The Hitting Times of A Stochastic Epidemic Model

In this paper, we focus on the hitting times of a stochastic epidemic model presented by \cite{Gray}. Under the help of the auxiliary stopping times, we investigate the asymptotic limits of the hitting times by the variations of calculus and the large deviation inequalities when the noise is sufficiently small. It can be shown that the relative position between the initial state and the hitting state determines the scope of the hitting times greatly

Investigation of wind load on 1,000 m-high super-tall buildings based on HFFB tests

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Relation between design load level and lifetime of individual building and its elements

The common wisdom is to design cladding and components using a lower level wind load than the main structural frames, i.e. a shorter recurrence period wind load is used for cladding design than for frame design. This paper first discusses the design wind load levels for structural frames and for cladding and components. Next, the design wind loads of scaffolds for building construction, those of buildings in the construction stage, and those of so-called “temporary” structures such as site offices are discussed. In Japan, the design wind load for scaffolds is defined as 1-year-recurrence wind load, because its average setting period at one construction site is around 6 months, but this paper clearly proves the inappropriateness of this design wind load estimation concept. Then, it is shown that there is no relation between the design wind load level and its lifetime at an individual site. Finally, even for the design wind load for main structural frames, it is clearly demonstrated that the design load level may not be able to be determined based on the lifetime of an individual building. Therefore, although the LCC concept is applied in design load estimation, it is strongly recommended that the optimal design load level should be decided considering total LCC for the city or nation as a whole, and treat design as involving a group of buildings, rather than attempting to optimize the LCC of individual buildings. Clearly, the cost associated with social or national security must be included

Thunderstorm outflow characteristics in the Beijing urban area

The study of thunderstorm outflows and their effects on structures is a key topic in modern wind engineering. Based on the in-situ monitoring network in the northern Mediterranean carried out for the European \u201cWind and Ports\u201d and \u201cWind, Ports and Sea\u201d projects, the key characteristics of thunderstorm outflows in this area relevant to wind engineering with special concern for the wind loading of structures were analyzed in previous researches. Recently this work has been repeated and extended to the dataset detected by 9 anemometers installed at different levels on the Beijing 325 m high meteorological tower. This provides a unique opportunity to study the characteristics of thunderstorms in the Beijing urban area, to compare these with northern Mediterranean ones and to understand if thunderstorms in different areas have similar properties. Herein, the extraction and the cataloguing of thunderstorm outflows are illustrated firstly and then the directional signal decomposition strategy, in which their horizontal resultant velocity is decomposed along time-varying longitudinal and lateral directions, are presented. These analyses are preliminary for the further study and comparison of their characteristics

PIM KINASE INHIBITION: SINGLE AGENT AND COMBINATION APPROACHES IN B-CELL LYMPHOMA

Proviral integration site for Moloney murine leukemia virus (Pim) kinases are Ser/Thr/Tyr kinases. They modulate B-cell development but become oncoproteins and promote cancer development once overexpressed. Containing three isoforms, Pim-1, -2 and -3 are known to phosphorylate various substrates that regulate transcription, translation, cell cycle, and survival pathways in both hematological and solid tumors. Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma. Elevated Pim kinase levels are common in MCL, and it negatively correlates with patient outcome. SGI-1776 is a small molecule inhibitor selective for Pim-1/-3. We hypothesize that SGI-1776 treatment in MCL will inhibit Pim kinase function, and inhibition of downstream substrates phosphorylation will disrupt transcriptional, translational, and cell cycle processes while promoting apoptosis. SGI-1776 treatment induced moderate to high levels of apoptosis in four MCL cell lines (JeKo-1, Mino, SP-53 and Granta-519) and peripheral blood mononuclear cells (PBMCs) from MCL patients. Phosphorylation of transcription and translation regulators, c-Myc and 4E-BP1 declined in both model systems. Additionally, levels of short-lived Mcl-1 mRNA and protein also decreased and correlated with decline of global RNA synthesis. Collectively, our investigations highlight Pim kinases as viable drug targets in MCL and emphasize their roles in transcriptional and translational regulation. We further investigated a combination strategy using SGI-1776 with bendamustine, an FDA-approved DNA-damaging alkylating agent for treating non-Hodgkin’s lymphoma. We hypothesized this combination will enhance SGI-1776-induced transcription and translation inhibition, while promoting bendamustine-triggered DNA damage and inducing additive to synergistic cytotoxicity in B-cell lymphoma. Bendamustine alone resulted in moderate levels of apoptosis induction in MCL cell lines (JeKo-1 and Mino), and in MCL and splenic marginal zone lymphoma (a type of B-cell lymphoma) primary cells. An additive effect in cell killing was observed when combined with SGI-1776. Expectedly, SGI-1776 effectively decreased global RNA and protein synthesis levels, while bendamustine significantly inhibited DNA synthesis and generated DNA damage response. In combination, intensified inhibitory effects in DNA, RNA and protein syntheses were observed. Together, these data suggested feasibility of using Pim kinase inhibitor in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma, and provided foundation of their mechanism of actions in lymphoma cells

Human-induced vibration serviceability of arch pre-stressed concrete truss system

Human-induced vibration has become a serious serviceability problem due to the larger opening of girder, lighter floor systems and longer spans designed and used in practice. Vibration tests were undertaken in laboratory to research the vibrational characteristics of the arch pre-stressed concrete truss (APT) system spanning 16.0 m. Results from ambient vibration, impulse excitations (heel-drop and jumping) and steady-state incentives (walking and running) were presented. Dynamic characteristics such as natural frequencies, damping ratios, mode shapes and acceleration responses were studied and checked against the existing codes. Experimental results show that the investigated APT girder possesses high fundamental frequency and low damping ratio. Moreover, the perception factors based on the root-mean-square acceleration, vibration dose value (VDV) and psychological comfort data were obtained. Lastly, the threshold accelerations and VDVs were suggested for evaluating the human-induced vibration