77 research outputs found

    The influence of cultivar, weather conditions and nitrogen fertilizer on winter wheat grain yield

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    ArticleWinter wheat (Triticum aestivum L.) is one of the most productive and significant cereal species in Latvia used for food grain production. The aim of the research was to e valuate winter wheat grain yield depending on nitrogen fertilizer rate, crop - year (meteorological conditions) and cultivar and determine the impact and interaction of research factors on grain yield. Field experiments with winter wheat cultivars ‘Bussard’ and ‘Zentos’ were conducted at the Latvia University of Agriculture, Study and Research farm Peterlauki during a three year period (2009/2010, 2010/2011 and 2011/2012). Nitrogen (N) was applied (N60, N90, N120, N150 kg ha - 1 ) in spring after resumption of v egetative growth. Assessment of both winter wheat cultivars showed that crop - year, cultivar, nitrogen fertilizer, crop - year × cultivar had a significant (p < 0.05) impact on grain yield. Nitrogen fertilizer did significantly (p < 0.05) affect the grain yie ld of winter wheat, treatment with N90 showed of yield increase, compared to N60, while further use of increasing amounts of N fertilizer did not increase grain yields significantly. Results suggest, that winter wheat grain yield by 34% depended on cultiva r, by 33% on crop - year (weather conditions), and by 13% on crop - year × cultivar. Influence of the nitrogen fertilizer effect was small – 3%. Medium strong positive correlation was found between HTC in the vegetation period from winter wheat heading to grai n ripening

    Bone Mineral Density and Bone Metabolism In Children Treated for Bone Sarcomas

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    In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality o

    Analysis of Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Collagen Iα1 Genes and Their Relationship With Height in Children With Bone Cancer

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    The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene

    Static Charges in the Low-Energy Theory of the S-Duality Twist

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    We continue the study of the low-energy limit of N=4 super Yang-Mills theory compactified on a circle with S-duality and R-symmetry twists that preserve N=6 supersymmetry in 2+1D. We introduce external static supersymmetric quark and anti-quark sources into the theory and calculate the Witten Index of the resulting Hilbert space of ground states on a torus. Using these results we compute the action of simple Wilson loops on the Hilbert space of ground states without sources. In some cases we find disagreement between our results for the Wilson loop eigenvalues and previous conjectures about a connection with Chern-Simons theory.Comment: 73 pages, two paragraphs added, one to the introduction and one to the discussio

    Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity

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    The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles

    5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit

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    Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole 7 as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with drug-like chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood–brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling

    Discovery of 2-phenoxyacetamides as inhibitors of the Wnt-depalmitoleating enzyme NOTUM from an X-ray fragment screen

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    NOTUM is a carboxylesterase that has been shown to act by mediating the O-depalmitoleoylation of Wnt proteins resulting in suppression of Wnt signaling. Here, we describe the development of NOTUM inhibitors that restore Wnt signaling for use in in vitro disease models where NOTUM over activity is an underlying cause. A crystallographic fragment screen with NOTUM identified 2-phenoxyacetamide 3 as binding in the palmitoleate pocket with modest inhibition activity (IC50 33 μM). Optimization of hit 3 by SAR studies guided by SBDD identified indazole 38 (IC50 0.032 μM) and isoquinoline 45 (IC50 0.085 μM) as potent inhibitors of NOTUM. The binding of 45 to NOTUM was rationalized through an X-ray co-crystal structure determination which showed a flipped binding orientation compared to 3. However, it was not possible to combine NOTUM inhibition activity with metabolic stability as the majority of the compounds tested were rapidly metabolized in an NADPH-independent manner

    Project goals, target selection, and stellar characterization

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    The detection of habitable worlds is one of humanitya-s greatest endeavors. Thus far, astrobiological studies have shown that one of the most critical components for allowing life to develop is liquid water. Its chemical properties and its capacity to dissolve and, hence, transport other substances makes this constituent a key piece in this regard. As a consequence, looking for life as we know it is directly related to the search for liquid water. For a remote detection of life in distant planetary systems, this essentially means looking for planets in the so-called habitable zone. In this sense, K-dwarf stars are the perfect hosts to search for planets in this range of distances. Contrary to G-dwarfs, the habitable zone is closer, thus making planet detection easier using transit or radial velocity techniques. Contrary to M-dwarfs, stellar activity is on a much smaller scale, hence, it has a smaller impact in terms of both the detectability and the true habitability of the planet. Also, K-dwarfs are the quietest in terms of oscillations, and granulation noise. In spite of this, there is a dearth of planets in the habitable zone of K-dwarfs due to a lack of observing programs devoted to this parameter space. In response to a call for legacy programs of the Calar Alto observatory, we have initiated the first dedicated and systematic search for habitable planets around these stars: K-dwarfs Orbited By habitable Exoplanets (KOBE). This survey is monitoring the radial velocity of 50 carefully pre-selected K-dwarfs with the CARMENES instrument over five semesters, with an average of 90 data points per target. Based on planet occurrence rates convolved with our detectability limits, we expect to find 1.68 ± 0.25 planets per star in the KOBE sample. Furthermore, in half of the sample, we expect to find one of those planets within the habitable zone. Here, we describe the motivations, goals, and target selection for the project as well as the preliminary stellar characterization. © 2022 EDP Sciences. All rights reserved
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