83 research outputs found
Emerging Techniques in Breast MRI
As indicated throughout this chapter, there is a constant effort to move to more sensitive, specific, and quantitative methods for characterizing breast tissue via magnetic resonance imaging (MRI). In the present chapter, we focus on six emerging techniques that seek to quantitatively interrogate the physiological and biochemical properties of the breast. At the physiological scale, we present an overview of ultrafast dynamic contrast-enhanced MRI and magnetic resonance elastography which provide remarkable insights into the vascular and mechanical properties of tissue, respectively. Moving to the biochemical scale, magnetization transfer, chemical exchange saturation transfer, and spectroscopy (both βconventionalβ and hyperpolarized) methods all provide unique, noninvasive, insights into tumor metabolism. Given the breadth and depth of information that can be obtained in a single MRI session, methods of data synthesis and interpretation must also be developed. Thus, we conclude the chapter with an introduction to two very different, though complementary, methods of data analysis: (1) radiomics and habitat imaging, and (2) mechanism-based mathematical modeling
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High-Resolution Structures and Orientations of Antimicrobial Peptides Piscidin 1 and Piscidin 3 in Fluid Bilayers Reveal Tilting, Kinking, and Bilayer Immersion
While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high-resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of 1Hβ15N dipolar couplings and 15N chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially bound Ξ±-helical peptides. The tilt of the helical axis, Ο, is between 83Β° and 93Β° with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, Ο, is 235Β°, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their Ο angles (<10Β°) and significant difference in their Ο angles (βΌ25Β°). Remarkably, the kink, at the end of a G(X)4G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt Ο angles that maximize their hydrophobic moments. Two structural features differentiate the more potent p1 from p3: p1 has a larger Ο angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG, but p3 is 1.2 Γ
more deeply inserted than p1 in PE/PG. In contrast to the ideal Ξ±-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted Ξ±-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie βΌ1.2β3.6 Γ
below the plane defined by the C2 atoms of the lipid acyl chains
Phase Measurement for Driven Spin Oscillations in a Storage Ring
This paper reports the first simultaneous measurement of the horizontal and
vertical components of the polarization vector in a storage ring under the
influence of a radio frequency (rf) solenoid. The experiments were performed at
the Cooler Synchrotron COSY in J\"ulich using a vector polarized, bunched
deuteron beam. Using the new spin feedback system, we
set the initial phase difference between the solenoid field and the precession
of the polarization vector to a predefined value. The feedback system was then
switched off, allowing the phase difference to change over time, and the
solenoid was switched on to rotate the polarization vector. We observed an
oscillation of the vertical polarization component and the phase difference.
The oscillations can be described using an analytical model. The results of
this experiment also apply to other rf devices with horizontal magnetic fields,
such as Wien filters. The precise manipulation of particle spins in storage
rings is a prerequisite for measuring the electric dipole moment (EDM) of
charged particles
Spin tune mapping as a novel tool to probe the spin dynamics in storage rings
Precision experiments, such as the search for electric dipole moments of
charged particles using storage rings, demand for an understanding of the spin
dynamics with unprecedented accuracy. The ultimate aim is to measure the
electric dipole moments with a sensitivity up to 15 orders in magnitude better
than the magnetic dipole moment of the stored particles. This formidable task
requires an understanding of the background to the signal of the electric
dipole from rotations of the spins in the spurious magnetic fields of a storage
ring. One of the observables, especially sensitive to the imperfection magnetic
fields in the ring is the angular orientation of stable spin axis. Up to now,
the stable spin axis has never been determined experimentally, and in addition,
the JEDI collaboration for the first time succeeded to quantify the background
signals that stem from false rotations of the magnetic dipole moments in the
horizontal and longitudinal imperfection magnetic fields of the storage ring.
To this end, we developed a new method based on the spin tune response of a
machine to artificially applied longitudinal magnetic fields. This novel
technique, called \textit{spin tune mapping}, emerges as a very powerful tool
to probe the spin dynamics in storage rings. The technique was experimentally
tested in 2014 at the cooler synchrotron COSY, and for the first time, the
angular orientation of the stable spin axis at two different locations in the
ring has been determined to an unprecedented accuracy of better than
rad.Comment: 32 pages, 15 figures, 7 table
Batch-Mode Clinical-Scale Optical Hyperpolarization of Xenon-129 Using an Aluminum Jacket with Rapid Temperature Ramping
We present spin-exchange optical pumping (SEOP) using a third-generation (GEN-3) automated batch-mode clinical-scale 129Xe hyperpolarizer utilizing continuous high-power (βΌ170 W) pump laser irradiation and a novel aluminum jacket design for rapid temperature ramping of xenon-rich gas mixtures (up to 2 atm partial pressure). The aluminum jacket design is capable of heating SEOP cells from ambient temperature (typically 25 Β°C) to 70 Β°C (temperature of the SEOP process) in 4 min, and perform cooling of the cell to the temperature at which the hyperpolarized gas mixture can be released from the hyperpolarizer (with negligible amounts of Rb metal leaving the cell) in approximately 4 min, substantially faster (by a factor of 6) than previous hyperpolarizer designs relying on air heat exchange. These reductions in temperature cycling time will likely be highly advantageous for the overall increase of production rates of batch-mode (i.e., stopped-flow) 129Xe hyperpolarizers, which is particularly beneficial for clinical applications. The additional advantage of the presented design is significantly improved thermal management of the SEOP cell. Accompanying the heating jacket design and performance, we also evaluate the repeatability of SEOP experiments conducted using this new architecture, and present typically achievable hyperpolarization levels exceeding 40% at exponential build-up rates on the order of 0.1 minβ1
Phase locking the spin precession in a storage ring
This letter reports the successful use of feedback from a spin polarization
measurement to the revolution frequency of a 0.97 GeV/ bunched and polarized
deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control
both the precession rate ( kHz) and the phase of the horizontal
polarization component. Real time synchronization with a radio frequency (rf)
solenoid made possible the rotation of the polarization out of the horizontal
plane, yielding a demonstration of the feedback method to manipulate the
polarization. In particular, the rotation rate shows a sinusoidal function of
the horizontal polarization phase (relative to the rf solenoid), which was
controlled to within a one standard deviation range of rad. The
minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753
kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a
requirement for the use of storage rings to look for an intrinsic electric
dipole moment of charged particles
Pregnane X Receptor and Yin Yang 1 Contribute to the Differential Tissue Expression and Induction of CYP3A5 and CYP3A4
The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 site is conserved in CYP3A4, but its inhibitory effect can be offset by PXR acting on response elements such as XREM. Taken together, the loss of YY1 binding site from promoters of the CYP3A5 gene lineage during primate evolution may have enabled the utilization of CYP3A5 both in the adaptive hepato-intestinal response to xenobiotics and as a constitutively expressed gene in other organs. Our results thus constitute a first description of uncoupling induction from constitutive expression for a major detoxifying enzyme. They also suggest an explanation for the considerable tissue expression differences between CYP3A5 and CYP3A4
Promoter Complexity and Tissue-Specific Expression of Stress Response Components in Mytilus galloprovincialis, a Sessile Marine Invertebrate Species
The mechanisms of stress tolerance in sessile animals, such as molluscs, can offer fundamental insights into the adaptation of organisms for a wide range of environmental challenges. One of the best studied processes at the molecular level relevant to stress tolerance is the heat shock response in the genus Mytilus. We focus on the upstream region of Mytilus galloprovincialis Hsp90 genes and their structural and functional associations, using comparative genomics and network inference. Sequence comparison of this region provides novel evidence that the transcription of Hsp90 is regulated via a dense region of transcription factor binding sites, also containing a region with similarity to the Gamera family of LINE-like repetitive sequences and a genus-specific element of unknown function. Furthermore, we infer a set of gene networks from tissue-specific expression data, and specifically extract an Hsp class-associated network, with 174 genes and 2,226 associations, exhibiting a complex pattern of expression across multiple tissue types. Our results (i) suggest that the heat shock response in the genus Mytilus is regulated by an unexpectedly complex upstream region, and (ii) provide new directions for the use of the heat shock process as a biosensor system for environmental monitoring
Temperature-ramped 129Xe spin-exchange optical pumping
We describe temperature-ramped spin-exchange optical pumping (TR-SEOP) in an automated high-throughput batch-mode 129Xe hyperpolarizer utilizing three key temperature regimes: (i) βhotβwhere the 129Xe hyperpolarization rate is maximal, (ii) βwarmβ-where the 129Xe hyperpolarization approaches unity, and (iii) βcoolβ where hyperpolarized 129Xe gas is transferred into a Tedlar bag with low Rb content (<5 ng per βΌ1 L dose) suitable for human imaging applications. Unlike with the conventional approach of batch-mode SEOP, here all three temperature regimes may be operated under continuous high-power (170 W) laser irradiation, and hyperpolarized 129Xe gas is delivered without the need for a cryocollection step. The variable-temperature approach increased the SEOP rate by more than 2-fold compared to the constant-temperature polarization rate (e.g., giving effective values for the exponential buildup constant Ξ³SEOP of 62.5 Β± 3.7 Γ 10β3 minβ1 vs 29.9 Β± 1.2 Γ 10β3 minβ1) while achieving nearly the same maximum %PXe value (88.0 Β± 0.8% vs 90.1% Β± 0.8%, for a 500 Torr (67 kPa) Xe cell loadingcorresponding to nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) enhancements of βΌ3.1 Γ 105 and βΌ2.32 Γ 108 at the relevant fields for clinical imaging and HP 129Xe production of 3 T and 4 mT, respectively); moreover, the intercycle βdeadβ time was also significantly decreased. The higher-throughput TR-SEOP approach can be implemented without sacrificing the level of 129Xe hyperpolarization
or the experimental stability for automation-making this approach beneficial for improving the overall 129Xe production rate in clinical settings
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