Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound

Bioflavonoids, such as quercetin, have recently emerged as a new class of chemotherapeutic drugs for the treatment of various cancer types, but are marred by their low potency and poor selectivity. We report that a short application of low-frequency ultrasound selectively sensitises prostate and skin cancer cells against quercetin. Pretreatment of cells with ultrasound (20 kHz, 2 W cm−2, 60 s) selectively induced cytotoxicity in skin and prostate cancer cells, while having minimal effect on corresponding normal cell lines. About 90% of the viable skin cancer cell population was lost within 48 h after ultrasound-quercetin (50 μM) treatment. Ultrasound reduced the LC50 of quercetin for skin cancer cells by almost 80-fold, while showing no effect on LC50 for nonmalignant skin cells

Fundamental Limits on Wavelength, Efficiency and Yield of the Charge Separation Triad

In an attempt to optimize a high yield, high efficiency artificial photosynthetic protein we have discovered unique energy and spatial architecture limits which apply to all light-activated photosynthetic systems. We have generated an analytical solution for the time behavior of the core three cofactor charge separation element in photosynthesis, the photosynthetic cofactor triad, and explored the functional consequences of its makeup including its architecture, the reduction potentials of its components, and the absorption energy of the light absorbing primary-donor cofactor. Our primary findings are two: First, that a high efficiency, high yield triad will have an absorption frequency more than twice the reorganization energy of the first electron transfer, and second, that the relative distance of the acceptor and the donor from the primary-donor plays an important role in determining the yields, with the highest efficiency, highest yield architecture having the light absorbing cofactor closest to the acceptor. Surprisingly, despite the increased complexity found in natural solar energy conversion proteins, we find that the construction of this central triad in natural systems matches these predictions. Our analysis thus not only suggests explanations for some aspects of the makeup of natural photosynthetic systems, it also provides specific design criteria necessary to create high efficiency, high yield artificial protein-based triads

A ROC analysis-based classification method for landslide susceptibility maps

[EN] A landslide susceptibility map is a crucial tool for landuse spatial planning and management in mountainous areas. An essential issue in such maps is the determination of susceptibility thresholds. To this end, the map is zoned into a limited number of classes. Adopting one classification system or another will not only affect the map's readability and final appearance, but most importantly, it may affect the decision-making tasks required for effective land management. The present study compares and evaluates the reliability of some of the most commonly used classification methods, applied to a susceptibility map produced for the area of La Marina (Alicante, Spain). A new classification method based on ROC analysis is proposed, which extracts all the useful information from the initial dataset (terrain characteristics and landslide inventory) and includes, for the first time, the concept of misclassification costs. This process yields a more objective differentiation of susceptibility levels that relies less on the intrinsic structure of the terrain characteristics. The results reveal a considerable difference between the classification methods used to define the most susceptible zones (in over 20% of the surface) and highlight the need to establish a standard method for producing classified susceptibility maps. The method proposed in the study is particularly notable for its consistency, stability and homogeneity, and may mark the starting point for consensus on a generalisable classification method.Cantarino-Martí, I.; Carrión Carmona, MÁ.; Goerlich-Gisbert, F.; Martínez Ibáñez, V. (2018). A ROC analysis-based classification method for landslide susceptibility maps. Landslides. 1-18. doi:10.1007/s10346-018-1063-4S118Armstrong MP, Xiao N, Bennett DA (2003) Using genetic algorithms to create multicriteria class intervals for choropleth maps. 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Atom Optics Quantum Pendulum

We explain the dynamics of cold atoms, initially trapped and cooled in a magneto-optic trap, in a monochromatic stationary standing electromagnetic wave field. In the large detuning limit the system is modeled as a nonlinear quantum pendulum. We show that wave packet evolution of the quantum particle probes parametric regimes in the quantum pendulum which support classical period, quantum mechanical revival and super revival phenomena. Interestingly, complete reconstruction in particular parametric regime at quantum revival times is independent of potential height.Comment: 14 pages, 7 figure

The Detectability of Earth's Biosignatures Across Time

Over the past two decades, enormous advances in the detection of exoplanets have taken place. Currently, we have discovered hundreds of earth-sized planets, several of them within the habitable zone of their star. In the coming years, the efforts will concentrate in the characterization of these planets and their atmospheres to try to detect the presence of biosignatures. However, even if we discovered a second Earth, it is very unlikely that it would present a stage of evolution similar to the present-day Earth. Our planet has been far from static since its formation about 4.5 Ga ago; on the contrary, during this time, it has undergone multiple changes in it's atmospheric composition, it's temperature structure, it's continental distribution, and even changes in the forms of life that inhabit it. All these changes have affected the global properties of Earth as seen from an astronomical distance. Thus, it is of interest not only to characterize the observables of the Earth as it is today, but also at different epochs. Here we review the detectability of the Earth's globally-averaged properties over time. This includes atmospheric composition and biosignatures, and surface properties that can be interpreted as sings of habitability (bioclues). The resulting picture is that truly unambiguous biosignatures are only detectable for about 1/4 of the Earth's history. The rest of the time we rely on detectable bioclues that can only establish an statistical likelihood for the presence of life on a given planet.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018). arXiv admin note: text overlap with arXiv:astro-ph/0609398 by other author

An assessment of technology-based service encounters & network security on the e-health care systems of medical centers in Taiwan

<p>Abstract</p> <p>Background</p> <p>Enhancing service efficiency and quality has always been one of the most important factors to heighten competitiveness in the health care service industry. Thus, how to utilize information technology to reduce work load for staff and expeditiously improve work efficiency and healthcare service quality is presently the top priority for every healthcare institution. In this fast changing modern society, e-health care systems are currently the best possible way to achieve enhanced service efficiency and quality under the restraint of healthcare cost control. The electronic medical record system and the online appointment system are the core features in employing e-health care systems in the technology-based service encounters.</p> <p>Methods</p> <p>This study implemented the Service Encounters Evaluation Model, the European Customer Satisfaction Index, the Attribute Model and the Overall Affect Model for model inference. A total of 700 copies of questionnaires from two authoritative southern Taiwan medical centers providing the electronic medical record system and the online appointment system service were distributed, among which 590 valid copies were retrieved with a response rate of 84.3%. We then used SPSS 11.0 and the Linear Structural Relationship Model (LISREL 8.54) to analyze and evaluate the data.</p> <p>Results</p> <p>The findings are as follows: (1) Technology-based service encounters have a positive impact on service quality, but not patient satisfaction; (2) After experiencing technology-based service encounters, the cognition of the service quality has a positive effect on patient satisfaction; and (3) Network security contributes a positive moderating effect on service quality and patient satisfaction.</p> <p>Conclusion</p> <p>It revealed that the impact of electronic workflow (online appointment system service) on service quality was greater than electronic facilities (electronic medical record systems) in technology-based service encounters. Convenience and credibility are the most important factors of service quality in technology-based service encounters that patients demand. Due to the openness of networks, patients worry that transaction information could be intercepted; also, the credibility of the hospital involved is even a bigger concern, as patients have a strong sense of distrust. Therefore, in the operation of technology-based service encounters, along with providing network security, it is essential to build an atmosphere of psychological trust.</p

Do serum biomarkers really measure breast cancer?

Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.United States. Dept. of Defense. Breast Cancer Research Program (Grant No. W81XWH-05-1-0292)National Institutes of Health (U.S.) (R01 CA-112437-01)National Institutes of Health (U.S.) (NIH CA 84955

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies

Health state utilities associated with attributes of treatments for hepatitis C

BACKGROUND: Cost-utility analyses are frequently conducted to compare treatments for hepatitis C, which are often associated with complex regimens and serious adverse events. Thus, the purpose of this study was to estimate the utility associated with treatment administration and adverse events of hepatitis C treatments. DESIGN: Health states were drafted based on literature review and clinician interviews. General population participants in the UK valued the health states in time trade-off (TTO) interviews with 10- and 1-year time horizons. The 14 health states described hepatitis C with variations in treatment regimen and adverse events. RESULTS: A total of 182 participants completed interviews (50 % female; mean age = 39.3 years). Utilities for health states describing treatment regimens without injections ranged from 0.80 (1 tablet) to 0.79 (7 tablets). Utilities for health states describing oral plus injectable regimens were 0.77 (7 tablets), 0.75 (12 tablets), and 0.71 (18 tablets). Addition of a weekly injection had a disutility of −0.02. A requirement to take medication with fatty food had a disutility of −0.04. Adverse events were associated with substantial disutilities: mild anemia, −0.12; severe anemia, −0.32; flu-like symptoms, −0.21; mild rash, −0.13; severe rash, −0.48; depression, −0.47. One-year TTO scores were similar to these 10-year values. CONCLUSIONS: Adverse events and greater treatment regimen complexity were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of hepatitis C. The resulting utilities may be used in models estimating and comparing the value of treatments for hepatitis C. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10198-014-0649-6) contains supplementary material, which is available to authorized users

Climate simulations for 1880-2003 with GISS modelE

We carry out climate simulations for 1880-2003 with GISS modelE driven by ten measured or estimated climate forcings. An ensemble of climate model runs is carried out for each forcing acting individually and for all forcing mechanisms acting together. We compare side-by-side simulated climate change for each forcing, all forcings, observations, unforced variability among model ensemble members, and, if available, observed variability. Discrepancies between observations and simulations with all forcings are due to model deficiencies, inaccurate or incomplete forcings, and imperfect observations. Although there are notable discrepancies between model and observations, the fidelity is sufficient to encourage use of the model for simulations of future climate change. By using a fixed well-documented model and accurately defining the 1880-2003 forcings, we aim to provide a benchmark against which the effect of improvements in the model, climate forcings, and observations can be tested. Principal model deficiencies include unrealistically weak tropical El Nino-like variability and a poor distribution of sea ice, with too much sea ice in the Northern Hemisphere and too little in the Southern Hemisphere. The greatest uncertainties in the forcings are the temporal and spatial variations of anthropogenic aerosols and their indirect effects on clouds.Comment: 44 pages; 19 figures; Final text accepted by Climate Dynamic