Validity of Markovian modeling for transient memory-dependent epidemic dynamics

The initial transient phase of an emerging epidemic is of critical importance for data-driven model building, model-based prediction of the epidemic trend, and articulation of control/prevention strategies. In principle, quantitative models for real-world epidemics need to be memory-dependent or non-Markovian, but this presents difficulties for data collection, parameter estimation, computation and analyses. In contrast, the difficulties do not arise in the traditional Markovian models. To uncover the conditions under which Markovian and non-Markovian models are equivalent for transient epidemic dynamics is outstanding and of significant current interest. We develop a comprehensive computational and analytic framework to establish that the transient-state equivalence holds when the average generation time matches and average removal time, resulting in minimal Markovian estimation errors in the basic reproduction number, epidemic forecasting, and evaluation of control strategy. Strikingly, the errors depend on the generation-to-removal time ratio but not on the specific values and distributions of these times, and this universality will further facilitate prediction rectification. Overall, our study provides a general criterion for modeling memory-dependent processes using the Markovian frameworks

An Opposite Effect of the CDK Inhibitor, p18^INK4c on Embryonic Stem Cells Compared with Tumor and Adult Stem Cells

Self-renewal is a feature common to both adult and embryonic stem (ES) cells, as well as tumor stem cells (TSCs). The cyclin-dependent kinase inhibitor, p18INK4c, is a known tumor suppressor that can inhibit self-renewal of tumor cells or adult stem cells. Here, we demonstrate an opposite effect of p18 on ES cells in comparison with teratoma cells. Our results unexpectedly showed that overexpression of p18 accelerated the growth of mouse ES cells and embryonic bodies (EB); on the contrary, inhibited the growth of late stage teratoma. Up-regulation of ES cell markers (i.e., Oct4, Nanog, Sox2, and Rex1) were detected in both ES and EB cells, while concomitant down-regulation of various differentiation markers was observed in EB cells. These results demonstrate that p18 has an opposite effect on ES cells as compared with tumor cells and adult stem cells. Mechanistically, expression of CDK4 was significantly increased with overexpression of p18 in ES cells, likely leading to a release of CDK2 from the inhibition by p21 and p27. As a result, self-renewal of ES cells was enhanced. Our current study suggests that targeting p18 in different cell types may yield different outcomes, thereby having implications for therapeutic manipulations of cell cycle machinery in stem cells. © 2012 Li et al

Determination of dissolved nitric oxide in coastal waters of the Yellow Sea off Qingdao

We developed a new method for the determination of dissolved nitric oxide (NO) in discrete seawater samples based on the combination of a purge-and-trap setup and a fluorometric detection of NO. 2,3-diaminonaphthalene (DAN) reacts with NO in seawater to form the highly fluorescent 2,3-naphthotriazole (NAT). The fluorescence intensity was linear for NO concentrations in the range from 0.14 to 19 nmol L−1. We determined a detection limit of 0.068 nmol L−1, an average recovery coefficient of 83.8 % (80.2–90.0 %), and a relative standard deviation of ±7.2 %. With our method we determined for the first time the temporal and spatial distributions of NO surface concentrations in coastal waters of the Yellow Sea off Qingdao and in Jiaozhou Bay during a cruise in November 2009. The concentrations of NO varied from below the detection limit to 0.50 nmol L−1 with an average of 0.26 ± 0.14 nmol L−1. NO surface concentrations were generally enhanced significantly during daytime, implying that NO formation processes such as NO2− photolysis are much higher during daytime than chemical NO consumption, which, in turn, lead to a significant decrease in NO concentrations during nighttime. In general, NO surface concentrations and measured NO production rates were higher compared to previously reported measurements. This might be caused by the high NO2− surface concentrations encountered during the cruise. Moreover, additional measurements of NO production rates implied that the occurrence of particles and a temperature increase can enhance NO production rates. With the method introduced here, we have a reliable and comparably easy to use method at hand to measure oceanic NO surface concentrations, which can be used to decipher both its temporal and spatial distributions as well as its biogeochemical pathways in the oceans

Anti-thrombolytic effect of Salvia miltiorrhiza Bge extract in rats

Purpose: To study the effects of Salvia miltiorrhiza Bge. extract (SMBE) on thrombosis in rats.Methods: SMBE was obtained in water at 60 oC in an oven and then freeze-drying. Rats were divided into 6 groups of ten rats each: normal group, control group, reference group (aspirin 5 mg/kg) as well as three groups of SMBE groups (25, 50 and 100 mg/kg doses). Treatments were given orally once daily for 14 days. Common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6- keto-PGF1α) were measured in the rats.Results: Compared with control group, all doses of SMBE significantly and dose-dependently prolonged thrombosis occlusion time, reduced the weight of thrombus and increased the inhibition rate of thrombus (p < 0.01). Plasma TXB2 concentration of all SMBE groups decreased dose-dependently (p < 0.05) while that of 6-keto-PGF1α increased with decrease in extract dose (p < 0.05). There was association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all treatments, and also with occlusion time for SMBE treatment, but not for aspirin.Conclusion: The results demonstrate the anti-thrombosis effect of SMBE in rats. This finding suggests that the plant is a potential therapy for thrombosis.Keywords: Salvia miltiorrhiza Bge., Thrombosis, Thromboxane B2, 6-Keto-prostaglandin F1 alpha, Aspirin, Occlusion tim

Visual identification of gut bacteria and determination of natural inhibitors using a fluorescent probe selective for PGP-1

PGP-1 is a bacterial hydrolase that can hydrolyze the amide bond of the L-pyroglutamate (L-pGlu) residue at the amino terminus of proteins and peptides. Guided by the biological function of PGP-1, an off-on NIR fluorescent probe DDPA was developed for the visual sensing of PGP-1 by conjugating pyroglutamic acid (recognition group) and DDAN (fluorophore). Using intestinal bacteria cultivation, eight bacteria strains with active PGP-1 were identified and cultivated efficiently using DDPA. In addition, three natural inhibitors against PGP-1 were isolated from the medical herb Psoralea corylifolia, which could be used to interfere with bacterial metabolism in the gut. As such, the fluorescent probe DDPA provides an efficient method and potential tool for the investigation of intestinal microbiota.</p

Electromagnetic cloaking by layered structure of homogeneous isotropic materials

Electromagnetic invisibility cloak requires material with anisotropic distribution of the constitutive parameters deduced from a geometrical transformation as first proposed by Pendry et al. [Science 312, 1780 (2006)]. In this paper, we proposed a useful method to realize the required radius-dependent, anisotropic material parameters and to construct an electromagnetic cloak through concentric layered structure of thin, alternating layers of homogeneous isotropic materials. With proper design of the permittivity or the thickness ratio of the alternating layers, we demonstrated the low-reflection and power-flow bending properties of the proposed cloaking structure through rigorous analysis of the scattered electromagnetic fields. The proposed cloaking structure does not require anisotropy or inhomogeneity of the material constitutive parameters usually realized by metamaterials with subwavelength structured inclusions, therefore may lead to a practical path to an experimental demonstration of electromagnetic cloaking, especially in the optical range.Comment: 9 pages, 5 figure

Aldehyde Dehydrogenase 1 and Raf Kinase Inhibitor Protein Expression Defines the Proliferative Nature of Cervical Cancer Stem Cells

Purpose: To determine the differences in response following the use of aldehyde dehydrogenase 1 (ALDH1) and Raf kinase inhibitor protein (RKIP) as cervical cancer stem cell markers.Methods: To evaluate the cancer stem cell markers, a mouse model with low and high grade cervical cancer was developed and studied by histological examination. Immunohistochemical and Western blotting techniques were employed to study the expression profiles of ALDH1 and RKIP. The specificity of Sox2 that determines cancer stem cells served as control to validate ALDH1 and RKIP expressions.Results: Histological data helped to differentiate low from high grade cervical cancer. The results from immunohistochemistry show increased pattern of Sox2 expression as tumour progresses. Similarly, ALDH1, a protein that positively regulates stem cells shows mild expression in low grade cervical tumour, but positive signals are more amplified in an aggressive stage of tumour condition when compared with Sox2. The expression study with RKIP, a protein that negatively regulates stem cells, interestingly defines the higher expression in low grade cervical cancer to regulate the tumour, but shows little or no very mild expression in the aggressive stage of tumour. All the data obtained show a statistically significant value of p &lt; 0.05. The results with Immunohistochemistry were further validated using the western blotting analysis and it also confirms the similar results.Conclusion: ALDH1 and RKIP marker in association correlation with Sox2 aids in defining the proliferative ability of cervical cancer stem cells and also to validate them in initial and advanced stages of cervical cancer.Keywords: Cervical cancer, ALDH1, BALB/c-nu/nu, HeLa cells, RKIP, Sox

Photoproduction of nitric oxide in seawater

Nitric oxide (NO) is a short-lived intermediate of the oceanic nitrogen cycle. However, our knowledge about its production and consumption pathways in oceanic environments is rudimentary. In order to decipher the major factors affecting NO photochemical production, we irradiated several artificial seawater samples as well as 31 natural surface seawater samples in laboratory experiments. The seawater samples were collected during a cruise to the western tropical North Pacific Ocean (WTNP, a N-S section from 36 to 2 degrees N along 146 to 143 degrees E with 6 and 12 stations, respectively, and a W-E section from 137 to 161 degrees E along the Equator with 13 stations) from November 2015 to January 2016. NO photoproduction rates from dissolved nitrite in artificial seawater showed increasing trends with decreasing pH, increasing temperature, and increasing salinity. In contrast, NO photoproduction rates (average: 0.5 +/- 0.2 x 10(-12) mol L-1 s(-1)) in the natural seawater samples from the WTNP did not show any correlations with pH, water temperature, salinity, or dissolved inorganic nitrite concentrations. The flux induced by NO photoproduction in the WTNP (average: 13 x 10(-12) mol M-2 S-1) was significantly larger than the NO air-sea flux density (average: 1.8 x 10(-12) Mol M-2 S-1), indicating a further NO loss process in the surface layer