Auswahl der wissenschaftlichen Literatur zum Thema „G-087“
Geben Sie eine Quelle nach APA, MLA, Chicago, Harvard und anderen Zitierweisen an
Inhaltsverzeichnis
Machen Sie sich mit den Listen der aktuellen Artikel, Bücher, Dissertationen, Berichten und anderer wissenschaftlichen Quellen zum Thema "G-087" bekannt.
Neben jedem Werk im Literaturverzeichnis ist die Option "Zur Bibliographie hinzufügen" verfügbar. Nutzen Sie sie, wird Ihre bibliographische Angabe des gewählten Werkes nach der nötigen Zitierweise (APA, MLA, Harvard, Chicago, Vancouver usw.) automatisch gestaltet.
Sie können auch den vollen Text der wissenschaftlichen Publikation im PDF-Format herunterladen und eine Online-Annotation der Arbeit lesen, wenn die relevanten Parameter in den Metadaten verfügbar sind.
Zeitschriftenartikel zum Thema "G-087"
1
Panurach, Teresa, Ryan Urquhart, Jay Strader, Laura Chomiuk, Arash Bahramian, Craig O. Heinke, Thomas J. Maccarone, James C. A. Miller-Jones und Gregory R. Sivakoff. „Tracking the Enigmatic Globular Cluster Ultracompact X-Ray Binary X1850–087: Extreme Radio Variability in the Hard State“. Astrophysical Journal 946, Nr. 2 (01.04.2023): 88. http://dx.doi.org/10.3847/1538-4357/acc4bf.
Der volle Inhalt der QuelleAnnotation:
Abstract The conditions under which accreting neutron stars launch radio-emitting jets and/or outflows are still poorly understood. The ultracompact X-ray binary X1850–087, located in the globular cluster NGC 6712, is a persistent atoll-type X-ray source that has previously shown unusual radio-continuum variability. Here we present the results of a pilot radio-monitoring program of X1850–087 undertaken with the Karl G. Jansky Very Large Array, with simultaneous or quasi-simultaneous Swift/XRT data obtained at each epoch. The binary is clearly detected in the radio in two of the six new epochs. When combined with previous data, these results suggest that X1850–087 shows radio emission at a slightly elevated hard-state X-ray luminosity of L X ≳ 2 × 1036 erg s−1, but no radio emission in its baseline hard state L X ∼ 1036 erg s−1. No clear X-ray spectral changes are associated with this factor of ≳10 radio variability. At all detected epochs, X1850–087 has a flat to inverted radio spectral index, more consistent with the partially absorbed optically thick synchrotron of a compact jet rather than the evolving optically thick to thin emission associated with transient expanding synchrotron-emitting ejecta. If the radio emission in X1850–087 is indeed due to a compact jet, then it is plausibly being launched and quenched in the hard state on timescales as short as a few days. Future radio monitoring of X1850–087 could help elucidate the conditions under which compact jets are produced around hard-state accreting neutron stars.
2
Kweon, Suc-hyun, Jin sung Park und Byung Ha Park. „Sarcopenia and Its Association With Change of Bone Mineral Density and Functional Outcome in Old-Aged Hip Arthroplasty Patients“. Geriatric Orthopaedic Surgery & Rehabilitation 13 (Januar 2022): 215145932210928. http://dx.doi.org/10.1177/21514593221092880.
Der volle Inhalt der QuelleAnnotation:
Aim This study aimed to investigate the relationship between sarcopenia and change in bone mineral density (BMD) and functional outcome in hip arthroplasty patients. Methods: Among the 221 patients who had undergone hip arthroplasty, 147 patients were enrolled. All patients were divided into 2 groups according to presence of sarcopenia. Bone mineral density (BMD) at hospitalization and 1-year after surgery and Barthel index was measured at the time of before injury, hospitalization, 3 months and 1-year after surgery. Results: BMD at hospitalization showed .627 ± .082 (g/cm2) in Sarcopenia and .726 ± .059 (g/cm2) in Non-sarcopenia at femur (total) site ( P < .001), .531 ± .085 (g/cm2) vs .629 ± .057 (g/cm2) at femur neck site (P=.002), .715 ± .084 (g/cm2) vs .807 ± .058 (g/cm2) at lumbar (L1-L4) site ( P < .001). BMD at 1-year follow-up period, Sarcopenia showed .626 ± .082 (g/cm2) and Non-sarcopenia showed .725 ± .060 (g/cm2) at femur (total) site ( P < .001), .530 ± .085 (g/cm2) vs .629 ± .058 (g/cm2) at femur neck site ( P < .001), .715 ± .084 (g/cm2) vs .806 ± .058 (g/cm2) at lumbar (L1-L4) site ( P < .001). Change of BMD showed −.01 ± .25% for Sarcopenia and −.15 ± .47% for Non-sarcopenia in femur (total) site (P=.089), −.08 ± .63% vs −.01 ± 1.01% in femur neck site ( P = .058), .00 ± .09% vs −.12 ± .33% for each group in lumbar (L1-L4) site ( P = .052). Barthel index score showed 79.94 ± 5.66 for Sarcopenia and 84.74 ± 5.36 for Non-sarcopenia at pre-injury status ( P < .001), 33.89 ± 4.94 vs 33.87 ± 5.36 at the time of hospitalization ( P = .977), 57.42 ± 7.19 vs 60.06 ± 5.39 at 3 months follow up ( P = .015), 73.86 ± 5.94 vs 80.71 ± 4.81 for each group at 1-year follow up ( P < .001). Conclusions: Our study found that the sarcopenia showed lower BMD than the non-sarcopenia, but there was no significant difference of BMD change in the follow-up period. In addition, the sarcopenia showed poor functional results at all points except at the time of hospitalization.
3
Gourley, K. M., J. C. Woodworth, J. M. DeRouchey, M. D. Tokach, S. S. Dritz und R. D. Goodband. „087 Determining the phosphorus release for Natuphos E 5000 G phytase for nursery pigs“. Journal of Animal Science 95, suppl_2 (01.03.2017): 41. http://dx.doi.org/10.2527/asasmw.2017.087.
Der volle Inhalt der Quelle
4
Eryilmaz, G., C. Salcini, B. Onen Unsalver, I. Gogcegoz und E. Saglam. „P.1.g.087 Hyperammonemic encephalopathy caused by combined electroconvulsive therapy and valproate use“. European Neuropsychopharmacology 23 (Oktober 2013): S241. http://dx.doi.org/10.1016/s0924-977x(13)70374-2.
Der volle Inhalt der Quelle
5
Chapagain, Tika Ram, Surendra Prasad Yadav, Sabita Sharma und Surendra Lal Shrestha. „Improvement of Productivity and Quality of Nepalese Tomato Genotypes Using Black Polyethylene Film as Mulching Material“. Asian Journal of Agricultural and Horticultural Research 10, Nr. 2 (27.02.2023): 33–40. http://dx.doi.org/10.9734/ajahr/2023/v10i2224.
Der volle Inhalt der QuelleAnnotation:
An experiment was conducted to evaluate the effect of black plastic mulch on yield and other associated characters of promising tomato genotypes developed by the National Horticulture Research Centre, Nepal at the Directorate of Agricultural Research, Tarahara, Nepal, during the winter season of 2019. Nine tomato genotypes (HRDTOM 011, HRD 109, HRDTOM 035, HRDTOM 080, HRDTOM 079, HRDTOM 084, HRDTOM 085, HRDTOM 086, and Pusa Ruby as a check) were evaluated in a randomized complete block design (RCBD) with three replications. Genotypes were transplanted 60 cm apart. Analysis of variance showed significant differences for marketable fruits and yield per plant, average fruit weight, total marketable and unmarketable fruit yield, and total fruit yield. Among the tested genotypes, HARDTOM 011 developed the highest (174) number of marketable fruits per plant with the lowest (12.92 g) individual average fruit weight. In contrast, HRDTOM 080 produced the lowest (36) number of marketable fruits per plant with the highest (49.70 g) individual fruit weight. HRD 109 and Pusa Ruby provided the highest (69.74 t ha-1) and the lowest (38.51 t ha-1) marketable fruit yields, respectively. The highest total fruit yield was also obtained from the HRD 109. Similarly, HRDTOM 085 and HRDTOM 035 had the highest total soluble solids and fruit size, respectively. Firmness of the fruit and pH content did not differ among the genotypes. With the same genotypes and location (Tarahara), a 98% greater yield demonstrated that tomato production may be significantly boosted with the use of polyethylene film as a mulching medium in winter tomato production in Nepal.
6
Khlebnikova, N., und N. Krupina. „P.1.g.087 Long-term behavioural effects of neonatal administration of the dipeptidyl peptidase-IV inhibitors diprotin A and sitagliptin“. European Neuropsychopharmacology 24 (Oktober 2014): S254. http://dx.doi.org/10.1016/s0924-977x(14)70398-0.
Der volle Inhalt der Quelle
7
Scheidt, Peter C., Barry I. Graubard, Howard J. Hoffman, Dolores A. Bryla, Karin B. Nelson, Deborah G. Hirtz und Lawrence M. Gartner. „Intelligence at Six Years in Relation to Neonatal Bilirubin Level: Follow-up of The National Institute of Child Health and Human Development Clinical Trial of Phototherapy“. Pediatrics 87, Nr. 6 (01.06.1991): 797–805. http://dx.doi.org/10.1542/peds.87.6.797.
Der volle Inhalt der QuelleAnnotation:
Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (β = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity.
8
Wong, Ka-Chun, Wai-Yin Pang, Xin-Lun Wang, Sao-Keng Mok, Wan-Ping Lai, Hung-Kay Chow, Ping-Chung Leung, Xin-Sheng Yao und Man-Sau Wong. „Drynaria fortunei-derived total flavonoid fraction and isolated compounds exert oestrogen-like protective effects in bone“. British Journal of Nutrition 110, Nr. 3 (10.01.2013): 475–85. http://dx.doi.org/10.1017/s0007114512005405.
Der volle Inhalt der QuelleAnnotation:
Drynaria fortunei (Kunze) J. Sm. (DF), a Chinese herb commonly used for the treatment of bone fracture, was previously shown to exert anabolic effects on bone. However, its active ingredients as well as the mechanisms of action are far from clear. The present study aimed to characterise the bone anabolic effects of DF flavonoid fraction (DFTF) in ovariectomised (OVX) mice and to determine if DFTF and its isolated compounds exert oestrogen-like effects in rat osteoblast-like UMR-106 cells. Young OVX C57/BL6J mice were treated orally with DFTF (0·087, 0·173 or 0·346 mg/g per d), 17β-oestradiol (2 μg/g per d) or its vehicle for 6 weeks. Serum and urine samples were collected for biochemical marker analysis. Bones were collected for computed tomography analysis. UMR-106 cells were treated with DFTF and isolated compounds naringin, (2S)-5,7,3′,5′-tetrahydroxy-flavonone 7-O-neohesperidoside (compound 1) and 5,7-dihydroxychromone 7-O-neohesperidoside (compound 2). DFTF exerted dose-dependent effects in improving bone mineral densities as well as bone strength at the femur, tibia and lumbar spine L1 in OVX mice. DFTF and the three isolated compounds stimulated osteoblastic cell proliferation and alkaline phosphatase activities in a dose-dependent manner. In addition, they stimulated the ratio of osteoprotegrin and receptor-activator NF-κB ligand mRNA expression, suggesting their involvement in inhibiting osteoclastogenesis. These stimulatory effects on osteoblastic functions were abolished in the presence of oestrogen receptor (ER) antagonist, ICI 182780. The present results suggested that DFTF is effective in protecting against OVX-induced bone loss in mice, and its actions in regulating osteoblastic activities appear to be mediated by ER.
9
Elimam, M. E., und E. R. Ørskov. „Factors affecting the fractional outflow of protein supplements from the rumen 3. Effects of frequency of feeding, intake of water induced by the addition of sodium chloride, and the particle size of protein supplements“. Animal Science 40, Nr. 2 (April 1985): 309–13. http://dx.doi.org/10.1017/s0003356100025423.
Der volle Inhalt der QuelleAnnotation:
ABSTRACTFour experiments were conducted with lactating dairy cows offered a hay and concentrate diet (0·5:0·5) to investigate the effects of (1) the frequency of feeding a completely mixed diet (experiment 1) compared with feeding the concentrate fraction and the roughage fraction separately (experiment 2), and (2) the addition of sodium chloride to a completely mixed diet (experiment 3), on the fractional rate of outflow (FRO) of chromium (Cr)-treated fish meal from the rumen, and on milk yield and composition. The cows were offered the diet at either twice the maintenance requirement (experiments 1 and 2), or 2-5 x maintenance (experiment 3) in a 4 x 4 Latin-square design. The effect of the particle size of the Cr-treated soya bean meal was investigated in experiment 4.The frequency of feeding of the completely mixed diet had no significant effect on the rate of outflow of Cr-treated fish meal from the rumen, or on milk yield or composition. FRO per h were 0·070, 0·085, 0·079 and 0·086 when the diet was offered once, twice, four times or 12 times per day respectively. Increasing the frequency of feeding of the concentrate fraction of the diet had no significant effect on FRO. FRO per h were 0·073, 0·078, 0·081 and 0·081 when the concentrate fraction was offered once, twice, four times or 12 times per day respectively.The addition of NaCl to the diet significantly increased water intake (P < 0·001), but had no significant effects on FRO or milk yield. FRO per h were 0·074, 0·075, 0·076 and 0080 when 50, 265, 529 or 794 g of NaCl were added into the diet respectively. The respective intakes of water were 66·6, 74·1, 88·4 and 101·6 kg/day.The FRO per h of fine particles of Cr-treated soya bean meal was 0·085 and for coarse particles, 0·096. The difference was not significant.
10
Mills, S. J., A. R. Kampf, J. Sejkora, P. M. Adams, W. D. Birch und J. Plášil. „Iangreyite: a new secondary phosphate mineral closely related to perhamite“. Mineralogical Magazine 75, Nr. 2 (April 2011): 327–36. http://dx.doi.org/10.1180/minmag.2011.075.2.327.
Der volle Inhalt der QuelleAnnotation:
AbstractIangreyite, ideally Ca2Al7(PO4)2(PO3OH)2(OH,F)15·8H2O, is a new mineral (IMA2009-087) from the Silver Coin mine, Nevada, USA and the Krásno ore district, Horní Slavkov, Czech Republic. At Silver Coin, iangreyite occurs as thin, colourless to white or cream, hexagonal tablets up to 0.4 mm in diameter and 0.02 mm thick associated with meurigite-Na, plumbogummite, kidwellite, lipscombite. strengite, chalcosiderite, wardite, leucophosphite, wavellite, goethite, barite, quartz and F-rich perhamite. At Krásno, white, yellowish or light pink iangreyite coatings consist of 0.3 mm wide clusters of minute and very thin intergrown tabular crystals with a maximum diameter of 0.2 mm. Individual iangreyite crystals are transparent with a vitreous lustre, while iangreyite clusters tend to be pearly and translucent. The estimated hardness is 3 on the Mohs scale, the fracture is irregular and the mineral is non-fluorescent under SW and LW ultraviolet light. Individual crystals are somewhat flexible and there is perfect cleavage on ﹛001﹜. The density (Silver Coin), measured by the sink-float method in an aqueous solution of sodium polytungstate, is 2.46(3) g/cm3, while the calculated density is 2.451 g/cm3. Crystals from Silver Coin are uniaxial (+), with the indices of refraction: ε = 1.544(2) and s = 1.554(2), measured in white light, and are non-pleochroic. The empirical formula for iangreyite from Silver Coin (calculated on the basis of 39 anions per formula unit) is: Ca1.42K0.22Na0.09Ba0.03 Sr0.01Al6.51Mg0.09Fe0.02Cu0.01Zn0.01P3.81F5.24H30.21O33.76, while the empirical formula from Krásno is: Ca2.15K0.10Na0.01Ba0.02Sr0.12Al6.28Mg0.01Fe0.12Cu0.08Zn0.01P3.64Si0.43F4.65H29.62O34.35. Iangreyite is trigonal, space group P321 and Z = 1, with the unit-cell parameters (Silver Coin): a = 6.988(1), c = 16.707(3) Å and V= 706.5(2) Å3 and (Krasno): a = 6.989(1), c = 16.782(4) Å and V = 709.8(2) Å3. The structure of iangreyite, modelled from powder data, consists of blocks of the crandallite-type structure that are interconnected along c via corner-sharing of crandallite-block PO4 tetrahedra with A1O2(OH)3 bipyramids. This linkage generates large channels along [110] bounded by 10-member rings of octahedra, tetrahedra and trigonal biyramids, that are occupied by Ca and water molecules.
Dissertationen zum Thema "G-087"
1
Rigo, Riccardo. „The fine architecture of guanine-rich regions within oncogene promoters“. Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3427311.
Der volle Inhalt der QuelleAnnotation:
Suppression of oncogenes transcription represents an ideal tool to integrate the currently available therapeutics to treat several cancer types and to overcome the potential occurrence of resistance. An experimentally validated mechanism of intervention is represented by the induction/stabilization of G-quadruplex structures in genes promoter by small molecules. G-quadruplexes are DNA non-canonical secondary structures consisting of stacked G-quartets, cyclic arrangements of four guanine residues held together by Hoogsteen hydrogen bonds and stabilized by a central cation. At the moment, none of the identified G-quadruplex ligands reached the clinic. Several reasons can contribute to this poor outcome comprising both the plastic structural features of nucleic acids and the multiple metabolic pathways which might be affected when a small molecule interacts with G-quadruplex structures. Thus, one of the major issues lies on the proper structural analysis of targeted G-quadruplex.
To overcome this bias, in this Ph.D.’s thesis kinetic and thermodynamic behaviours of G-quadruplexes have been characterized to obtain an improved description of these structures as potential pharmaceutical targets. The study has been focused on G-rich sequences within c-KIT and EGFR oncogene promoters.
By applying a set of complementary structural and biophysical approaches, the folding pathways of these G-quadruplexes and influence of flanking regions in terms of structural stability and folding rearrangement have been described. The obtained information indicates that the promoter architecture might be not properly derived by analysis of minimal G-quadruplex forming sequences at the thermodynamic equilibrium, commonly used for screening assayes. Indeed, reported data suggest the existence of different unique mechanisms/pathways involved in the regulation of these oncogenes transcription which comprise kinetically favored folding intermediates or unprecedented structural arrangements.
The final outcome of Ph.D.‘s project is a deeper understanding of nucleic acid tridimensional arrangement of EGFR and c-KIT promoters which might help in setting up new drug-design programs based on models of G-quadruplex target more closely related to the physiological ones.
2
Da, Ros Silvia. „Oncogene c-KIT: promoter region and downstream effectors as novel therapeutic targets“. Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3424508.
Der volle Inhalt der QuelleAnnotation:
An attractive anticancer strategy deals with the impairment of the functions of selected genes relevant for cell proliferation. Among them an interesting target is represented by KIT. c-KIT - V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog - is a tyrosine kinase receptor involved in the regulation of cell survival and proliferation as well as in progression of some tumors. Its expression has been confirmed to be crucial for leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas often associated to c-kit mis-regulation. Also the most common skin cancer in domestic dog, mast cell tumor (MCT), is linked to a mutation and/or to an over-expression of c-kit, thus supporting dog as an excellent animal model.
In this work we explore two strategies to suppress the cell growth activity of this oncogene.
The first one was based on the downregulation of gene expression by induction of non-canonical DNA structures at promotorial level. Indeed, in this region of the human oncogene KIT two guanine-rich sequences (KIT1_man and KIT2_man) were identified. Here, we characterized the canine KIT promoter region in terms of sequence and conformational equilibria in physiologically relevant conditions. Our results demonstrate that the conformational features of the canine KIT1 sequence are substantially shared with the human one whereas an altered distribution among several folded conformations characterizes the two isoforms identified in dog-derived KIT2 sequences.
These structural diversities identified KIT1 and KIT2 as two potential distinct targets, which means that G-4 ligands can be designed to preferentially bind human/dog sequences. Thus, an “in house” library of compounds belonging to different chemical scaffolds (i.e., anthracene, anthracenedione, indole, quinoline, isoquinoline, fluorenone and heterocyclic diamidines derivatives) was screened for the recognition of these particular folding. Three promising G4-ligands, belonging to anthracenedione (Bal1,5 – Bapl2,6) and anthracene (Bis1,8) families, were selected and different techniques (Fluorescent Intercalator Displacement, Fluorescence melting studies, CD titrations, Surface Plasmon Resonance and Polymerase Stop Assay) were applied to fully dissect their interaction with KIT-related sequences. Our results showed that Bal1,5 is an efficient G-4 binder towards all the tested sequences, while Bapl2,6 and Bis1,8 preferentially recognize KIT2 sequences. Interestingly, a parallel level of cytotoxicity and suppression of KIT production was observed in cells treated with Bal1,5.
In the second approach, downstream effectors of c-KIT pathway were considered as putative therapeutic targets. In particular we focused on a cytoplasmic tyrosine kinase FER.
During the third year of my PhD I spent 7 months at Centre de Recherche en Cancérologie de Marseille (France) in the Dr P. Dubreuil’s team. In this period we worked to confirm a potential tumor suppressor role of FER. For this purpose mouse embryonic fibroblasts MEFs wild type and knockout for fer immortalized with SV40 were used. Removing fer, an uncontrolled growth was observed for KO MEFs in the contact inhibition test. However, at the moment a detailed description of the molecular events was not designed. Indeed no defined differences between molecular mechanisms, related to protein complexes involved in cell adhesion mechanisms, were observed between wt and KO MEFs.
In conclusion, present results suggest that G-quadruplex structures at the promotorial level represent a promising therapeutic target in order to prevent oncogene KIT transcription. As far as FER is concerned, further studies are necessary to better define its possible tumor-suppressor role.Una delle promettenti strategie anticancro prevede il blocco delle funzioni di quei geni essenziali per la proliferazione cellulare. Tra questi geni c-KIT - V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog – costituisce un interessante bersaglio. c-KIT codifica per un recettore tirosin chinasico coinvolto nella regolazione della crescita e proliferazione cellulare nonché della progressione di alcuni tumori. E’ stato confermato che la sua espressione è cruciale in quelle forme di leucemia, mastocitosi, tumore gastrointestinale stromale e tumore ai polmoni associate a mancata regolazione di c-KIT. Anche il più comune tumore alla pelle nel cane – mast cell tumor MCT – presenta mutazioni e/o sovraespressione di c-KIT. Per questo il cane è considerato un solido modello animale. In questo lavoro vengono studiate due strategie al fine di impedire l’attività proliferativa di questo oncogene. La prima di queste strategie si basa sull’induzione di strutture non canoniche del DNA nella regione promotoriale al fine di ostacolare l’espressione genica. Infatti, nella regione promotoriale del gene c-KIT sono state identificate due sequenze ricche in guanine (KIT1_man e KIT2_man). In questo lavoro caratterizziamo la regione promotoriale del gene nel cane in termini di sequenza e di equilibri conformazionali in condizioni fisiologiche. I nostri risultati dimostrano che le caratteristiche conformazionali della sequenza KIT1 nel cane sono confrontabili con quelle nell’uomo. Le due isoforme di KIT2 identificate nel cane presentano invece una diversa distribuzione di conformazioni rispetto alla sequenza KIT2 nell’uomo. Queste diversità permettono di considerare KIT1 e KIT2 due distinti bersagli e quindi i possibili ligandi per G-4 possono essere sintetizzati in modo da riconoscere preferenzialmente l’una o l’altra sequenza. A tal fine una libreria di composti di strutture chimiche diverse (derivati di antracene, antracenedione, indolo, chinolina, isochinolina, fluorenone e di diammidi eterocicliche) è stata testata per valutarne la capacità di legame a queste particolari sequenze G-4. All’interno di questa libreria sono stati selezionati 3 composti, due derivati dell’antracenedione (Bal1,5 e Bapl2,6) e uno dell’antracene (Bis1,8). Tecniche diverse - Fluorescent Intercalator Displacement, Fluorescence melting studies, titolazioni CD, Surface Plasmon Resonance e Polymerase Stop Assay – sono state usate per comprenderne l’interazione con le strutture G-4 di KIT. Dai risultati emerge che Bal1,5 lega efficientemente tutte le sequenze testate, mentre Bapl2,6 e Bis1,8 legano preferenzialmente le sequenze KIT2. Inoltre è stato registrato un livello simile di citotossicità e blocco della trascrizione di KIT nelle cellule trattate con Bal1,5. Nel secondo approccio, invece, gli effettori a valle di c-KIT vengono considerati come potenziali bersagli terapeutici. Tra questi effettori abbiamo studiato FER. Durante il 3° anno del mio Dottorato ho trascorso 7 mesi presso il Centre de Recherche en Cancérologie de Marseille (France) nel gruppo del Dr. P. Dubreuil. Lo scopo di questo progetto era quello di confermare la funzione onco soppressiva di FER. Per questo motivo sono stati usati fibroblasti da embrioni di topo MEFs alcuni nativi e altri privati del gene fer. Entrambe queste due tipologie di fibroblasti sono state immortalizzate con il retrovirus SV40. Silenziando il gene fer è stata osservata una crescita incontrollata dei fibroblasti nel test di inibizione di contatto. Ma al momento non è stato possibile spiegare questa osservazione a livello molecolare. Infatti non sono state osservate differenze nei meccanismi molecolari tra le cellule con fer e quelle in cui il gene è stato silenziato. In conclusione, i risultati qui presentati dimostrano che le strutture G-quadruplex a livello promotoriale costituiscono un promettente bersaglio al fine di prevenire la trascrizione dell’oncogene KIT. Per quanto riguarda FER, sono invece necessari ulteriori studi per avvalorare il suo ruolo onco soppressivo.
3
Marson, Giuseppe. „DNA, variations on the theme“. Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3423105.
Der volle Inhalt der QuelleAnnotation:
Molecular biology's central dogma, laid down in 1950s, affirmed that genetic information flows from DNA to RNA to protein synthesis. For a long time, the first element of this logic scheme, DNA, was regarded as inactive molecule with the sole purpose to act as a repository of genetic code. Indeed, the molecular dialogue between DNA and proteins has been generally interpreted as an univocal relationship between an inert partner (nucleic acid) and a versatile one (proteins), that remodels DNA as a clay object. Rather, has been emerged that each kind of interactions between macromolecules requires a mutual structural adaptation and chemical complementarity.
As in Kurosawa’s classic movie “Rashomon” (1950) the same central event, a heinous crime, is recalled from the differing perspective of each character (a bandit, a samurai, samurai’s wife and a woodcutter) this present study aims to highlight some different, but complementary, aspects of the full dynamic repertoire of DNA macromolecules. In the first part of this thesis, I will demonstrate that DNA, according to a peculiar three dimensional arrangement, is not only a simple recipe for proteins production but something more. In particular, I will focus on guanosine quadruplex structure, a not canonical B-form of DNA could be described through multiple points of view.
On one side, synthetic guanosine quadruplex can act as “smart” biomolecules able to recognize multiple targets, with potential implications both as diagnostic as well as therapeutic agent. This short DNA/RNA sequences, called aptamers, according to a unique molecular flexibility, are able to recognize and bind a broad range of targets with specificities reminiscent those exhibited by antibodies. As working model, here I will present a detailed characterization in vitro of not physiological guanosine rich sequences able to bind human thrombin, a protein of physiological and pathological relevance. Our research was aimed to describe the relative role of the structural modules composing their molecular architecture. This allowed us to propose a structure activity relationship of synthetic G quadruplex aptamers, in order to fully rationalize and optimize their binding property.
On the other side, G-quadruplex forming sequences are also found in human genome. Some of them have been described as unique biochemical on/off switch able to regulate tumorigenic pathways.
In particular, the expression of the oncogene c-Myc is controlled through the formation of non–B-form DNA structures within its promoter. The conformational shift of this promoter between a transcription inactive form (G-quadruplex form) to an active one (a canonical double strand form) is strictly regulated by several nuclear proteins. In the second section I’ll present a study concerning the heterologous expression, the purification scheme of the resulting products and the biochemical characterization of the functional domains of human nucleolin, a nucleolar protein that is able to inhibit c-Myc oncogene transcription by a peculiar recognition of its promoter in a G quadruplex form. This approach was pursued to deeper clarify the mechanism of this binding event. Doubtless, this represents a promising goal in order to develop new selective and effective chemotherapy drugs.
Although revolutionary, the idea that genetic information was encoded only by DNA sequence, in a protein-free mechanism has been appeared definitely too simplistic. Indeed, in organisms with nuclei chromosomal DNA is organized along with protein templates (histones), forming a complex called chromatin. This is target of diverse array of posttranslational modifications that modulate the interaction among chromatin-associated proteins, which ultimately dictate dynamic transitions between transcriptionally active (euchromatin) or transcriptionally silent chromatin states (heterochromatin). In the last section, I will focus on the structural insights standing on the recognition event between a modified histone N-terminal tail and a specialized ‘effector’ protein (ORC1b), generally known for its role in pre-replication complex assembly.
The identification of the molecular details that clarify how distinct protein modules are able to recognize specific histone modifications is a critical step to understanding how chromatin dynamics influence fundamental DNA-templated processes such as transcription, DNA recombination and DNA repair. In particular, our results identify the tandem PHD-BAH domains of Arabidopsis thaliana ORC1b as a novel unmethylated-lysine-binding module, thereby establishing the first direct link between histone methylation grade and the epigenetic role of ORC1b, previously known as a transcriptional regulation factor only for a series of specific interactions with silencing regulators.Il dogma fondante della biologia molecolare afferma che le informazioni genetiche sono decodificate attraverso un ordinato flusso logico, che parte dal DNA e passando attraverso il RNA arriva alla sintesi proteica. Per lungo tempo, all’interno di questo assunto, il DNA è stato esclusivamente considerato come il deposito biochimico delle informazioni genetiche. Con un ottica totalmente differente, in questo lavoro di tesi di dottorato presenterò tre aspetti, differenti ma complementari dell’intero repertorio funzionale del DNA. La prima sezione di questa tesi è rivolta ad un dettagliato studio degli aptameri leganti la trombina, ovvero sequenze non fisiologiche di DNA capaci di riconoscere selettivamente il target proteico in funzione di una specifica conformazione formata da quartetti di polideossiguanosine. Mediante una precisa caratterizzazione biofisica dei polimorfismi strutturali e dei profili di legame abbiamo potuto proporre delle solide ipotesi sul ruolo degli elementi modulari che ne compongono l’architettura molecolare, al fine di razionalizzare ed eventualmente incrementarne la capacità di riconoscimento del substrato proteico. Diversamente, porzioni di DNA capaci di autoassemblarsi in quartetti di guanosina sono state identificate all’interno del genoma umano. Alcune tra queste sono state descritte come straordinari interruttori biochimici capaci di regolare i processi tumorali. Nello specifico, l’espressione dell’oncogene c-Myc è fortemente controllata attraverso la formazione di strutture di DNA non canoniche all’interno del suo promotore. Questo equilibrio conformazionale del promotore tra una forma inattiva trascrizionalmente (struttura a quartetti di guanosina) ed una attiva (la canonica forma a doppia elica) è assistito e modulato da svariate proteine nucleari. Nella seconda parte del mio lavoro di tesi presenterò uno studio inerente all’espressione eterologa, la purificazione proteica del prodotto ricombinante e la caratterizzazione biochimica dei domini funzionali della nucleolina umana, una proteina nucleolare capace di inibire la trascrizione dell’oncogene c-Myc attraverso un peculiare riconoscimento del suo promotore nella sua forma silente. Questo approccio è stato perseguito al fine di porre le prime basi per l’identificazione del meccanismo di riconoscimento proteina – DNA, fortemente implicato nella soppressione tumorale. Anche se rivoluzionaria, l’idea che le informazioni genetiche siano codificate solamente all’interno della sequenza del DNA, secondo un meccanismo che contempla le proteine solo come “lettori” di questo codice, appare un concetto decisamente desueto. Il DNA cromosomiale, infatti, è organizzato su strutture proteiche (istoni) per le quali è stato esclusa una funzione esclusivamente “strutturale”. E’ stato dimostrato, infatti, che tali proteine sono soggette ad una serie di modifiche post trasduzionali che regolano attivamente l’attivazione e l’inibizione della trascrizione del DNA. Nell’ultima sezione presenterò uno studio finalizzato a chiarire i dettagli molecolari del riconoscimento tra un frammento istonico e i domini funzionali dell’effettore atORC1b (origin recognition complex 1b di arabidopsis thaliana). L’identificazione dei meccanismi molecolari mediante i quali distinti moduli proteici riconoscono le specifiche modificazioni istoniche rappresenta un passaggio chiave nella comprensione di fondamentali processi cellulari come la trascrizione, la ricombinazione cromosomiale e la riparazione del DNA. Nello specifico, il nostro studio ha evidenziato come i domini PHD e BAH dell’ORC1b, opportunamente combinati, possono agire come moduli di lettura del frammento N-terminale dell’istone 3 nella sua specifica forma non metilata. Tale evidenza, per la prima volta, dimostra una correlazione diretta tra il grado di metilazione dell’istone e il ruolo epigenetico dell’ORC1b, precedentemente noto come regolatore indiretto della trascrizione solamente in funzione di interazione specifiche con fattori eterocromatinici.
4
Ribaudo, Giovanni. „Synthesis, characterization and biophysical evaluation of novel G-Quadruplex stabilizing agents“. Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3423890.
Der volle Inhalt der QuelleAnnotation:
The so-called quadruplex forming DNA sequences, with their peculiar feature of being particularly rich in guanines, can be found in many portions of both human and non-human genome. Considering the human genetic information, while one of the traditional localization of these sequences, the telomere, still represents an appealing target in anticancer therapy through indirect telomerase inhibition, many novel involvements are emerging in other portions of the genome. It has to be considered, first of all, that more than 376000 guanine rich sequences were identified in the human genome, with a preferential localization in some regions represented by proto-oncogenes. In this context Gquadruplexes could act as switches turning on and off, or regulating, the transcription of some sequences, according to the fact that structured DNA usually is not processed by the involved enzymes. G-quadruplexes have also been described over the years to be involved in many other key cellular processes such as chromosomal alignment, replication, transcription, genome recombination. This year another important piece of information was added to the quest for G-quadruplex stabilizers as antiviral agents. BRACO-19, an already described acridine-based stabilizing agent, was reported to show anti HIV-1 effects. These attractive targets boost the interest for the discovery of novel G-quadruplex stabilizer and
for the investigation of their binding properties with different nucleic acids (DNA, RNA or hybrids), expanding their possible application from the anticancer to the antiviral field.
The research project is aimed to the synthesis of small molecules acting as potential stabilizers of this peculiar super molecular arrangement reported to be relatively easily formed by guanine-rich sequences, such as the ones in telomeres. The molecules that were synthesized during this project share, in general, the common structural motifs of previously reported G-quadruplex stabilizing agents (athraquinones, anthracenes, naphtalenediimides, acridines) and are inspired to a compound previously synthesized by the research group of Prof. Zagotto that showed a remarkable activity in stabilizing Gquadruplex DNA.
Enhanced techniques such as molecular modeling, fluorescence melting, ESI-MS binding studies and ion mobility MS were then employed for the investigation of the capability of the synthesized molecules of interacting with, and stabilizing, G-quadruplex DNA. These complementary techniques enlightened the relevance of some structural aspects of the synthesized compounds, such as conformational properties, in influencing the efficacy of the DNA stabilization. The results allow to describe preliminary structure-activity relationship data and some promising compounds were finally disclosed.Sequenze di DNA particolarmente ricche di guanine e potenzialmente in grado di formare strutture di tipo G-quadruplex sono diffuse sia nel genoma umano che in quello di altre specie. Il telomero ne rappresenta un esempio ormai largamente discusso e costituisce tuttora un interessante obiettivo nella strategia antitumorale basata sulla inibizione indiretta della telomerasi tramite stabilizzazione di G-quadruplex. Va comunque considerato che nel genoma umano sono state individuate oltre 376000 sequenze di questo tipo, ossia con la peculiarità di essere ricche in guanine, con una localizzazione preferenziale in alcune regioni rappresentate dai proto-oncogeni. In questo ambito i G-quadruplex potrebbero agire come interruttori di accensione e spegnimento, o di regolazione, della trascrizione di tali sequenze; il DNA strutturato generalmente non viene infatti processato dagli enzimi coinvolti. I G-quadruplex sono stati descritti in letteratura quali regolatori di molti processi cellulari di rilievo come l'allineamento cromosomico, la replicazione, la trascrizione e la ricombinazione del genoma. Recentemente, inoltre, la ricerca nell’ambito della stabilizzazione del G-quadruplex si è affacciata all’ambito antivirale. Ad esempio BRACO-19, uno stabilizzatore di G-quadruplex a struttura acridinica, ha mostrato effetti anti-HIV-1 ed in generale la capacità di interagire con G-quadruplex costituiti da acidi nucleici a base di DNA, RNA o ibridi. Lo scopo del progetto di ricerca è costituito dalla sintesi di piccole molecole che agisconocome potenziali stabilizzatori di acidi nucleici strutturati in G-quadruplex. Le molecole che sono state sintetizzate nel corso di questo progetto condividono, in generale, alcuni motivi strutturali comuni a composti riportati in letteratura quali antrachinoni, antraceni, naftalenediimmidi, acridine; gli schemi di sintesi sono inoltre stati progettati per riprendere le caratteristiche chimico-strutturali di un composto precedentemente sintetizzato dal gruppo di ricerca del Prof. Zagotto che ha mostrato una notevole capacità nello stabilizzare il DNA G-quadruplex. Tecniche avanzate e complementari quali modellistica molecolare, fluorescence melting, studi di legame ESI-MS e ion mobility MS sono state impiegate per lo studio della capacità delle molecole sintetizzate di interagire con il DNA e di stabilizzare tale particolare struttura. Gli esperimenti hanno messo in luce il ruolo di alcuni aspetti strutturali dei composti sintetizzati, come ad esempio le proprietà conformazionali, nell'influenzare l'efficacia nella stabilizzazione del quadruplex. La ricerca ha permesso infine di ottenere interessanti informazioni di relazione struttura-attività e di inviduare composti con una promettente capacità di stabilizzare il G-quadruplex.
5
Pivetta, Claudia. „Nuovi agenti antineoplastici basati sull'inibizione selettiva della DNA telomerasi“. Doctoral thesis, Università degli studi di Padova, 2008. http://hdl.handle.net/11577/3425160.
Der volle Inhalt der QuelleAnnotation:
In the search for new anticancer drugs a major goal is to devise more efficient and selective strategies to reduce typical side effects of traditional chemotherapy.
Telomerase represents an attractive and selective target. It is expressed in 80-90% of tumor cells whereas its expression in non-malignant cells is limited to stem cells and to hematopoietic system cells. Telomerase inhibition should lead to cancer cells death, with minor side effects on somatic cell lines.
Several strategies were developed in order to interfere with telomerase activity and affect cancer cell death pathways. Among potential targets we considered the substrate of the enzyme, telomeric DNA. It consists in a variable number of tandem repeats of G-rich sequences which can fold into G-quadruplex structures.
G-quadruplex formation inhibits telomerase activity by preventing enzyme- DNA recognition. In addition, it forms telomere uncapping cytotoxic processes.
In this work we examined several new compounds as G-quadruplex stabilizers, hence indirect inhibitors of telomerase activity and telomere damage inducers.
Enzyme inhibition and selective interaction with quadruplex vs. double stranded DNA were assessed by biophysical and biochemical techniques such as electromobility shift assay, TRAP assay, UV spectroscopy, fluorescence and circular dichroism.
Cytotoxic effects were evaluated by cell proliferation assays on different tumor cell lines.
Tested compounds belong to three different classes: a library of 2,6 bis-substituted anthraquinones, a series of compounds related to bisantrene and perylene derivatives structurally related to PIPER, a well known G-quadruplex stabilizer.
All compounds were designed to understand SA relationships. In particular the following features were considered:
v extension of the aromatic surface;
v number, nature, length and location of side chains.
For all tested compounds we were able to show a satisfactory correlation between telomerase inhibitory properties and ability to stabilize G-quadruplex structures; the most active binders were also able to induce G-quadruplex from random structures. Finally, data obtained by experiments on cell lines confirmed molecular results.
As far as SA relationships, we highlighted the importance of the extension of the aromatic nucleus and positively charged side chains to obtain a good interaction with G-4 arrangements. We were able to define some structural requirements to improve G-quadruplex stabilization and G-quadruplex-duplex selectivity (based on differences between double stranded and G-quadruplex DNA).
An anthracene nucleus extended by planar groups in the side chains produce similar telomerase inhibitory properties and G-quadruplex stabilization effects if compared to perylene derivatives.
The need for at least two side chains clearly emerged; however an increment in G-quadruplex vs. duplex selectivity could be obtained by incrementing the number of side chains in the aromatic system (based on the different number of grooves in duplex and G-quadruplex DNA structures).
A further point concerns the role of the distance between charged groups in side chains and planar surface of compounds.
Location of side chains substantially affects telomerase inhibitory properties, G-4 stabilization, G-quadruplex-double stranded DNA selectivity and interaction mode with the nucleic acid.
In the study of bisantrene analogues we identified 1,5 positions as the most effective in telomerase inhibition and G-quadruplex stabilization. 2,6 and 2,7 bis- substituted derivatives showed also good anti-telomerase properties but cellular studies suggest a greater cytotoxic effects probably due to a different DNA interaction mode.
SAR data will be used to develop, by rational design, new selective telomerase inhibitors.
6
Di, Antonio Marco. „New Molecular Devices for Selective Structural Modifications of G-Quadruplex Folded Oligonucleotides“. Doctoral thesis, Università degli studi di Padova, 2011. http://hdl.handle.net/11577/3427493.
Der volle Inhalt der QuelleAnnotation:
The attention around selective recognition of G-Quadruplex has steadily grown during the past 10 years. G-4 are non-canonical DNA structures which can be generated from the self-assembling of guanine rich oligonucleotides. Such an interest is justified by the fact that it is widely recognized that the above structures could act as regulators of biological processes in vivo.
In fact, there are several examples of G-Quadruplexes stabilization, by small molecules or engineered antibodies, which is translated into a strong influence of the biological process in which the oligonucleotide is involved. The inhibition of telomerase enzyme as well as the gene transcriptional alteration induced by the stabilization of such structures, represent the most important applications, together with the more recently studied effect on translation mediated by G-4 RNA structures. This makes G-Quadruplex a real therapeutic target useful for the developing of new antitumor drugs. The aim of this work is to develop a new generation of G-4 ligands capable to undergo alkylation triggered by biocompatible protocols. The key aspect of this idea is to regulate the alkylation process, exploiting mild chemical or physical modifications, in order to temporally separate it from the reversible recognition.
These molecules would therefore act as molecular devices capable of pre-concentration onto the target and stabilizing the complex through non covalent interactions. These ligands after activation of the masked electrophile are capable to generate the alkylating specie and therefore to achieve a strong covalent interaction.
These features would induce an irreversible damage which would not be repaired by the common cellular process, enhancing the effectively drug potency in biological response terms.
The basic idea is to exploit molecular recognition properties of already described ligands and tethering to them a masked electrophile. The releasing of the alkylating specie will be achieved exploiting physical or chemical triggers. Such molecules would represent a brand new class of irreversible G-4 ligands which has never been conceived before.
The common features that such a class of ligands must have are:
1) A wide electron poor and flat surface, which confers molecular recognition properties, exploiting superficial π stacking interactions with the biological target.
2) A precursor of an alkylating specie, triggerable by mild physical and chemical activation protocols, possibly exploitable under physiological conditions
3) A moiety which can be easily modified through substrate interactions or chemical activation. Such moiety will represent the trigger of the alkylating reactivity.
In more details, we had focused our attention on the chemical functionalization of Naphthalimide (NI) and Naphthalendiimide (NDI) derivatives, which both are good G-4 binders according to literature. Quinone Methide precurors (QM) electrophiles have been tethered to the above molecules.
QM based alkylating species are particularly suitable for this project because they can be generated from very stable precursors through several biocompatible activation protocols. Moreover, their reactivity could be tuned changing the electronic nature of the phenolic precursor.
In this PhD thesis we describe the synthesis, the reactivity and the study concerning the interaction of the synthesized molecules with oligonucleotides capable of G-4 folding.
Particular emphasis will be given to the consequences induced by the alkylation damage with potentially achievable application both therapeutic and diagnostic. Moreover, we will discuss a parallel project developed during a period spent in the Cambridge University in Prof. Balasubramanian’s reaserch group.Nell’ultimo decennio un sempre più crescente interesse è stato rivolto nei confronti del riconoscimento selettivo dei quartetti di guanina (G-quadruplex), strutture supramolecolari in grado di auto-assemblarsi in condizioni fisiologiche da oligonucleotidi ricchi di residui guaninici. La ragione di ciò risiede nel fatto che tali strutture sembrano agire come regolatori di processi a livello cellulare. Infatti, esistono svariati esempi in cui, soprattutto in vitro, molecole o anticorpi in grado di riconoscere e stabilizzare quartetti di guanina influenzino drasticamente il processo biologico in cui l’oligonucleotide stesso è implicato. L’inibizione indiretta della telomerasi e gli studi dell’effetto sulla trascrizione di oncogeni ne rappresentano le applicazioni più importati, assieme ai più recenti effetti sulla traduzione di RNA. Ciò rende G-quadruplex un vero e proprio target terapeutico per lo sviluppo di nuove terapie antitumorali. Questo lavoro nasce con lo scopo di creare una nuova generazione di leganti di G-4 che manifestino proprietà alchilanti attivabili mediante protocolli biocompatibili. Proprietà alchilanti non intrinseche, ma attivabili attraverso modifiche chimiche e fisiche, permetterebbero un controllo temporale del processo di alchilazione. Tali molecole agirebbero pertanto da veri e propri dispositivi molecolari preconcentrandosi sul target e stabilizzando il complesso attraverso interazioni non covalenti per poi, mediante attivazione, generare la specie alchilante così da ancorare fortemente la molecola all’oligonucleotide. Queste caratteristiche renderebbero il danno indotto irreversibile o non riparabile dai comuni processi cellulari, aumentando notevolmente l’efficacia di azione in termini di effetti farmaco-biologici. L’idea pertanto è quella di sfruttare le proprietà di riconoscimento di alcuni tra i leganti noti in letteratura equipaggiandoli, però, con una specie alchilante silente, il cui rilascio può essere controllato temporalmente mediante azione fisica o chimica. Questo nuovo tipo di molecole rappresenterebbe pertanto una classe di leganti irreversibili di G-4, mai progettata in precedenza. Per far ciò la molecola da sintetizzare deve possedere: 1) una superficie aromatica estesa ed elettron-povera che conferisca le proprietà di riconoscimento molecolare attraverso interazioni di π stacking con il target biologico. 2) un precursore di una specie alchilante che presenti una scarsa o assente reattività intrinseca modulabile mediante attivazione, possibilmente compatibile con condizioni fisiologiche. 3) una porzione molecolare facilmente modificabile per interazioni con il substrato o per attivazione chimica, che funga da “grilletto” della reattività del precursore alchilante. Nella fattispecie ci siamo concentrati sulla derivatizzazione di strutture, che dalla letteratura risultano dei buoni leganti di G-4, come Naftalendiimidi (NDI) o Naftalimmidi (NI), variamente sostituite con dei precursori di alchilanti tipo chinone metide (QM). Questi ultimi risultano particolarmente adatti a questo scopo in quanto posso essere generati da precursori molto stabili, attraverso dei protocolli di attivazione biocompatibili. Soprattutto risultano elettrofili la cui reattività è modulabile variando la natura elettronica del precursore stesso. In questo lavoro di tesi descriviamo la sintesi, la reattività e gli studi di interazione con oligonucleotidi ripegabili a strutture tipo G-4, delle molecole progettate e preparate nel corso del dottorato di ricerca. Particolare enfasi verrà posta sull’effetto indotto dal danno da alchilazione osservato e sulle potenziali applicazioni sia terapeutiche che diagnostiche. Inoltre descriveremo brevemente un progetto parallelo svolto durante il periodo trascorso all’Università di Cambridge, presso il gruppo di ricerca del Prof. Balasubramanian.
7
Cantone, Sara. „A new conception of polymeric supports for the solid phase peptide synthesis: rigidity and porosity as determinant factors for the success in industrial applications“. Doctoral thesis, Università degli studi di Trieste, 2008. http://hdl.handle.net/10077/2628.
Der volle Inhalt der QuelleAnnotation:
2006/2007In questo studio di tesi sono stati sviluppati ed ottimizzati nuovi supporti rigidi per la sintesi in fase solida in collaborazione con l’azienda Resindion srl. (Mitsubishi Chemical Corporation). Tali supporti, denominati Synbeads, sono stati poi caratterizzati dal punto di vista chimico e fisico ed applicati alla sintesi peptidica in fase solida. La parte iniziale dello studio si è concentrata sulla messa a punto del processo di polimerizzazione in modo da ottenere dei polimeri Synbeads caratterizzati da un grado di porosità ottimale e da una omogenea distribuzione del diametro particellare. Questi due parametri infatti influiscono notevolmente sull’applicabilità dei polimeri per sintesi su fase solida: - il grado di porosità, nei polimeri rigidi e che quindi non rigonfiano in solvente, deve garantire un buon trasferimento di massa dei reagenti e nello stesso tempo assicurare una buona resistenza dei polimeri stessi allo stress meccanico - la distribuzione particellare deve essere compresa in un ben definito range di diametro, in modo da permettere l’utilizzo dei Synbeads anche in sistemi automatizzati, senza che vi siano presente né particelle fini che potrebbero intasare i filtri, né particelle di dimensioni troppo grandi che potrebbero rendere difficoltoso il trasferimento delle stesse nei sistemi automatici. La successiva fase di ottimizzazione dei Synbeads si è concentrata su altri due parametri molto importanti, ossia la lunghezza dello spaziatore tra la matrice polimerica e il gruppo funzionale e la densità di gruppi funzionali presenti sui polimeri: - una distanza ottimale del gruppo funzionale dalla matrice del polimero ne garantisce la completa accessibilità chimica, evitando problematiche legate all’ingombro sterico - la densità di gruppi funzionali deve assicurare sia una buona capacità di carico (mmoli di gruppi funzionali per gdry di polimero) sia una completa accessibilità chimica di tutti i gruppi funzionali presenti sul polimero. In seguito a questo studio di ottimizzazione sono stati preparati i Synbeads con gruppo funzionale amminico (Synbeads A310). Partendo quindi dalle caratteristiche chimico-fisiche ottimizzate per la produzione dei Synbeads A310, sono stai messi a punto dei protocolli per la preparazione e la caratterizzazione dei altri Synbeads recanti gruppi funzionali diversi, ossia clorometilenici, bromometilenic, carbossilici ed idrossilici. Successivamente, i Synbeads A310 sono stati funzionalizzati con diversi linker che ne permettano applicazioni diverse nella sintesi in fase solida. Infatti, i Synbeads recanti i linker sono stati utilizzati per la preparazione da diversi Fmoc-AA-Wang-Synbeads e per la sintesi di un pentapeptide. Questo pentapeptide costituisce la sequenza dei primi cinque aminoacidi del Fuzeon®, un peptide che presenta attività inibitoria nei confronti dell’HIV. L’applicazione dei Synbeads è stata studiata anche per quanto riguarda il loro possibile utilizzo nella sintesi peptidica automatizzata con l’impiego di microonde, in particolare nel sistema Liberty CEM®. Grazie alle caratteristiche chimico-fisiche dei Synbeads e alla messa a punto di protocolli sintetici adatti a questi polimeri rigidi, si è potuto ottenere il prodotto desiderato con buone rese e un elevato grado di purezza. Nella parte finale di questo studio di tesi è stata indagata la distribuzione dei gruppi funzionali all’interno della matrice dei Synbeads. Combinando la tecnica ATR-FT IR con luce convenzionale e con luce di sincrotrone è possibile seguire la diffusione dei reagenti all’interno della matrice polimerica e verificare l’omogeneità della matrice stessa. Dopo aver messo a punto questa metodologia analitica, che permette un’indagine approfondita di ciò che avviene all’interno della matrice dei polimeri rigidi non trasparenti, un altro approccio analitico è stato sviluppato. Al fine di poter verificare in modo più rapido l’omogeneità della matrice polimerica, sezioni di Synbeads funzionalizzati con diverse concentrazioni di fluoresceina sono stati analizzati, permettendo in tal modo di verificare anche la distribuzione dei gruppi funzionali. Questo studio di dottorato quindi ha permesso di ottenere una nuova classe di polimeri rigidi per la sintesi su fase solida, i Synbeads, che hanno dimostrato di permettere l’ottenimento di ottimi risultati sia nella sintesi classica che in quella assistita da microonde. Nuovi approcci analitici sono stati studiati e applicati per verificare l’omogeneità della matrice polimerica e seguire i fenomeni di diffusione all’interno della matrice stessa. In tal modo, i Synbeads presentano un ottimo potenziale per un’applicazione su larga scala in processi industriali.
XX Ciclo
1979
8
MELEDDU, RITA. „Synthesis of different series of small molecules targeting HIV-1 RT, Candida albicans, MAO and G-Quadruplex“. Doctoral thesis, Università degli Studi di Cagliari, 2013. http://hdl.handle.net/11584/266235.
Der volle Inhalt der QuelleAnnotation:
My PhD work has been focused towards four different targets: HIV-1 RT, Candida albicans, Monoamine oxidase, and G-Quadruplex. Thus in order to give the reader a clearer exposition this report has been divided in four different chapters. Each of the chapters has his own figures, schemes, tables and references. The main part of my work has been dedicated to HIV-1 RT, thus this chapter is the major and first one.
9
Greco, Maria Laura. „Conformational switch of oncogene promotorial sequences towards non-canonical DNA secondary structures“. Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3424026.
Der volle Inhalt der QuelleAnnotation:
The folding of DNA molecule into non-canonical secondary structures has been shown to be implicated in many important biological processes which regulate cell proliferation and proteins expression. In particular one of these peculiar secondary structures, called G-quadruplex (G4), has been shown to potentially impair cancer development. G4 occurs along DNA sequences rich of consecutive guanines which can fold through Hoostein pairs by forming stacked planes of guanines tetrads. This conformation prevalently forms along the termini of chromosomes (telomeres) but also along the promoter sites of several oncogenes directly involved in many cancers. The G4 formation leads to an hindrance on DNA molecule which hinder the telomere elongation and transcription process. The result is a switching off of these mechanisms which are directly involved in cancer progression. Several factors can influence the G4 equilibria for example, saline conditions, temperature, pH, the binding with specific proteins as well as the presence of dehydrating cosolutes. Additionally, the overall structural feature of the G4 is strictly dependent upon the DNA sequence. As a results, different G4 can be identified inside the cells.
In this project, we focused on the conformational study of the promotorial regions of EGFR and BRAF oncogenes since, on these sites the existence of G4 putative forming regions was found. In particular, the sequences at positions -272, -37 of EGFR and -176 of BRAF from the transcription start site were analyzed. Indeed, no previous literature data were reported about the structural equilibria in solution of these sequences. We found that our tested sequences are actually able to fold into G4 by setting the most proper experimental conditions and also close to the intracellular physiological environment (KCl 150 mM, pH 7.5).
However, oncogenes are double stranded sequences and the folding of the complementary cytosine rich strand into i-motif (iM) can be involved in the switching off of gene transcription. Although, so far, no physiological evidence has been observed for i-motif conformation, here, we aimed to investigate also the cytosine rich strand conformation, to assess if this folding in the case of our sequences is compatible with the physiological conditions and if it can synergically works with the G4 to destabilize the double strand. Our data showed that in physiological condition the preferential form is represented by the double strand . However, some selected ligands showed to shift the DNA B-form toward the non canonical conformation. Indeed, here we implemented our work with the screening of two libraries of compounds in order to find a selective and efficient binder. We carried on the binding study of anthraquinones and naphthalene diimides derivatives, known to have the chemical features of efficient G4 binders. These ligands were first tested on different G4 templates, known to be validated models for G4 binding study, and their efficiency on G4 has been compared with the double strand. The most G4 selective derivatives were than investigated towards our oncogenic G4s. Although more work is required to identify a lead compound, we were able to demonstrate how the use of asymmetrical substitution pattern on a aromatic core can implement the selectivity among different G4s.
Finally, in order to map the occurrence of G4 conformation in vivo, we set up a novel technique which consists in an in vivo footprinting protocol. This work, performed at University of Mississippi, Oxford, MS (USA), under the supervision of Dr Tracy A. Brooks, should provide novel insight on the G4 formation in the cells according to their physiological and environmental conditionsMolti studi dimostrano che l’assunzione di strutture “non canoniche” da parte della molecola di DNA sia coinvolto in molti importanti processi biologici che regolano la proliferazione cellulare e l’espressione proteica. In particolare, è stata dimostrata l’implicazione di una di queste particolari strutture secondarie, chiamata G-quadruplex (G4), nel blocco della progressione del cancro. La struttura G4 è propria di sequenze di DNA ricche in guanine consecutive che assemblandosi tramite legami di Hoostein, formano piani di tetradi di guanine impilati tra loro. Questa particolare conformazione si forma prevalentemente lungo i tratti terminali dei cromosomi, i telomeri, ma anche lungo siti promotoriali di diversi oncogeni coinvolti in molti tipi di cancro. La formazione del G4 porta ad una sorta di ingombro sulla molecola di DNA che inibisce l’elongazione del telomero e i processi di trascrizione. Questo porta ad uno “spegnimento” di questi meccanismi che sono direttamente coinvolti nello sviluppo del cancro. Molti fattori possono influenzare gli equilibri delle conformazioni G4, per esempio, le condizioni saline, la temperatura, il pH, il legame con specifiche proteine, così come la presenza di cosoluti. Inoltre, la struttura globale del G4 é rigorosamente dipendente dalla sequenza oligonucleotidica. Pertanto, diverse strutture G4 possono essere identificate a livello cellulare. In questo progetto, è stato condotto uno studio conformazionale di regioni promotoriali degli oncogeni EGFR e BRAF, dal momento che, su questi oncogeni è stata riscontrata la presenza di regioni “G-rich” (ricche in guanine) potenzialmente in grado di assumere una struttura G4. In particolare, sono state analizzate le sequenze a partire dalle posizioni -272, -37 di EGFR e -176 di BRAF dal “transcription start site” (sito di inizio della trascrizione). Finora, non sono presenti dati in letteratura riguardanti la caratterizzazione strutturale di queste sequenze in soluzione. Con questo studio, è stata dimostrata la capacità delle suddette sequenze di assumere una conformazione G4 nelle idonee condizioni sperimentali e soprattutto in un ambiente che mimi quello fisiologico (150mM KCl e pH 7.5). Poiché gli oncogeni sono sequenze a doppio filamento, anche la conformazione i-motif assunta dal filamento complementare ricco in citosine (“C-rich”) può essere coinvolta nella regolazione del processo di trascrizione genica. Tuttavia, sinora non è stata riscontrata alcuna rilevanza fisiologica della conformazione i-motif. In questo lavoro, è stata caratterizzata anche la conformazione assunta dal filamento “C-rich”, in particolare se essa possa esistere in condizioni fisiologiche e se fosse in grado di destabilizzare la doppia elica insieme al G4. I dati ottenuti dimostrano che in condizioni fisiologiche la forma prevalente è il doppio filamento. Tuttavia, è stato dimostrato come alcuni ligandi siano in grado di spostare l’equilibrio del DNA dalla sua forma di doppia elica-B, verso le conformazioni non canoniche. È stato infatti condotto uno studio su due librerie di composti con lo scopo di evidenziare un composto selettivo ed efficace. Ci siamo focalizzati su derivati antrachinonici e di naftalendiimidi noti come efficaci ligandi per il G4. Questi composti sono stati prima testati su diversi templati G4, noti per essere dei modelli validati per lo studio di binding sul G4. Quindi la loro efficienza sul G4 è stata poi comparata a quella sul doppio filamento. I derivati più selettivi verso il G4 sono stati poi testati su G4 oncogenici. Sebbene una continuazione dello studio fosse necessaria per identificare un composto “lead”, con questo lavoro è stato dimostrato come l’uso di una sostituzione asimmetrica sull’anello aromatico possa implementare la selettività tra più G4. Infine, per identificare la formazione del G4 in vivo, è stata messa a punto una nuova tecnica che consiste in un protocollo di footprinting in vivo. Questo lavoro, svolto nell’Università del Mississippi, Oxford, MS (USA) sotto la supervisione della dr.ssa Tracy A. Brooks, dovrebbe fornire nuovi sviluppi per la formazione del G4 nelle cellule in accordo con le loro condizioni fisiologiche
10
CIANCIMINO, Cristina. „Synthesis of Azole-Heterocycles as Potential Antitumor and/or Antiviral Agents“. Doctoral thesis, Università degli Studi di Palermo, 2014. http://hdl.handle.net/10447/90986.
Der volle Inhalt der QuelleBücher zum Thema "G-087"
1
V, Efremov A., Hrsg. Aktualʹnye problemy upravlenii︠a︡ prot︠s︡essom sozdanii︠a︡ zdorovʹesberegai︠u︡shcheĭ obrazovatelʹnoĭ sredy v uchrezhdenii︠a︡kh profobrazovanii︠a︡ KhMAO-I︠U︡gry: Sbornik tezisov, dokladov i vystupleniĭ na okruzhnoĭ nauchno-prakticheskoĭ konferent︠s︡ii v g. Surgute, 08-09.02.06 g. Khanty-Mansiĭsk: Okruzhnoĭ in-t povyshenii︠a︡ kvalifikat︠s︡ii i razvitii︠a︡ regionalʹnogo obrazovanii︠a︡, 2006.
Den vollen Inhalt der Quelle finden
2
Coloquio Internacional de Crítica Literaria "Tomás G. Escajadillo" (2009 Lima, Peru). Tomás G. Escajadillo: Aportes a la crítica y a los estudios literarios : Actas del Coloquio Internacional de Crítica Literaria "Tomás G. Escajadillo", Lima, 08-10 de julio del 2009. [Lima]: Universidad Nacional Mayor de San Marcos, Facultad de Letras y Ciencias Humanas, 2011.
Den vollen Inhalt der Quelle finden
3
Ėriashvili, N. D., und N. M. Korshunov. Nauchnyĭ kommentariĭ k Federalʹnomu zakonu RF "O gosudarstvennykh i munit︠s︡ipalʹnykh unitarnykh predprii︠a︡tii︠a︡kh": Ot 14 noi︠a︡bri︠a︡ 2002 g. no. 161-FZ : v red. Federalʹnogo zakona ot 08 dekabri︠a︡ 2003 g. no. 169-FZ. Moskva: I︠U︡NITI, 2006.
Den vollen Inhalt der Quelle finden
4
Republic, Dominican. Ley no. 41-08: Sobre la función pública : Crea la Secretaría de Administración Pública : G. O. no. 14458 del 25 de enero del 2008. Santo Domingo, República Dominicana: Editora Centenario, 2008.
Den vollen Inhalt der Quelle finden
5
D, Solovʹev V., Baranov V. A und Kazanskiĭ gosudarstvennyĭ universitet, Hrsg. Sovremennye informat︠s︡ionnye tekhnologii i pisʹmennoe nasledie: Ot drevnikh tekstov k ėlektronnym bibliotekam : El'Manuscript-08 : materialy mezhdunarodnoĭ nauchnoĭ konferent︠s︡ii, Kazanʹ, 26-30 avgusta 2008 g. Kazanʹ: Kazanskiĭ gos. universitet, 2008.
Den vollen Inhalt der Quelle finden
6
D, Solovʹev V., Baranov V. A und Kazanskiĭ gosudarstvennyĭ universitet, Hrsg. Sovremennye informat︠s︡ionnye tekhnologii i pisʹmennoe nasledie: Ot drevnikh tekstov k ėlektronnym bibliotekam : El'Manuscript-08 : materialy mezhdunarodnoĭ nauchnoĭ konferent︠s︡ii, Kazanʹ, 26-30 avgusta 2008 g. Kazanʹ: Kazanskiĭ gos. universitet, 2008.
Den vollen Inhalt der Quelle finden
7
Kirʹi︠a︡kova, A. V. Regionalʹno orientirovannye issledovanii︠a︡ filologicheskogo prostranstva: Materialy Vserossiĭskoĭ nauchno-prakticheskoĭ konferent︠s︡ii, provodimoĭ Pri finansovoĭ podderzhke rossiĭskogo gumanitarnogo nauchnogo fonda (RGNF) grant 08-04-81480 g/U. Orenburg: IPK GOU OGU, 2008.
Den vollen Inhalt der Quelle finden
8
(Federation), Russia. Materialʹnyie i prot︠s︡essualʹnye pravovye normy, kasai︠u︡shchiesi︠a︡ borʹby s vozmozhnymi pravonarushenii︠a︡mi v svi︠a︡zi s izbiratelʹnoĭ kampanieĭ v Gosudarstvennui︠u︡ Dumu Federalʹnogo Sobranii︠a︡ Rossiĭskoĭ Federat︠s︡ii: Po sostoi︠a︡nii︠u︡ na 08 senti︠a︡bri︠a︡ 2003 g. Moskva: R. Valent, 2003.
Den vollen Inhalt der Quelle finden
9
Botín, Fundación Marcelino, Hrsg. Itinerarios 07-08: XV becas de artes plásticas : Leonor Antunes, Christian Bagnat, Mira Bernabeu, Rafel G. Bianchi, Cabello/Carceller, Iñaki Garmendia, Carlos Irijalba, Isabel María, Renata Lucas : del 23 de enero al 15 de marzo de 2009. Santander: Fundación Marcelino Botín, 2009.
Den vollen Inhalt der Quelle finden
10
Informat͡sionnai͡a politika i kulʹturnoe razvitie regionov: Pechatʹ, kniga, ėlektronnye SMI Sibiri i Dalʹnego Vostoka v postsovetskiĭ period, 90-e gg. XX-nachalo XXI v. : sbornik nauchnykh trudov po itogam vypolnenii͡a proekta RGNF No. 08-01-00277a v 2008 g. Novosibirsk: GPNTB SO RAN, 2008.
Den vollen Inhalt der Quelle findenBuchteile zum Thema "G-087"
1
„G“. In Phoenix (1835–1838); Frankfurter Museum (1855–1859); Neues Frankfurter Museum (1861); Weimarer Sonntags-Blatt (1855–1857). Berlin, Boston: De Gruyter, 1995. http://dx.doi.org/10.1515/9783110963069-087.
Der volle Inhalt der Quelle
2
CERÓN-BRETÓN, Julia Griselda, Rosa María CERÓN-BRETÓN, Reyna del Carmen LARA-SEVERINO und Arely VICHIQUE-MORALES. „Diurnal variation and health risk of atmospheric aromatic hydrocarbons concentrations in an urban site located in Nuevo Leon, Mexico“. In CIERMMI Women in Science T-XVIII Health Sciences, 56–78. ECORFAN, 2022. http://dx.doi.org/10.35429/h.2022.5.1.56.78.
Der volle Inhalt der QuelleAnnotation:
Diurnal variation of aromatic hydrocarbons (BTEX: benzene, toluene, ethylbenzene and p-xylene) in ambient air was determined in an urban site located in Monterrey, during North’s season 2020. Samples were collected using active sampling by a vacuum pump at a controlled flow of 200 ml/min during 1.5 h, considering three sampling periods: morning (07:00 - 08:30 h), midday (14:00 - 15:30 h) and afternoon (17:30- 19:00 h). Samples were desorbed with carbon disulfide and the extracts were analyzed by gas chromatography with ionization flame detection. Ethylbenzene and p-xylene were the dominant hydrocarbons (mean concentration: 18.581 g/m3 and 18.039 g/m3, respectively). Mean values for benzene and toluene were 15.137 g/m3 and 15.503 g/m3, respectively. All BTEX showed a diurnal pattern with higher values during the afternoon. From a meteorological study (wind roses) and chimiometric analysis (principal component analysis) were identified relations among the measured variables and their possible emission sources (industrial and vehicular sources). It was carried out a health risk assessment, considering both, carcinogenic and non-carcinogenic (respiratory and cardiovascular diseases) related to BTEX inhalation founding that population in the study site could develop cancer in the lifetime by benzene inhalation.
3
„Guide: Guide to Modeling Earth’s Trapped Radiation Environment (AIAA G-083-1999)“. In Guide: Guide to Modeling Earth’s Trapped Radiation Environment (AIAA G-083-1999). Washington, DC: American Institute of Aeronautics and Astronautics, Inc., 1999. http://dx.doi.org/10.2514/4.473678.001.
Der volle Inhalt der Quelle
4
„Guide: Space Systems — Composite Overwrapped Pressure Vessels with a Plastic Liner (AIAA G-082-2022)“. In Guide: Space Systems — Composite Overwrapped Pressure Vessels with a Plastic Liner (AIAA G-082-2022). 12700 Sunrise Valley Drive, Suite 200, Reston, VA 20191: American Institute of Aeronautics and Astronautics, Inc., 2023. http://dx.doi.org/10.2514/4.107061.001.
Der volle Inhalt der Quelle
5
Fittipaldi, A. D., A. Q. Nascimento, J. B. Farias und M. R. E. Arruda. „ANÁLISE DO NÍVEL DE COMPROMETIMENTO DA ALTA DIREÇÃO COM O SISTEMA DE GESTÃO DA QUALIDADE“. In Sustentabilidade, Tecnologia e Meio Ambiente: tópicos atuais em pesquisa, 32–49. Editora Científica Digital, 2024. http://dx.doi.org/10.37885/240215762.
Der volle Inhalt der QuelleAnnotation:
O objetivo desse artigo foi analisar o nível de comprometimento da Alta Direção de empresas construtoras de Pernambuco certificadas na NBR ISO 9001:2015 e no Referencial Normativo Nível “A” do SIAC 2021 com os seus Sistemas de Gestão da Qualidade. Para a consecução desse objetivo, foram revisados os padrões normativos referidos e foi elaborado um questionário a partir dos requisitos desses padrões referentes à Alta Direção, que foi aplicado a 08 empresas construtoras. Para definir o nível de comprometimento da Alta Direção, criou-se uma escala, tomando por base a ideia de Likert, e os primeiros resultados obtidos, levando-se em conta apenas a primeira parte do questionário, foram os seguintes: nível de comprometimento excelente, para as empresas B, C e D; muito bom, para as empresas A, F e G; bom, para a empresa H e regular, para a empresa E. Quando se levaram em consideração as principais dificuldades sentidas pelas construtoras para o cumprimento dos requisitos relativos ao envolvimento da Alta Direção, vieram à tona os reais níveis de comprometimento: excelente, para a empresa D; muito bom, para as empresas C e G; bom, para a empresa B; regular, para as empresas A, E e F e péssimo, para a empresa H. Pôde-se concluir que, ainda que a norma tenha aumentado suas exigências sobre a Alta Direção, esse fato não despertou totalmente o envolvimento e a atenção dessas Altas Direções para os Sistemas de Gestão da Qualidade de suas empresas.
6
„Figure 2: Dust concentration (mg/m3 ), ventilation rate (m3/ pig h), temperature (°C), and relative humidity dust p ig 1) he n 2) origi n o tin g without bedding battery bedding from •/. % •/. feed 8 0 -9 080 -9 0n.r. bedding --5 5 -6 8an im a ls 5 -1 1 2 -1 2 m an u re n.r. OOiao1i“. In Odour Prevention and Control of Organic Sludge and Livestock Farming, 342. CRC Press, 1986. http://dx.doi.org/10.1201/9781482286311-136.
Der volle Inhalt der Quelle
7
„TABLE8TocolDerivativeContentinCerealGrainsTocolderivatives ( m g / 100g ) aGrainsa -T a -T -3 1 3 -T I 3 -T -3 y -T y -T -3 6 -T 6 -T -3 TotalRef . Barley0 . 2 -0 . 4 1 . 1 -1 . 3 0 . 0 4 -0 . 4 0 . 3 -0 . 7 0 . 0 3 -0 . 5 0 . 2 0 . 0 1 -0 . 040 . 1 6 < 5 . 030 . 4 1 . 3 0 . 3 0 . 7 0 . 050 . 2 0 . 1 -8 9 0 . 5 1 . 3 0 . 020 . 7 0 . 070 . 8 0 . 020 . 0750 . 3 1 . 6 < 0 . 1 0 . 6 0 . 1 0 . 6 < 0 . 1 -9 0Genotype0 . 7 2 -1 . 162 . 3 8 -4 . 300 . 0 5 -0 . 130 . 3 1 -1 . 210 . 0 4 -0 . 120 . 2 4 -0 . 960 . 0 4 -0 . 140 . 0 2 -0 . 204 . 2 2 -8 . 0091Location0 . 8 8 -1 . 113 . 0 5 -3 . 630 . 002 -0 . 190 . 6 7 -0 . 750 . 070 . 5 0 -0 . 560 . 0 4 -0 . 130 . 0 7 -0 . 115 . 6 7 -6 . 0891Malt1 . 003 . 070 . 140 . 460 . 040 . 390 . 040 . 065 . 292Spentgrain2 . 029 . 210 . 311 . 600 . 091 . 760 . 120 . 1815 . 392Corn0 . 6 -2 . 1 0 . 2 -0 . 5 -0 . 5 -1 . 1 3 -0 . 6 0 . 2 0 . 4 3 . 8 0 . 5tr890 . 1 -2 . 3 0 . 3 -0 . 7 1 . 1 -7 . 1 0 . 1 -1 . 9 2 . 6 -1 0 . 29Millet0 . 05tr1 . 3 0 . 489 -0 . 1 < 0 . 1 0 . 1 1 . 7 < 0 . 1 0 . 690Bulrushmillet0 . 1 3 -5 . 540 . 530 . 080 . 25Foxtailmillet0 . 190 . 040 . 042 . 780 . 065Fingermillet0 . 320 . 050 . 031 . 7 6 -5 Pearlmillet0 . 041 . 5 -0 . 355 -O ats0 . 3 -1 . 7 0 . 7 -1 . 1 0 . 1 -0 . 2 0 . 1 -0 . 3 0 . 3 -3 0 . 7 0 . 7 0 . 2 0 . 1 0 . 3 -8 9 1 . 3 -4 . 0 0 . 2 -6 . 3 0 . 3 -0 . 5 0 . 3 -1 . 1 0 . 7 -6 . 1 0 . 910 . 140 . 321 . 3 -3 . 011Genotype0 . 5 5 -0 . 960 . 9 1 -1 . 860 . 0 7 -0 . 130 . 0 5 -0 . 150 . 0 5 -0 . 130 . 0 0 -0 . 061 . 9 -3 . 091Location0 . 7 2 -0 . 961 . 1 7 -1 . 830 . 0 7 -0 . 110 . 0 5 -0 . 140 . 0 8 -0 . 110 . 0 1 -0 . 032 . 1 -3 . 191RiceBrownrice0 . 6 0 . 4 0 . 1 < 0 . 010 . 1 0 . 7 < 0 . 190Polishedrice < 0 . 1 0 . 1 < 0 . 1 < 0 . 1 < 0 . 1 0 . 3 < 0 . 190Milledrice0 . 0 5 -0 . 3 0 . 2 -0 . 5 0 . 1 -0 . 3 -< 0 . 0440 . 3tr0 . 3 0 . 5 0 . 04890 . 060 . 080 . 260 . 020 . 025 -R ye0 . 5 -1 . 8 0 . 7 -1 . 5 0 . 3 -0 . 7 0 . 8 -0 . 9 0 . 6 -3 0 . 8 1 . 3 0 . 4 0 . 9 0 . 689Flour0 . 6 0 . 4 0 . 3 0 . 6 -9 0Meal1 . 0 1 . 4 0 . 3 1 . 190Sorghum0 . 081 . 155Triticale0 . 911 . 030 . 301 . 515Winter0 . 7 -0 . 9593Spring1 . 3 5 -1 . 4593 -W heat1 . 0 0 . 2 0 . 4 1 . 9 -5 0 . 9 -1 . 8 0 . 3 -0 . 7 2 . 5 -3 . 6 4 . 9 -5 . 831 . 0 0 . 4 0 . 9 2 . 5 0 . 0889aTocopherolsincludea -T , 0 -T , y -T , and5 -T , andtocotrienolsincludea -T -3 , 0 -T -3 , y -T -3 , andS -T -3 . ( -) denotedatanotreported .“ In Handbook of Cereal Science and Technology, Revised and Expanded, 449–94. CRC Press, 2000. http://dx.doi.org/10.1201/9781420027228-47.
Der volle Inhalt der QuelleKonferenzberichte zum Thema "G-087"
1
Díaz-Villamarín, X., C. Dávila-Fajardo, M. González-Medina, D. Blánquez-Martínez, P. Moreno-Raya und J. Cabeza-Barrera. „CP-086 CD69 A>G (RS11052877) genetic polymorphism on the response to tocilizumab in rheumatoid arthritis patients“. In 22nd EAHP Congress 22–24 March 2017 Cannes, France. British Medical Journal Publishing Group, 2017. http://dx.doi.org/10.1136/ejhpharm-2017-000640.85.
Der volle Inhalt der Quelle
2
Gabureanu, Simona, und Petre Botnariuc. „AN ANALYSIS OF THE VIRTUAL COMMUNITIES SUPPORTING THE "GOOGLE FOR EDUCATION" PROGRAMME IN ROMANIA“. In eLSE 2016. Carol I National Defence University Publishing House, 2016. http://dx.doi.org/10.12753/2066-026x-16-087.
Der volle Inhalt der QuelleAnnotation:
Authors: Petre Botnariuc Institutul de ?tiin?e ale Educa?iei Stirbei Vod?, 37, 010102, Bucure?ti. Email: bpetre[at]ise.ro Simona G?bureanu Universitatea Politehnica Bucure?ti Splaiul Independen?ei Str. No 313, Bucharest 060042, Romania E-mail: simona.gabureanu[at]upb.ro This article aims to complement through an content analysis endeavour the quantitative approach adopted by a programme evaluation, research that was conducted in 2015 by a team of researchers. The evaluation has addressed the training programme ,,Google for education" which aimed to develop teachers skills in employing in ones own activity of the different Google applications (Gmail, Calendar, Drive, sheets, forms, sites, Google+). The investigation aimed to reveal the added value of the training programme. The quantitative data set was collected through a questionnaire distributed through the ,,Google for education" communities and through the iTeach platform addressed to the professional development of teachers in preuniversitary education. For the analysis 159 answers were validated as attendants to the formal training session in using the Google apps in education from the total of 161 teachers who have actually filled in the questionnaire. The content for the qualitative analysis consists in the discussions taking place in 13 counties from Romania, which could be identified online. In this paper we will explore the trainees preferences and difficulties encountered in applying the Google tools in the process of resources and learning management, with a focus on the way in which the google groups are used as a mean of communication and collaboration in the professional communities of teachers from din 13 counties (Arge?, Bistri?a-N?s?ud, Boto?ani, Bra?ov, Br?ila, Bucure?ti, Constan?a, D?mbovi?a, Giurgiu, Hunedoara, Mehedin?i, Mure?, Timi?). We have used a mixed methodology of analysis with quantitative and qualitative treatment of the collected data (questionnaire applied to the trainees of the training programme and content analysis of the online discussions forums). The focus of analysis was on the effectiveness of the training programme and on building a teachers learning community as well as to provide a set of suggestions for improving the future training activities. The quantitative results are analysed and further explained against the qualitative results taking into account different factors: type of training provider type, trainees preferences for training, opportunities, difficulties and factors of success in application in preparation activity and actual classes, areas, extent and frequency of application, participants estimated training impact on educational design and classes, teaching experiences. The analysed effects of training include: use of Google apps for management and school-family collaboration, better integration of google apps in the teaching, integration of google apps in the learning tasks, use of state of the art teaching methodologies (pupil and competence centeredness), introducing creative methods and strategies in the learning situations, relevance and practicality of the learning activities, opportunities for collaborative learning and team work, personalised and individualised learning, as well as interactive and participative learning, adequate, varied evaluation methods and tools, exploitation of received feedback for ones own improvement and professional development. In what the outcome of the training is concerned the following topics will be analysed: increased learning performance for pupils, attractiveness of learning activities, facilitation of retention, comprehension and higher order thinking skills, encouragement of both demanding students and high performing students, facilitation of creative approaches in learning, better and increased use of google apps for individual study, better communication with the students, increased individual involvement in collaborative projects, more effective resource management.
3
Ауесханова, М. „МЕКТЕПКЕ ДЕЙІНГІ ИНКЛЮЗИВТІ БІЛІМ БЕРУ ЖАҒДАЙЫНДА ПЕДАГОГТЕРДІҢ КӘСІБИ ҰСТАНЫМЫН ДАМЫТУ“. In Республиканская научно-практическая онлайн-конференция «ТЕОРИЯ И ПРАКТИКА ПРОФЕССИОНАЛЬНОЙ КОМПЕТЕНТНОСТИ ПЕДАГОГОВ В УСЛОВИЯХ СОВРЕМЕННОГО ОБРАЗОВАНИЯ». Crossref, 2022. http://dx.doi.org/10.53355/y3780-0444-0877-g.
Der volle Inhalt der Quelle
4
Talwai, Prem M. „Abstract B2-08: Model order reduction for cell signaling pathways: An investigation of G-protein coupled receptor signaling“. In Abstracts: AACR Special Conference: Computational and Systems Biology of Cancer; February 8-11, 2015; San Francisco, CA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.compsysbio-b2-08.
Der volle Inhalt der Quelle
5
Maia, Júlio Eduardo Santana, Reginaldo De Camargo, Miguel H. Henrique Rosa Franco und Bianca Stefani Arantes Leite. „USO DE ORGANOMINERAL ASSOCIADO A MICRORGANISMOS NO DESENVOLVIMENTO E CONTROLE DE NEMATOIDES NA CULTURA DA SOJA“. In II Congresso Brasileiro de Biotecnologia Online. Revista Multidisciplinar de Educação e Meio Ambiente, 2022. http://dx.doi.org/10.51189/conbiotec/69.
Der volle Inhalt der QuelleAnnotation:
Introdução: A soja possui grande importância econômica para o Brasil e o mundo. O controle químico para nematoides na soja não é considerado o melhor método de manejo devido sua alta toxicidade ao meio ambiente. Dessa forma, o controle biológico vem se destacando, através do uso de material orgânico e rizobactérias que promovem um melhor desenvolvimento de plantas e controle dos fitoparasitas. Objetivo: O trabalho teve como objetivo avaliar o desenvolvimento e controle dos nematoides na cultura da soja na influência dos FOMs associados a microrganismos. Material e Métodos: O experimento foi realizado com solo arenoso, em casa de vegetação. O delineamento experimental utilizado foi o de DBC, com 7 tratamentos e 6 repetições. Os tratamentos utilizados foram: OM granulado AGROCP 08-08-08 + Microrganismos (70 ml de solução microbiana para cada uma tonelada de fertilizante); OM farelado AGROCP 10-10-10 + Microrganismos (70 ml de solução microbiana para cada uma tonelada de fertilizante); OM granulado AGROCP 08-08-08; OM farelado AGROCP 10-10-10; Mineral convencional 18-18-18; Mineral convencional 18-18-18 + químico (600 ml/ha para o @Nimitz) e Mineral convencional 18-18-18 + biológico (200 g/ha para o @QUARTZO). Aos 75 dias após semeadura foram avaliados: altura de planta; diâmetro de colmo; massa fresca de parte aérea e raiz; massa seca de parte aérea e volume de raiz. Resultados: A presença do fertilizante organomineral colaborou para uma maior média nos valores referentes de desenvolvimento de plantas. Já para a massa seca da parte aérea das plantas, observou-se poucas diferenças entre os tratamentos. Para as variáveis diâmetro de colmo e massa verde de parte aérea, não houve diferença significativa entre os tratamentos. E para o controle de nematoides o resultado é inconclusivo, devido ao fato de que através de influências abióticas, no caso temperatura, a presença dos mesmos foi prejudicada. Conclusão: A aplicação do FOM na soja teve respostas positivas no desenvolvimento da cultura, tais como: maior peso de massa seca e altura de plantas. Aliado ao Bacillus apresentou bons resultados no crescimento das plantas. Para a variável controle de nematoide o estudo se demonstra inconclusivo isso porque devido a influências externas se impossibilitou a utilização dos dados.
6
Sjöström, M., L. Hartman, T. Fornander, D. Grabau, P. Malmström, B. Nordenskjöld, L. Skoog, O. Stål, F. Leeb-Lundberg und M. Fernö. „Abstract P1-08-12: G protein-coupled estrogen receptor in the plasma membrane is prognostic in early breast cancer“. In Abstracts: Thirty-Sixth Annual CTRC-AACR San Antonio Breast Cancer Symposium - Dec 10-14, 2013; San Antonio, TX. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/0008-5472.sabcs13-p1-08-12.
Der volle Inhalt der Quelle
7
Nasution, Bagus Muliadi, Andrew Yonathan, Muthi Abdillah und Wang Zhen. „Pre-Treatment Experimental Study of Organic Acid: An Alternative Means to Overcome Inorganic Scale Build-Up Problem in Deep Well“. In SPE/IATMI Asia Pacific Oil & Gas Conference and Exhibition. SPE, 2021. http://dx.doi.org/10.2118/205693-ms.
Der volle Inhalt der QuelleAnnotation:
Abstract Organic acid has been widely applied for inorganic scale treatment in oil and gas industry including well stimulation and scale inhibitor. Thanks to its low corrosivity and slower reaction rate with rock, organic acid is considered to offer better performance comparing to strong acid - Hydrochloric Acid (HCl). Yet, proper treatment requires vigorous analysis and experiment in order to meet foremost expectations. Besides, mistreatment of scale could result in formation damage including clay precipitation. Pre-treatment experiments were performed on Zelda field at South East Sumatera block, that has faced with scale problem for ages. Water sample was taken from flowing Zelda A-08 well to be analyzed for mineral's saturation level. Scale was extracted from three sources including tubing, sand bailer, and Electrical Submersible Pump (ESP) of Zelda A-08. Those scale were treated in X-Ray Powder Diffraction (XRD) for mineral composition, and solubility test that utilized two types of acid system - formic acid (HCOOH) and hydrochloric acid (HCl) for comparison. Anti-swelling test and corrosion test were performed to examine the effectiveness of clay stabilizer and corrosion inhibitor. As for carbonate analysis, both formic acid 9% and HCl 15% have comparable solubility (98.17% vs 98% for tubing's scale, 91.86% vs 82.79% for ESP's scale, and 70.30% vs 68.07% for sand bailer's scale). Yet, longer reaction is carried out by formic acid 9% (1 hour) comparing to HCl 15% (18 minutes). For silicate analysis, HF-formic acid provided the higher solubility than HF-HCl (8.34% vs 5.67% for ESP's scale and 30.48% vs 25.68% for sand bailer's scale). On anti-swelling test, by reducing swelling tendency up to 62.6%, it proves that examined clay stabilizer works perfectly against swelling potential of clay, despite of high swelling tendency of sand bailer's scale (25.8%). On corrosion test, adding on corrosion inhibitor (pyridine-based) into solution results in regular HCl 15% has corrosion rate 26.279 g/m2.h which is much higher (300%) than HF-HCl (7.977 g/m2.h) and HF-formic acid (8.229 g/m2.h). Based on pre-treatment test, formic acid 9% together with examined corrosion inhibitor and clay stabilizer, can be used as an alternative to regular HCl 15% for stimulation purpose where more areas will be covered that previously left unreachable by regular acid 15%. In addition, potentially more effective squeezed scale inhibitor using organic acid can also be achieved by performing further experiments. The method presented in this paper for pre-treatment experimental studies of organic acid can provide engineers with intensive guide to meet the best result of organic acid treatment.
8
Betancourth, Mauro Pazmino, Richard Hogg und David Childs. „Portable External Cavity Quantum Cascade for mid-infrared spectroscopy applications“. In 2021 International Conference on Solid State Devices and Materials. The Japan Society of Applied Physics, 2021. http://dx.doi.org/10.7567/ssdm.2021.g-5-08.
Der volle Inhalt der Quelle
9
Tero, Ryugo, und Natsumi Kobayashi. „Substrate-Induced Electrostatic Potential Varies Composition of<br />Supported Lipid Bilayer Containing Anionic Lipid“. In 2021 International Conference on Solid State Devices and Materials. The Japan Society of Applied Physics, 2021. http://dx.doi.org/10.7567/ssdm.2021.g-6-08.
Der volle Inhalt der Quelle
10
Lishchenko, Pavel. „New variety of yellow lupine Antey“. In Multifunctional adaptive fodder production. ru: Federal Williams Research Center of Forage Production and Agroecology, 2022. http://dx.doi.org/10.33814/mak-2022-28-76-97-102.
Der volle Inhalt der QuelleAnnotation:
The article presents the results of studies on the creation of a variety of lupine Antey, resistant to anthracnose intended for sod-podzolic sandy and sandy soils. The initial forms, which are distinguished by the average resistance to the disease, were selected in 2009 in the field in the absence of an anthracnosis infectious background in the hybrid nursery F1. The most stable combination of 1-08 turned out to be the most stable. In the period 2010–2012 the assessment and selection of the most resistant to anthracnosis of forms. In 2012, number 1-08-75 was allocated, which after a competitive variety test in 2019 was transferred to the state variety test, and in 2021 it was registered in the state register of protected breeding achievements as a variety of yellow Lupine Antey. The variety is universal, used as green food, silos, hay and grain. Over the years of research, the Antey variety formed from 45 to 52 t/ha of green mass, 1.5–2.0 t/ha of grain. The protein content in green mass and in grain compiled 42–44 and 18–19 %, alkaloids — 0.04 and 0.03 %. The length of the vegetation pies is 96–98 days, the mass of 1000 seeds is 100–120 g, the height of the herb is 70–80 cm, it is treated with good lateral branching (5–7 lateral branches, including 3–4 fruiting). The variety is resistant to fusariosis, anthracnose, especially to the formation of superficial and perforated necrotic ulcers on beans.
Berichte der Organisationen zum Thema "G-087"
1
Coyle, M. Residual total magnetic field, Southampton Island aeromagnetic survey, NTS 46 F/08 and 46 G/05, Nunavut. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2008. http://dx.doi.org/10.4095/225224.
Der volle Inhalt der Quelle
2
Buckle, J. L., M. Coyle, J. M. Carson, B. J. A. Harvey und G. Delaney. Geophysical Series, southern Athabasca Basin geophysical survey, Saskatchewan, parts of NTS 74 G/08 and 74 H/05. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2009. http://dx.doi.org/10.4095/247369.
Der volle Inhalt der Quelle
3
Coyle, M. First vertical derivative of the magnetic field, Southampton Island aeromagnetic survey, NTS 46 F/08 and 46 G/05, Nunavut. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2008. http://dx.doi.org/10.4095/225243.
Der volle Inhalt der Quelle
4
Carson, J. M., K. L. Ford und B. J. A. Harvey. Geophysical series, NTS 40 J/02 and parts of 40 J/01, 03, 06, 07, 08, G/15, 16, airborne geophysical survey, Essex, Ontario. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2010. http://dx.doi.org/10.4095/285909.
Der volle Inhalt der Quelle