Motion correction of 4D dynamic contrast enhanced MRI (DCE-MRI) series is required for diagnostic evaluation of liver lesions. The registration, however, is a challenging task, owing to rapid changes ...in image appearance. In this study, two different registration approaches are compared; a conventional pairwise method applying mutual information as metric and a groupwise method applying a principal component analysis based metric, introduced by Huizinga et al (2016). The pairwise method transforms the individual 3D images one by one to a reference image, whereas the groupwise registration method computes the metric on all the images simultaneously, exploiting the temporal information, and transforms all 3D images to a common space. The performance of the two registration methods was evaluated using 70 clinical 4D DCE-MRI series with the focus on the liver. The evaluation was based on the smoothness of the time intensity curves in lesions, lesion volume change after deformation and the smoothness of spatial deformation. Furthermore, the visual quality of subtraction images (pre-contrast image subtracted from the post contrast images) before and after registration was rated by two observers. Both registration methods improved the alignment of the DCE-MRI images in comparison to the non-corrected series. Furthermore, the groupwise method achieved better temporal alignment with smoother spatial deformations than the pairwise method. The quality of the subtraction images was graded satisfactory in 32% of the cases without registration and in 77% and 80% of the cases after pairwise and groupwise registration, respectively. In conclusion, the groupwise registration method outperforms the pairwise registration method and achieves clinically satisfying results. Registration leads to improved subtraction images.
Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of ...the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system.
PSR J1906+0746 is a young pulsar in the relativistic binary with the second-shortest known orbital period, of 3.98 hr. We here present a timing study based on five years of observations, conducted ...with the five largest radio telescopes in the world, aimed at determining the companion nature. Through the measurement of three post-Keplerian orbital parameters, we find the pulsar mass to be 1.291(11) M sub(middot in circle), and the companion mass 1.322(11)M sub(middot in circle), respectively. These masses fit well in the observed collection of double neutron stars (DNSs), but are also compatible with other systems where a young pulsar such as J1906+0746 is orbited by a white dwarf (WD). Neither radio pulsations nor dispersion-inducing outflows that could have further established the companion nature were detected. We derive an Hi-absorption distance, which indicates that an optical confirmation of a WD companion is very challenging. The pulsar is fading fast due to geodetic precession, limiting future timing improvements. We conclude that the young pulsar J1906+0746 is likely part of a DNS, or is otherwise orbited by an older WD, in an exotic system formed through two stages of mass transfer.
In an era of antimicrobial resistance, a better understanding of the interaction between bacteria and the sentinel immune system is needed to discover new therapeutic targets for combating bacterial ...infectious disease. Sentinel immune cells such as macrophages phagocytose intact bacteria and thereby initiate ensuing immune responses. The bacterial surface composition is a key element that determines the macrophage signaling. To study the role of the bacterial cell surface composition in immune recognition, we developed a platform technology for altering bacterial surfaces in a controlled manner with versatile chemical scaffolds. We show that these scaffolds are efficiently loaded onto both Gram-positive and -negative bacteria and that their presence does not impair the capacity of monocyte-derived macrophages to phagocytose bacteria and subsequently signal to other components of the immune system. We believe this technology thus presents a useful tool to study the role of bacterial cell surface composition in disease etiology and potentially in novel interventions utilizing intact bacteria for vaccination.
: The skin stage of malaria is a vital and vulnerable migratory life stage of the parasite. It has been characterised in rodent models, but remains wholly uninvestigated for human malaria parasites. ...To enable in depth analysis of not genetically modified (non-GMO)
sporozoite behaviour in human skin, we devised a labelling technology (Cy5M
, targeting the sporozoite mitochondrion) that supports tracking of individual non-GMO sporozoites in human skin.
: Sporozoite labelling with Cy5M
was performed
as well as via the feed of infected
mosquitos. Labelling was validated using confocal microscopy and flow cytometry and the fitness of labelled sporozoites was determined by analysis of infectivity to human hepatocytes
, and
in a rodent infection model
Using confocal video microscopy and custom software, single-sporozoite tracking studies in human skin-explants were performed.
: Both
and
labelling strategies yielded brightly fluorescent sporozoites of three different
species. Cy5M
uptake colocalized with MitoTracker
green and could be blocked using the known Translocator protein (TSPO)-inhibitor PK11195. This method supported the visualization and subsequent quantitative analysis of the migration patterns of individual non-GMO
sporozoites in human skin and did not affect the fitness of sporozoites.
: The ability to label and image non-GMO
sporozoites provides the basis for detailed studies on the human skin stage of malaria with potential for
translation. As such, it is an important tool for development of vaccines based on attenuated sporozoites and their route of administration.
We present radio transient search algorithms, results, and statistics from the ongoing Arecibo Pulsar ALFA (PALFA) survey of the Galactic plane. We have discovered seven objects through a search for ...isolated dispersed pulses. All of these objects are Galactic and have measured periods between 0.4 and 4.7 s. One of the new discoveries has a duty cycle of 0.01%, smaller than that of any other radio pulsar. We discuss the impact of selection effects on the detectability and classification of intermittent sources, and compare the efficiencies of periodicity and single-pulse (SP) searches for various pulsar classes. For some cases we find that the apparent intermittency is likely to be caused by off-axis detection or a short time window that selects only a few bright pulses and favors detection with our SP algorithm. In other cases, the intermittency appears to be intrinsic to the source. No transients were found with DMs large enough to require that they originate from sources outside our Galaxy. Accounting for the on-axis gain of the ALFA system, as well as the low gain but large solid-angle coverage of far-out sidelobes, we use the results of the survey so far to place limits on the amplitudes and event rates of transients of arbitrary origin.
The light spectrum above 650 nm allows for good tissue penetration depths, therefore far-red and near-infrared fluorescent dyes are popular fluorophores applied in (bio)medical diagnostics, including ...image-guided surgery. Unfortunately, near-infrared fluorescent dyes often suffer from instability and limited brightness, two important features that, together with the labelling efficiency (e.g., non- one- or di-conjugated products) and serum-dye interactions are key elements that drive in vivo characteristics. Due to the fact that stability and brightness of far-red fluorophores are often superior over near-infrared dyes, interest in the use of dyes such as Cy5 is increasing. As there are clear indications that the chemical structure of a dye influences the (photo)physical properties, these properties of ten structural variants of asymmetrical Cy5-(R1)R2-(R3)COOH (R representing the varied substituents) dyes were extensively studied. While stacking in solution was not induced in most of the Cy5 far-red dyes, multimers and stacking characteristics were observed in protein conjugates. Although all dye variants were shown to be stable towards photobleaching, clear differences in brightness and serum interactions were found. Combined, these findings indicate that there is a direct relation between chemical substituents and the properties of Cy5 dyes, and that this feature should be considered when using fluorescent dyes in future tracer development.
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•Clear differences in brightness were found upon changing the fluorophore substituents.•The investigated fluorophores were optical and chemically stable.•Increasing number of sulfonates on the Cy5 decreased non-specific serum protein interactions.•Clear differences in labelling efficiencies between the dyes were found during protein conjugation.
Far-red dyes such as cyanine 5 (Cy5) are gaining interest in (bio)medical diagnostics as they have promising features in terms of stability and brightness. Here, the electrostatic density and ...stacking tendency in different solvents of nine systematically altered asymmetrical Cy5 dyes are reported. In addition to this, the influence of molecular alterations on the vibronic coupling was reported. The data presented supplement to the recent study “The influence of systematic structure alterations on the photophysical properties and conjugation characteristics of asymmetric cyanine 5 dyes” (Spa et al., 2018).
Pulsar Discovery by Global Volunteer Computing Knispel, B; Allen, B; Cordes, J.M ...
Science (American Association for the Advancement of Science),
09/2010, Letnik:
329, Številka:
5997
Journal Article
Recenzirano
Odprti dostop
Einstein@Home aggregates the computer power of hundreds of thousands of volunteers from 192 countries to mine large data sets. It has now found a 40.8-hertz isolated pulsar in radio survey data from ...the Arecibo Observatory taken in February 2007. Additional timing observations indicate that this pulsar is likely a disrupted recycled pulsar. PSR J2007+2722's pulse profile is remarkably wide with emission over almost the entire spin period; the pulsar likely has closely aligned magnetic and spin axes. The massive computing power provided by volunteers should enable many more such discoveries.
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