When the thickness of piezoelectric film increase from 0.6μm to 2μm, as shown in Fig. 6, the difference of the s of the 8 HBARs decrease, and the maximum of HBAR(E) is 1.32 times of the minimum of HBAR(D) for sapphire substrate HBARs; the maximum of HBAR(G) is 1.28 times of the minimum of HBAR(J) for fused quartz substrate HBARs. It is because the influence of electrodes reduce with the increase of the thickness ratio of the piezoelectric film to electrodes. As shown in Fig. 7, the maximum deviation from 1 to decrease from 105% of HBAR(j) to 38% of HBAR(J). The deviation from 1 to obviously decreases with the thickness increase of piezoelectric film, while the variation of the deviation from 2 to is not obvious. It is found that using 2 to estimate is not need to consider the thickness ratio of the piezoelectric film to electrodes.
There are two main applications for HBAR. One is used to the microwave source; another is used to characterize the piezoelectric film. The k2 distribution, especially the resonator frequency (or mode) having the maximum k2, is the key properties to the applications. In this leukotriene receptor antagonist paper, influence of the electrodes on k2 distribution of HBAR is ejaculatory duct investigated using the four-layer thickness extension mode composite resonator model. The relation between and the SPRF distribution and resonance frequency of the top-electrode piezoelectric film bottom-electrode sandwich structure are discussed, respectively.
Some conclusions can be summarized from the analysis for the HBARs having comparable thickness of piezoelectric film and electrodes:
Two HBARs of (I) Al(100nm)–ZnO(0.6μm)–Al(130nm)–Sapphire(404μm) and (II) Al(100nm)–ZnO(0.6μm)–Au(80nm)–Sapphire(404μm) are fabricated, which show identical outlines of k2 and SPRF curves with the simulations. The k2 distribution of HBAR is affected significantly by different electrode materials. The fabricated HBAR(I) and HBAR(II) have s of about 2GHz and 3GHz, respectively. The k2 of ZnO films are extracted from the first peak (, k2) of the k2 curve. The ZnO film deposited on Al and Au electrodes have k2 of 0.0597 and 0.0615, respectively.
This work was supported by the National Natural Science Foundation of China (11374327).
Again the low frequency section delivered in Fig. 28(b) shows how the principal modal responses of PhCr plate are altered by introducing gradient structure with varying unitcells. For example, the transmission is highly diminished at modal frequencies 5th and 6th by in order 32 and 27dB, and highly escalated at subsequent modal frequencies 7th and 8th by in order 22 and 18dB. Hence, the low frequency response of this graded PhCr plate is considerably manipulated besides maintaining its high frequency bandgap properties. In fact multiscale functionality is observed for this structure: in unitcell scale (with length 2mm) the bandgap properties are altered from around 1.5MHz, while in structure scale (with length 20mm) the basic modal responses are influenced after around 0.15MHz.
Due to the complexity of equations in helical systems, analytical solutions are difficult or impossible to achieve. Purely numerical approaches have to be adopted. A classical method that has been widely used for straight waveguides is the so-called semi-analytical finite prostaglandin receptor (SAFE) method. This method restricts the FE discretization to transverse directions only [1–4]. It has been applied for modeling closed helical waveguides (guides in vacuum) in Ref. , where the SAFE modeling of a free single helical wire has been presented based on helical coordinates. A particular twisting coordinate system has then been proposed for the analysis of single helical wires as well as multi-wire strands .
Regardless helicity, structural waveguides are often embedded in large solid media that can be considered as unbounded. Waves can radiate energy into the surrounding medium and strongly attenuate along the guide axis, which reduces the propagation distance. Such wave modes are referred to as leaky modes [7,8]. This energy leakage can be enhanced in curved or helical structures, which makes their NDE more difficult. The curvature effect on radiation loss has been thoroughly studied in electromagnetism [9–13] and sometimes investigated in elastodynamics [14,15]. In the context of NDE, searching the less attenuated modes is necessary in order to maximize the inspection distance.
As opposed to closed waveguides, the numerical modeling of embedded waveguides encounters two difficulties: the cross-section is unbounded and the amplitude of leaky modes transversely grows [16–19]. In order to overcome these difficulties, the SAFE method must be combined with other numerical techniques.
As far as straight waveguides are concerned, several techniques have been recently proposed to extend the SAFE method to guides embedded in a solid matrix. A simple numerical procedure is the absorbing layer (AL) method proposed in Refs. [20,21], which consists in creating artificial viscoelastic layers in the surrounding medium for absorbing waves. Instead of using artificial layers, Mazzotti et al.  have combined the boundary element method (BEM) with the SAFE method, which avoids the discretization of the unbounded surrounding domain. An alternative technique is the perfectly matched layer (PML) method. Recently, the authors have presented and analyzed SAFE-PML methods for modeling embedded solid multi-layer plates  and three dimensional waveguides of arbitrary cross-section . These works are yet limited to straight waveguides. In electromagnetism, a SAFE-PML formulation has been proposed for the analysis of twisted microstructured optical fibers [25,26]. Yet to the authors knowledge, the modeling of embedded helical structures has not yet been considered in elastodynamics.
The goal of this paper is to propose a SAFE-PML technique to compute leaky modes in embedded helical structures. The twisted SAFE-PML method is described in Section 2. The equilibrium equations of elastodynamics are written in twisting coordinates to account for the helical geometry. In this coordinate system, a radial PML is applied. This radial PML can be centered or off-centered. The method is validated in Section 3 thanks to the cylindrical bar test case, which can support any arbitrary twist. The effect of twist on the eigenspectrum is briefly discussed. Two numerical applications are then presented in Section 4. The first example consists in studying an embedded helical wire of circular cross-section. The effect of twist on the axial attenuation of modes is investigated. The second application is a seven-wire strand embedded into concrete. Seven-wire strands are widely used in civil engineering cables. They are typically made by one straight cylindrical wire surrounded by one layer of six helical wires.
A second series of experiments employed a laser Doppler vibrometer to acquire signals at points on the plate to investigate the propagation characteristics of the mode. A PZT transducer (3×3mm), coupled to the plate with cyanoacrylate, was used for efficient out-of-plane excitation having an out-of-plane to in-plane displacement ratio of 10:1. The laser vibrometer was used to measure out-of-plane displacement at a series of points incrementally spaced (25mm) along several different propagation directions. A single beam vibrometer was used, which was physically moved to different measurement locations. At each point the recorded signal was the average of 300 acquisitions. Small patches of retro-reflective tape were applied at the measurement locations for better optical performance. A 2-cycle Hanning-windowed toneburst with a centre frequency of 60kHz was used for the excitation signal. This frequency was chosen because it gave the greatest amplitude response in the fibre direction. It is worth noting that the same experiment performed on metallic plates produced an amplitude response that peaks at much higher frequencies. This is probably due to the much stronger frequency dependence of attenuation in CFRP materials.
Energy velocity angular profile
Energy velocity (), the velocity at which a wavepacket travels, is a useful propagation parameter for determining the spatial position of a signal recorded by an NDE/SHM system. If the arrival time () of a signal corresponding to a defect or structural feature is recorded by a transducer operating in pulse-echo configuration, the defect or structural feature can be estimated to be at a distance, , from the transducer. If a network of sensors is used to inspect the structure, the information from all the sensors can be combined to spatially localize signals using one of the many localization algorithms [11–13]. Therefore, nisoldipine velocity is an essential parameter for defect localization by NDE/SHM systems. In anisotropic plates, the energy velocity of guided waves is directionally dependent and hence an angular profile of energy velocity, , is needed for the localization algorithms. The profile, which is also mode dependent, is thus an important mode choice criterion.
The energy velocity angular profiles of the and modes in the low frequency-thickness band for unidirectional and cross-ply CFRP plates were determined experimentally. The time of the first arrival () measured at different distances (r) and directions () was estimated using a Rayleigh Maximum Likelihood Estimator (RMLE) . RMLE is a statistical estimator, which determines the time of the first signal arrival in a waveform, even if the amplitude of the arrival is very small. A linear fit was applied to for each direction and an example of this is given in Fig. 4. was estimated from the slope of the linear fit and the error in was calculated from the variance of the deviations of from the line (99% confidence interval). It is worth noting, that energy velocity estimation using this method is not susceptible to systematic measurement errors in and r. The temperature has to be kept constant during experiments as it was shown that temperature changes can have a significant effect on guided wave velocity .
Fig. 5(a) shows the measured energy velocity profiles for the and modes in the unidirectional composite plate. Both modes have larger velocities in the fibre direction that decrease towards the 90° direction, but the velocity change is more pronounced for the mode. Fig. 5(b) shows measured energy velocity profiles for the and modes in the cross-ply composite plate. The mode has greater velocity in fibre directions and a minimum in the 45° direction. Interestingly, the mode velocity is virtually independent of direction. The measured energy velocity angular profiles are qualitatively in good agreement with theoretically predicted group velocities for unidirectional and cross-ply plates built from T700 M21 plies. Small discrepancies between the individual values are likely to be due to the arbitrary choice of T700 M21 material for predictions as properties of the plates used in the experiments were unknown. The results also agree with theoretical studies made by other authors [5,15]. The shapes of the group velocity profiles for and modes are generally maintained at low frequencies as can be seen in Fig. 6. The theoretical group velocity solutions were generated using plate properties given in Section 2 and a SAFE solver .
Lets assume that each point of the structure can be described not only by its coordinates , but also with a velocity model which is a function of frequency f and cross-section , cf. . The latter term is a function of the coordinates , the local thickness of the structure d and, for anisotropic materials, a function of the direction of wave propagation . This leads in a composite structure with varying thickness to the case that the velocity model at one point is different to the velocity model at another point. The simple case of a homogeneous plate with constant thickness is included in this formulation as a special case.
Consequently, the time delay from the actuator i to the voxel P and from this voxel to the receiver j can be computed as
The total time delay is . Unlike conventional beamforming techniques this method operates in the time rather than the distance domain, cf. . Assuming a sensor network of transducers that act in turn as emitters, the carboxypeptidase at the focal point can be expressed aswhere the employed time window leads to a greater robustness against jitter and measurement noise , and is typically in the order of 10μs. In this equation denotes the differential sensor signal, i.e. the sensor signal measured in the healthy state of the structure minus the sensor signal of the damaged structure.
Description of the setup
In this paper, a glass fiber reinforced structure of 1m by 1m is considered in which the thickness changes in twelve discrete steps from 0.695mm to 4.132mm. Each segment has an equidistant length of approximately 83mm. The phase and group velocity are based on those values that have been used in a previous experimental study to predict the antisymmetric wave motion in a similar structure . Fig. 1 shows the corresponding phase and group velocity wave curve at 50kHz for different thicknesses. Besides the anisotropic properties of the wave field the phase and group velocity changes strongly with the thickness of the structure. These wave curves have been calculated by means of the well-known global matrix method for anisotropic multi-layered waveguides exploiting third order plate theory [17,18]. The material properties are listed in Table 1.
The simulation framework proposed elsewhere  uses Fourier domain techniques to propagate the ultrasound wave in the irregular waveguide by including the dispersion maps in the phase term. The scatterer is approximated as a point-target with idealized scattering properties. Here, nine piezoelectric transducers are placed randomly on the structure. Each transducer acts in turn as emitter and sends a toneburst signal with five cycles at a carrier frequency of 50kHz. In total, this leads to receiver signals. The point-like damage in this example is located at (0.25m, 0.36m). It has been assumed that dispersion does not have a significant influence on the sensor signals as demonstrated in .
Each voxel of the discretized structure is defined by its coordinates and a velocity model that corresponds to the thickness of the structure. The implementation of the method uses a database of velocity models where each voxel has an identification number pointing to the respective velocity model. In order to determine the time delay associated with Eq. (1) the coordinates, and also the velocities, from the actuator to the voxel and from the voxel to the sensor must be interpolated by a straight line and the individual contributions added in an incremental way. In this work, a total number of 40 segments per each line is used that minimizes the errors in the incremental time delay calculation.
Fig. 2 shows the localization result for the actual velocity model and the average velocity, respectively. It can be observed that the scatterer can be precisely located when the actual wave curve in the generalized beamforming algorithm is considered. As soon as the average velocity is used the localization accuracy degrades although the average velocity is the best guess that can be made for the conventional delay-and-sum beamforming technique. In this example the localization error for the latter case is about 84mm.
The German edition of Analytical Transmission Electron Microscopy by J. Thomas and T. Gemming has already been mentioned here (No. 17 in ). They have now produced this English text (the epigraph above comes from the Preface). “Why do we need an additional textbook about this topic?” they ask, and reply that one cannot do analytical hippo pathway microscopy unless one knows about electron microscope imaging, electron diffraction, characteristic x-rays and EELS, which are the themes of their book . Certainly Williams and Carter cover all these topics as do older texts such as Reimer\’s well-known volumes, but Thomas and Gemming are less than confident that their audience is keen to learn. Thus chapter 1, ‘Why such an effort?’, starts “with an example. When we are waiting for a tram at a tram stop and the tram approaches but we cannot read the number of the tram line, we have to wait until the tram approaches us. The experience teaches: To see smaller details we have to shorten the viewing distance. Or in other words: The visual angle σ (Fig. 1.1) must be large enough”. Several pages of very elementary optics follow, grim reminders of the decline in the teaching of basic optics in modern school curricula. Chapters on sample preparation, use of the microscope, electron diffraction contrast, higher magnification, STEM, analytical tools and finally ‘Basics explained in more detail (with a bit more mathematics)’. The tone is chatty throughout and it is assumed that the microscopist will need to be told to acquire such tools as tweezers. Since most newcomers to the electron microscope would presumably learn their business in a laboratory already equipped with such things, this advice struck me as otiose. My overall opinion is that the authors are aiming rather low – but they know their audience better than I do! One last criticism: in the past, Springer encouraged authors whose first language was not English to have their text vetted by a native English speaker. This would have been wise here to eliminate such sentences as “Changing the focal length allows to image object planes being in different distances onto the screen. Later, we will see which capabilities can be opened by this”. Foreign authors, please do remember that ‘allow’, ‘permit’ and (normally) ‘enable’ require a direct object: ‘we permit someone to do something’ or ‘we permit something [to be done]’; we never ‘permit to do’ whatever is planned. Despite all this, let me add that the authors know their subject thoroughly and newcomers to AEM will find this text helpful.
Next two huge volumes in the Methods in Molecular Biology series, Springer Protocols: the third edition of Electron Microscopy, Methods and Protocols edited by J. Kuo  and Electron Crystallography of Soluble and Membrane Proteins edited by I. Schmidt-Krey and Y. Cheng . There are 34 chapters in Kuo\’s volume so I can only give a sample. Numerous contributions deal with one aspect or another of cryo-electron microscopy and an interesting chapter is devoted to ‘Biological applications of phase-contrast electron microscopy’ in which modern phase plates are discussed. Correlative light and electron microscopy is covered by C. Spiegelhalter et al. and there are other chapters on the same theme. M. Saunders and J.A. Shaw describe ‘Biological applications of energy-filtered TEM’. I could not find any mention of the role of aberration-corrected electron microscopy. As always in these Protocol volumes, exact instructions for carrying out the various procedures are provided – an enormous amount of information is compressed into the nearly 800 pages of this collection. The volume on electron crystallography is no less impressive a compendium, which covers in very down-to-earth terms every aspect of the subject. ‘Introduction to electron crystallography’ by W. Kühlbrandt and ‘Future directions of electron crystallography’ by Y. Fujiyoshi act as bookends for 28 other contributions, each occupying about 19 pages. Recording data, manipulating the records, automation are all described and a chapter by K.H. Downing describes ‘Future developments in instrumentation of electron crystallography’. Extremely useful if this is what you do, or would like to do.
As shown for the TiC particle case above, the Ti/C overlap in the uncorrected dataset prevents the correct stoichiometry from being estimated by either a proxigram or composition profile as shown in Fig. 8. Using the corrected dataset (r=1nm), we can now use the same proxigram tool to observe the corrected composition for the TiC particle, as estimated by this method. Compared to the uncorrected version, the ratio moves far closer to the expected Ti50–C50 stoichiometry. Some carbon loss is observed, but this is a common problem in APT [121–125].
The primary drawback to this method is that it mixes data from the sampling volume of each ion, i.e. the volume from which the composition was drawn. In the implementation used here, the sampling volume is a sphere, centred around each ion, resulting in a sampling blur equivalent to the sphere used as the selection volume. Practically speaking, the blur will widen step profiles, such as in proxigrams and composition profiles. Fig. 9 shows the blurring of a simulation containing an initially sharp interface, where the algorithm has sampled data from both sides of the interface. In the pure regions away from the interface, there is no incorrect reassignment, as the composition goes to 100%, and thus no discernable blurring occurs. However as can be seen from the profile across the interface, the blurring has converted the initial step into a ramp, equal to 2 distance units wide.
Atom probe tomography is usually characterised as a three dimensional chemical imaging tool. However, the challenges in the interpretation of data reconstruction are complex and influenced by numerous complex and interacting parameters [126–128] (Fig. 10). At this stage of development in the field, we do not have the full equivalent in (-)-p-Bromotetramisole Oxalate cost probe tomography of a contrast transfer function as we have in transmission electron microscopy [129,130].
When such explicit functional relationships based on theory and/or phenomenological data are not available to capture all the diversity of variables (Fig. 10), one needs to explore ways to statistically capture such information. As discussed earlier in this paper, there are a multitude of different types of information that can be empirically identified, measured or some in cases even modelled. The challenge is to find a way to simultaneously obtain the cross-correlations among all these parametric studies. Hence we can describe atom probe data as having a “high dimensionality” since for each of the millions of atoms detected there are multiple parameters associated with each hit including spatial coordinates, instrumental parameters, composition, the evaporation physics and parameters associated with the reconstruction analysis.
A key step is to find ways to map the correlations between all these parameters (and a diverse array of other attributes that underlie them), in a manner that can be interpreted. Hence there is a need to map or “project” this high dimensional information into lower dimensions, preferably two or three dimensions, which is the only way these correlations can be visualised. In this “reduced” dimensional space, we can then seek to find patterns and associations of data that permit us to unravel the complexity and truly “mine” the rich information embedded in atom probe images and spectra. The process of reducing the dimensionality of data mathematically is one that has to be done carefully, to avoid losing or distorting true correlations between characteristics in the original data set [73,131–134]. There are numerous techniques to accomplish this and in the following discussion we shall provide a couple of brief examples of the value of using such methods.
When accounting for the multivariate nature of most materials chemistry problems and the numerous variables and parameters that can be associated with instrument operation and data acquisition, this data cube is actually an n-dimensional hypercube. Hence the challenge is to “unfold” the high dimensional data matrix and identify the key or principal characteristics that capture the key spatial relationships of chemistry in a chemical image.
Since the channelling from Ga-rich columns is likely different from that of Al-rich columns, a question arises as to the extent to which the Ga K-peak and Al K-peak STEM EDX signals are complementary. Fig. 5(a) compares the column-averaged Al K-peak and Ga K-peak signals as a function of the number of Al dopants. The expected anticorrelation is evident—more Al atoms mean fewer Ga atoms so the Ga signal tends to go down as the Al signal goes up—and the variability due to different configurations is comparable. The Ga K-peak signal is also around a factor of 2 larger than the Al K-peak signal giving a marginal Amyloid Beta-Peptide (1-40) of shot noise. The correlation between the Ga K-peak and Al K-peak signal is explored directly in Fig. 5(b), which plots the Al K-peak signal against the Ga K-peak signal from the same column. A strong anticorrelation is evident, with the variability between different configurations as a fraction of average column signal increasing slightly with increasing thicknesses. In recent work we have advocated the advantages of absolute scale comparisons [32,33], but, since quantitative EDX has traditionally often been based on ratios, plots of the Al K-peak to Ga K-peak signal ratios are shown in Fig. 5(c). The results for the thinner samples, where the composition spans a wider range, are not simply linear in the Al composition, evidence of the appreciable change in channelling conditions between Al-rich columns (atomic number ) and Ga-rich columns . The ratio approach does not improve the degree to which differences in composition can be distinguished from differences in configuration.
Investigating the effect of shot noise
The variation seen in Fig. 3(b) and the plots of that same type in Figs. 4 and 5 are due to differences in configuration and not to shot noise, since these simulations are effectively infinite dose results. It may well be, however, that shot noise is at least as limiting, if not more so. One advantage of absolute scale simulations is that for given experimental conditions the expectation value for the number of X-ray counts and hence the corresponding shot noise level can be predicted, since shot noise is a Poisson process. Consider the case of 20 Al atoms in the column for a 160Å thick sample as shown in Fig. 4(a) [reproduced more clearly in Fig. 6(a)]. The average number of counts/nA/sr/s across the configurations considered is 1317. For a typical current of 0.1nA, a multiple detector system with total solid angle 0.5sr, and a column dwell time of 0.4s (8ms per pixel after scan averaging  and four probe points per 1Å linear scan), the total number of X-ray counts would be 26, giving a shot noise standard deviation of around 20% (since for Poisson statistics the standard deviation is the square root of the mean). Consequently, discriminating configurational and/or compositional differences will only be possible if Lethal locus lead to signals which differ by more than this. Reducing the shot noise to 5%—which the next section shows to be about the standard deviation due to configurational differences in our present case study—would require a 16-fold increase in X-ray counts. Obtaining precision limited by the configurational variation may therefore only be possible in samples which will withstand high currents and/or a large degree of scan averaging. Novel configurations which increase the detector solid angle would help too .
Shot noise is the fundamental limit due to the probabilistic nature of (quantum mechanical) ionization. Further limitations are likely in practice. Eqs. (1) and (3) contain several factors, and uncertainties in the determination of these values propagate through to the predicted number of X-ray counts. In addition, experimental X-ray spectra require subtraction of the continuous bremsstrahlung X-ray background before seeking to identify the number of X-ray counts due to core-shell ionization . Reliable background fitting and subtraction is challenging if the count rates are low, adding a further source of noise/error.
Interestingly, the ability of SAMHD1 to block HIV-1 infection and LINE-1 retrotransposition exhibit separate requirements. The ability of SAMHD1 to block HIV-1 infection requires SAMHD1’s enzymatic activity (Laguette et al., 2011; Lahouassa et al., 2012; Seamon et al., 2015). By contrast, the ability of SAMHD1 to block LINE-1 retrotransposition does not require SAMHD1’s enzymatic activity (Zhao et al., 2013). Here, we revealed another clue that will be important for teasing apart the mechanistic divide between these two restriction scenarios. One possibility is that SAMHD1 uses its sterile alpha motif (SAM) to interact with the RNA of complexes undergoing retrotransposition blocking the process by steric hindrance, which is in agreement with the fact that SAMHD1 variants that do not contain a SAM domain lost their ability to block LINE-1 retrotransposition (Zhao et al., 2013).
Although we sequenced SAMHD1 bafilomycin from 80 Korean individuals, we were unable to document the previously described single nucleotide polymorphisms that results in the S33A change (Kim et al., 2009; Park et al., 2010). This might be due to a low frequency of this particular alleles. Either way this mutant provides a valuable tool for the separation of HIV-1 restriction from LINE-1 inhibition by SAMHD1.
We are grateful to Dr. Kyudong Han for helping us accessing the sequence database in Korea, and the sequencing of SAMHD1 in 80 Korean individuals. We are thankful to the NIH/AIDS repository program for providing valuable reagents such as antibodies and drugs. We would like to thank Dr. John Goodier for sharing his protocols and antibodies against LINE-1 ORFp with us. This work was funded by NIHR01 AI087390, R21 AI102824, and R56 AI108432 grants to F.D.-G. Sara Sawyer was supported by an NIH grant R01-GM-093086 to S.S.
T4-like phages classically representing Myoviridae phages have a contractile tail sheath and infect a broad range of bacterial hosts. Studies of T4-like phage genomes as models have suggested that myovirus genomes are mosaic of conserved core genes, which include structural genes for head and tail proteins and enzyme genes for DNA and nucleotide metabolism, and the remaining variable accessory non-core genes (Filee et al., 2006). The functions of non-core genes are largely unknown, although it is assumed that they provide a selective benefit to phages (Hendrix, 2009). Petrov and coworkers recently defined “T4-related phages” to group phages that share a “Core Genome” encoding approximately 37 proteins (Lavigne et al., 2009; Petrov et al., 2010). T4-related phages include the members of the genus T4likevirus, the genus SchizoT4likevirus (http://ictvonline.org) and other phages including cyanomyoviruses and Delftia acidovorans phage ϕW-14. More recently, another genus “Viunalikevirus” inside the T4-related phages was proposed for phages showing a number of features that distinguish them from other members of the T4-related phages (Adriaenssens et al., 2012a). Viunalikeviruses are characterized as virulent phages showing similar genome size (150–170kbp), extensive DNA homology, strong gene synteny, and a complex adsorption apparatus on the virion. Members of this genus include phages infecting bacterial hosts belonging to Enterobacteriaceae (Gammaproteobacteria).
The phytopathogen Ralstonia solanacearum, a soil-borne Gram-negative bacterium (Betaproteobacterium), causes bacterial wilt disease in many important crops (Hayward, 1991; Yabuuchi et al., 1995). The unusually wide host-range of this bacterium extends to over 200 species belonging to >50 botanical families (Hayward, 2000). R. solanacearum strains constitute a heterogeneous group subdivided into five races on the basis of their host range, six biovars based on their physiological and biochemical characteristics (Hayward, 2000), and four phylotypes according to phylogenetic information (Fegan and Prior, 2005; Remenant et al., 2010). Yamada et al. (2007), Yamada (2012) and Bhunchoth et al. (2015, 2016b) isolated and characterized various types of bacteriophages infecting R. solanacearum strains belonging to different races and/or biovars. Among them, ϕRP15, which was initially characterized as a myovirus with a wide host-range, replicates exclusively through a lytic cycle and forms clear plaques.
The ability of BLSOmp31-P407-Ch to stimulate cellular immune response was also examined. As the most important finding, we demonstrated that conjunctival immunization induced a significant cellular immune response. In fact, cells from vaccinated rams produced significant levels (p<0.01) of γ–IFN upon in vitro stimulation with BLSOmp31 at day 90 after the first immunization (Fig. 4A) indicating that this formulation administered by conjunctival route induced a specific cellular immune response mediated by activation of macrophages, which are the main effector mechanism mediating the killing of Brucella spp. (Estein et al., 2009). Similarly, BLSOmp31 elicited an in vivo significantly higher hypersensitivity response with respect to the unvaccinated control group (p<0.001) after intradermal injection in immunized rams (Fig. 4B).
In summary, the results obtained in the present work indicate that conjunctival immunization with BLSOmp31-P407-Ch gel induced local and systemic immune response in rams without interfering in the serological diagnosis of ovine brucellosis caused by B. ovis. The protective activity of this formulation in challenged sheep remains to be investigated.
Conflict of interest
This work was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT-Argentina) (to S.M.E. and to S.P). S.M.E., D.A.Q., S.E.G., D.A.A., V.Z. and F.A.G are members of the Research Career of CONICET (Argentina). A.G.D. is recipient of a fellowship from CONICET (Argentina).
Various approaches have been used to develop monoclonal GSK343 (mAbs) to cell differentiation molecules [CDM, previously referred to as leukocyte differentiation antigens (LDA)] for research in veterinary species. Our initial approach was to hyper-immunize mice with leukocytes from one or more species and then use flow cytometry (FC) to screen primary cultures of hybridomas for mAbs that recognize different CDMs (Davis et al., 1987, 1984). Screening revealed unique patterns of labeling that could be visualized in two-parameter dot plots, using side light scatter vs. fluorescence (SSC vs. FL). MAbs recognizing the same molecule could be clustered based on patterns of labeling. One or more of the cell lines forming a cluster could then be cloned for further analysis. If the cluster contained mAbs of different isotypes, two-color labeling could be used to verify that the mAbs recognized the same molecule. In instances where the mAbs in the cluster were the same isotype, Zenon second step reagents could be used to compare specificity (Davis and Hamilton, 2008). MAbs that recognize different epitopes on the same molecule form a diagonal pattern of labeling, or, if mAbs recognize the same epitope, one mAb may block labeling by the other (Davis et al., 1995; Park et al., 2015b). Participation in international workshops from 1983 to 1998 and in 2004 facilitated final characterization of many mAbs that are currently available for use in veterinary research (Haverson et al., 2001a; Howard et al., 1991; Lunn et al., 1996; Morrison and Davis, 1991; Naessens and Hopkins, 1996; Naessens and Howard, 1993; Saalmüller et al., 2005). Although the workshops were an effective way to complete characterization of many mAbs, limited resources and participants have curtailed efforts to continue convening international workshops, leaving many potentially useful mAb-defined molecules only partially characterized. The recent sequencing of the bovine genome and the development of mass spectrometry have provided information and technology needed for individual laboratories to continue the endeavor. Amino acid sequences identified from small quantities of immunoaffinity-purified proteins can be used to screen the genome databases of humans or other species to match sequences of known orthologous molecules. This proved useful recently in identifying the specificity of four mAb-defined molecules in cattle: CD26, CD50, the chaperone molecule gp96, and SLAMF9, the newest member of the signaling lymphocyte activation molecule family (Park et al., 2015b). Many potentially useful mAbs that recognize existing or new bovine molecules await complete characterization. Because of increased interest in determining the phylogenetic and functional similarities of ruminant monocytes to those characterized in mice and humans, the sets of partially characterized mAbs left over from the workshops were screened to determine if any of them recognize new molecules that might help clarify how closely ruminant monocyte ontogeny compares with ontogeny of monocytes in mice and humans. Any differences in ontogeny and expression of surface molecules on monocyte subsets could lead to misinterpretation of findings when comparing the ruminant (Italiani and Boraschi, 2014; Ziegler-Heitbrock and Hofer, 2013). Twelve mAbs were selected for further analysis. After analysis, the mAbs were used with mAbs specific for CD16, CD172a, and CD209 to extend information on what is known about the composition of monocyte subsets in ruminant blood.
Penile Mondor disease is a rare condition characterized by thrombosis or thrombophlebitis of the superficial dorsal vein of the penis. Henry Mondor described a sclerosing thrombophlebitis in the superficial veins of the chest wall first; Braun Falco then described a generalized form of the disease involving penis in 1955, and an isolated thrombosis of the superficial vein of the penis was first reported by Helm and Hodge in 1958.
Penile Mondor\’s disease has a prevalence of approximately 1.4% and is usually seen in sexually active men aged between 21 to 70 years. It is an under-reported and underdiagnosed medical condition owing to patients\’ fear and reluctance to consult a physician and insufficient description of the complaints.
The exact etiology of the disease remains unclear; however, it is generally believed to involve enteroviral infection, contact with menstrual blood (due to irritation), tuberculosis, circumcisional scar tissues, prolonged sexual activity (sexual intercourse or masturbation), prolonged sexual abstinence, trauma to the purchase Sulfo-NHS-Biotin or external genitalia, surgical intervention on the pelvis or external genitalia, and tumors located in the pelvis. There are also case reports of penile Mondor\’s disease after inguinal hernia repair and subinguinal varicocelectomy. Penile Mondor\’s disease is considered idiopathic if none of these etiologic factors are present in a patient. Deficiencies of antithrombin 3, protein-C, and protein-S are thought to be involved in these idiopathic cases. A main etiologic cause of the disease is considered to be mechanical trauma, and the patients generally report prolonged sexual activity in the past 24-48 hours.
Penile Mondor\’s disease can usually be diagnosed by medical history and physical examination. There are no specific laboratory tests or markers for the diagnosis. Penile Doppler ultrasonography (USG) can be performed for exact or differential diagnosis. Patients usually admit with pain and discomfort during erection and palpable swelling and hardness on the dorsal surface of the penis. Thrombosed dorsal vein of the penis often extends to the suprapubic region, with associated swelling, erythema, and edema of the penile skin. Thus, penile angioedema should also be considered in the differential diagnosis. In this study, we aim to investigate the treatment outcomes among our patients diagnosed with penile Mondor\’s disease and to evaluate the effect of the disease on erectile function.
Descriptive statistics were expressed as means and standard deviations. Correlation between the quantitative variables was analyzed using the Pearson correlation coefficient. The Kolmogorov-Smirnov test was used to verify the normal distribution of the data. The differences between the 3 IIEF-5 scores (IIEF-5-1, IIEF-5-2, and IIEF-5-3) were evaluated using repeated measures analysis of variance and post hoc Bonferroni tests. A P value of <.005 was considered statistically significant.
The mean age of the patients diagnosed with penile Mondor disease at our clinic was 34.3 years (range, 25-48 years). They admitted to our outpatient clinic with the complaints of palpable hardness at the dorsum of the penis, pain during erection, and redness and tenderness of the penile dorsal surface lasting for an average of 5 days (ranged from 4 to 9 days). Six patients had a history of admission to another hospital with the same complaints, but a diagnosis could not have been made. On physical examination, a hard venous structure suggestive of a thrombus was palpated in all patients (Fig. 1). In 20 patients, the above described structure was on the dorsal surface of the penis extending parallel to the bottom of the glans penis, whereas in the remaining 10 patients, codon extended from the dorsal penis into the suprapubic region. In 10 patients (33%), redness of the tissue over the venous structure and a subcutaneous edema of the glans penis were also observed. A digital rectal examination was performed in patients aged >40 years (7 patients) and revealed no pathologic finding.