501 research outputs found
Berry's Phases of Ground States of Interacting Spin-One Bosons: Chains of Monopoles and Monosegments
We study Berry's connection potentials of many-body ground states of spin-one
bosons with antiferromagnetic interactions in adiabatically varying magnetic
fields. We find that Berry's connection potentials are generally determined by,
instead of usual singular monopoles, linearly positioned monosegments each of
which carries one unit of topological charge; in the absence of a magnetic
field gradient this distribution of monosegments becomes a linear chain of
monopoles. Consequently, Berry's phases consist of a series of step functions
of magnetic fields; a magnetic field gradient causes rounding of these
step-functions. We also calculate Berry's connection fields, profiles of
monosegments and show that the total topological charge is conserved in a
parameter space
MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells
Background: Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal. Methods: MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells. Results: MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non-apoptotic cell death. Conclusion: These results highlight the importance of miR-193b in determining oesophageal cancer cell viability and demonstrate an enhancement of chemotoxicity that is independent of apoptosis induction
Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2
Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients
Verifying Different-modality Properties for Concepts Produces Switching Costs
According to perceptual symbol systems (Barsalou, 1999), sensory-motor
simulations underlie the representation of concepts. It follows that
sensory-motor phenomena should arise in conceptual processing. Previous
studies have shown that switching from one modality to another during
perceptual processing incurs a processing cost. If perceptual simulation
underlies conceptual processing, then verifying the properties of
concepts should exhibit a switching cost as well. For example, verifying
a property in the auditory modality (e.g., BLENDER-loud) should be
slower after verifying a property in a different modality (e.g.,
CRANBERRIES-tart) than in the same modality (e.g., LEAVES-rustling).
Only words were presented to subjects, and there were no instructions to
use imagery. Nevertheless switching modalities incurred a cost,
analogous to switching modalities in perception. A second experiment
showed that this effect was not due to associative priming between
properties in the same modality. These results support the hypothesis
that perceptual simulation underlies conceptual processing
TCT-657 Multi Center, Prospective, Randomized, Single Blind, Consecutive Enrollment Evaluation Of Elixir DESyneTM Novolimus-Eluting Coronary Stent System With Durable Polymer To Endeavor Zotarolimus-Eluting Coronary Stent System: 3-Year Clinical and 9-Month Angiographic And IVUS Results: EXCELLA II Study
Spatial analysis of the frequency-magnitude distribution and decay rate of aftershock activity of the 2000 Western Tottori earthquake
Deregulated microRNAs in neurofibromatosis type 1 derived malignant peripheral nerve sheath tumors
Malignant peripheral nerve sheath tumors (MPNST) are aggressive cancers that occur spontaneously (sporadic MPNST) or from benign plexiform neurofibromas in neurofibromatosis type 1 (NF1) patients. MPNSTs metastasize easily, are therapy resistant and are frequently fatal. The molecular changes underlying the malignant transformation in the NF1 setting are incompletely understood. Here we investigate the involvement of microRNAs in this process. MicroRNA expression profiles were determined from a series of archival, paired samples of plexiform neurofibroma and MPNST. Ninety differentially expressed microRNAs were identified between the paired samples. Three downregulated microRNAs (let-7b-5p, miR-143-3p, miR-145-5p) and two upregulated microRNAs (miR135b-5p and miR-889-3p) in MPNST were selected for functional characterization. In general, their differential expression was validated in a relevant cell line panel but only partly in a series of unpaired, fresh frozen tumor samples. As part of the validation process we also analyzed microRNA expression profiles of sporadic MPNSTs observing that microRNA expression discriminates NF1-associated and sporadic MPNSTs. The role of microRNAs in cancer progression was examined in NF1-derived MPNST cell lines by transiently modulating microRNA levels. Our findings indicate that some microRNAs affect migratory and invasive capabilities and Wnt signaling activity but the effects are distinct in different cell lines. We conclude that miRNAs play essential regulatory roles in MPNST facilitating tumor progression
A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing
Abstract Butyrophilin (BTN)–3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members
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