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Design and testing of microbubble‐based MRI contrast agents for gastric pressure measurement
Purpose: This work demonstrates specifically tailored microbubble‐based preparations and their suitability as MRI contrast agents for ingestion and measuring temporal and spatial pressure variation in the human stomach.
Methods: Enhanced alginate spheres were prepared by incorporating gas‐filled microbubbles into sodium alginate solution followed by the polymerization of the mixture in an aqueous calcium lactate solution. The microbubbles were prepared with a phospholipid shell and perfluorocarbon gas filling, using a mechanical cavitational agitation regime. The NMR signal changes to externally applied pressure and coming from the enhanced alginate spheres were acquired and compared with that of alginate spheres without microbubbles. In vivo investigations were also carried out on healthy volunteers to measure the pressure variation in the stomach.
Results: The MR signal changes in the contrast agent exhibits a linear sensitivity of approximately 40% per bar, as opposed to no measurable signal change seen in the control gas‐free spheres. This novel contrast agent also demonstrates an excellent stability in simulated gastric conditions, including at body temperature. In vivo studies showed that the signal change exhibited in the meal within the antrum region is between 5% and 10%, but appears to come from both pressure changes and partial volume artifacts.
Conclusion: This study demonstrates that alginate spheres with microbubbles can be used as an MRI contrast agent to measure pressure changes. The peristaltic movement within the stomach is seen to substantially alter the overall signal intensity of the contrast agent meal. Future work must focus on improving the contrast agent's sensitivity to pressure changes
Ultrasensitive force and displacement detection using trapped ions
The ability to detect extremely small forces is vital for a variety of
disciplines including precision spin-resonance imaging, microscopy, and tests
of fundamental physical phenomena. Current force-detection sensitivity limits
have surpassed 1 (atto ) through coupling of micro or
nanofabricated mechanical resonators to a variety of physical systems including
single-electron transistors, superconducting microwave cavities, and individual
spins. These experiments have allowed for probing studies of a variety of
phenomena, but sensitivity requirements are ever-increasing as new regimes of
physical interactions are considered. Here we show that trapped atomic ions are
exquisitely sensitive force detectors, with a measured sensitivity more than
three orders of magnitude better than existing reports. We demonstrate
detection of forces as small as 174 (yocto ), with a
sensitivity 390 using crystals of Be
ions in a Penning trap. Our technique is based on the excitation of normal
motional modes in an ion trap by externally applied electric fields, detection
via and phase-coherent Doppler velocimetry, which allows for the discrimination
of ion motion with amplitudes on the scale of nanometers. These experimental
results and extracted force-detection sensitivities in the single-ion limit
validate proposals suggesting that trapped atomic ions are capable of detecting
of forces with sensitivity approaching 1 . We anticipate that
this demonstration will be strongly motivational for the development of a new
class of deployable trapped-ion-based sensors, and will permit scientists to
access new regimes in materials science.Comment: Expanded introduction and analysis. Methods section added. Subject to
press embarg
A trapped single ion inside a Bose-Einstein condensate
Improved control of the motional and internal quantum states of ultracold
neutral atoms and ions has opened intriguing possibilities for quantum
simulation and quantum computation. Many-body effects have been explored with
hundreds of thousands of quantum-degenerate neutral atoms and coherent
light-matter interfaces have been built. Systems of single or a few trapped
ions have been used to demonstrate universal quantum computing algorithms and
to detect variations of fundamental constants in precision atomic clocks. Until
now, atomic quantum gases and single trapped ions have been treated separately
in experiments. Here we investigate whether they can be advantageously combined
into one hybrid system, by exploring the immersion of a single trapped ion into
a Bose-Einstein condensate of neutral atoms. We demonstrate independent control
over the two components within the hybrid system, study the fundamental
interaction processes and observe sympathetic cooling of the single ion by the
condensate. Our experiment calls for further research into the possibility of
using this technique for the continuous cooling of quantum computers. We also
anticipate that it will lead to explorations of entanglement in hybrid quantum
systems and to fundamental studies of the decoherence of a single, locally
controlled impurity particle coupled to a quantum environment
What we talk about when we talk about capacitance measured with the voltage-clamp step method
Capacitance is a fundamental neuronal property. One common way to measure capacitance is to deliver a small voltage-clamp step that is long enough for the clamp current to come to steady state, and then to divide the integrated transient charge by the voltage-clamp step size. In an isopotential neuron, this method is known to measure the total cell capacitance. However, in a cell that is not isopotential, this measures only a fraction of the total capacitance. This has generally been thought of as measuring the capacitance of the “well-clamped” part of the membrane, but the exact meaning of this has been unclear. Here, we show that the capacitance measured in this way is a weighted sum of the total capacitance, where the weight for a given small patch of membrane is determined by the voltage deflection at that patch, as a fraction of the voltage-clamp step size. This quantifies precisely what it means to measure the capacitance of the “well-clamped” part of the neuron. Furthermore, it reveals that the voltage-clamp step method measures a well-defined quantity, one that may be more useful than the total cell capacitance for normalizing conductances measured in voltage-clamp in nonisopotential cells
Refined clothespin relocation test and assessment of motion
Background: Advancements in upper limb prosthesis design have focused on providing increased degrees of freedom for the end effector through multiple articulations of a prosthetic hand, wrist and elbow. Measuring improvement in patient function with these devices requires development of appropriate assessment tools.
Objectives: This study presents a refined clothespin relocation test for measuring performance and assessing compensatory motion between able-bodied subjects and subjects with upper limb impairments.
Study Design: Comparative analysis
Methods: Trunk and head motions of 13 able-bodied subjects who performed the refined clothespin relocation test were compared to the motion of a transradial prosthesis user with a single degree of freedom hand.
Results: There were observable differences between the prosthesis user and the able-bodied group. The assessment used provided a clear indication of the differences in motion through analysis of compensatory motion.
Conclusion: The refined clothespin relocation test provides additional benefits over the standard clothespin assessment and makes identification of compensatory motions easily identifiable to the researcher. While this paper establishes the method for the new assessment, further validation will need to be performed with more users
Exclusive Photoproduction of the Cascade (Xi) Hyperons
We report on the first measurement of exclusive Xi-(1321) hyperon
photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The
final state is identified by the missing mass in p(gamma,K+ K+)X measured with
the CLAS detector at Jefferson Laboratory. We have detected a significant
number of the ground-state Xi-(1321)1/2+, and have estimated the total cross
section for its production. We have also observed the first excited state
Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss
the possibilities of a search for the recently proposed Xi5-- and Xi5+
pentaquarks.Comment: submitted to Phys. Rev.
Mutations in the WTX - gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers
Background: Genetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of beta-CATENIN are frequently mutated. Whereas in CIN CRCs APC (Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like the APC-, AXIN2- or CTNNBI (beta-CATENIN) gene itself. Recently in Wilms tumors, WTX (Wilms tumor gene on the X-chromosome) was discovered as another gene involved in the destruction of beta-CATENIN. As the WTX-gene harbors a short T(6)-microsatellite in its N-terminal coding region, we hypothesized that frameshift-mutations might occur in MSI-H CRCs in the WTX gene, thus additionally contributing to the stabilization of beta-CATENIN in human CRCs. Methods: DNA was extracted from 632 formalin-fixed, paraffin-embedded metastatic CRCs (UICCIV) and analyzed for MSI-H by investigating the stability of the highly sensitive microsatellite markers BAT25 and BAT26 applying fluorescence capillary electrophoresis (FCE). Then, in the MSI-H cases, well described mutational hot spot regions from the APC-, AXIN2- and CTNNBI genes were analyzed for genomic alterations by didesoxy-sequencing while the WTX T(6)-microsatellite was analyzed by fragment analysis. Additionally, the PCR products of T(5)-repeats were subcloned and mutations were validated using didesoxy-sequencing. Furthermore, the KRAS and the BRAF proto-oncogenes were analyzed for the most common activating mutations applying pyro-sequencing. mRNA expression of WTX from MSI-H and MSS cases and a panel of colorectal cancer cell lines was investigated using reverse transcription (RT-) PCR and FCE. Results: In our cohort of 632 metastatic CRCs (UICCIV) we identified 41 MSI-H cases (6.5%). Two of the 41 MSI-H cases (4.8%) displayed a frameshift mutation in the T(6)-repeat resulting in a T(5) sequence. Only one case, a male patient, expressed the mutated WTX gene while being wild type for all other investigated genes. Conclusion: Mutations in the WTX-gene might compromise the function of the beta-CATENIN destruction complex in only a small fraction of MSI-H CRCs thus contributing to the process of carcinogenesis
Fine-Tuning and the Stability of Recurrent Neural Networks
A central criticism of standard theoretical approaches to constructing stable, recurrent model networks is that the synaptic connection weights need to be finely-tuned. This criticism is severe because proposed rules for learning these weights have been shown to have various limitations to their biological plausibility. Hence it is unlikely that such rules are used to continuously fine-tune the network in vivo. We describe a learning rule that is able to tune synaptic weights in a biologically plausible manner. We demonstrate and test this rule in the context of the oculomotor integrator, showing that only known neural signals are needed to tune the weights. We demonstrate that the rule appropriately accounts for a wide variety of experimental results, and is robust under several kinds of perturbation. Furthermore, we show that the rule is able to achieve stability as good as or better than that provided by the linearly optimal weights often used in recurrent models of the integrator. Finally, we discuss how this rule can be generalized to tune a wide variety of recurrent attractor networks, such as those found in head direction and path integration systems, suggesting that it may be used to tune a wide variety of stable neural systems
Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways
Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated (P < 5 × 10−8) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression
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