Pattern Analysis of Microtubule-Polymerizing and -Depolymerizing Agent Combinations as Cancer Chemotherapies

Subcellular distribution of mass can be analyzed by a technique that involves culturing cells on interferometers and digitizing their interference contours. Contour sampling resulted in 102 variables per cell, which were predictors of oncogenic transformation. Cell phenotypes can be deconstructed by use of latent factors, which represent the covariance of the real variables. The reversal of the cancertype phenotype by a combination of microtubule- stabilizing and -depolymerizing agents was described previously. The implications of these results have been explored by clinicians who treated patients with the combination of docetaxel and vinorelbine (Navelbine®). The current study was performed to determine the effects of different combinations on phenotype and in phases of the cell cycle other than mitosis. Combinations of paclitaxel with either colchicine, podophyllotoxin, nocodazole, or vinblastine caused phenotype reversal. Paclitaxel analogue, 7-deoxytaxol, by itself caused reversal. Factors #4, (filopodia), #5 (displacement and/or deep invaginations in the periphery), #8, and #12 took on values typical of normal cells, whereas the values of #7 (p21-activated kinase), and #13 (rounding up) shifted toward the cancer-type. All combinations altered microtubule arrangement at the cell edge. Delivery schedules and drug ratios used in clinical studies were subjected to analysis. Clinical response rates were better when the combination was not interspersed with a single agent (P=0.004). The results support the idea that efficacy depends upon simultaneous exposure to both agents, and suggest a novel mechanism for combination therapies. These therapies appear to restore in transformed cells some of the features of a contact-inhibited cell, and to impede progress through the cell cycle even when provided at nanomolar concentrations

Dynamics of coherently pumped lasers with linearly polarized pump and generated fields

The influence of light polarization on the dynamics of an optically pumped single-mode laser with a homogeneously broadened four-level medium is theoretically investigated in detail. Pump and laser fields with either parallel or crossed linear polarizations are considered, as are typical in far-infrared-laser experiments. Numerical simulations reveal dramatically different dynamic behaviors for these two polarization configurations. The analysis of the model equations allows us to find the physical origin of both behaviors. In particular, the crossed-polarization configuration is shown to be effective in decoupling the pump and laser fields, thus allowing for the appearance of Lorenz-type dynamics

Lymphocyte and monocyte flow cytometry immunophenotyping as a diagnostic tool in uncharacteristic inflammatory disorders

<p>Abstract</p> <p>Background</p> <p>Patients with uncharacteristic inflammatory symptoms such as long-standing fatigue or pain, or a prolonged fever, constitute a diagnostic and therapeutic challenge. The aim of the present study was to determine if an extended immunophenotyping of lymphocytes and monocytes including activation markers can define disease-specific patterns, and thus provide valuable diagnostic information for these patients.</p> <p>Methods</p> <p>Whole blood from patients with gram-negative bacteraemia, neuroborreliosis, tuberculosis, acute mononucleosis, influenza or a mixed connective tissue disorders, as diagnosed by routine culture and serology techniques was analysed for lymphocyte and monocyte cell surface markers using a no-wash, no-lyse protocol for multi-colour flow cytometry method. The immunophenotyping included the activation markers HLA-DR and CD40. Plasma levels of soluble TNF alpha receptors were analysed by ELISA.</p> <p>Results</p> <p>An informative pattern was obtained by combining two of the analysed parameters: (i), the fractions of HLA-DR-expressing CD4+ T cells and CD8+ T cells, respectively, and (ii), the level of CD40 on CD14+ CD16- monocytes. Patients infected with gram-negative bacteria or EBV showed a marked increase in monocyte CD40, while this effect was less pronounced for tuberculosis, borrelia and influenza. The bacterial agents could be distinguished from the viral agents by the T cell result; CD4+ T cells reacting in bacterial infection, and the CD8+ T cells dominating for the viruses. Patients with mixed connective tissue disorders also showed increased activation, but with similar engagement of CD4+ and CD8+ T cells. Analysis of soluble TNF alpha receptors was less informative due to a large inter-individual variation.</p> <p>Conclusion</p> <p>Immunophenotyping including the combination of the fractions of HLA-DR expressing T cell subpopulations with the level of CD40 on monocytes produces an informative pattern, differentiating between infections of bacterial and viral origin. Furthermore, a quantitative analysis of these parameters revealed the novel finding of characteristic patterns indicating a subacute bacterial infection, such as borreliosis or tuberculosis, or a mixed connective tissue disorder. The employed flow cytometric method is suitable for clinical diagnostic laboratories, and may help in the assessment of patients with uncharacteristic inflammatory symptoms.</p

Hyperon weak radiative decays in chiral perturbation theory

We investigate the leading-order amplitudes for weak radiative decays of hyperons in chiral perturbation theory. We consistently include contributions from the next-to-leading order weak-interaction Lagrangian. It is shown that due to these terms Hara's theorem is violated. The data for the decays of charged hyperons can be easily accounted for. However, at this order in the chiral expansion, the four amplitudes for the decays of neutral hyperons satisfy relations which are in disagreement with the data. The asymmetry parameters for all the decays can not be accounted for without higher-order terms. We shortly comment on the effect of the 27-plet part of the weak interaction.Comment: 8 pages of REVTeX and using macro-package "feynman.tex" (available at http://xxx.lanl.gov/ftp/hep-ph/papers/macros) for the 2 figure

Incumbency as the Major Advantage: The Electoral Advantage for Parties of Incumbent Mayors

This paper provides empirical evidence on the party incumbency advantage in mayoral elections in Germany. Using a regression discontinuity design on a data set of about 25,000 elections, I estimate a causal incumbency effect of 38-40 percentage points in the probability of winning the next mayor election. The electoral advantage is larger for fulltime mayors, increasing in municipality size, independent of the specific partisanship of the mayor and constant between 1945 and 2010. Moreover, it increases with local spending hikes and it is independent of municipal debt. I also illustrate the causal dynamic effects of the incumbent status on distant future elections and therefore evaluate the global properties of the LATE estimate. Finally, I show that the total effect is due to an effect on the probability that the party participates in the next election (about 40% of the total effect) and an effect on the vote share (about 60%)

Factorization in the model of unstable particles with continuous masses

We study processes with unstable particles in intermediate time-like states. It is shown that the amplitudes squared of such processes factor exactly in the framework of the model of unstable particles with continuous masses. Decay widths and cross sections can then be represented in a universal factorized form for an arbitrary set of interacting particles. This exact factorization is caused by specific structure of propagators in the model. We formulate the factorization method and perform a phenomenological analysis of the factorization effects. The factorization method considerably simplifies calculations while leading to compact and reasonable results.Comment: 20 pages, 6 figure

Postpartum women’s use of medicines and breastfeeding practices: a systematic review

The objectives of this article are to systematically review i) the extent of medicine use in postpartum women, and ii) the impact of maternal medicine use (excluding contraceptives and galactogogues) on breastfeeding outcomes (initiation and/or duration). PubMed, Medline (Ovid), Scopus (Elsevier), Cinahl (EBSCO), PsycINFO (Ovid), Embase (Ovid) and Web of Science (ISI) databases were searched to find original studies on medicine use in women after the birth. Additional studies were identified by searching Google Scholar, Wiley Online Library, Springer Link, selected journals and from the reference list of retrieved articles. Observational studies with information about postpartum women’s use of any type of medicine either for chronic or acute illnesses with or without breastfeeding information were included. The majority of relevant studies suggest that more than 50 % of postpartum women (breastfeeding or not) required at least one medicine. Due to the lack of uniform medication use reporting system and differences in study designs, settings and samples, the proportion of medicine use by postpartum women varies widely, from 34 to 100 %. Regarding the impact of postpartum women’s medicine use on breastfeeding, a few studies suggest that women’s use of certain medicines (e.g. antiepileptics, propylthiouracil, antibiotics) during lactation can reduce initiation and/ or duration of breastfeeding. These studies are limited by small sample size, and with one exception, all were conducted in Canada more than a decade ago. Large scale studies are required to establish the relationship between maternal medicine use and breastfeeding, considering type of illness, period of use and total duration of medicine use

Divided Government Versus Incumbency Externality Effect: Quasi-Experimental Evidence on Multiple Voting Decisions

This paper explores the interdependency of political institutions from the voter's perspective. Specifically, we are interested in: (1) Does the partisan identity of the mayor influence the voter's decision in the subsequent town council election?; (2) Does this partisan identity influence the vote in ensuing higher level elections?; and (3) Do voters condition their vote for the mayor on the result of the last council election? We rely on a regression discontinuity design focusing on close election outcomes based on municipal level data for Germany. We find (1) that the party of the mayor can receive a bonus of 4-6 percentage points in vote share in the next town council election (depending on the timing of the local elections). (2) The mayor partisan identity does not affect federal or European election outcomes within the same municipality. And (3), we show that voters punish mayor candidates of parties that performed strongly in earlier council elections. Throughout the paper, we explore how the findings can be related to an incumbency externality effect and to the theory of voter preferences for divided government

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites