Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins.

Space–oriented EEG segmentation reveals changes in brain electric–field maps under the influence of a nootropic drug

Map landscape-based segmentation of the sequences of momentary potential distribution maps (42-channel recordings) into brain microstates during spontaneous brain activity was used to study brain electric field spatial effects of single doses of piracetam (2.9, 4.8, and 9.6 g Nootropil® UCB and placebo) in a double-blind study of five normal young volunteers. Four 15-second epochs were analyzed from each subject and drug condition. The most prominent class of microstates (covering 49% of the time) consisted of potential maps with a generally anterior-posterior field orientation. The map orientation of this microstate class showed an increasing clockwise deviation from the placebo condition with increasing drug doses (Fisher's probability product, p < 0.014). The results of this study suggest the use of microstate segmentation analysis for the assessment of central effects of medication in spontaneous multichannel electroencephalographic data, as a complementary approach to frequency-domain analysis.

Ridge alterations post-extraction in the esthetic zone: a 3D analysis with CBCT

Dimensional alterations of the facial bone wall following tooth extractions in the esthetic zone have a profound effect on treatment outcomes. This prospective study in 39 patients is the first to investigate three-dimensional (3D) alterations of facial bone in the esthetic zone during the initial 8 wks following flapless tooth extraction. A novel 3D analysis was carried out, based on 2 consecutive cone beam computed tomographies (CBCTs). A risk zone for significant bone resorption was identified in central areas, whereas proximal areas yielded only minor changes. Correlation analysis identified a facial bone wall thickness of ≤ 1 mm as a critical factor associated with the extent of bone resorption. Thin-wall phenotypes displayed pronounced vertical bone resorption, with a median bone loss of 7.5 mm, as compared with thick-wall phenotypes, which decreased by only 1.1 mm. For the first time, 3D analysis has allowed for documentation of dimensional alterations of the facial bone wall in the esthetic zone of humans following extraction. It also characterized a risk zone prone to pronounced bone resorption in thin-wall phenotypes. Vertical bone loss was 3.5 times more severe than findings reported in the existing literature.

Race and discourse analysis: Building a dialogue in health service research and health care settings

Using a framework for discourse analysis developed by Van Dijk, the investigator will pinpoint the pathological forms of discourse on race, defined as 'race talk' in three professional domains: health services research, public health provider organizations, and literature on multiculturalism. Attention will then turn to developing an analytical strategy for building more meaningful dialogue on race. The retrieval of potential resources for dialogue will be drawn from the third domain. Analysis will focus on enhancing the prospects of converting 'race talk' into dialogue. This will be accomplished by characterizing the normative preconditions as formal procedural requirements for dialogue and then supplementing these conditions with others related specifically to race. From here, the practical implications of combining procedural requirements and resources in each of the domains will be considered. Finally, the author will attempt to determine how these selected resources might be employed to transform 'race talk' in practice and lay the groundwork for a dialogue of understanding. ^

A Wavelet Analysis of Pliopleistocene Climate Indicators: A New View of Periodicity Evolution

Wavelet analysis offers an alternative to Fourier based time-series analysis, and is particularly useful when the amplitudes and periods of dominant cycles are time dependent. We analyse climatic records derived from oxygen isotopic ratios of marine sediment cores with modified Morlet wavelets. We use a normalization of the Morlet wavelets which allows direct correspondence with Fourier analysis. This provides a direct view of the oscillations at various frequencies, and illustrates the nature of the time-dependence of the dominant cycles.

Sensitivity of the WRF model to PBL parametrisations and nesting techniques: evaluation of wind storms over complex terrain

Simulating surface wind over complex terrain is a challenge in regional climate modelling. Therefore, this study aims at identifying a set-up of the Weather Research and Forecasting Model (WRF) model that minimises system- atic errors of surface winds in hindcast simulations. Major factors of the model configuration are tested to find a suitable set-up: the horizontal resolution, the planetary boundary layer (PBL) parameterisation scheme and the way the WRF is nested to the driving data set. Hence, a number of sensitivity simulations at a spatial resolution of 2 km are carried out and compared to observations. Given the importance of wind storms, the analysis is based on case studies of 24 historical wind storms that caused great economic damage in Switzerland. Each of these events is downscaled using eight different model set-ups, but sharing the same driving data set. The results show that the lack of representation of the unresolved topography leads to a general overestimation of wind speed in WRF. However, this bias can be substantially reduced by using a PBL scheme that explicitly considers the effects of non-resolved topography, which also improves the spatial structure of wind speed over Switzerland. The wind direction, although generally well reproduced, is not very sensitive to the PBL scheme. Further sensitivity tests include four types of nesting methods: nesting only at the boundaries of the outermost domain, analysis nudging, spectral nudging, and the so-called re-forecast method, where the simulation is frequently restarted. These simulations show that restricting the freedom of the model to develop large-scale disturbances slightly increases the temporal agreement with the observations, at the same time that it further reduces the overestimation of wind speed, especially for maximum wind peaks. The model performance is also evaluated in the outermost domains, where the resolution is coarser. The results demonstrate the important role of horizontal resolution, where the step from 6 to 2 km significantly improves model performance. In summary, the combination of a grid size of 2 km, the non-local PBL scheme modified to explicitly account for non-resolved orography, as well as analysis or spectral nudging, is a superior combination when dynamical downscaling is aimed at reproducing real wind fields.

Impact of anti-inflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: Longitudinal analysis from a nation-wide paediatric rheumatological database

PURPOSE Based on a nation-wide database, this study analysed the influence of methotrexate (MTX), TNF inhibitors and a combination of the two on uveitis occurrence in JIA patients. METHODS Data from the National Paediatric Rheumatological Database in Germany were used in this study. Between 2002 and 2013, data from JIA patients were annually documented at the participating paediatric rheumatological sites. Patients with JIA disease duration of less than 12 months at initial documentation and ≥2 years of follow-up were included in this study. The impact of anti-inflammatory treatment on the occurrence of uveitis was evaluated by discrete-time survival analysis. RESULTS A total of 3,512 JIA patients (mean age 8.3±4.8 years, female 65.7%, ANA-positive 53.2%, mean age at arthritis onset 7.8±4.8 years) fulfilled the inclusion criteria. Mean total follow-up time was 3.6±2.4 years. Uveitis developed in a total of 180 patients (5.1%) within one year after arthritis onset. Uveitis onset after the first year was observed in another 251 patients (7.1%). DMARD treatment in the year before uveitis onset significantly reduced the risk for uveitis: MTX (HR 0.63, p=0.022), TNF inhibitors (HR 0.56, p<0.001) and a combination of the two (HR 0.10, p<0.001). Patients treated with MTX within the first year of JIA had an even a lower uveitis risk (HR 0.29, p<0.001). CONCLUSION The use of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early MTX use within the first year of disease and the combination of MTX with a TNF inhibitor had the highest protective effect. This article is protected by copyright. All rights reserved.

Grain size analysis on CRP sediment cores from the Ross Sea, Antarctica

The upper 1200 m of pre-Pliocene sediment recovered by Cape Roberts Project (CRP) drilling off the Victoria Land coast of Antarctica between 1997-1999 has been subdivided into 54 unconformity-bound stratigraphic sequences, spanning the period c. 32 to 17 Ma. The sequences are recognised on the basis of the cyclical vertical stacking of their constituent lithofacies, which are enclosed by erosion surfaces produced during the grounding of the advancing ice margin onto the sea floor. Each sequence represents deposition in a range of offshore shelf to coastal glacimarine sedimentary environments during oscillations in the ice margin across the Western Ross Sea shelf, and coeval fluctuations in water depth. This paper applies spectral analysis techniques to depth- and time-series of sediment grain size (500 samples) for intervals of the core with adequate chronological data. Time series analysis of 0.5-l.0m-spaced grainsize data spanning sequences 9-11 (CRP-2/2A) and sequences 1-7 (CRP-3) suggests that the length of individual sequences correspond to Milankovitch frequencies, probably 41 k.y., but possibly as low as 100 k.y. Higher frequency periodic components at 23 k.y. (orbital precession) and 15-10 k.y. (sub-orbital) are recognised at the intrasequence-scale, and may represent climatic cycles akin to the ice rafting episodes described in the North Atlantic Ocean during the Quaternary. The cyclicity recorded by glacimarine sequences in CRP core provides direct evidence from the periphery of Antarctica for orbital oscillations in the size of the Oligocene-Early Miocene East Antarctic Ice Sheet.

Stable isotopes and calcium carbonate at DSDP Holes 85-574 and 85-574A

Detailed stable isotopic and calcium carbonate records (with a sampling resolution of 3000 yr.) from the middle Miocene section of hydraulic piston corer (HPC) Hole 574A provide a sequence that records the major shift in the oxygen isotopic composition of the world's oceans that occurred at about 14 Ma. The data suggest that this transition was rapid and spans about 30,000 yr. of sediment deposition. In intervals before and after the shift, the mean d18O values are characterized by a constant mean with a high degree of variability. The degree of variability in both the d18O and d13C records is comparable to that observed for the Pliocene and earliest Pleistocene and does not show a significant change before or after the major shift in the d18O record. Whereas the oxygen isotopic record is characterized by relatively stable mean values before and after the middle Miocene event, the d13C record shows a number of significant offsets in the mean value separated by intervals of high-frequency variations. Time and frequency domain analysis of all records from Hole 574A indicate that the frequency components shown to be related to orbital changes in the Pleistocene record are also present in the middle Miocene. The high variability observed in the Site 574 isotopic records places important constraints on models describing the role of formation of the Antarctic ice sheet during the middle Miocene climatic transitions. Thus, HPC Hole 574A provides a valuable sequence for detailed study of climatic variability during an important time in the Earth's history, although we cannot provide a definitive explanation of the major oxygen isotopic event of the middle Miocene.

A Light-Weight On-Chip Monitoring Network for Dynamic Adaptation and Calibration

Current nanometer technologies suffer within-die parameter uncertainties, varying workload conditions, aging, and temperature effects that cause a serious reduction on yield and performance. In this scenario, monitoring, calibration, and dynamic adaptation become essential, demanding systems with a collection of multi purpose monitors and exposing the need for light-weight monitoring networks. This paper presents a new monitoring network paradigm able to perform an early prioritization of the information. This is achieved by the introduction of a new hierarchy level, the threshing level. Targeting it, we propose a time-domain signaling scheme over a single-wire that minimizes the network switching activity as well as the routing requirements. To validate our approach, we make a thorough analysis of the architectural trade-offs and expose two complete monitoring systems that suppose an area improvement of 40% and a power reduction of three orders of magnitude compared to previous works.

Determination of suitable irrigation lengths and intervals using capacitance humidity sensors for a sandy soil

production, during the summer of 2010. This farm is integrated at the Spanish research network for the sugar beet development (AIMCRA) which regarding irrigation, focuses on maximizing water saving and cost reduction. According to AIMCRA 0 s perspective for promoting irrigation best practices, it is essential to understand soil response to irrigation i.e. maximum irrigation length for each soil infiltration capacity. The Use of Humidity Sensors provides foundations to address soil 0 s behavior at the irrigation events and, therefore, to establish the boundaries regarding irrigation length and irrigation interval. In order to understand to what extent farmer 0 s performance at Tordesillas farm could have been potentially improved, this study aims to address suitable irrigation length and intervals for the given soil properties and evapotranspiration rates. In this sense, several humidity sensors were installed: (1) A Frequency Domain Reflectometry (FDR) EnviroScan Probe taking readings at 10, 20, 40 and 60cm depth and (2) different Time Domain Reflectometry (TDR) Echo 2 and Cr200 probes buried in a 50cm x 30cm x 50cm pit and placed along the walls at 10, 20, 30 and 40 cm depth. Moreover, in order to define soil properties, a textural analysis at the Tordesillas Farm was conducted. Also, data from the Tordesillas meteorological station was utilized.

Aeroelastic characteristics of slender wing/bodies with freeplay non-linearities

This article presents a time domain approach to the flutter analysis of a missile-type wing/body configuration with concentrated structural non-linearities. The missile wing is considered fully movable and its rotation angle contains the structural freeplay-type non-linearity. Although a general formulation for flexible configurations is developed, only two rigid degrees of freedom are taken into account for the results: pitching of the whole wing/body configuration and wing rotation angle around its hinge. An unsteady aerodynamic model based on the slender-body approach is used to calculate aerodynamic generalized forces. Limit-cycle oscillations and chaotic motion below the flutter speed are observed in this study.

Towards data-aware resource analysis for service orchestrations

Compile-time program analysis techniques can be applied to Web service orchestrations to prove or check various properties. In particular, service orchestrations can be subjected to resource analysis, in which safe approximations of upper and lower resource usage bounds are deduced. A uniform analysis can be simultaneously performed for different generalized resources that can be directiy correlated with cost- and performance-related quality attributes, such as invocations of partners, network traffic, number of activities, iterations, and data accesses. The resulting safe upper and lower bounds do not depend on probabilistic assumptions, and are expressed as functions of size or length of data components from an initiating message, using a finegrained structured data model that corresponds to the XML-style of information structuring. The analysis is performed by transforming a BPEL-like representation of an orchestration into an equivalent program in another programming language for which the appropriate analysis tools already exist.

Automatic motion compensation of free breathing acquired myocardial perfusion data by using independent component analysis

Images acquired during free breathing using first-pass gadolinium-enhanced myocardial perfusion magnetic resonance imaging (MRI) exhibit a quasiperiodic motion pattern that needs to be compensated for if a further automatic analysis of the perfusion is to be executed. In this work, we present a method to compensate this movement by combining independent component analysis (ICA) and image registration: First, we use ICA and a time?frequency analysis to identify the motion and separate it from the intensity change induced by the contrast agent. Then, synthetic reference images are created by recombining all the independent components but the one related to the motion. Therefore, the resulting image series does not exhibit motion and its images have intensities similar to those of their original counterparts. Motion compensation is then achieved by using a multi-pass image registration procedure. We tested our method on 39 image series acquired from 13 patients, covering the basal, mid and apical areas of the left heart ventricle and consisting of 58 perfusion images each. We validated our method by comparing manually tracked intensity profiles of the myocardial sections to automatically generated ones before and after registration of 13 patient data sets (39 distinct slices). We compared linear, non-linear, and combined ICA based registration approaches and previously published motion compensation schemes. Considering run-time and accuracy, a two-step ICA based motion compensation scheme that first optimizes a translation and then for non-linear transformation performed best and achieves registration of the whole series in 32 ± 12 s on a recent workstation. The proposed scheme improves the Pearsons correlation coefficient between manually and automatically obtained time?intensity curves from .84 ± .19 before registration to .96 ± .06 after registration

Optical detection of mealiness in apples using laser TDRS

Mealiness is a textural attribute related to an internal fruit disorder that involves quality loss. It is characterised by the combination of abnormal softness of the fruit and absence of free juiciness in the mouth when eaten by the consumer. Recent research concluded with the development of precise instrumental procedure to measure a scale of mealiness based on the combination of several rheological properties and empirical magnitudes. In this line, time-domain laser reflectance spectroscopy (TDRS) is a medical technology, new in agrofood research, which is capable of obtaining physical and chemical information independently and simultaneously, and this can be of interest to characterise mealiness. Using VIS & NIR lasers as light sources, TDRS was applied in this work to Golden Delicious and Cox apples (n=90), conforming several batches of untreated samples and storage-treated (20°C & 95%RH) to promote the development of mealiness. The collected database was clustered into different groups according to their instrumental test values (Barreiro et al, 1998). The optical coefficients were used as explanatory variables when building discriminant analysis functions for mealiness, achieving a classification score above 80% of correctly identified mealy versus fresh apples.