Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants

Although nitric oxide (NO) and antioxidants inhibit adhesion molecule expression, their inhibitory effects on nuclear factor kappaB (NF-kappaB) activation may differ. The NO donors, but not 8-bromo-cGMP, decreased tumor necrosis factor alpha (TNF-alpha)-induced VCAM-1, ICAM-1, and E-selectin expression by 11-70%. In contrast, NAC completely abolished VCAM-1 and E-selectin expression and decreased ICAM-1 expression by 56%. Gel shift assays demonstrate that NF-kappaB activation was inhibited by both NO and antioxidants. The activation of NF-kappaB involves the phosphorylation and degradation of its cytoplasmic inhibitor IkappaB-alpha by 26S proteasomes. The 26S proteasome inhibitor MG132 prevented the degradation of phosphorylated IkappaB-alpha. NAC inhibited IkappaB kinase (IKK) activity and prevented IkappaB-alpha phosphorylation and degradation. In contrast, NO did not inhibit IKK activity, IkappaB-alpha phosphorylation, or IkappaB-alpha degradation. However, NO, but not antioxidants, induced IkappaB-alpha promoter activity. The inhibitory effects of NO on adhesion molecule expression, therefore, differs from that of antioxidants in terms of the mechanism by which NF-kappaB is inactivated.     

An implementation and evaluation of the MPI 3.0 one‐sided communication interface

The Message Passing Interface (MPI) 3.0 standard includes a significant revision to MPI's remote memory access (RMA) interface, which provides support for one‐sided communication. MPI‐3 RMA is expected to greatly enhance the usability and performance of MPI RMA. We present the first complete implementation of MPI‐3 RMA and document implementation techniques and performance optimization opportunities enabled by the new interface. Our implementation targets messaging‐based networks and is publicly available in the latest release of the MPICH MPI implementation. Using this implementation, we explore the performance impact of new MPI‐3 functionality and semantics. Results indicate that the MPI‐3 RMA interface provides significant advantages over the MPI‐2 interface by enabling increased communication concurrency through relaxed semantics in the interface and additional routines that provide new window types, synchronization modes, and atomic operations. Copyright © 2016 John Wiley & Sons, Ltd.     

Phenological change detection while accounting for abrupt and gradual trends in satellite image time series

A challenge in phenology studies is understanding what constitutes phenological change amidst background variation. The majority of phenological studies have focused on extracting critical points in the seasonal growth cycle, without exploiting the full temporal detail. The high degree of phenological variability between years demonstrates the necessity of distinguishing long-term phenological change from temporal variability. Here, we demonstrate the phenological change detection ability of a method for detecting change within time series. BFAST, Breaks For Additive Seasonal and Trend, integrates the decomposition of time series into trend, seasonal, and remainder components with methods for detecting change. We tested BFAST by simulating 16-day NDVI time series with varying amounts of seasonal amplitude and noise, containing abrupt disturbances (e.g. fires) and long-term phenological changes. This revealed that the method is able to detect the timing of phenological changes within time series while accounting for abrupt disturbances and noise. Results showed that the phenological change detection is influenced by the signal-to-noise ratio of the time series. Between different land cover types the seasonal amplitude varies and determines the signal-to-noise ratio, and as such the capacity to differentiate phenological changes from noise. Application of the method on 16-day NDVI MODIS images from 2000 until 2009 for a forested study area in south eastern Australia confirmed these results. It was shown that a minimum seasonal amplitude of 0.1 NDVI is required to detect phenological change within cleaned MODIS NDVI time series using the quality flags. BFAST identifies phenological change independent of phenological metrics by exploiting the full time series. The method is globally applicable since it analyzes each pixel individually without the setting of thresholds to detect change within a time series. Long-term phenological changes can be detected within NDVI time series of a large range of land cover types (e.g. grassland, woodlands and deciduous forests) having a seasonal amplitude larger than the noise level. The method can be applied to any time series data and it is not necessarily limited to NDVI.     

Time Constrained Verification of Analog Circuits using Model-Checking Algorithms

In this contribution we present algorithms for model checking of analog circuits enabling the specification of time constraints. Furthermore, a methodology for defining time-based specifications is introduced. An already known method for model checking of integrated analog circuits has been extended to take into account time constraints. The method will be presented using three industrial circuits. The results of model checking will be compared to verification by simulation.     

Detecting trend and seasonal changes in satellite image time series

A wealth of remotely sensed image time series covering large areas is now available to the earth science community. Change detection methods are often not capable of detecting land cover changes within time series that are heavily influenced by seasonal climatic variations. Detecting change within the trend and seasonal components of time series enables the classification of different types of changes. Changes occurring in the trend component often indicate disturbances (e.g. fires, insect attacks), while changes occurring in the seasonal component indicate phenological changes (e.g. change in land cover type). A generic change detection approach is proposed for time series by detecting and characterizing Breaks For Additive Seasonal and Trend (BFAST). BFAST integrates the decomposition of time series into trend, seasonal, and remainder components with methods for detecting change within time series. BFAST iteratively estimates the time and number of changes, and characterizes change by its magnitude and direction. We tested BFAST by simulating 16-day Normalized Difference Vegetation Index (NDVI) time series with varying amounts of seasonality and noise, and by adding abrupt changes at different times and magnitudes. This revealed that BFAST can robustly detect change with different magnitudes (> 0.1 NDVI) within time series with different noise levels (0.01-0.07 σ) and seasonal amplitudes (0.1-0.5 NDVI). Additionally, BFAST was applied to 16-day NDVI Moderate Resolution Imaging Spectroradiometer (MODIS) composites for a forested study area in south eastern Australia. This showed that BFAST is able to detect and characterize spatial and temporal changes in a forested landscape. BFAST is not specific to a particular data type and can be applied to time series without the need to normalize for land cover types, select a reference period, or change trajectory. The method can be integrated within monitoring frameworks and used as an alarm system to flag when and where changes occur.     

Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH⁺, CD87⁺CD276⁺, and EGF⁺Axl⁺) in smokers. A number of CTCs and CSCs in patients with SCLC have been shown to be resistant to chemotherapy (CT). High cytotoxic activity and resistance to apoptosis of reprogrammed CD3⁺CD8⁺ T-lymphocytes (rTcells) in relation to naive CD3⁺CD8⁺ T-lymphocytes was demonstrated in a smoking patient with SCLC (Patient G) in vitro. The target for rTcells was patient G’s blood CSCs. Reprogramming of CD3⁺CD8⁺ T-lymphocytes was carried out with the MEK1/2 inhibitor and PD-1/PD-L1 pathway blocker nivolumab. The training procedure was performed with a suspension of dead CTCs and CSCs obtained from patient’s G blood. The presented data show a new avenue for personalized SCLC diagnosis and targeted improvement of chemotherapy based on the use of both CTCs and CSCs.     

An alternative method for evaluating congruence coefficients with Procrustes rotation: A bootstrap procedure.

Comparing factor structures across samples has long been an important topic in psychological research. Traditionally, the congruence coefficient is used to measure the degree of similarity between 2 factor matrices. However, as the congruence coefficients do not have known sampling distributions, it is difficult to assess factor replicability statistically. In this study, a bootstrap procedure was proposed to test factor invariance by examining the statistical significance of 3 types of congruence coefficients. A Monte Carlo study evaluated the performance of the proposed bootstrap procedure. Results provide strong support for this procedure as a powerful tool to assess factor replicability across groups. Two real examples demonstrate the usefulness of the proposed method. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A critical view on transport and entanglement in models of photosynthesis

We revisit critically the recent claims, inspired by quantum optics and quantum information, that there is entanglement in the biological pigment-protein complexes, and that it is responsible for the high transport efficiency. While unexpectedly long coherence times were experimentally demonstrated, the existence of entanglement is, at the moment, a purely theoretical conjecture; it is this conjecture that we analyse. As demonstrated by a toy model, a similar transport phenomenology can be obtained without generating entanglement. Furthermore, we also argue that, even if entanglement does exist, it is purely incidental and seems to play no essential role for the transport efficiency. We emphasize that our paper is not a proof that entanglement does not exist in light-harvesting complexes-this would require a knowledge of the system and its parameters well beyond the state of the art. Rather, we present a counter-example to the recent claims of entanglement, showing that the arguments, as they stand at the moment, are not sufficiently justified and hence cannot be taken as a proof for the existence of entanglement, let alone of its essential role, in the excitation transport.     

A probabilistic nonlocal model for crack initiation and propagation in heterogeneous brittle materials

A probabilistic damage model is developed to study crack initiation and growth in quasi‐brittle materials. Two different thresholds are considered to describe these mechanisms. A Weibull model is used to account for the randomness of crack initiation(s) and then a fracture mechanics based threshold is considered to model crack propagation. The model is integrated in a finite element code via a nonlocal damage approach. A regularization operator based on a stress regularization is introduced. Both damage thresholds are checked using the ‘regularized’ stress field to avoid mesh dependence. The interaction between propagating cracks and potential initiation sites is accounted for. Copyright © 2012 John Wiley & Sons, Ltd.