Interplay between receptor tyrosine kinases and hypoxia signaling in cancer.

Deregulated signaling via receptor tyrosine kinase (RTK) pathways is prevalent in numerous types of human cancers and is commonly correlated with worst prognosis, resistance to various treatment modalities and increased mortality. Likewise, hypoxic tumors are often manifested by aggressive mode of growth and progression following an adaptive genetic reprogramming with consequent transcriptional activation of genes encoding proteins, which support tumor survival under low oxygen-related conditions. Consequently, both the hypoxia-inducible factor (HIF) system, which is the major mediator of hypoxia-related signaling, and numerous RTK systems are considered critical molecular targets in current cancer therapy. It is now evident that there is an intricate molecular crosstalk between RTKs and hypoxia-related signaling in the sense that hypoxia can activate expression of particular RTKs and/or their corresponding ligands, while some RTK systems have been shown to trigger activation of the HIF machinery. Moreover, signaling regulation of some RTK systems under hypoxic conditions has also been documented to take place in a HIF-independent manner. With this review we aim at overviewing the most current observations on that topic and highlight the importance of the potential co-drugging the HIF system along with particular relevant RTKs for better tumor growth control.

Causes of keel bone damage and their solutions in laying hens

Keel bone damage (KBD) is a critical issue facing the contemporary laying hen industry due to the likely pain leading to compromised welfare and reduced productivity. Recent reports suggest that KBD, while highly variable and likely dependent on a host of factors, extends to all housing systems (including traditional battery cages, furnished cages and non-cage systems), genetic lines, and management styles. Despite the extent of the problem, the research community remains uncertain as to the causes and influencing factors of KBD. To combat these issues, the current review was produced following discussions from the 1st International Keel Bone Damage Workshop held in Switzerland in April 2014. This exercise sought to assess current knowledge, foster novel collaborations, propose unique methodologies and highlight the key areas where innovative research is needed. The following paper is based on the content of those discussions and presents nine recommendations for future research efforts.

The association between maternal use of selective serotonin reuptake inhibitors during pregnancy and adverse pregnancy outcomes

Maternal use of SSRIs for depression and anxiety during pregnancy has increased over the last decade. Recent studies have questioned the safety of these antidepressants when used in during pregnancy. The aim of this project is to assess the associations between maternal SSRI use and GH, SGA, and preterm birth using data from a U.S. population-based study with self-reported exposure information. ^ The study population is comprised of mothers of control infants from the NBDPS, an ongoing, multi-state, population-based case-control study. Mothers were asked about any use of medications during pregnancy, including the dates they started and stopped taking each medication. Maternal GH was self-reported, while gestational age and birth weight were calculated from information on birth certificates or medical records. ^ Our study found that women exposed to SSRIs in the first trimester and beyond had a higher odds of GH compared to unexposed women (aOR=1.96, 95% CI=1.02-3.74). Women who used SSRIs only in the first trimester had no increased odds of GH (aOR=0.77, 95% CI=0.24-2.50). Women who used SSRIs throughout their entire pregnancy had a two-fold increase in the odds of delivering an SGA infant compared to unexposed women (aOR=2.16, 95% CI=1.01-4.62), while women who reported SSRI use only in the first trimester had a decreased odds of delivering an SGA infant (aOR=0.56, 95% CI=0.14-2.34). Finally, both women who used SSRIs in the first trimester only (aOR=1.58, 95% CI=0.71-3.51) and women who used SSRIs in the first trimester and beyond (aOR=1.49, 95% CI=0.76-2.90) had an increased odds of delivering preterm compared to unexposed women. ^ Results from our study suggest that women who use SSRIs in the first trimester and beyond have an increased and significant odds of GH and SGA. An increase in the odds of preterm birth was also observed among women exposed in this period and is consistent with the results of previous studies which had much larger sample sizes. Women who use SSRIs only in the first trimester appear to have no increased odds of GH or SGA, but may have an increased odds of preterm birth. These findings are consistent with previous studies and highlight how exposure to SSRIs at different points in gestation may result in different risks for these outcomes. ^

Posttraumatic stress disorder among veterans of the Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) wars: Psychological comorbidities, postdeployment social support and unit support

Much attention has been given to treating Operation Iraqi Freedom/Operation Enduring (OIF/OEF) Veterans with posttraumatic stress disorder (PTSD). However, little attention is given to those Veterans who do not meet diagnostic criteria for PTSD but who may still benefit from intervention. Research is needed to investigate the impact of how different racial/ethnic backgrounds, different levels of social support and comorbid mental health disorders impact OIF/OEF Veterans with varying levels of PTSD. The purpose of this dissertation is to examine the association of comorbid Axis I disorders, race/ethnicity, different levels of postdeployment social support and unit support on OIF/OEF Veterans with varying levels of PTSD. Data for this dissertation were from postdeployment screenings of OIF/OEF Veterans from a large Veterans Affairs hospital in southeast Texas. To examine the study hypotheses, we conducted multinomial logistic regressions of the clinician reported data. ^ The first article examined the prevalence of subthreshold and full levels of PTSD and compared Axis I and alcohol use comorbidity rates among 1,362 OIF/OEF Veterans with varying levels of PTSD. Results suggest that OIF/OEF Veterans with subthreshold PTSD experience similar levels of psychological distress as those with full PTSD and highlight the need to provide timely and appropriate mental health services to individuals who may not meet the diagnostic criteria for full PTSD. ^ These results suggest that OIF/OEF Veterans of all race/ethnicities can benefit from strong social support systems. Postdeployment social support was found to be a protective factor against the development of PTSD among White, Black and Hispanic veterans while deployment unit support was a protective factor only among Black Veterans. The second article investigated the association between postdeployment social support and unit support with varying levels of PTSD by race/ethnicity among 1,115 OIF/OEF Veterans. ^ The results of this study can help to formulate treatment and interventions for OIF/OEF Veterans with varying levels of PTSD and social support systems.^

At surface behaviour, dive depth and dive duration and associated hydrographic data of adult male southern elephant seals from King George Island from expedition JUB2010 with links to datasets

Understanding the distribution and foraging ecology of major consumers within pelagic systems, specifically in relation to physical parameters, can be important for the management of bentho-pelagic systems undergoing rapid change associated with global climate change and other anthropogenic disturbances such as fishing (i.e., the Antarctic Peninsula and Scotia Sea). We tracked 11 adult male southern elephant seals (Mirounga leonina), during their five-month post-moult foraging migrations from King George Island (Isla 25 de Mayo), northern Antarctic Peninsula, using tags capable of recording and transmitting behavioural data and in situ temperature and salinity data. Seals foraged mostly within the Weddell-Scotia Confluence, while a few foraged along the western Antarctic Peninsula shelf of the Bellingshausen Sea. Mixed model outputs suggest that the at-sea behaviour of seals was associated with a number of environmental parameters, especially seafloor depth, sea-ice concentrations and the temperature structure of the water column. Seals increased dive bottom times and travelled at slower speeds in shallower areas and areas with increased sea-ice concentrations. Changes in dive depth and durations, as well as relative amount of time spent during the bottom phases of dives, were observed in relation to differences in overall temperature gradient, likely as a response to vertical changes in prey distribution associated with temperature stratification in the water column. Our results illustrate the likely complex influences of bathymetry, hydrography and sea ice on the behaviour of male southern elephant seals in a changing environment and highlight the need for region-specific approaches to studying environmental influences on behaviour.

(Table 1) Chlorophyll a content and microalgae abundance and biovolume in pack ice in the Bellingshausen Sea

Pack ice in the Bellingshausen Sea contained moderate to high stocks of microalgal biomass (3-10 mg Chl a/m**2) spanning the range of general sea-ice microalgal microhabitats (e.g., bottom, interior and surface) during the International Polar Year (IPY) Sea Ice Mass Balance in the Antarctic (SIMBA) studies. Measurements of irradiance above and beneath the ice as well as optical properties of the microalgae therein demonstrated that absorption of photosynthetically active radiation (PAR) by particulates (microalgae and detritus) had a substantial influence on attenuation of PAR and irradiance transmission in areas with moderate snow covers (0.2-0.3 m) and more moderate effects in areas with low snow cover. Particulates contributed an estimated 25 to 90% of the attenuation coefficients for the first-year sea ice at wavelengths less than 500 nm. Strong ultraviolet radiation (UVR) absorption by particulates was prevalent in the ice habitats where solar radiation was highest - with absorption coefficients by ice algae often being as large as that of the sea ice. Strong UVR-absorption features were associated with an abundance of dinoflagellates and a general lack of diatoms - perhaps suggesting UVR may be influencing the structure of some parts of the sea-ice microbial communities in the pack ice during spring. We also evaluated the time-varying changes in the spectra of under-ice irradiances in the austral spring and showed dynamics associated with changes that could be attributed to coupled changes in the ice thickness (mass balance) and microalgal biomass. All results are indicative of radiation-induced changes in the absorption properties of the pack ice and highlight the non-linear, time-varying, biophysical interactions operating within the Antarctic pack ice ecosystem.

(Table 1) 87Sr/86Sr ratios and ages of DSDP Site 144A samples

Glassy Turonian foraminifera preserved in clay-rich sediments from the western tropical Atlantic yield the warmest equivalent d18O sea-surface temperatures (SSTs) yet reported for the entire Cretaceous-Cenozoic. We estimate Turonian SSTs that were at least as warm as (conservative mean ~30 °C) to significantly warmer (warm mean ~33 °C) than those in the region today. However, if independent evidence for high middle Cretaceous pCO2 is reliable and resulted in greater isotopic fractionation between seawater and calcite because of lower sea-surface pH, our conservative and warm SST estimates would be even higher (32 and 36°C, respectively). Our new tropical SSTs help reconcile geologic data with the predictions of general circulation models that incorporate high Cretaceous pCO2 and lend support to the hypothesis of a Cretaceous greenhouse. Our data also strengthen the case for a Turonian age for the Cretaceous thermal maximum and highlight a 20-40 m.y. mismatch between peak Cretaceous-Cenozoic global warmth and peak inferred tectonic CO2 production. We infer that this mismatch is either an artifact of a hidden Turonian pulse in global ocean-crust cycling or real evidence of the influence of some other factor on atmospheric CO2 and/or SSTs. A hidden pulse in crust cycling would explain the timing of peak Cretaceous-Cenozoic sea level (also Turonian), but other factors are needed to explain high-frequency (~10-100 k.y.) instability in middle Cretaceous SSTs reported elsewhere.

South Pacific dissolved Nd isotope compositions, rare earth element and nutrient concentrations from SONNE cruise SO213

Despite its enormous extent and importance for global climate, the South Pacific has been poorly investigated in comparison to other regions with respect to chemical oceanography. Here we present the first detailed analysis of dissolved radiogenic Nd isotopes (epsilon-Nd) and rare earth elements (REEs) in intermediate and deep waters of the mid-latitude (~40°S) South Pacific along a meridional transect between South America and New Zealand. The goal of our study is to gain better insight into the distribution and mixing of water masses in the South Pacific and to evaluate the validity of Nd isotopes as a water mass tracer in this remote region of the ocean. The results demonstrate that biogeochemical cycling (scavenging processes in the Eastern Equatorial Pacific) and release of LREEs from the sediment clearly influence the distribution of the dissolved REE concentrations at certain locations. Nevertheless, the Nd isotope signatures clearly trace water masses including AAIW (Antarctic Intermediate Water) (average epsilon-Nd = -8.2 ± 0.3), LCDW (Lower Circumpolar Deep Water) (average epsilon-Nd = -8.3 ± 0.3), NPDW (North Pacific Deep Water) (average epsilon-Nd = -5.9 ± 0.3), and the remnants of NADW (North Atlantic Deep Water) (average epsilon-Nd = -9.7 ± 0.3). Filtered water samples taken from the sediment-water interface under the deep western boundary current off New Zealand suggest that boundary exchange processes are limited at this location and highlight the spatial and temporal variability of this process. These data will serve as a basis for the paleoceanographic application of Nd isotopes in the South Pacific.

Bacteriohopanepolyol data of sediment cores GeoB3918-2 and GeoB1514-6 from the Amazon River

We have investigated the delivery of terrestrial organic carbon (OC) to the Amazon shelf and deep sea fan based on soil marker bacteriohopanepolyols (BHPs; adenosylhopane and related compounds) and branched glycerol dialkyl glycerol tetraethers (GDGTs), as well as on 14C dating of bulk organic matter. The microbial biomarker records show persistent burial of terrestrial OC, evidenced by almost constant and high BIT values (0.6) and soil marker BHP concentration [80-230 µg/g TOC (total OC)] on the late Holocene shelf and even higher BIT values (0.8-0.9), but lower and more variable soil-marker BHP concentration (40-100 µg/g TOC), on the past glacial deep sea fan. Radiocarbon data show that OC on the shelf is 3-4 kyr older than corresponding bivalve shells, emphasizing the presence of old carbon in this setting. We observe comparable and unexpectedly invariant BHP composition in both marine sediment records, with a remarkably high relative abundance of C-35 amino BHPs including compounds specific for aerobic methane oxidation on the shelf (avg. 50% of all BHPs) and the fan (avg. 40%). Notably, these marine BHP signatures are strikingly similar to those of a methane-producing floodplain area in one of the Amazonian wetland (várzea) regions. The observation indicates that BHPs in the marine sediments may have initially been produced within wetland regions of the Amazon basin and may therefore document persistent export from terrestrial wetland regions, with subsequent re-working in the marine environment, both during recent and past glacial climate conditions.

Analysis of Thematic Classified Aerial Images Trough Multispectral and LIDAR Data

The application of thematic maps obtained through the classification of remote images needs the obtained products with an optimal accuracy. The registered images from the airplanes display a very satisfactory spatial resolution, but the classical methods of thematic classification not always give better results than when the registered data from satellite are used. In order to improve these results of classification, in this work, the LIDAR sensor data from first return (Light Detection And Ranging) registered simultaneously with the spectral sensor data from airborne are jointly used. The final results of the thematic classification of the scene object of study have been obtained, quantified and discussed with and without LIDAR data, after applying different methods: Maximum Likehood Classification, Support Vector Machine with four different functions kernel and Isodata clustering algorithm (ML, SVM-L, SVM-P, SVM-RBF, SVM-S, Isodata). The best results are obtained for SVM with Sigmoide kernel. These allow the correlation with others different physical parameters with great interest like Manning hydraulic coefficient, for their incorporation in a GIS and their application in hydraulic modeling.

New methods for the estimation of Takagi-Sugeno model based extended Kalman filter and its applications to optimal control for nonlinear systems

This paper describes new approaches to improve the local and global approximation (matching) and modeling capability of Takagi–Sugeno (T-S) fuzzy model. The main aim is obtaining high function approximation accuracy and fast convergence. The main problem encountered is that T-S identification method cannot be applied when the membership functions are overlapped by pairs. This restricts the application of the T-S method because this type of membership function has been widely used during the last 2 decades in the stability, controller design of fuzzy systems and is popular in industrial control applications. The approach developed here can be considered as a generalized version of T-S identification method with optimized performance in approximating nonlinear functions. We propose a noniterative method through weighting of parameters approach and an iterative algorithm by applying the extended Kalman filter, based on the same idea of parameters’ weighting. We show that the Kalman filter is an effective tool in the identification of T-S fuzzy model. A fuzzy controller based linear quadratic regulator is proposed in order to show the effectiveness of the estimation method developed here in control applications. An illustrative example of an inverted pendulum is chosen to evaluate the robustness and remarkable performance of the proposed method locally and globally in comparison with the original T-S model. Simulation results indicate the potential, simplicity, and generality of the algorithm. An illustrative example is chosen to evaluate the robustness. In this paper, we prove that these algorithms converge very fast, thereby making them very practical to use.

Current Mode with RMS Voltage and Offset Control Loops for a Single-Phase Aircraft Inverter Suitable for Parallel and 3-Phase Operation Modes

Rms voltage regulation may be an attractive possibility for controlling power inverters. Combined with a Hall Effect sensor for current control, it keeps its parallel operation capability while increasing its noise immunity, which may lead to a reduction of the Total Harmonic Distortion (THD). Besides, as voltage regulation is designed in DC, a simple PI regulator can provide accurate voltage tracking. Nevertheless, this approach does not lack drawbacks. Its narrow voltage bandwidth makes transients last longer and it increases the voltage THD when feeding non-linear loads, such as rectifying stages. On the other hand, the implementation can fall into offset voltage error. Furthermore, the information of the output voltage phase is hidden for the control as well, making the synchronization of a 3-phase setup not trivial. This paper explains the concept, design and implementation of the whole control scheme, in an on board inverter able to run in parallel and within a 3-phase setup. Special attention is paid to solve the problems foreseen at implementation level: a third analog loop accounts for the offset level is added and a digital algorithm guarantees 3-phase voltage synchronization.

Fault Tolerance Analysis and Self-Healing Strategy of Autonomous, Evolvable Hardware Systems

This paper presents an analysis of the fault tolerance achieved by an autonomous, fully embedded evolvable hardware system, which uses a combination of partial dynamic reconfiguration and an evolutionary algorithm (EA). It demonstrates that the system may self-recover from both transient and cumulative permanent faults. This self-adaptive system, based on a 2D array of 16 (4×4) Processing Elements (PEs), is tested with an image filtering application. Results show that it may properly recover from faults in up to 3 PEs, that is, more than 18% cumulative permanent faults. Two fault models are used for testing purposes, at PE and CLB levels. Two self-healing strategies are also introduced, depending on whether fault diagnosis is available or not. They are based on scrubbing, fitness evaluation, dynamic partial reconfiguration and in-system evolutionary adaptation. Since most of these adaptability features are already available on the system for its normal operation, resource cost for self-healing is very low (only some code additions in the internal microprocessor core)

Icosahedral Ni nanowires formed from nanocontacts breaking: Identification and characterization by Molecular Dynamics

We present and discuss an algorithm to identify and characterize the long icosahedral structures (staggered pentagonal nanowires with 1-5-1-5 atomic structure) that appear in Molecular Dynamics simulations of metallic nanowires of different species subjected to stretching. The use of this algorithm allows the identification of pentagonal rings forming the icosahedral structure as well as the determination of its number np , and the maximum length of the pentagonal nanowire Lpm. The algorithm is tested with some ideal structures to show its ability to discriminate between pentagonal rings and other ring structures. We applied the algorithm to Ni nanowires with temperatures ranging between 4K and 865K, stretched along the [111], [100] and [110] directions. We studied statistically the formation of pentagonal nanowires obtaining the distributions of length Lpm and number of rings np as function of the temperature. The Lpm distribution presents a peaked shape, with peaks located at fixed distances whose separation corresponds to the distance between two consecutive pentagonal rings.

Efficient management of backtracking in and-parallelism

A backtracking algorithm for AND-Parallelism and its implementation at the Abstract Machine level are presented: first, a class of AND-Parallelism models based on goal independence is defined, and a generalized version of Restricted AND-Parallelism (RAP) introduced as characteristic of this class. A simple and efficient backtracking algorithm for R A P is then discussed. An implementation scheme is presented for this algorithm which offers minimum overhead, while retaining the performance and storage economy of sequent ial implementations and taking advantage of goal independence to avoid unnecessary backtracking ("restricted intelligent backtracking"). Finally, the implementation of backtracking in sequential and AND-Parallcl systems is explained through a number of examples.