two Recycled Tyre Rubber (RTR) modifiers together with two base binders were blended in the laboratory to produce various combinations of Recycled Tyre Rubber Modified Bitumens (RTR-MBs). The first RTR is a standard recycled polymer derived from discarded truck and passenger car tyres by ambient grinding. The second RTR consists of 100% recycled truck tyres derived by cryogenic grinding and pre-treated with special oil and WMA to allow further decrease of asphalt mixture production temperatures. A fracture mechanics testing approach was used for evaluating the binder fatigue resistance; consisting of the double-edge-notched tension (DENT) test. The critical tip opening displacement (CTOD) obtained from the DENT test was used for fracture characterization of the binders within the ductile failure region. The study applied the partitioning concept of the total energy of bituminous binders to have a more reliable parameter that could be independent of the stress state of the ligament. The results show that generally the addition of RTR improves the fracture properties of binders indicating better fatigue performance. Pre-treatment with Sasobit® makes the materials more brittle and hence more susceptible to fracture

R-h-erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis

Anaemia of chronic disease (ACD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFα) plays an important role in the development of ACD. The objective of the present study was to assess inhibition of in vitro colony-forming unit erythrocyte (CFUe) and blast-forming unit erythrocyte (BFUe) growth by TNFα and to examine whether this suppression could be counteracted by adding increasing concentrations of recombinant human erythropoietin (EPO) (r-h-EPO) to bone marrow cultures of RA patients with ACD and without anaemia (controls). Bone marrow cells of RA patients with ACD and control patients were cultured. The cultures were incubated with increasing concentrations of r-h-EPO (0.25; 0.5; 1; 2 U/ml), each in combination with increasing quantities of TFNα (0; 50; 100; 200; 400 U/ml). CFUe and BFUe were assessed after 7 and 14 days, respectively. Dose-dependent inhibition of BFUe and CFUc by increasing concentrations of TNFα was observed in ACD and controls. Regarding CFUe (ACD patients) incubated with 0.25 U/ml EPO, 50 U/ml TNFα caused 28% suppression compared to cultures without TNFα. Increasing the concentration of r-h-EPO from 0.25 U/ml to 2 U/ml completely restored the number of CFUe. A similar pattern was observed in BFUe growth in both groups. These data demonstrated the suppressive effects of TNFα on erythropoiesis in vitro and that the suppresed erythropoiesis could be partly corrected by the addition of excess r-h-EPO to the cultures. No significant differences were observed between ACD and control RA patients. This in vitro model may help explain the clinical response to r-h-EPO therapy as documented in RA patients with ACD