Overshoot in biological systems modeled by Markov chains: a nonequilibrium dynamic phenomenon

A number of biological systems can be modeled by Markov chains. Recently, there has been an increasing concern about when biological systems modeled by Markov chains will perform a dynamic phenomenon called overshoot. In this article, we found that the steady-state behavior of the system will have a great effect on the occurrence of overshoot. We confirmed that overshoot in general cannot occur in systems which will finally approach an equilibrium steady state. We further classified overshoot into two types, named as simple overshoot and oscillating overshoot. We showed that except for extreme cases, oscillating overshoot will occur if the system is far from equilibrium. All these results clearly show that overshoot is a nonequilibrium dynamic phenomenon with energy consumption. In addition, the main result in this article is validated with real experimental data.Comment: 15 pages, 3 figure

Effects of a novel pH-sensitive liposome with cleavable esterase-catalyzed and pH-responsive double smart mPEG lipid derivative on ABC phenomenon

Daquan Chen1,2, Wanhui Liu1,2, Yan Shen3, Hongjie Mu1,2, Yanchun Zhang4 , Rongcai Liang1,2, Aiping Wang1,2, Kaoxiang Sun1,2, Fenghua Fu1,2 1School of Pharmacy, Yantai University, Yantai, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, People’s Republic of China; 3College of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 4College of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China Background: The ABC phenomenon is described as a syndrome of accelerated clearance of polyethylene glycol (PEG)-modified liposomes from the bloodstream when repeatedly injected, with their increased accumulation in the liver and spleen. Methods: To clarify this immune response phenomenon, we evaluated a novel modified pH-sensitive liposome with a cleavable double smart PEG-lipid derivative (mPEG-Hz-CHEMS). Results: The ABC phenomenon in mice was brought about by repeated injection of conventional PEG-PE liposomes and was accompanied by a greatly increased uptake in the liver. However, a slight ABC phenomenon was brought about by repeated injection of mPEG-CHEMS liposomes and was accompanied by only a slightly increased uptake in the liver, and repeated injection of mPEG-Hz-CHEMS liposomes did not induce the ABC phenomenon and there was no increase in liver accumulation. This finding indicates that the cleavable mPEG-Hz-CHEMS derivative could lessen or eliminate the ABC phenomenon induced by repeated injection of PEGylated liposomes. Conclusion: This research has shed some light on a solution to the ABC phenomenon using a cleavable PEG-Hz-CHEMS derivative encapsulated in nanoparticles. Keywords: accelerated blood clearance, double smart, cleavable, mPEG-lipid derivates, pH-sensitive liposom

The characteristics and survival of second primary lung cancer after Hodgkin's lymphoma: A comparison with first primary lung cancer using the SEER database.

ObjectiveThe study aimed to compare the characteristics and prognosis between patients with second primary lung cancer following Hodgkin's lymphoma and those with primary lung cancer.Materials and methodsUsing the SEER 18 database, the characteristics and prognosis were compared between the second primary non-small cell lung cancer following Hodgkin's lymphoma (HL-NSCLC) (n = 466) and the first primary non-small cell lung cancer (n = 469,851)(NSCLC-1), as well as between the second primary small cell lung cancer following Hodgkin's lymphoma (n = 93) (HL-SCLC) and the first primary small cell lung cancer (n = 94,168) (SCLC-1). Comparisons of categorical variables were performed using Chi-square or Fisher's test. Continuous variables were compared using the Mann-Whitney U test. Overall survival (OS) was estimated using the Kaplan-Meier method, and the difference between groups was analyzed by log-rank test.ResultsHL-NSCLC group had more males than NSCLC-1 group, and the median age of HL-NSCLC group was younger than that of NSCLC-1 group. Patients with HL-NSCLC showed inferior OS than those with NSCLC-1 (median: 10 months vs. 11 months, P = 0.006). Both HL-SCLC and SCLC-1 groups had poor prognosis, with median OS of 7 months (P = 0.4). The 3-year cumulative risks of death from any cause for patients with the latencies from HL to NSCLC of 0 to 5 years, >5 to 10 years, >10 to 15 years, >15 to 20 years, and>20 years were 71.8%, 82.6%, 86.8%, 85.7% and 78.5%, respectively(P = 0.020).ConclusionHL-NSCLC patients had worse prognosis than NSCLC-1 patients, while HL-SCLC patients shared similar characteristics and survival with SCLC-1 patients

Development of 3D Wafer Level Hermetic Packaging with Through Glass Vias (TGVs) and Transient Liquid Phase Bonding Technology for RF Filter

The development of 5G mobile communication created the need for high-frequency communication systems, which require vast quantities of radio frequency (RF) filters with a high-quality factor (Q) and low inband losses. In this study, the packaging of an RF filter with a through-glass via (TGV) interposer was designed and fabricated using a three-dimensional wafer-level package (3D WLP). TGV fabrication is a high-yielding process, which can produce high precision vias without masking and lithography and reduce the manufacturing cost compared with the through silicon via (TSV) solution. The glass interposer capping wafer contains Cu-filled TGV, a metal redistribution layer (RDL), and the bonding layer. The RF filter substrate with Au bump is bonded to the capping wafer based on Au-Sn transient liquid phase (TLP) bonding at 280 °C with a 40 kN (approximately 6.5 MPa) bonding force. Experimental results show that shear strengths of approx. 54.5 MPa can be obtained, higher than the standard requirement (~6 MPa). In addition, a comparison of the electrical performance of the RF filter package after the pre-conditional level three (Pre-Con L3) and unbiased highly accelerated stress (uHAST) tests showed no difference in insertion attenuation across the passband (<0.2 dB, standard value: <1 dB). The final packages passed the reliability tests in the field of consumer electronics. The proposed RF filter WLP achieves high performance, low cost, and superior reliability