Suppressing Two-Plasmon Decay with Laser Frequency Detuning.

Three-dimensional laser-plasma interaction simulations show that laser frequency detuning by an amount achievable with current laser technology can be used to suppress the two-plasmon decay (TPD) instability and the corresponding hot-electron generation. For the plasma conditions and laser configuration in a direct-drive inertial confinement fusion implosion on the OMEGA laser, the simulations show that ∼0.7% laser frequency detuning is sufficient to eliminate TPD-driven hot-electron generation in current experiments. This allows for higher ablation pressures in future implosion designs by using higher laser intensities.

Vaginal film for prevention of HIV: using visual and tactile evaluations among potential users to inform product design.

Topical prevention of HIV and other STIs is a global health priority. To provide options for users, developers have worked to design safe, effective and acceptable vaginal dissolving film formulations. We aimed to characterize user experiences of vaginal film size, texture and color, and their role in product-elicited sensory perceptions (i.e. perceptibility), acceptability and willingness to use. In the context of a user-centered product evaluation study, we elicited users' 'first impressions' of various vaginal film formulation designs via visual and tactile prototype inspection during a qualitative user evaluation interview. Twenty-four women evaluated prototypes. Participants considered size and texture to be important for easy insertion. Color was more important following dissolution than prior to insertion. When asked to combine and balance all properties to arrive at an ideal film, previously stated priorities for individual characteristics sometimes shifted, with the salience of some individual characteristics lessening when multiple characteristics were weighted in combination. While first impressions alone may not drive product uptake, users' willingness to initially try a product is likely impacted by such impressions. Developers should consider potential users' experiences and preferences in vaginal film design. This user-focused approach is useful for characterizing user sensory perceptions and experiences relevant to early design of prevention technologies.

Preoperative effects of mifepristone for dilation and evacuation after 19 weeks of gestation: a randomised controlled trial.

OBJECTIVE: To evaluate mifepristone as an adjunct to, or replacement for, osmotic dilators for cervical preparation in surgical abortion after 19 weeks of gestation. DESIGN: Site-stratified, double-blinded randomised controlled trial. SETTING: Two tertiary care teaching hospitals. POPULATION: Women undergoing dilation and evacuation at 19-236/7 weeks of gestation from November 2013 through November 2015. METHODS: Participants were randomised to receive (1) mifepristone alone (n = 27), (2) osmotic dilators with mifepristone (n = 27) or (3) osmotic dilators with placebo (n = 21) with all receiving pre-procedure misoprostol. MAIN OUTCOME MEASURES: Operative time, preoperative cervical dilation and complications. RESULTS: We enrolled 75 participants; mean gestation 21 weeks. Pre-procedure cervical dilation was ≥3 cm in 4, 52, and 57% of participants in groups 1, 2, and 3, respectively (P < 0.005). Mifepristone with misoprostol for cervical preparation resulted in longer procedure times compared with osmotic dilators, with median total procedure times of (1) 18.5 (8-52), (2) 12 (7-25), and (3) 13 (6-26) minutes (P ≤ 0.005). Excluding time required for manual dilation, procedure times were similar: median times from dilation complete to evacuation complete were (1) 10.5 (4-23), (2) 8.5 (5-24), and (3) 10 (4-20) minutes (P = 0.10). Complications occurred in seven cases, six with trainees and one with an attending physician (P = 0.03), with difference by study group not reaching statistical significance (P = 0.12). CONCLUSIONS: Elimination of osmotic dilators has the potential to decrease burden and opportunity cost of cervical preparation. The longer procedure time, related to manual dilation, is offset by decreasing dilator-related preoperative time and discomfort. Provider experience may impact risk when eliminating dilators. TWEETABLE ABSTRACT: Mifepristone and misoprostol for cervical preparation prior to D&E has potential to reduce barriers to care.

Influence of the combination and phase variation status of the haemoglobin receptors HmbR and HpuAB on meningococcal virulence.

Neisseria meningitidis can utilize haem, haemoglobin and haemoglobin-haptoglobin complexes as sources of iron via two TonB-dependent phase variable haemoglobin receptors, HmbR and HpuAB. HmbR is over-represented in disease isolates, suggesting a link between haemoglobin acquisition and meningococcal disease. This study compared the distribution of HpuAB and phase variation (PV) status of both receptors in disease and carriage isolates. Meningococcal disease (n = 214) and carriage (n = 305) isolates representative of multiple clonal complexes (CCs) were investigated for the distribution, polyG tract lengths and ON/OFF status of both haemoglobin receptors, and for the deletion mechanism for HpuAB. Strains with both receptors or only hmbR were present at similar frequencies among meningococcal disease isolates as compared with carriage isolates. However, >90 % of isolates from the three CCs CC5, CC8 and CC11 with the highest disease to carriage ratios contained both receptors. Strains with an hpuAB-only phenotype were under-represented among disease isolates, suggesting selection against this receptor during systemic disease, possibly due to the receptor having a high level of immunogenicity or being inefficient in acquisition of iron during systemic spread. Absence of hpuAB resulted from either complete deletion or replacement by an insertion element. In an examination of PV status, one or both receptors were found in an ON state in 91 % of disease and 71 % of carriage isolates. We suggest that expression of a haemoglobin receptor, either HmbR or HpuAB, is of major importance for systemic spread of meningococci, and that the presence of both receptors contributes to virulence in some strains.

Nonlinear transmission of laser light through coronal plasma due to self-induced incoherence.

The success of direct laser-driven inertial confinement fusion (ICF) relies critically on the efficient coupling of laser light to plasma. At ignition scale, the absolute stimulated Raman scattering (SRS) instability can severely inhibit this coupling by redirecting and strongly depleting laser light. This article describes a new dynamic saturation regime of the absolute SRS instability near one-quarter of the critical density. The saturation occurs when spatiotemporal ion-acoustic fluctuations in the plasma density detune the instability resonance. The dynamic saturation mitigates the strong depletion of laser light and enhances its transmission through the instability region, explaining the coupling of laser light to ICF targets at higher plasma densities.

Multibeam absolute stimulated Raman scattering and two-plasmon decay.

Multibeam absolute instability thresholds for stimulated Raman scattering (SRS) and two-plasmon decay (TPD) are calculated in three dimensions for conditions relevant to direct-drive inertial confinement fusion experiments on the OMEGA laser and at the National Ignition Facility (NIF). Although multibeam effects are found to be significant for both instabilities, SRS is found to have less efficient multibeam coupling than TPD. The results are consistent with the observation of a TPD-dominated regime on the OMEGA laser and a SRS-dominated regime on the NIF despite the single-beam SRS threshold being lower than the single-beam TPD threshold on both facilities. The minimum instability threshold for NIF plasma parameters occurs for SRS near quarter-critical densities with a shared electromagnetic wave propagating along the beam axis.

Mitigation of cross-beam energy transfer in inertial-confinement-fusion plasmas with enhanced laser bandwidth.

Cross-beam energy transfer (CBET) is a significant energy-loss mechanism in directly driven inertial-confinement-fusion (ICF) targets. One strategy for mitigating CBET is to increase the bandwidth of the laser light, thereby disrupting the resonant three-wave interactions that underlie this nonlinear scattering process. Here, we report on numerical simulations performed with the wave-based code lpse that show a significant reduction in CBET for bandwidths of 2-5 THz (corresponding to a normalized bandwidth of 0.2%-0.6% at a laser wavelength of 351nm) under realistic plasma conditions. Such bandwidths are beyond those available with current high-energy lasers used for ICF, but could be achieved using stimulated rotation Raman scattering in diatomic gases like nitrogen.

Mutagenesis, cloning and complementation analysis of C4 -dicarboxylate transport genes from Rhodobacter capsulatus.

Transposon mutagenesis was used to isolate insertion mutants of the photosynthetic bacterium Rhodobacter capsulatus which were unable to grow under aerobic conditions in the dark on malate, succinate or fumarate as sole carbon sources. Of five mutants isolated, all were deficient in C4 -dicarboxylate transport. However, these mutants were still capable of photoheterotrophic growth, although at a slower rate than the wild type, on malate and succinate (but not fumarate). The mutated locus (designated dct) was complemented in trans using a cosmid gene bank. Subcloning and complementation analysis indicated that at least three closely linked genes essential for aerobic dicarboxylate transport were contained within an 8.3kb region of the Rhodobacter capsulatus chromosome.

Noninvasive Doppler determination of cardiac output during submaximal and peak exercise.

We compared pulsed Doppler (PD) measurements of stroke volume (SV) and cardiac output (CO) as a function of work load with previously reported values that were obtained by standard invasive methods. Suprasternal notch measurements of Doppler-shifted frequency (delta f) were obtained from the ascending aorta and SV calculated with the Doppler equation and an independent measurement of aortic diameter. Motion artifacts were minimized with the aid of a restraining table cycle ergometer. Signal aliasing was accommodated with manual summation of delta f waveforms. A total of 207 determinations were made in 10 sitting subjects exercising to exhaustion. Linear regression analysis of CO vs. work load was significant (P less than 0.001). The correlation coefficient (r = 0.95) and standard error of estimate value (1.21 1/min) were similar to values from the literature. Absolute values of CO and SV underestimated the literature values across all work loads. Technical reproducibility was assessed by comparing with paired t tests the differences between 65 duplicate serial measurements of CO and SV at rest and exercise. No significant differences (P less than 0.001) were found. We concluded that PD-determined SV and CO are reproducible and correlate linearly with work load in a manner consistent with reported invasive techniques. Thus the PD method appears suitable for use during submaximal and peak exercise.

Adherence of Aeromonas caviae to human cell lines Hep-2 and Caco-2.

Adherence of Aeromonas caviae to HEp-2 and Caco-2 cell monolayers was investigated with 24 clinical isolates. Growth phase, temperature, multiplicity of infection and length of incubation affected adherence. Treatment of the bacteria with trypsin, sodium metaperiodate, mechanical shearing and the addition of cytochalasin B and cycloheximide to the monolayer significantly reduced the adherence capabilities of the strains investigated. The use of chloramphenicol to inhibit protein synthesis reduced the adhesive capabilities of bacteria grown in liquid medium and those subjected to mechanical shearing. Light microscopy, scanning and transmission electron microscopy were employed in the investigation of bacteria-bacteria and bacteria-monolayer interactions and indicated similarities with the aggregative adherence patterns of the Enterobacteriaceae. The presence of extracellular bacterial appendages and their correlation with increased adhesive capacity may indicate a role in the process of adherence.

Induction of antibodies to plant viral proteins by DNA-based immunization.

DNA-based immunization is a promising new technique for generating antibodies in laboratory animals for diagnostic purposes in biological science. The main advantages are the elimination of time and labor and the technically demanding steps of antigen purification. The DNA sequence of the protein of interest, cloned in a suitable in vivo expression vector that is administered intramuscularly or intradermally, is sufficient to induce an immune response in animals. We report the induction of antibodies to tobacco mosaic virus (TMV) coat protein (CP) as a highly immunogenic structural protein and potato virus Y (PVY) P1 protein (P1) as a nonstructural protein. The appropriate nucleotide sequences were introduced in a mammalian expression vector (pSG5) and injected intramuscularly into New Zealand White rabbits (Oryctolagus cuniculus). By 10 days post-injection (dpi) a specific immune response was detected against TMV-CP, while it took about 5 weeks for a response to PVY P1. In both cases the antibody titers were significantly above the corresponding pre-immune serum, however, they were considerably below the titer of the matching conventionally produced antiserum. To our knowledge, this is the first report of DNA-based immunization in order to generate antibodies to plant viral proteins, but further improvements are necessary to increase antibody titers before this promising new technique can be introduced broadly in plant science for diagnostic purposes.

Health library partnership programmes between resource-poor countries and Western Europe.

A survey of health library partnerships between the UK and northern European countries and African or eastern European countries was undertaken to complement a similar survey of 24 North American health libraries. Out of 11 partnerships described, six provided sufficient data to be included in a quantitative analysis. These results give some baseline data about such partnerships and their activities, reasons for success and problems encountered. Some libraries have little involvement other than sending duplicate books and journals; others are more deeply involved in all aspects of library activity including professional development. Good communications, both human and technological, are important for maintaining partnership momentum. Staff commitment on both sides and institutional support for the partnership are essential, especially when programmes have costs which must be met either by the institution or outside funders. The financial consequences of partnership may inhibit their initiation, but successful partnerships with demand driven programmes bring benefits to both sides.

Tobacco mosaic virus and the study of early events in virus infections.

In order to establish infections, viruses must be delivered to the cells of potential hosts and must then engage in activities that enable their genomes to be expressed and replicated. With most viruses, the events that precede the onset of production of progeny virus particles are referred to as the early events and, in the case of positive-strand RNA viruses, they include the initial interaction with and entry of host cells and the release (uncoating) of the genome from the virus particles. Though the early events remain one of the more poorly understood areas of plant virology, the virus with which most of the relevant research has been performed is tobacco mosaic virus (TMV). In spite of this effort, there remains much uncertainty about the form or constituent of the virus that actually enters the initially invaded cell in a plant and about the mechanism(s) that trigger the subsequent uncoating (virion disassembly) reactions. A variety of approaches have been used in attempts to determine the fate of TMV particles that are involved in the establishment of an infection and these are briefly described in this review. In some recent work, it has been proposed that the uncoating process involves the bidirectional release of coat protein subunits from the viral RNA and that these activities may be mediated by cotranslational and coreplicational disassembly mechanisms.

Evidence that a viral replicase protein is involved in the disassembly of tobacco mosaic virus particles in vivo.

Tobacco mosaic virus (TMV) particles have been shown to undergo bidirectional disassembly when they are introduced into host cells. Approximately three-quarters of the genomic RNA (i.e., the 126-kDa and 183-kDa protein ORFs) is first uncoated in the 5'-to-3' direction and the process is then completed by removal of coat protein molecules in the 3'-to-5' direction. An effort was made to determine whether the 126-kDa protein or the 183-kDa protein, both of which are involved in replication of the viral RNA, is required for the second part of the disassembly reaction. It was shown that progeny negative-strand viral RNA begins to be produced in inoculated cells at about the same time that 3'-to-5' disassembly is initiated thus suggesting that the two processes may be coupled. Particles containing mutant forms of the viral RNA in which large sections of the 126-kDa and 183-kDa protein ORFs were missing were not disassembled in the 3'-to-5' direction when they were introduced into cells. However, they were disassembled when the inoculum contained purified TMV RNA from which, presumably, the two functional proteins could be translated Particles containing mutants of the RNA from which a few codons had been deleted in or near conserved regions in the 126-kDa protein ORF also did not undergo 3'-to-5' disassembly unless mixed with wild type viral RNA prior to inoculation. These results suggest that the 126-kDa and/or 183-kDa protein plays a role in the completion of disassembly of TMV particles at the onset of the infection process.

Infection of tobacco leaf epidermal protoplasts with tobacco mosaic virus.

Protoplasts from the epidermal cells of tobacco leaves were prepared and inoculated with tobacco mosaic virus. Up to 50% of the protoplasts became infected and, within 3 days, contained an average of 5 x 10(5) virus particles per protoplast. Hexagonal crystalline inclusions were observed in many of the infected protoplasts.