1. Ecological research produces a tremendous amount of data, but the diversity in scales and topics covered and the ways in which studies are carried out result in large numbers of small, ...idiosyncratic data sets using heterogeneous terminologies. Such heterogeneity can be attributed, in part, to a lack of standards for acquiring, organizing and describing data. Here, we propose a terminological resource, a Ṯhesaurus O̱f P̱lant characteristics (TOP), whose aim is to harmonize and formalize concepts for plant characteristics widely used in ecology. 2. TOP concentrates on two types of plant characteristics: traits and environmental associations. It builds on previous initiatives for several aspects: (i) characteristics are designed following the entity-quality (EQ) model (a characteristic is modelled as the 'Quality' of an 'Entity' ) used in the context of Open Biological Ontologies; (ii) whenever possible, the Entities and Qualities are taken from existing terminology standards, mainly the Plant Ontology (PO) and Phenotypic Quality Ontology (PATO) ontologies; and (iii) whenever a characteristic already has a definition, if appropriate, it is reused and referenced. The development of TOP, which complies with semantic web principles, was carried out through the involvement of experts from both the ecology and the semantics research communities. Regular updates of TOP are planned, based on community feedback and involvement. 3. TOP provides names, definitions, units, synonyms and related terms for about 850 plant characteristics. TOP is available online (www.top-thesaurus.org), and can be browsed using an alphabetical list of characteristics, a hierarchical tree of characteristics, a faceted and a free-text search, and through an Application Programming Interface. 4. Synthesis. Harmonizing definitions of concepts, as proposed by TOP, forms the basis for better integration of data across heterogeneous data sets and terminologies, thereby increasing the potential for data reuse. It also allows enhanced scientific synthesis. TOP therefore has the potential to improve research and communication not only within the field of ecology, but also in related fields with interest in plant functioning and distribution.
A prototype of hybrid gamma imager has been developed, based on a single Timpex3 readout chip hybridized with a 1 mm thick cadmium telluride semiconductor. This prototype combines coded-aperture ...imaging spectrometry and Compton imaging techniques to perform hybrid gamma imaging. It associates and takes advantage of both techniques to locate gamma emitters. The prototype is designed to be portable and compact in order to ease its field use. In this work, we present experimental results obtained with this prototype in coded-aperture imaging spectrometry mode, Compton imaging mode, and hybrid gamma imaging.
Intense and purified radioactive beam of post-accelerated $^{14}$O was used to study the low-lying states in the unbound $^{15}$F nucleus. Exploiting resonant elastic scattering in inverse kinematics ...with a thick target, the second excited state, a resonance at E$_R$=4.757(6)(10)~MeV with a width of $\Gamma$=36(5)(14)~keV was measured for the first time with high precision. The structure of this narrow above-barrier state in a nucleus located two neutrons beyond the proton drip line was investigated using the Gamow Shell Model in the coupled channel representation with a $^{12}$C core and three valence protons. It is found that it is an almost pure wave function of two quasi-bound protons in the $2s_{1/2}$ shell.
The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients.
A Multivariable logistic regression model of rheumatoid arthritis ...patients starting MTX was developed in a derivation cohort with 285 patients starting MTX in a clinical multicentre, stratified single-blinded trial, performed in seven secondary care clinics and a tertiary care clinic. The model was validated in a validation cohort with 102 patients starting MTX at a tertiary care clinic. Outcome was insufficient response (disease activity score (DAS)28 >3.2) after 3 months of MTX treatment. Clinical characteristics, lifestyle variables, genetic and metabolic biomarkers were determined at baseline in both cohorts. These variables were dichotomized and used to construct a multivariable prediction model with backward logistic regression analysis.
The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m2, ABCB1 rs1045642 genotype, ABCC3 rs4793665 genotype, and erythrocyte-folate<750 nmol/L. In the derivation cohort, AUC of ROC curve was 0.80 (95%CI: 0.73-0.86), and 0.80 (95%CI: 0.69-0.91) in the validation cohort. Betas of the prediction model were transformed into total risk score (range 0-8). At cutoff of ≥4, probability for insufficient response was 44%. Sensitivity was 71%, specificity 72%, with positive and negative predictive value of 72% and 71%.
A prognostics prediction model for insufficient response to MTX in 2 prospective RA cohorts by combining genetic, metabolic, clinical and lifestyle variables was developed and validated. This model satisfactorily identified RA patients with high risk of insufficient response to MTX.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Molecular classification of ERG‐rearranged prostate cancer clarifies the role of TMPRSS2‐ERG in the development and progression of prostate cancer. The objective of our study was to identify direct ...ERG target genes in ERG‐rearranged prostate cancer. Two independent cohorts of primary prostate cancer (Cohort A, n=48; Cohort B, n=31), a cohort of late‐stage prostate cancer (n=51) and expression array data of a cohort of primary prostate tumors from a different institute (n=128) were analyzed for expression of genes that were coexpressed with ERG overexpression. By genome‐wide expression analysis and Q‐RT‐PCR it was shown that the gene Tudor domain containing 1 (TDRD1) was by far the strongest correlated gene with ERG overexpression in both Cohort A and B. Expression array analysis of the patient cohort from a different institute showed a large overlap in genes that were positively correlated with ERG overexpression, including TDRD1. In late‐stage prostate cancer, TDRD1 was also coexpressed with ERG overexpression, although a proportion of ERG‐negative late‐stage samples expressed TDRD1. TDRD1 expression was not associated with ETV1 overexpression. In the prostate cancer cell line VCaP, downregulation of ERG by shRNA lead to a lower expression level of TDRD1 and resulted in a decreased activity of the TDRD1 promoter. By mutation analysis we identified a functional ERG binding site in the TDRD1 promoter. Our findings show TDRD1 as the first identified upregulated direct ERG target gene that is strongly associated with ERG overexpression in primary prostate cancer.
What's new?
Fusion between ERG and the androgen‐regulated, prostate‐specific gene transmembrane protease, serine 2 (TMPRSS2) is the most frequently occurring genomic rearrangement in prostate cancer. To better understand the significance of ERG specifically, ERG‐rearranged prostate cancers were analyzed here in an attempt to identify ERG target genes. The analysis reveals a strong association between Tudor domain containing 1 (TDRD1) expression and ERG overexpression in primary prostate tumors and provides evidence that TDRD1 is a direct ERG target gene. This new knowledge sheds much‐needed light on the molecular pathways underlying ERG‐positive tumor development.
Context. Current generation millimeter wavelength detectors suffer from scaling limits imposed by complex cryogenic readout electronics. These instruments typically employ multiplexing ratios well ...below a hundred. To achieve multiplexing ratios greater than a thousand, it is imperative to investigate technologies that intrinsically incorporate strong multiplexing. One possible solution is the kinetic inductance detector (KID). To assess the potential of this nascent technology, a prototype instrument optimized for the 2 mm atmospheric window was constructed. Known as the Néel IRAM KID Array (NIKA), it has recently been tested at the Institute for Millimetric Radio Astronomy (IRAM) 30-m telescope at Pico Veleta, Spain. Aims. There were four principle research objectives: to determine the practicality of developing a giant array instrument based on KIDs, to measure current in-situ pixel sensitivities, to identify limiting noise sources, and to image both calibration and scientifically-relevant astronomical sources. Methods. The detectors consisted of arrays of high-quality superconducting resonators electromagnetically coupled to a transmission line and operated at ~100 mK. The impedance of the resonators was modulated by incident radiation; two separate arrays were tested to evaluate the efficiency of two unique optical-coupling strategies. The first array consisted of lumped element kinetic inductance detectors (LEKIDs), which have a fully planar design properly shaped to enable direct absorbtion. The second array consisted of antenna-coupled KIDs with individual sapphire microlenses aligned with planar slot antennas. Both detectors utilized a single transmission line along with suitable room-temperature digital electronics for continuous readout. Results. NIKA was successfully tested in October 2009, performing in line with expectations. The measurement resulted in the imaging of a number of sources, including planets, quasars, and galaxies. The images for Mars, radio star MWC349, quasar 3C345, and galaxy M 87 are presented. From these results, the optical NEP was calculated to be around 1 × 10-15 W/Hz1/2. A factor of 10 improvement is expected to be readily feasible by improvements in the detector materials and reduction of performance-degrading spurious radiation.
The gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor-mediated nuclear ...imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC.
mRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction. Receptor mRNA expression levels were associated with clinico-pathological factors and expression levels of primary tumors and corresponding metastases were compared.
Binding of GRPR and SSTR radioligands to tumor tissue correlated significantly with receptor mRNA expression. High GRPR and SSTR2 mRNA levels were associated with estrogen receptor (ESR1)-positive tumors (p<0.001 for both receptors). There was no significant difference in GRPR mRNA expression of primary tumors versus paired metastases. Regarding SSTR2 mRNA expression, there was also no significant difference in the majority of cases, apart from liver and ovarian metastases which showed a significantly lower expression compared to the corresponding primary tumors (p = 0.02 and p = 0.03, respectively).
Targeting the GRPR and SSTR2 for nuclear imaging and/or treatment has the potential to improve BC care in primary as well as metastatic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To evaluate if non‐invasive prenatal testing (NIPT) affects livebirth (LB) prevalence of Down syndrome (DS) in the Netherlands.
Method
Data from clinical genetics laboratories and the ...Working Party on Prenatal Diagnosis and Therapy (2014–2018) and previous published data (1991–2013) were used to assess trends for DS LB prevalence and reduction percentage (the net decrease in DS LBs resulting from selective termination of pregnancies). Statistics Netherlands provided general population data.
Results
DS LB prevalence increased from 11.6/10,000 in 1991 to 15.9/10,000 in 2002 (regression coefficient 0.246 95% CI: 0.105–0.388; p = 0.003). After 2002, LB prevalence decreased to 11.3/10,000 in 2014 and further to 9.9/10,000 in 2018 (regression coefficient 0.234 (95% CI: −0.338 to −0.131; p < 0.001). The reduction percentage increased from 26% in 1991 to 55.2% in 2018 (regression coefficient 0.012 (95% CI: 0.010–0.013; p < 0.001)). There were no trend changes after introducing NIPT as second‐tier (2014) and first‐tier test (2017).
Conclusions
Introducing NIPT did not change the decreasing trend in DS LB prevalence and increasing trend in reduction percentage. These trends may be caused by a broader development of more prenatal testing that had already started before introducing NIPT.
Key points
What's already known about this topic?
The introduction of NIPT changed the landscape in prenatal screening worldwide.
No long‐term population‐based study on the impact of NIPT on DS LB prevalence has been published.
What does this study add?
This study shows how to calculate DS LB prevalence in the absence of a national registration program.
Introducing NIPT caused no trend changes in DS LB prevalence and reduction percentage in the Netherlands.
The deep tissue penetration and submicron spatial resolution of multiphoton microscopy and the high detection efficiency and nanometer spectral resolution of a spectrograph were utilized to record ...spectral images of the intrinsic emission of mouse skin tissues. Autofluorescence from both cellular and extracellular structures, second-harmonic signal from collagen, and a narrowband emission related to Raman scattering of collagen were detected. Visualization of the spectral images by wavelength-to-RGB color image conversion allowed us to identify and discriminate tissue structures such as epidermal keratinocytes, lipid-rich corneocytes, intercellular structures, hair follicles, collagen, elastin, and dermal cells. Our results also showed morphological and spectral differences between excised tissue section, thick excised tissue, and in vivo tissue samples of mouse skin. Results on collagen excitation at different wavelengths suggested that the origin of the narrowband emission was collagen Raman peaks. Moreover, the oscillating spectral dependency of the collagen second-harmonic intensity was experimentally studied. Overall, spectral imaging provided a wealth of information not easily obtainable with present conventional multiphoton imaging systems.
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