Jaynes' MaxEnt, Steady State Flow Systems and the Maximum Entropy Production Principle

Jaynes' maximum entropy (MaxEnt) principle was recently used to give a conditional, local derivation of the ``maximum entropy production'' (MEP) principle, which states that a flow system with fixed flow(s) or gradient(s) will converge to a steady state of maximum production of thermodynamic entropy (R.K. Niven, Phys. Rev. E, in press). The analysis provides a steady state analog of the MaxEnt formulation of equilibrium thermodynamics, applicable to many complex flow systems at steady state. The present study examines the classification of physical systems, with emphasis on the choice of constraints in MaxEnt. The discussion clarifies the distinction between equilibrium, fluid flow, source/sink, flow/reactive and other systems, leading into an appraisal of the application of MaxEnt to steady state flow and reactive systems.Comment: 6 pages; paper for MaxEnt0

Rewiring the Epigenetic Networks in MLL-Rearranged Leukemias: Epigenetic Dysregulation and Pharmacological Interventions

Leukemias driven by chromosomal translocation of the mixed-lineage leukemia gene (MLL or KMT2A) are highly prevalent in pediatric oncology. The poor survival rate and lack of an effective targeted therapy for patients with MLL-rearranged (MLL-r) leukemias emphasize an urgent need for improved knowledge and novel therapeutic approaches for these malignancies. The resulting chimeric products of MLL gene rearrangements, i.e., MLL-fusion proteins (MLL-FPs), are capable of transforming hematopoietic stem/progenitor cells (HSPCs) into leukemic blasts. The ability of MLL-FPs to reprogram HSPCs toward leukemia requires the involvement of multiple chromatin effectors, including the histone 3 lysine 79 methyltransferase DOT1L, the chromatin epigenetic reader BRD4, and the super elongation complex. These epigenetic regulators constitute a complicated network that dictates maintenance of the leukemia program, and therefore represent an important cluster of therapeutic opportunities. In this review, we will discuss the role of MLL and its fusion partners in normal HSPCs and hematopoiesis, including the links between chromatin effectors, epigenetic landscapes, and leukemia development, and summarize current approaches to therapeutic targeting of MLL-r leukemias

Neutrino Mass from R-parity Violation in Split Supersymmetry

We investigate how the observed neutrino data can be accommodated by R-parity violation in Split Supersymmetry. The atmospheric neutrino mass and mixing are explained by the bilinear parameters $\xi_i$ inducing the neutrino-neutralino mixing as in the usual low-energy supersymmetry. Among various one-loop corrections, only the quark-squark exchanging diagrams involving the order-one trilinear couplings $\lambda'_{i23,i32}$ can generate the solar neutrino mass and mixing if the scalar mass $m_S$ is not larger than $10^9$ GeV. This scheme requires an unpleasant hierarchical structure of the couplings, e.g., $\lambda_{i23,i32}\sim 1$, $\lambda'_{i33} \lesssim 10^{-4}$ and $\xi_i \lesssim 10^{-6}$. On the other hand, the model has a distinct collider signature of the lightest neutralino which can decay only to the final states, $l_i W^{(*)}$ and $\nu Z^{(*)}$, arising from the bilinear mixing. Thus, the measurement of the ratio; $\Gamma(e W^{(*)}) : \Gamma(\mu W^{(*)}) : \Gamma(\tau W^{(*)})$ would provide a clean probe of the small reactor and large atmospheric neutrino mixing angles as far as the neutralino mass is larger than 62 GeV.Comment: 10 pages, 3 figures, version submitted to JHE

Anomalous Corrections to Hall Resistivity of Spin-Polarized Two-Dimensional Holes in a GaAs/AlGaAs Heterostructure

Hall effect of two-dimensional holes that are spin-polarized by a strong parallel magnetic field was explored with a small tilt angle. The Hall resistivity increases nonlinearly with the magnetic field and exhibits negative corrections. The anomalous negative corrections increase with the perpendicular magnetization of the two-dimensional hole system. We attribute this to the anomalous Hall effect of spin-polarized carriers in a nonmagnetic system. The anomalous corrections to the conductivity exhibit non-monotonic dependence on the magnetic field.Comment: 4 pages, 4 figures, accepted in Phys. Rev.

A Chinese Chan-Based Mind-Body Intervention Improves Sleep on Patients with Depression: A Randomized Controlled Trial

Sleep disturbance is a common problem associated with depression, and cognitive-behavioral therapy (CBT) is a more common behavioral intervention for sleep problems. The present study compares the effect of a newly developed Chinese Chan-based intervention, namely Dejian mind-body intervention (DMBI), with the CBT on improving sleep problems of patients with depression. Seventy-five participants diagnosed with major depressive disorder were randomly assigned to receive 10 weekly sessions of CBT or DMBI, or placed on a waitlist. Measurements included ratings by psychiatrists who were blinded to the experimental design, and a standardized questionnaire on sleep quantity and quality was obtained before and after the 10-week intervention. Results indicated that both the CBT and DMBI groups demonstrated significantly reduced sleep onset latency and wake time after sleep onset (effect size range = 0.46–1.0, P ≤ 0.05) as compared to nonsignificant changes in the waitlist group (P > 0.1). Furthermore, the DMBI group, but not the CBT or waitlist groups, demonstrated significantly reduced psychiatrist ratings on overall sleep problems (effect size = 1.0, P = 0.00) and improved total sleep time (effect size = 0.8, P = 0.05) after treatment. The present findings suggest that a Chinese Chan-based mind-body intervention has positive effects on improving sleep in individuals with depression

Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells

Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 phosphorylation limited mitochondrial hyperfusion in glucose-starved breast cancer cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative phosphorylation and ROS production. In clinical specimens of breast cancer, reduced expression of MFN2 corresponded to poor prognosis in patients. In a mouse xenograft model of human breast cancer, there was an association in the core region of tumors between MFN2 downregulation and the presence of highly fragmented mitochondria. Collectively, our results suggest that KAP1 Ser473 phosphorylation acts through MFN2 reduction to restrict mitochondrial hyperfusion, thereby contributing to cancer cell survival under conditions of sustained metabolic stress

Cytokine Response Patterns in Severe Pandemic 2009 H1N1 and Seasonal Influenza among Hospitalized Adults

BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1) influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation). Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years), and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%), although severe pneumonia with hypoxemia (54.0% vs 28.3%) and ICU admissions (25.4% vs 1.9%) were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal) and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17)-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01). This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10)unit increase; P = 0.002), and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01) in influenza infections. PBMCs in seasonal influenza patients were activated and expressed cytokines ex vivo (e.g. IL-6, CXCL8/IL-8, CCL2/MCP-1, CXCL10/IP-10, CXCL9/MIG); their 'responsiveness' to stimuli was shown to change dynamically during the illness course. CONCLUSIONS: A hyperactivated proinflammatory, but suppressed adaptive-immunity (Th1/Th17)-related cytokine response pattern was found in severe pH1N1 pneumonia, different from seasonal influenza. Cytokine/immune-dysregulation may be important in its pathogenesis

Suppression of low-density lipoprotein oxidation, vascular smooth muscle cell proliferation and migration by a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis is a major cause of death in developed world. Atherosclerosis is characterized by low-density lipoprotein deposition in the arterial wall which ultimately begets the formation of lesions. Rupture of lesions finally leads to clinical events such as heart attack and stroke. Atherosclerosis is a complication associated with diabetes. In patients with diabetes, the risk of atherosclerosis is three to five folds greater than in non-diabetics. Our previous study showed that a herbal extract of <it>Radix Astragali, Radix Codonopsis </it>and <it>Cortex Lycii</it>, namely SR10, could improve glucose homeostasis both <it>in vitro </it>and <it>in vivo</it>. In this study, we want to further investigate the efficacy of SR10 in treating atherosclerosis.</p> <p>Method</p> <p>The inhibitory effect of SR10 on low-density lipoprotein oxidation was investigated using free radical-induced erythrocyte hemolysis model and copper ion-induced low-density lipoprotein oxidation model. Since vascular smooth muscle cell proliferation and migration are important processes in atherogenesis, we also examined the effect of SR10 in inhibiting these events.</p> <p>Results</p> <p>Our results showed that SR10 inhibited erythrocyte hemolysis with IC₅₀value at 0.25 mg/ml and significantly prolonged low-density lipoprotein oxidation <it>in vitro</it>. SR10 attenuated platelet derived growth factor-BB-induced vascular smooth muscle cell proliferation by promoting cell cycle arrest at G₀/G₁phase as well as inhibiting vascular smooth muscle cell migration.</p> <p>Conclusion</p> <p>The potential application of SR10 in treating atherosclerosis has been implied in this study. Animal model will be needed to further verify the efficacy of SR10 in future.</p

Effects of mother-offspring and father-offspring dynamics on emerging adults’ adjustment: The mediating role of emotion regulation

The present study tested a theoretical model of emotion regulation between parent-offspring dynamics and emerging adults’ adjustment. The mediating role of emotion regulation strategies, including cognitive reappraisal and expressive suppression, were investigated for the effects of mother-offspring and father-offspring dynamics on emerging adults’ adjustment. A sample of 352 Chinese emerging adults in Hong Kong (230 female, 121 male) participated in this study. Participants were asked to complete a set of self-reported questionnaires. Findings based on structural equation modeling indicated that greater mother-offspring intimacy and father-offspring intimacy predicted emerging adults’ better cognitive reappraisal and psychological, social, and general health. Greater mother-offspring conflict also predicted more expressive suppression and poorer psychological and social functioning. Distinctive mediation pathways as a function of parents’ gender were identified. These findings enrich the literature for parent-offspring dynamics and emotion regulation as explanatory processes of emerging adults’ adjustment