Kinematic Basis of Emergent Energetics of Complex Dynamics

Stochastic kinematic description of a complex dynamics is shown to dictate an energetic and thermodynamic structure. An energy function $\varphi(x)$ emerges as the limit of the generalized, nonequilibrium free energy of a Markovian dynamics with vanishing fluctuations. In terms of the $\nabla\varphi$ and its orthogonal field $\gamma(x)\perp\nabla\varphi$, a general vector field $b(x)$ can be decomposed into $-D(x)\nabla\varphi+\gamma$, where $\nabla\cdot\big(\omega(x)\gamma(x)\big)=$ $-\nabla\omega D(x)\nabla\varphi$. The matrix $D(x)$ and scalar $\omega(x)$, two additional characteristics to the $b(x)$ alone, represent the local geometry and density of states intrinsic to the statistical motion in the state space at $x$. $\varphi(x)$ and $\omega(x)$ are interpreted as the emergent energy and degeneracy of the motion, with an energy balance equation $d\varphi(x(t))/dt=\gamma D^{-1}\gamma-bD^{-1}b$, reflecting the geometrical $\|D\nabla\varphi\|^2+\|\gamma\|^2=\|b\|^2$. The partition function employed in statistical mechanics and J. W. Gibbs' method of ensemble change naturally arise; a fluctuation-dissipation theorem is established via the two leading-order asymptotics of entropy production as $\epsilon\to 0$. The present theory provides a mathematical basis for P. W. Anderson's emergent behavior in the hierarchical structure of complexity science.Comment: 7 page

The foundations of statistical physics: entropy, irreversibility, and inference

Statistical physics aims to describe properties of macroscale systems in terms of distributions of their microscale agents. Its central tool is the maximization of entropy, a variational principle. We review the history of this principle, first considered as a law of nature, more recently as a procedure for inference in model-making. And while equilibria (EQ) have long been grounded in the principle of Maximum Entropy (MaxEnt), until recently no equally foundational generative principle has been known for non-equilibria (NEQ). We review evidence that the variational principle for NEQ is Maximum Caliber. It entails maximizing \textit{path entropies}, not \textit{state entropies}. We also describe the role of entropy in characterizing irreversibility, and describe the relationship between MaxCal and other prominent approaches to NEQ physics, including Stochastic Thermodynamics (ST), Large Deviations Theory (LDT), Macroscopic Fluctuation Theory (MFT), and non-extensive entropies.Comment: 21 pages, 3 figure

Non-leisure time physical activity is an independent predictor of longevity for a Taiwanese elderly population: an eight-year follow-up study

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to determine the relationship between leisure time physical activity (LTPA) and non-leisure time physical activity (NLTPA) on mortality among the elderly in Taiwan.</p> <p>Methods</p> <p>This is a prospective observational cohort study. We analyzed the mortality data from a cohort of 876 non-institutionalized community-dwelling men and women aged 65 years or over, who were recruited by stratified clustering random sampling from Tainan city and participated in the 1996 Elderly Medication Survey. Information about activities and other variables were collected by structured interviews at baseline in the participants' home. The Cox proportional hazards model and crude death rate were applied to estimate mortality risk.</p> <p>Results</p> <p>Among the 876 participants, 312 died during the follow-up period (1996-2004). In the unadjusted Cox regression model, subjects aged over 75, having difficulty in carrying out activities of daily living (ADLs), a BMI less than 18.5, a history of diabetes mellitus or stroke, without LTPA or being inactive in NLTPA, were found to have a higher risk of eight-year mortality. With the adjustment for age, gender, education level, habitual smoking and drinking, living status, BMI and medical history, the mortality was found to be higher among the sedentary subjects, either defined by lack of LTPA or NLTPA, with the hazard ratio of 1.27 (95% confidence interval [CI] = 0.97-1.66) and 1.45 (95% CI = 1.07-1.97), respectively. Furthermore, when both LTPA and NLTPA were put into the model simultaneously, NLTPA (HR = 1.40; 95% CI = 1.03-1.91) but not LTPA (HR = 1.21, 95% CI = 0.92-1.59) significantly predicted mortality during eight-year follow-up. In addition, subjects who were actively engaged in NLTPA had a lower mortality risk especially in subjects without performing LTPA.</p> <p>Conclusions</p> <p>NLTPA is an independent predictor of longevity among older people in Taiwan. A physically active lifestyle, especially engaged in NLTPA, is associated with lower mortality risk in the elderly population. We thus suggest that encouraging older people to keep on engaging in customary NLTPA is good for their health.</p

Development of high-producing CHO cell lines through target-designed strategy

Productivity and stability are critical for the protein drug producing cell lines for manufacturing. Given that the integration sites of gene of interest (GOI) could contribute remarkable effect on the productivity and stability of GOI expression, we intended to develop a targeting-designed approach to generate the high-producing cell lines in a time-saving and less labor-intensive method through targeting the active and stable regions. To identify the active and stable regions located in CHO genome, two approaches were applied in our experiments. Firstly, the integration sites of GOI in cell clones developed by random integration were identified by whole genome sequencing. Secondly, we developed transposon-mediated low copy integration to discover novel active region located in CHO genome. It is interesting that the productivity per integrated GOI in cell clones developed by transposon system was more than two times to that in cell clones developed by random integration (random integration: 20-40 mg/L/copy; transposon-mediated integration: 40-140mg/L/copy). In addition, about 80% of cell clones developed by transposon system maintained the stability of antibody titer after culturing for 60 generations. These results implied that the potential active and stable integration region in the cell clones developed by transposon system. The identified integration regions could be applied for target integration. In order to verify the expression activity and stability of the integration sites, we employed CRISPR/Cas9 to specifically integrate the antibody gene into CHO genome for expression. Our data showed the cell pool generated by knock-in of expression vector into the IS1 integration site present higher expression titer than cell pools generated by integration into other sites or random integration. We further cultured the single cell clones derived from this cell pool by Clonepix and limiting dilution. These single cell clones have high expression titer ranging from 254 to 804 mg/L in batch culture of after 6 Days. A single cell clone(376 mg/L in batch culture) can reached 2 g/L in fed-batch culture. The stability analysis showed this clone maintain stable expression of GOI after 60 generation. Here, we demonstrated the generation of stable cell line with high protein expression by CRISPR/Cas9 mediated target integration. This approach will cost less time and labor than traditional method

Triggering Apoptotic Death of Human Malignant Melanoma A375.S2 Cells by Bufalin: Involvement of Caspase Cascade-Dependent and Independent Mitochondrial Signaling Pathways

Bufalin was obtained from the skin and parotid venom glands of toad and has been shown to induce cytotoxic effects in various types of cancer cell lines, but there is no report to show that whether bufalin affects human skin cancer cells. The aim of this investigation was to study the effects of bufalin on human malignant melanoma A375.S2 cells and to elucidate possible mechanisms involved in induction of apoptosis. A375.S2 cells were treated with different concentrations of bufalin for a specific time period and investigated for effects on apoptotic analyses. Our results indicated that cells after exposure to bufalin significantly decreased cell viability, and induced cell morphological changes and chromatin condensation in a concentration-dependent manner. Flow cytometric assays indicated that bufalin promoted ROS productions, loss of mitochondrial membrane potential (ΔΨm), intracellular Ca2+ release, and nitric oxide (NO) formations in A375.S2 cells. Additionally, the apoptotic induction of bufalin on A375.S2 cells resulted from mitochondrial dysfunction-related responses (disruption of the ΔΨm and releases of cytochrome c, AIF, and Endo G), and activations of caspase-3, caspase-8 and caspase-9 expressions. Based on those observations, we suggest that bufalin-triggered apoptosis in A375.S2 cells is correlated with extrinsic- and mitochondria-mediated multiple signal pathways