Cardiotonic Modulation in Heart Failure Insights From Traditional Chinese Medicine∗

Medicinal herbs have been used over the past centuries for restoring the body's homeostatic balance. Contemporary use of herbal supplements remains widespread in many cultures as treatment for specific ailments. Many possess cardiovascular actions, and some interact with cardiac medications. However, there is variable scientific evidence with respect to their safety and efficacy, and few have been subjected to the same rigorous evaluation processes and regulations as contemporary pharmaceuticals (1). In the field of heart failure, we have also witnessed the failure of promising naturopathic therapies like hawthorn extract in translating their potential benefits in rigorous clinical trials (2,3)

A multiple hashing approach to complete identification of missing RFID tags

PublishedJournal ArticleOwing to its superior properties, such as fast identification and relatively long interrogating range over barcode systems, Radio Frequency Identification (RFID) technology has promising application prospects in inventory management. This paper studies the problem of complete identification of missing RFID tag, which is important in practice. Time efficiency is the key performance metric of missing tag identification. However, the existing protocols are ineffective in terms of execution time and can hardly satisfy the requirements of real-time applications. In this paper, a Multi-hashing based Missing Tag Identification (MMTI) protocol is proposed, which achieves better time efficiency by improving the utilization of the time frame used for identification. Specifically, the reader recursively sends bitmaps that reflect the current slot occupation state to guide the slot selection of the next hashing process, thereby changing more empty or collision slots to the expected singleton slots. We investigate the optimal parameter settings to maximize the performance of the MMTI protocol. Furthermore, we discuss the case of channel error and propose the countermeasures to make the MMTI workable in the scenarios with imperfect communication channels. Extensive simulation experiments are conducted to evaluate the performance of MMTI, and the results demonstrate that this new protocol significantly outperforms other related protocols reported in the current literature. © 2014 IEEE.This work was supported by NSFC (Grant No.s 60973117, 61173160, 61173162, 60903154, and 61321491), New Century Excellent Talents in University (NCET) of Ministry of Education of China, the National Science Foundation for Distinguished Young Scholars of China (Grant No. 61225010), and the Project funded by China Postdoctoral Science Foundation

Drug nanoparticles by emulsion-freeze-drying via the employment of branched block copolymer nanoparticles

A large percentage of drug compounds exhibit low water solubility and hence low bioavailability and therapeutic efficacy. This may be addressed by preparation of drug nanoparticles, leading to enhanced dissolution rate and direct use for treatment. Various methods have been developed to produce drug nanocrystals, including wet milling, homogenization, solution precipitation, emulsion diffusion, and the recently developed emulsion freeze-drying. The drawback for these methods may include difficult control in particles size, use of surfactants & polymer, and low ratio of drug to stabilizer. Here, biocompatible branched block copolymer nanoparticles with lightly-crosslinked hydrophobic core and hydrophilic surface groups are synthesized by the direct monomer-to-particle methodology, characterized, and then used as scaffold polymer/surfactant to produce drug nanoparticles via the emulsion-freeze-drying approach. This method can be used for model organic dye and different poorly water-soluble drugs. Aqueous drug nanoparticle dispersions can be obtained with high ratio of drug to stabilizer and relatively uniform nanoparticle sizes

Goodness-of-Fit Tests and Model Diagnostics for Negative Binomial Regression of RNA Sequencing Data

This work is about assessing model adequacy for negative binomial (NB) regression, particularly (1) assessing the adequacy of the NB assumption, and (2) assessing the appropriateness of models for NB dispersion parameters. Tools for the first are appropriate for NB regression generally; those for the second are primarily intended for RNA sequencing (RNA-Seq) data analysis. The typically small number of biological samples and large number of genes in RNA-Seq analysis motivate us to address the trade-offs between robustness and statistical power using NB regression models. One widely-used power-saving strategy, for example, is to assume some commonalities of NB dispersion parameters across genes via simple models relating them to mean expression rates, and many such models have been proposed. As RNA-Seq analysis is becoming ever more popular, it is appropriate to make more thorough investigations into power and robustness of the resulting methods, and into practical tools for model assessment. In this article, we propose simulation-based statistical tests and diagnostic graphics to address model adequacy. We provide simulated and real data examples to illustrate that our proposed methods are effective for detecting the misspecification of the NB mean-variance relationship as well as judging the adequacy of fit of several NB dispersion models

A Novel Redox Regulator, MnTnBuOE-2-PyP\u3csup\u3e5+\u3c/sup\u3e, Enhances Normal Hematopoietic Stem/Progenitor Cell Function

The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP5+(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs. Mechanistically, MnP reduces superoxide to hydrogen peroxide, which activates intracellular Nrf2 signaling leading to the induction of antioxidant enzymes, including MnSOD and catalase, and mitochondrial uncoupling protein 3. The results reveal a novel role of ROS signaling in regulating stem cell function, and suggest a possible beneficial effect of MnP in treating pathological bone marrow cell loss and in increasing stem cell population for bone marrow transplantation

Top quark associated production of the neutral top-pion at high energy e+e−e^{+}e^{-} colliders

In the context of topcolor-assisted technicolor (TC2) models, we calculate the associated production of the neutral top-pion $\pi_{t}^{0}$ with a pair of top quarks via the process $e^{+}e^{-}\longrightarrow t\bar{t}\pi_{t}^{0}$. We find that the production cross section is larger than that of the process $e^{+}e^{-}\longrightarrow t\bar{t}H$ both in the standard model (SM) and in the minimal supersymmetric SM. With reasonable values of the parameters in TC2 models, the cross section can reach $20fb$. The neutral top-pion $\pi_{t}^{0}$ may be direct observed via this process.Comment: Latex files, 10 pages and 3 figure

Differential Expression of Genes Involved in Host Recognition, Attachment, and Degradation in the Mycoparasite Tolypocladium ophioglossoides

This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Genetics Society of America. The published article can be found at: https://doi.org/10.1534/g3.116.027045The ability of a fungus to infect novel hosts is dependent on changes in gene content, expression, or regulation. Examining gene expression under simulated host conditions can explore which genes may contribute to host jumping. Insect pathogenesis is the inferred ancestral character state for species of Tolypocladium, however several species are parasites of truffles, including Tolypocladium ophioglossoides. To identify potentially crucial genes in this interkingdom host switch, T. ophioglossoides was grown on four media conditions: media containing the inner and outer portions of its natural host (truffles of Elaphomyces), cuticles from an ancestral host (beetle), and a rich medium (Yeast Malt). Through high-throughput RNASeq of mRNA from these conditions, many differentially expressed genes were identified in the experiment. These included PTH11-related G-protein-coupled receptors (GPCRs) hypothesized to be involved in host recognition, and also found to be upregulated in insect pathogens. A divergent chitinase with a signal peptide was also found to be highly upregulated on media containing truffle tissue, suggesting an exogenous degradative activity in the presence of the truffle host. The adhesin gene, Mad1, was highly expressed on truffle media as well. A BiNGO analysis of overrepresented GO terms from genes expressed during each growth condition found that genes involved in redox reactions and transmembrane transport were the most overrepresented during T. ophioglossoides growth on truffle media, suggesting their importance in growth on fungal tissue as compared to other hosts and environments. Genes involved in secondary metabolism were most highly expressed during growth on insect tissue, suggesting that their products may not be necessary during parasitism of Elaphomyces. This study provides clues into understanding genetic mechanisms underlying the transition from insect to truffle parasitism

Ionic high-pressure form of elemental boron

Boron is an element of fascinating chemical complexity. Controversies have shrouded this element since its discovery was announced in 1808: the new 'element' turned out to be a compound containing less than 60-70 percent of boron, and it was not until 1909 that 99-percent pure boron was obtained. And although we now know of at least 16 polymorphs, the stable phase of boron is not yet experimentally established even at ambient conditions. Boron's complexities arise from frustration: situated between metals and insulators in the periodic table, boron has only three valence electrons, which would favour metallicity, but they are sufficiently localized that insulating states emerge. However, this subtle balance between metallic and insulating states is easily shifted by pressure, temperature and impurities. Here we report the results of high-pressure experiments and ab initio evolutionary crystal structure predictions that explore the structural stability of boron under pressure and, strikingly, reveal a partially ionic high-pressure boron phase. This new phase is stable between 19 and 89 GPa, can be quenched to ambient conditions, and has a hitherto unknown structure (space group Pnnm, 28 atoms in the unit cell) consisting of icosahedral B12 clusters and B2 pairs in a NaCl-type arrangement. We find that the ionicity of the phase affects its electronic bandgap, infrared adsorption and dielectric constants, and that it arises from the different electronic properties of the B2 pairs and B12 clusters and the resultant charge transfer between them.Comment: Published in Nature 453, 863-867 (2009

Extracellular Vesicles Released by Cardiomyocytes in a Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers of Early Cardiac Injury

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury. Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content. Results—Treatment with DOX caused a significant increase in circulating EVs (DOX_EV) compared with saline-treated controls. DOX_EVs exhibited a higher level of 4-hydroxynonenal adducted proteins, a lipid peroxidation product linked to DOX-induced cardiotoxicity. Proteomic profiling of DOX_EVs revealed the distinctive presence of brain/heart, muscle, and liver isoforms of glycogen phosphorylase (GP), and their origins were verified to be heart, skeletal muscle, and liver, respectively. The presence of brain/heart GP (PYGB) in DOX_EVs correlated with a reduction of PYGB in heart, but not brain tissues. Manganese superoxide dismutase (MnSOD) overexpression, as well as pretreatment with cardioprotective agents and MnSOD mimetics, resulted in a reduction of EV-associated PYGB in mice treated with DOX. Kinetic studies indicated that EVs containing PYGB were released prior to the rise of cardiac troponin in the blood after DOX treatment, suggesting that PYGB is an early indicator of cardiac injury. Conclusion—EVs containing PYGB are an early and sensitive biomarker of cardiac injury