Women and Industry in Taiwan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68847/2/10.1177_009770047900500303.pd

Analysis of the Association between CIMP and BRAFV600E in Colorectal Cancer by DNA Methylation Profiling

A CpG island methylator phenotype (CIMP) is displayed by a distinct subset of colorectal cancers with a high frequency of DNA hypermethylation in a specific group of CpG islands. Recent studies have shown that an activating mutation of BRAF (BRAFV600E) is tightly associated with CIMP, raising the question of whether BRAFV600E plays a causal role in the development of CIMP or whether CIMP provides a favorable environment for the acquisition of BRAFV600E. We employed Illumina GoldenGate DNA methylation technology, which interrogates 1,505 CpG sites in 807 different genes, to further study this association. We first examined whether expression of BRAFV600E causes DNA hypermethylation by stably expressing BRAFV600E in the CIMP-negative, BRAF wild-type COLO 320DM colorectal cancer cell line. We determined 100 CIMP-associated CpG sites and examined changes in DNA methylation in eight stably transfected clones over multiple passages. We found that BRAFV600E is not sufficient to induce CIMP in our system. Secondly, considering the alternative possibility, we identified genes whose DNA hypermethylation was closely linked to BRAFV600E and CIMP in 235 primary colorectal tumors. Interestingly, genes that showed the most significant link include those that mediate various signaling pathways implicated in colorectal tumorigenesis, such as BMP3 and BMP6 (BMP signaling), EPHA3, KIT, and FLT1 (receptor tyrosine kinases) and SMO (Hedgehog signaling). Furthermore, we identified CIMP-dependent DNA hypermethylation of IGFBP7, which has been shown to mediate BRAFV600E-induced cellular senescence and apoptosis. Promoter DNA hypermethylation of IGFBP7 was associated with silencing of the gene. CIMP-specific inactivation of BRAFV600E-induced senescence and apoptosis pathways by IGFBP7 DNA hypermethylation might create a favorable context for the acquisition of BRAFV600E in CIMP+ colorectal cancer. Our data will be useful for future investigations toward understanding CIMP in colorectal cancer and gaining insights into the role of aberrant DNA hypermethylation in colorectal tumorigenesis

Mechanical Activation of a Multimeric Adhesive Protein Through Domain Conformational Change

The mechanical force-induced activation of the adhesive protein von Willebrand factor (VWF), which experiences high hydrodynamic forces, is essential in initiating platelet adhesion. The importance of the mechanical force-induced functional change is manifested in the multimeric VWF's crucial role in blood coagulation, when high fluid shear stress activates plasma VWF (PVWF) multimers to bind platelets. Here, we showed that a pathological level of high shear stress exposure of PVWF multimers results in domain conformational changes, and the subsequent shifts in the unfolding force allow us to use force as a marker to track the dynamic states of the multimeric VWF. We found that shear-activated PVWF multimers are more resistant to mechanical unfolding than nonsheared PVWF multimers, as indicated in the higher peak unfolding force. These results provide insight into the mechanism of shear-induced activation of PVWF multimers

Rapid intensification of Typhoon Hato (2017) over shallow water

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pun, I., Chan, J. C. L., Lin, I., Chan, K. T. E., Price, J. F., Ko, D. S., Lien, C., Wu, Y., & Huang, H. Rapid intensification of Typhoon Hato (2017) over shallow water. Sustainability, 11(13), (2019): 3709, doi:10.3390/su11133709.On 23 August, 2017, Typhoon Hato rapidly intensified by 10 kt within 3 h just prior to landfall in the city of Macau along the South China coast. Hato’s surface winds in excess of 50 m s−1 devastated the city, causing unprecedented damage and social impact. This study reveals that anomalously warm ocean conditions in the nearshore shallow water (depth < 30 m) likely played a key role in Hato’s fast intensification. In particular, cooling of the sea surface temperature (SST) generated by Hato at the critical landfall point was estimated to be only 0.1–0.5 °C. The results from both a simple ocean mixing scheme and full dynamical ocean model indicate that SST cooling was minimized in the shallow coastal waters due to a lack of cool water at depth. Given the nearly invariant SST in the coastal waters, we estimate a large amount of heat flux, i.e., 1.9k W m−2, during the landfall period. Experiments indicate that in the absence of shallow bathymetry, and thus, if nominal cool water had been available for vertical mixing, the SST cooling would have been enhanced from 0.1 °C to 1.4 °C, and sea to air heat flux reduced by about a quarter. Numerical simulations with an atmospheric model suggest that the intensity of Hato was very sensitive to air-sea heat flux in the coastal region, indicating the critical importance of coastal ocean hydrography.The work of I.-F.P. is supported by Taiwan’s Ministry of Science and Technology Grant MOST 107-2111-M-008-001-MY3. The work of J.C.L.C. is supported by the Research Grants Council of Hong Kong Grant E-CityU101/16. The work of I.-I.L. is supported by Taiwan’s Ministry of Science and Technology (MOST 106-2111-M-002-011-MY3, MOST 108-2111-M-002-014-MY2). The work of K.T.F.C. is jointly supported by the National Natural Science Foundation of China (41775097), and the National Natural Science Foundation of China and Macau Science and Technology Development Joint Fund (NSFC-FDCT), China and Macau (41861164027)

Modelling search for people in 900 scenes: A combined source model of eye guidance

How predictable are human eye movements during search in real world scenes? We recorded 14 observers’ eye movements as they performed a search task (person detection) in 912 outdoor scenes. Observers were highly consistent in the regions fixated during search, even when the target was absent from the scene. These eye movements were used to evaluate computational models of search guidance from three sources: Saliency, target features, and scene context. Each of these models independently outperformed a cross-image control in predicting human fixations. Models that combined sources of guidance ultimately predicted 94% of human agreement, with the scene context component providing the most explanatory power. None of the models, however, could reach the precision and fidelity of an attentional map defined by human fixations. This work puts forth a benchmark for computational models of search in real world scenes. Further improvements in modelling should capture mechanisms underlying the selectivity of observers’ fixations during search.National Eye Institute (Integrative Training Program in Vision grant T32 EY013935)Massachusetts Institute of Technology (Singleton Graduate Research Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship)National Science Foundation (U.S.) (CAREER Award (0546262))National Science Foundation (U.S.) (NSF contract (0705677))National Science Foundation (U.S.) (Career Award (0747120)

Infrared nanoscopy of Dirac plasmons at the graphene-SiO2 interface

We report on infrared (IR) nanoscopy of 2D plasmon excitations of Dirac fermions in graphene. This is achieved by confining mid-IR radiation at the apex of a nanoscale tip: an approach yielding two orders of magnitude increase in the value of in-plane component of incident wavevector q compared to free space propagation. At these high wavevectors, the Dirac plasmon is found to dramatically enhance the near-field interaction with mid-IR surface phonons of SiO2 substrate. Our data augmented by detailed modeling establish graphene as a new medium supporting plasmonic effects that can be controlled by gate voltage.Comment: 12 pages, 4 figure

Premature ventricular contractions originating from the left ventricular septum: Results of Radiofrequency Catheter Ablation in twenty patients

<p>Abstract</p> <p>Background</p> <p>RFCA has been established as an effective and curative therapy for severely symptomatic PVC from the outflow tract in structurally normal hearts. However, it is unknown whether PVCs originating from the left ventricular septum, are effectively eliminated by RFCA. This study aimed to investigate electrophysiologic characteristics and effects of Radiofrequency catheter ablation (RFCA) for patients with symptomatic premature ventricular contraction (PVC) originating from the left ventricular septum without including fascicular PVCs.</p> <p>Methods</p> <p>Characteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings endocardiogram in a successful RFCA target were analyzed in 20 patients with symptomatic PVCs originating from the left ventricular septum. RFCA was performed using pace mapping and activation mapping.</p> <p>Results</p> <p>The QRS morphology of PVCs originating from the left ventricular septum is similar to that seen in fascicular tachycardia. Most of the PVCs originated from the left septum appears in the form of ventricular parasystole. The incidence of ventricular parasystole was 70%. Sustained ventricular tachycardia was not inducible by electrical stimulation and isoproterenol infusion in all 20 patients, ablation at the site recording the earliest Purkinje potential was not effective in all 20 patients, and Purkinje potentials were not identified at successful sites during point mapping. Sixteen patients were successful with RFCA using pace mapping and activation mapping, 3 failed, and 1 recurrent.</p> <p>Conclusion</p> <p>Although the ECG characteristics of the PVCs arising from the left ventricular septum are similar to that seen in fascicular tachycardia, the electrophysiologic characteristics are different between the two types of PVCs. The distinguishing characteristic of the PVCs is that Purkinje potentials were not present at the site of successful ablation, suggesting a myocardial as opposed to fascicular substrate. RFCA is an effective curative therapy for symptomatic PVCs originating from the left ventricular septum (not from the left anterior and posterior fascicle).</p

A Complete Developmental Sequence of a Drosophila Neuronal Lineage as Revealed by Twin-Spot MARCM

Labeling every neuron in a lineage in the fruit fly olfactory system reveals that every cell is born with a pre-determined cell fate that is invariant and dependent upon neuron birth orde

Burial Depth and Stolon Internode Length Independently Affect Survival of Small Clonal Fragments

Disturbance can fragment plant clones into different sizes and unstabilize soils to different degrees, so that clonal fragments of different sizes can be buried in soils at different depths. As a short-term storage organ, solon internode may help fragmented clones of stoloniferous plants to withstand deeper burial in soils. We address (1) whether burial in soils decreases survival and growth of small clonal fragments, and (2) whether increasing internode length increases survival and growth of small fragments under burial. We conducted an experiment with the stoloniferous, invasive herb Alternanthera philoxeroides, in which single-node fragments with stolon internode of 0, 2, 4 and 8 cm were buried in soils at 0, 2, 4 and 8 cm depth, respectively. Increasing burial depth significantly reduced survival of the A. philoxeroides plants and increased root to shoot ratio and total stolon length, but did not change growth measures. Increasing internode length significantly increased survival and growth measures, but there was no interaction effect with burial depth on any traits measured. These results indicate that reserves stored in stolon internodes can contribute to the fitness of the A. philoxeroides plants subject to disturbance. Although burial reduced the regeneration capacity of the A. philoxeroides plants, the species may maintain the fitness by changing biomass allocation and stolon length once it survived the burial. Such responses may play an important role for A. philoxeroides in establishment and invasiveness in frequently disturbed habitats