Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis. © 2013 Lee et al

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)

Near-Infrared Survey and Photometric Redshifts in the Extended GOODS-North field

We present deep $J$ and $H$-band images in the extended Great Observatories Origins Deep Survey-North (GOODS-N) field covering an area of 0.22 $\rm{deg}^{2}$. The observations were taken using WIRCam on the 3.6-m Canada France Hawaii Telescope (CFHT). Together with the reprocessed $K_{\rm s}$-band image, the $5\sigma$ limiting AB magnitudes (in 2" diameter apertures) are 24.7, 24.2, and 24.4 AB mag in the $J$, $H$, and $K_{\rm s}$ bands, respectively. We also release a multi-band photometry and photometric redshift catalog containing 93598 sources. For non-X-ray sources, we obtained a photometric redshift accuracy $\sigma_{\mathrm{NMAD}}=0.036$ with an outlier fraction $\eta = 7.3\%$. For X-ray sources, which are mainly active galactic nuclei (AGNs), we cross-matched our catalog with the updated 2M-CDFN X-ray catalog from Xue et al. (2016) and found that 658 out of 683 X-ray sources have counterparts. $GALEX$ UV data are included in the photometric redshift computation for the X-ray sources to give $\sigma_{\mathrm{NMAD}} = 0.040$ with $\eta=10.5\%$. Our approach yields more accurate photometric redshift estimates compared to previous works in this field. In particular, by adopting AGN-galaxy hybrid templates, our approach delivers photometric redshifts for the X-ray counterparts with fewer outliers compared to the 3D-HST catalog, which fit these sources with galaxy-only templates

C-reactive protein concentration as a significant correlate for metabolic syndrome: a Chinese population-based study. Endocrine 43

Abstract Increasing evidence suggests that chronic, lowgrade inflammation may be a common soil involving the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease. We examined the association between C-reactive protein (CRP) concentration, an extensively studied biomarker of low-grade inflammation, and the MetS in a representative sample of Chinese adults in Taiwan. We performed a cross-sectional analysis of data from 4234 subjects [mean (±SD) age, 47.1 (±18.2) years; 46.4 % males] who participated in a population-based survey on prevalences of hypertension, hyperglycemia, and hyperlipidemia in Taiwan. CRP levels were measured by the immunoturbidimetric CRP-latex high-sensitivity assay. The MetS was defined by an unified criteria set by several major organizations. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated with logistic regression model. Overall, there were 938 subjects with MetS among 4,234 participants, resulting in a prevalence rate of 22.1 %. A significantly progressive increase in the prevalence of MetS across quartiles of CRP was observed (p for trend \0.001). Participants in the second, third, and upper quartiles of CRP had significantly higher risk of having MetS when compared with those in the lowest quartile [adjusted ORs (95 % CIs) were 2.18 (1.62-2.94), 4.39 (3.31-5.81), and 7.11 (5.39-9.38), respectively; p for trend \0.001]. Furthermore, there was a strong stepwise increase in CRP levels as the number of components of the MetS increased. The prevalence of MetS showed a graded increase according to CRP concentrations. The possible utility of CRP concentration as a marker for MetS risk awaits further evaluation in prospective studies

The Energy of Regular Black Hole in General Relativity Coupled to Nonlinear Electrodynamics

According to the Einstein, Weinberg, and M{\o}ller energy-momentum complexes, we evaluate the energy distribution of the singularity-free solution of the Einstein field equations coupled to a suitable nonlinear electrodynamics suggested by Ay\'{o}n-Beato and Garc\'{i}a. The results show that the energy associated with the definitions of Einstein and Weinberg are the same, but M{\o}ller not. Using the power series expansion, we find out that the first two terms in the expression are the same as the energy distributions of the Reissner-Nordstr\"{o}m solution, and the third term could be used to survey the factualness between numerous solutions of the Einstein field eqautions coupled to a nonlinear electrodynamics.Comment: 11 page

Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8×10^−5), establishing a novel phenotype for this genetic variant

Mitochondrial Apoptosis and FAK Signaling Disruption by a Novel Histone Deacetylase Inhibitor, HTPB, in Antitumor and Antimetastatic Mouse Models

BACKGROUND: Compound targeting histone deacetylase (HDAC) represents a new era in molecular cancer therapeutics. However, effective HDAC inhibitors for the treatment of solid tumors remain to be developed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we propose a novel HDAC inhibitor, N-Hydroxy-4-(4-phenylbutyryl-amino) benzamide (HTPB), as a potential chemotherapeutic drug for solid tumors. The HDAC inhibition of HTPB was confirmed using HDAC activity assay. The antiproliferative and anti-migratory mechanisms of HTPB were investigated by cell proliferation, flow cytometry, DNA ladder, caspase activity, Rho activity, F-actin polymerization, and gelatin-zymography for matrix metalloproteinases (MMPs). Mice with tumor xenograft and experimental metastasis model were used to evaluate effects on tumor growth and metastasis. Our results indicated that HTPB was a pan-HDAC inhibitor in suppressing cell viability specifically of lung cancer cells but not of the normal lung cells. Upon HTPB treatment, cell cycle arrest was induced and subsequently led to mitochondria-mediated apoptosis. HTPB disrupted F-actin dynamics via downregulating RhoA activity. Moreover, HTPB inhibited activity of MMP2 and MMP9, reduced integrin-β1/focal adhesion complex formation and decreased pericellular poly-fibronectin assemblies. Finally, intraperitoneal injection or oral administration of HTPB efficiently inhibited A549 xenograft tumor growth in vivo without side effects. HTPB delayed lung metastasis of 4T1 mouse breast cancer cells. Acetylation of histone and non-histone proteins, induction of apoptotic-related proteins and de-phosphorylation of focal adhesion kinase were confirmed in treated mice. CONCLUSIONS/SIGNIFICANCE: These results suggested that intrinsic apoptotic pathway may involve in anti-tumor growth effects of HTPB in lung cancer cells. HTPB significantly suppresses tumor metastasis partly through inhibition of integrin-β1/FAK/MMP/RhoA/F-actin pathways. We have provided convincing preclinical evidence that HTPB is a potent HDAC targeted inhibitor and is thus a promising candidate for lung cancer chemotherapy

Using spatial analysis to demonstrate the heterogeneity of the cardiovascular drug-prescribing pattern in Taiwan

<p>Abstract</p> <p>Background</p> <p>Geographic Information Systems (GIS) combined with spatial analytical methods could be helpful in examining patterns of drug use. Little attention has been paid to geographic variation of cardiovascular prescription use in Taiwan. The main objective was to use local spatial association statistics to test whether or not the cardiovascular medication-prescribing pattern is homogenous across 352 townships in Taiwan.</p> <p>Methods</p> <p>The statistical methods used were the global measures of Moran's <it>I </it>and Local Indicators of Spatial Association (LISA). While Moran's <it>I </it>provides information on the overall spatial distribution of the data, LISA provides information on types of spatial association at the local level. LISA statistics can also be used to identify influential locations in spatial association analysis. The major classes of prescription cardiovascular drugs were taken from Taiwan's National Health Insurance Research Database (NHIRD), which has a coverage rate of over 97%. The dosage of each prescription was converted into defined daily doses to measure the consumption of each class of drugs. Data were analyzed with ArcGIS and GeoDa at the township level.</p> <p>Results</p> <p>The LISA statistics showed an unusual use of cardiovascular medications in the southern townships with high local variation. Patterns of drug use also showed more low-low spatial clusters (cold spots) than high-high spatial clusters (hot spots), and those low-low associations were clustered in the rural areas.</p> <p>Conclusions</p> <p>The cardiovascular drug prescribing patterns were heterogeneous across Taiwan. In particular, a clear pattern of north-south disparity exists. Such spatial clustering helps prioritize the target areas that require better education concerning drug use.</p

International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma

Purpose: The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference. Methods and Materials: A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement. Results: Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed. Conclusions: Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk. (C) 2019 Elsevier Inc. All rights reserved