Nucleoside Analogues for Positron Emission Tomography Imaging and to Study Radiation Mediated Generation of Radicals from Azides

Gemcitabine is a potent anticancer cytidine analogue used to treat solid tumors. Its efficacy is diminished by rapid deamination to a toxic uridine derivative by cytidine deaminase. To overcome this limitation and add radioactive nuclei (18F or 68Ga) for PET imaging, I synthesized two 4-N­-alkylgemcitabine analogues i) bearing β-keto tosylate moiety for subsequent 18F-fluorination and ii) having SCN-Bn-NOTA chelator to complex 68Ga. The first was synthesized by replacement of tosylamide in 4-N­-tosylgemcitabine with 1-amino-10-undecene, followed by elaboration of terminal alkene through dihydroxylation, regioselective tosylation and oxidation. Subsequent fluorination using KF in presence of 18-Crown-6 at 75°C for 1 hr gave 4-N­-alkylgemcitabine fluoromethyl ketone. The second was synthesized by analogous replacement of tosylamide with N-Boc-1,3-propanediamine, followed by deprotection with TFA. The reactive terminal amine was condensed with SCN-Bn-NOTA, giving 4-N­-alkylgemcitabine-SCN-Bn-NOTA ligand, which efficiently complexed Ga or 68Ga for in vivo PET studies in rats. Clofarabine is a highly effective chemotherapeutic adenosine analogue used for treatment of acute lymphoblastic leukemia. Clofarabine undergoes rate limiting phosphorylation from its 5\u27-monophosphate to 5\u27-diphosphate by purine monophosphate kinase, and possible dephosphorylation of its respective 5\u27-monophosphate by 5\u27-nucleotidases. Synthesis of clofarabine diphosphate prodrugs, and potentially their 18F-radiolabeled analogues, were undertaken to overcome these limitations. Successful synthesis of model adenosine diphosphate prodrug, by coupling adenosine monophosphate with bis(benzoyloxybenzyl) phosphoramidite in presence of 5-phenyl-1-H­-tetrazole activator was achieved. The aminyl radical generated from azide moiety in 3\u27-azido-3\u27-deoxythymidine (3\u27-AZT) or 5-azidomethyl-2\u27-deoxyuridine (AmdU), upon addition of radiation-produced electrons, is thought to be the source of their radiosensitizing effects. Herein, I report synthesis of azido-modified purine and pyrimidine analogues for EPR study of formation of reactive aminyl radical in guanine, adenine and cytidine bases. The EPR studies of electron addition to 2-azidoguanosine (i.e. 2-azidoinsoine), protected 4-azidocytidine and 4-tetrazolocytidine analogues clearly establish that the position of the azide in base moiety dictates reactivity. The azide directly attached to nucleobases at ortho/para position to ring nitrogens produce stable RN3•- that does not rapidly convert to aminyl radical, except in the excited state. Hence, these did not display much radiosensitizing effects in in vivo biological studies in MDA-MB-231, MCF7 and U87 cell lines

Green manure in coffee systems in the region of Zona da Mata, Minas Gerais: characteristics and kinetics of carbon and nitrogen mineralization.

The use of green manure may contribute to reduce soil erosion and increase the soil organic matter content and N availability in coffee plantations in the Zona da Mata, State of Minas Gerais, in Southeastern Brazil. The potential of four legumes (A. pintoi, C. mucunoides, S. aterrimum and S. guianensis)to produce above-ground biomass, accumulate nutrients and mineralize N was studied in two coffee plantations of subsistence farmers under different climate conditions. The biomass production of C. mucunoides was influenced by the shade of the coffee plantation.C. mucunoides tended to mineralize more N than the other legumes due to the low polyphenol content and polyphenol/N ratio. In the first year, the crop establishment of A. pintoi in the area took longer than of the other legumes, resulting in lower biomass production and N2 fixation. In the long term, cellulose was the main factor controlling N mineralization. The biochemical characteristics, nutrient accumulation and biomass production of the legumes were greatly influenced by the altitude and position of the area relative to the sun

Thaptomys Thomas 1915 (Rodentia, Sigmodontinae, Akodontini) with karyotypes 2n = 50, FN = 48, and 2n = 52, FN = 52: Two monophyletic lineages recovered by molecular phylogeny

A novel karyotype with 2n = 50, FN = 48, was described for specimens of Thaptomys collected at Una, State of Bahia, Brazil, which are morphologically indistinguishable from Thaptomys nigrita, 2n = 52, FN = 52, found in other localities. It was hence proposed that the 2n = 50 karyotype could belong to a distinct species, cryptic of Thaptomys nigrita, once chromosomal rearrangements observed, along with the geographic distance, might represent a reproductive barrier between both forms. Phylogenetic analyses using maximum parsimony and maximum likelihood based on partial cytochrome b sequences with 1077 bp were performed, attempting to establish the relationships among the individuals with distinct karyotypes along the geographic distribution of the genus; the sample comprised 18 karyotyped specimens of Thaptomys, encompassing 15 haplotypes, from eight different localities of the Atlantic Rainforest. The intra-generic relationships corroborated the distinct diploid numbers, once both phylogenetic reconstructions recovered two monophyletic lineages, a northeastern clade grouping the 2n = 50 and a southeastern clade with three subclades, grouping the 2n = 52 karyotype. The sequence divergence observed between their individuals ranged from 1.9% to 3.5%

Somatotypes trajectories during adulthood and their association with COPD phenotypes

Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. Objectives: We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood follow different trajectories to reach distinct phenotypes. Methods: Using the validated Stunkard’s Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. Measurements and main results: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2 ) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m−2 ). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD

Search for Third Generation Vector Leptoquarks in p anti-p Collisions at sqrt(s) = 1.96 TeV

We describe a search for a third generation vector leptoquark (VLQ3) that decays to a b quark and tau lepton using the CDF II detector and 322 pb^(-1) of integrated luminosity from the Fermilab Tevatron. Vector leptoquarks have been proposed in many extensions of the standard model (SM). Observing a number of events in agreement with SM expectations, assuming Yang-Mills (minimal) couplings, we obtain the most stringent upper limit on the VLQ3 pair production cross section of 344 fb (493 fb) and lower limit on the VLQ3 mass of 317 GeV/c^2 (251 GeV/c^2) at 95% C.L.Comment: 7 pages, 2 figures, submitted to PR

Ambulatory health service users' experience of waiting time and expenditure and factors associated with the perception of low quality of care in Mexico

<p>Abstract</p> <p>Background</p> <p>A principal reason for low use of public health care services is the perception of inferior quality of care. Studying health service user (HSU) experiences with their care and their perception of health service quality is critical to understanding health service utilization. The aim of this study was to define reference points for some aspects of health care quality and to analyze which HSU experiences resulted in perceptions of overall low quality of care.</p> <p>Methods</p> <p>Data from the National Health Survey 2006 were used to compare the experiences of HSUs with their ambulatory care at Ministry of Health and affiliated institutions (MOH), social security institutions (SSI) and private institutions (PrivI). Reference points of quality of care related to waiting time and expenditure were defined for each of the three types of institutions by analyzing HSU experiences rated as 'acceptable'. A multivariable logistic regression model was used to identify the principal factors associated with the general perception of low quality of care.</p> <p>Results</p> <p>A total of 11,959 HSUs were included in the analysis, of whom 37.6% (n = 4,500) HSUs received care at MOH facilities; 31.2% (n = 3,730) used SSI and 31.2% (n = 3,729) PrivI. An estimated travel and waiting time of 10 minutes respectively was rated as acceptable by HSUs from all institutions. The differences between the waiting time rated as acceptable and the actual waiting time were the largest for SSI (30 min) in comparison to MoH (20 min) and PrivI (5 min) users. The principal factors associated with an overall perception of low quality of care are type of institution (OR 4.36; 95% CI 2.95-6.44), waiting time (OR 3.20; 95% CI 2.35-4.35), improvement of health after consultation (OR 2.93; CI 2.29-3.76) and consultation length of less than 20 minutes (2.03; 95% CI 1.60-2.57).</p> <p>Conclusions</p> <p>The reference points derived by the HSUs' own ratings are useful in identifying where quality improvements are required. Prioritizing the reduction of waiting times and improving health status improvement after consultation would increase overall quality of care ratings.</p

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV