Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 306
Filtrar
1.
Appl Radiat Isot ; 190: 110509, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36306679

RESUMO

To determine the safety of using argon as a deuteron beam stopping material, the  40Ar(d,p)41Ar cross section was measured at average deuteron energies of 3.6 MeV, 5.5 MeV, and 7.0 MeV using an activation method. A 16-MeV deuteron beam produced by Lawrence Berkeley National Laboratory's 88-Inch Cyclotron was degraded to each energy by nickel foils and the front wall of an aluminum gas chamber. The reduced-energy deuterons were used to activate a sample of natAr gas. After each irradiation, the gas chamber's  41Ar activation was measured with a high-purity germanium detector. The cross sections measured were larger than a previous measurement by ∼40%.


Assuntos
Ciclotrons
2.
J Adv Model Earth Syst ; 14(6): e2021MS002852, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35864944

RESUMO

The NASA Goddard Earth Observing System (GEOS) Composition Forecast (GEOS-CF) provides recent estimates and 5-day forecasts of atmospheric composition to the public in near-real time. To do this, the GEOS Earth system model is coupled with the GEOS-Chem tropospheric-stratospheric unified chemistry extension (UCX) to represent composition from the surface to the top of the GEOS atmosphere (0.01 hPa). The GEOS-CF system is described, including updates made to the GEOS-Chem UCX mechanism within GEOS-CF for improved representation of stratospheric chemistry. Comparisons are made against balloon, lidar, and satellite observations for stratospheric composition, including measurements of ozone (O3) and important nitrogen and chlorine species related to stratospheric O3 recovery. The GEOS-CF nudges the stratospheric O3 toward the GEOS Forward Processing (GEOS FP) assimilated O3 product; as a result the stratospheric O3 in the GEOS-CF historical estimate agrees well with observations. During abnormal dynamical and chemical environments such as the 2020 polar vortexes, the GEOS-CF O3 forecasts are more realistic than GEOS FP O3 forecasts because of the inclusion of the complex GEOS-Chem UCX stratospheric chemistry. Overall, the spatial patterns of the GEOS-CF simulated concentrations of stratospheric composition agree well with satellite observations. However, there are notable biases-such as low NO x and HNO3 in the polar regions and generally low HCl throughout the stratosphere-and future improvements to the chemistry mechanism and emissions are discussed. GEOS-CF is a new tool for the research community and instrument teams observing trace gases in the stratosphere and troposphere, providing near-real-time three-dimensional gridded information on atmospheric composition.

3.
J Intellect Disabil Res ; 64(10): 782-792, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32840041

RESUMO

BACKGROUND: People with intellectual disabilities (IDs) or autism are at great risk of being victims of physical and sexual abuse. This study uses transcriptions of real-life investigative interviews to examine the interview techniques (e.g. question type) used in investigative interviews of these groups of alleged victims. METHODS: A national sample of transcribed investigative interviews (N = 96) of alleged victims with mild ID (n = 48, age 5-70 years old), moderate ID (n = 18, age 14-43 years old) and autism (n = 16, age 5-50 years old) was analysed. RESULTS: The study shows a preponderance of alleged sexual offences (70.7%) and reveals that open-ended questions account for only 2.6% of the total number of questions asked. The interviewers relied heavily on yes/no (53.4%) and directive questions (32.2%). Suggestive questions (8.6%) were frequently used. CONCLUSIONS: The use of question type varied considerably within and across the diagnostic group. The study reveals the need for a more in-depth analysis of variables that influence investigative interviews of people with cognitive impairments.


Assuntos
Transtorno Autístico/epidemiologia , Vítimas de Crime/estatística & dados numéricos , Deficiência Intelectual/epidemiologia , Entrevistas como Assunto/métodos , Polícia , Delitos Sexuais/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Adulto Jovem
4.
Sci Total Environ ; 732: 138994, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32438157

RESUMO

Increasing soil organic carbon (SOC) can improve the capacity of agricultural systems to both adapt to and mitigate climate change. Despite its importance, the current understanding of the magnitude or even the direction of SOC change in agricultural landscapes is limited. While changes in land use/land cover (LULC) and climate are among the main drivers of changes in SOC, their relative importance for the spatiotemporal assessment of SOC is unclear. This study evaluated LULC and SOC dynamics using archived and recent soil samples, remote sensing, and digital soil mapping in the Lower Fraser Valley of British Columbia, Canada. We combined both pixel- and object-based analysis of Landsat satellite imagery to assess LULC changes from 1984 to 2018. We achieved an overall accuracy of 81% and kappa coefficient of 0.77 for LULC classification using a random forest model. For predicting SOC for the same time period, we applied soil and vegetation indices derived from Landsat images, topographic indices, historic soil survey variables, and climate data in a random forest model. The SOC prediction of 2018 resulted in a coefficient of determination (R2) of 0.67, concordance correlation coefficient (CCC) of 0.76, and normalized root mean square error (nRMSE) of 0.12. For 1984, the SOC prediction accuracies were 0.46, 0.58, and 0.18 for R2, CCC, and nRMSE, respectively. We detected SOC loss in 61%, gain in 12%, while 27% remained unchanged across the study area. Although we detected large losses of SOC due to LULC change, the majority of the SOC losses across the landscape were attributed to areas that were remained in the same type of agricultural production since 1984. Climate variability did not, however, have a strong effect on SOC changes. These results can inform decision making in the study area to support sustainable LULC management for enhancing SOC sequestration.

5.
J Phys Chem A ; 121(21): 4123-4131, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28452481

RESUMO

Lactones, cyclic esters of hydroxycarboxylic acids, are interesting biofuel candidates as they can be made from cellulosic biomass and have favorable physical and chemical properties for distribution and use. The reactions of γ-valerolactone (GVL), γ-crotonolactone (2(5H)-F), and α-methyl-γ-crotonolactone (3M-2(5H)-F) with Cl, OD, and O3 were investigated in a static chamber at 700 Torr and 298 ± 2 K. The relative rate method was used to determine kGVL+Cl = (4.56 ± 0.51) × 10-11, kGVL+OD = (2.94 ± 0.41) × 10-11, k2(5H)-F+Cl = (2.94 ± 0.41) × 10-11, k2(5H)-F+OD = (4.06 ± 0.073) × 10-12, k3M-2(5H)-F+Cl = (16.1 ± 1.8) × 10-11, and k3M-2(5H)-F+OD = (12.6 ± 0.52) × 10-12, all rate coefficients in units of cm3 molecule-1 s-1. An absolute rate method was used to determine k2(5H)-F+O3 = (6.73 ± 0.18) × 10-20 and k3M-2(5H)-F+O3 = (5.42 ± 1.23) × 10-19 in units of cm3 molecule-1 s-1. Products were identified for reactions of the lactones with Cl. In the presence of O2 the products are formic acid (HCOOH), formyl chloride (CHClO), and phosgene (CCl2O), and also maleic anhydride (C2H2(CO)2O) for 2(5H)-F. In addition both reactions produced a number of unidentified products that likely belong to molecules with the ring-structure intact. A review of literature data for reactions of other furans show that the reactivity of the lactones are generally lower compared to that of corresponding compounds without the carbonyl group.

6.
Ann Oncol ; 27(7): 1257-66, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27052653

RESUMO

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.


Assuntos
Carcinoma/patologia , Carcinossarcoma/patologia , Sarcoma/patologia , Neoplasias Uterinas/patologia , Adulto , Idoso , Carcinoma/tratamento farmacológico , Carcinoma/epidemiologia , Carcinoma/radioterapia , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/epidemiologia , Carcinossarcoma/radioterapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Ifosfamida , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/epidemiologia , Sarcoma/radioterapia , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/radioterapia
7.
Oncogene ; 35(10): 1283-91, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26050618

RESUMO

Recent efforts to comprehensively characterize the mutational landscape of non-small cell lung cancer have identified frequent mutations in the receptor tyrosine kinase ERBB4. However, the significance of mutated ERBB4 in non-small cell lung cancer remains elusive. Here, we have functionally characterized nine ERBB4 mutations previously identified in lung adenocarcinoma. Four out of the nine mutations, Y285C, D595V, D931Y and K935I, were found to be activating, increasing both basal and ligand-induced ErbB4 phosphorylation. According to structural analysis, the four activating mutations were located at critical positions at the dimerization interfaces of the ErbB4 extracellular (Y285C and D595V) and kinase (D931Y and K935I) domains. Consistently, the mutations enhanced ErbB4 dimerization and increased the trans activation in ErbB4 homodimers and ErbB4-ErbB2 heterodimers. The expression of the activating ERBB4 mutants promoted survival of NIH 3T3 cells in the absence of serum. Interestingly, serum starvation of NIH 3T3 cells expressing the ERBB4 mutants only moderately increased the phosphorylation of canonical ErbB signaling pathway effectors Erk1/2 and Akt as compared with wild-type ERBB4. In contrast, the mutations clearly enhanced the proteolytic release of signaling-competent ErbB4 intracellular domain. These results suggest the presence of activating driver mutations of ERBB4 in non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Mutação , Receptor ErbB-4/genética , Receptor ErbB-4/metabolismo , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Ativação Enzimática , Espaço Extracelular/enzimologia , Humanos , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Células NIH 3T3 , Multimerização Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Receptor ErbB-4/química
8.
Int J Toxicol ; 33(5): 367-72, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25185974

RESUMO

The explosive 3-nitro-1,2,4-triazol-5-one (NTO) is an insensitive formulation developed to replace high energetics that are susceptible to accidental detonation from heat, shock, and impact. Although studies have shown NTO to be nontoxic at acute exposures, recent subacute and subchronic tests have demonstrated effects on testes and subsequent sperm production in rats. This study assessed endocrine disruption as a potential mechanism for these reproductive effects via the Hershberger and uterotrophic bioassays. These assays are 2 of the US Environmental Protection Agency's tier 1 in vivo screens for the Endocrine Disruptor Screening Program that measure differences in androgen- and estrogen-sensitive tissue weights in castrated and ovariectomized rats. The gonadectomized rats were orally exposed to NTO in a corn oil vehicle at doses of 250, 500, or 1000 mg/kg body weight (bw)/d for 10 and 3 days for the Hershberger and uterotrophic assays, respectively, according to standard protocols. Male rats also received testosterone (0.2 mg/kg/d, subcutaneous) and antiandrogenic flutamide (3mg/kg/d, oral) as negative and positive controls, and females received 17 α-ethynyl estradiol (0.3 µg/d, subcutaneous) as positive controls. 3-Nitro-1,2,4-triazol-5-one caused neither a decrease in androgen-sensitive male reproductive selected tissue (seminal vesicles with fluid/without fluid, glans penis, Cowper gland, ventral prostrate, and levator ani-bulbocavernosus) weights nor a change in uterine weights. The results of this study provide no evidence to suggest that NTO acts like an estrogenic or antiandrogenic endocrine disruptor in rats at these doses.


Assuntos
Disruptores Endócrinos/toxicidade , Substâncias Explosivas/toxicidade , Nitrocompostos/toxicidade , Testículo/efeitos dos fármacos , Triazóis/toxicidade , Útero/efeitos dos fármacos , Antagonistas de Androgênios/farmacologia , Animais , Antagonistas de Estrogênios/farmacologia , Feminino , Genitália/efeitos dos fármacos , Genitália/crescimento & desenvolvimento , Masculino , Orquiectomia , Tamanho do Órgão , Ovariectomia , Ratos , Ratos Sprague-Dawley
9.
J Chem Phys ; 138(9): 094314, 2013 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-23485301

RESUMO

The ultraviolet photodissociation of carbonyl sulfide (OCS) was studied using three-dimensional potential energy surfaces and both quantum mechanical dynamics calculations and classical trajectory calculations including surface hopping. The transition dipole moment functions used in an earlier study [J. A. Schmidt, M. S. Johnson, G. C. McBane, and R. Schinke, J. Chem. Phys. 137, 054313 (2012)] were improved with more extensive treatment of excited electronic states. The new functions indicate a much larger contribution from the 1(1)A(") state ((1)Σ(-) in linear OCS) than was found in the previous work. The new transition dipole functions yield absorption spectra that agree with experimental data just as well as the earlier ones. The previously reported potential energy surfaces were also empirically modified in the region far from linearity. The resulting product state distributions Pv, j, angular anisotropy parameters ß(j), and carbon monoxide rotational alignment parameters A0 ((2))(j) agree reasonably well with the experimental results, while those computed from the earlier transition dipole and potential energy functions do not. The higher-j peak in the bimodal rotational distribution is shown to arise from nonadiabatic transitions from state 2(1)A(') to the OCS ground state late in the dissociation.


Assuntos
Teoria Quântica , Óxidos de Enxofre/química , Raios Ultravioleta , Processos Fotoquímicos
10.
J Chem Phys ; 137(5): 054313, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22894354

RESUMO

Global three dimensional potential energy surfaces and transition dipole moment functions are calculated for the lowest singlet and triplet states of carbonyl sulfide at the multireference configuration interaction level of theory. The first ultraviolet absorption band is then studied by means of quantum mechanical wave packet propagation. Excitation of the repulsive 2 (1)A' state gives the main contribution to the cross section. Excitation of the repulsive 1 (1)A" state is about a factor of 20 weaker at the absorption peak (E(ph) ≈ 45,000 cm(-1)) but becomes comparable to the 2 (1)A' state absorption with decreasing energy (35,000 cm(-1)) and eventually exceeds it. Direct excitation of the repulsive triplet states is negligible except at photon energies E(ph) < 38,000 cm(-1). The main structure observed in the cross section is caused by excitation of the bound 2 (3)A" state, which is nearly degenerate with the 2 (1)A' state in the Franck-Condon region. The structure observed in the low energy tail of the spectrum is caused by excitation of quasi-bound bending vibrational states of the 2 (1)A' and 1 (1)A" electronic states. The absorption cross sections agree well with experimental data and the temperature dependence of the cross section is well reproduced.

11.
J Chem Phys ; 136(13): 131101, 2012 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-22482532

RESUMO

The first absorption band of OCS (carbonyl sulfide) is analyzed using potential energy surfaces and transition dipole moment functions of the lowest four singlet and the lowest four triplet states. Excitation of the 2 (1)A' state is predominant except at very low photon energies. It is shown that the vibrational structures in the center of the band are due to excitation of the 2 (3)A'' triplet state, whereas the structures at very low energies are caused by bending excitation in the potential wells of states 2 (1)A' and 1 (1)A''.

12.
Heredity (Edinb) ; 108(3): 229-35, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21811302

RESUMO

Hotter conditions favour effectively unbanded (EUB) shells in the snail Theba pisana. T. pisana is also polymorphic for colour of the shell's apex, determined by a pair of alleles at a locus linked to the banding locus. Apex colour is epistatic to shell banding, such that banded snails with a dark apex have darker bands. Annual censuses over 22 years across an ecotone between a sheltered Acacia thicket and open dune vegetation showed a persistent association of both EUB shells and pale apex with the Open habitat. The parallel variation was due partly to strong phenotypic disequilibrium, as the combination of EUB with dark apex was rare. Nevertheless, in fully banded shells the frequency of pale apex was also higher in the Open habitat, confirming independent, parallel associations of the two contributors to paleness. Within the Acacia habitat, temporal variation of the frequencies of banding morphs was much greater than for apex colour, and EUB shells were associated with hotter summers. Consistent with its primary effect only on the very small snails, apex colour did not vary with summer conditions, but instead, higher frequencies of pale apices were associated with sunnier winters. The intensity of selection was lower on apex colour than shell banding, due partly to the constraint of phenotypic disequilibrium. The shell traits in T. pisana are an example of complex responses to climatic variation, in which phenotypic disequilibrium constrains evolution of apex colour, but separate mechanisms of selection are evident.


Assuntos
Clima , Epistasia Genética , Fenótipo , Caramujos/genética , Exoesqueleto/anatomia & histologia , Animais , Evolução Biológica , Ecossistema , Interação Gene-Ambiente , Seleção Genética
13.
J Chem Phys ; 135(19): 194303, 2011 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-22112078

RESUMO

The role of triplet states in the UV photodissociation of N(2)O is investigated by means of quantum mechanical wave packet calculations. Global potential energy surfaces are calculated for the lowest two (3)A' and the lowest two (3)A'' states at the multi-reference configuration interaction level of electronic structure theory using the augmented valence quadruple zeta atomic basis set. Because of extremely small transition dipole moments with the ground electronic state, excitation of the triplet states has only a marginal effect on the far red tail of the absorption cross section. The calculations do not show any hint of an increased absorption around 280 nm as claimed by early experimental studies. The peak observed in several electron energy loss spectra at 5.4 eV is unambiguously attributed to the lowest triplet state 1(3)A'. Excitation of the 2(1)A' state and subsequent transition to the repulsive branch of the 2(3)A'' state at intermediate NN-O separations, promoted by spin-orbit coupling, is identified as the main pathway to the N(2)((1)Σ(g)(+))+O((3)P) triplet channel. The yield, determined in two-state wave packet calculations employing calculated spin-orbit matrix elements, is 0.002 as compared to 0.005 ± 0.002 measured by Nishida et al. [J. Phys. Chem. A 108, 2451 (2004)].


Assuntos
Óxido Nitroso/química , Teoria Quântica , Processos Fotoquímicos
14.
J Chem Phys ; 135(2): 024311, 2011 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-21766946

RESUMO

The energy partitioning in the UV photodissociation of N(2)O is investigated by means of quantum mechanical wave packet and classical trajectory calculations using recently calculated potential energy surfaces. Vibrational excitation of N(2) is weak at the onset of the absorption spectrum, but becomes stronger with increasing photon energy. Since the NNO equilibrium angles in the ground and the excited state differ by about 70°, the molecule experiences an extraordinarily large torque during fragmentation producing N(2) in very high rotational states. The vibrational and rotational distributions obtained from the quantum mechanical and the classical calculations agree remarkably well. The shape of the rotational distributions is semi-quantitatively explained by a two-dimensional version of the reflection principle. The calculated rotational distribution for excitation with λ = 204 nm and the translational energy distribution for 193 nm agree well with experimental results, except for the tails of the experimental distributions corresponding to excitation of the highest rotational states. Inclusion of nonadiabatic transitions from the excited to the ground electronic state at relatively large N(2)-O separations, studied by trajectory surface hopping, improves the agreement at high j.


Assuntos
Óxido Nitroso/química , Elétrons , Fotólise , Teoria Quântica
15.
Br J Pharmacol ; 164(5): 1558-72, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21649638

RESUMO

BACKGROUND AND PURPOSE: Some large antagonist ligands (ARC239, chlorpromazine, prazosin, spiperone, spiroxatrine) bind to the human α(2A) -adrenoceptor with 10- to 100-fold lower affinity than to the α(2B)- and α(2C)-adrenoceptor subtypes. Previous mutagenesis studies have not explained this subtype selectivity. EXPERIMENTAL APPROACH: The possible involvement of the extracellular amino terminus and transmembrane domain 1 (TM1) in subtype selectivity was elucidated with eight chimaeric receptors: six where TM1 and the N-terminus were exchanged between the α(2)-adrenoceptor subtypes and two where only TM1 was exchanged. Receptors were expressed in CHO cells and tested for ligand binding with nine chemically diverse antagonist ligands. For purposes of interpretation, molecular models of the three human α(2)-adrenoceptors were constructed based on the ß(2)-adrenoceptor crystal structure. KEY RESULTS: The affinities of three antagonists (spiperone, spiroxatrine and chlorpromazine) were significantly improved by TM1 substitutions of the α(2A)-adrenoceptor, but reciprocal effects were not seen for chimaeric receptors based on α(2B)- and α(2C)-adrenoceptors. Molecular docking of these ligands suggested that binding occurs in the orthosteric ligand binding pocket. CONCLUSIONS AND IMPLICATIONS: TM1 is involved in determining the low affinity of some antagonist ligands at the human α(2A)-adrenoceptor. The exact mechanism is not known, but the position of TM1 at a large distance from the binding pocket indicates that TM1 does not participate in specific side-chain interactions with amino acids within the binding pocket of the receptor or with ligands bound therein. Instead, molecular models suggest that TM1 has indirect conformational effects related to the charge distribution or overall shape of the binding pocket.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Clorpromazina/farmacologia , Dioxanos/farmacologia , Receptores Adrenérgicos alfa 2/metabolismo , Espiperona/farmacologia , Compostos de Espiro/farmacologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Ligação Competitiva , Células CHO , Técnicas de Cultura de Células , Cricetinae , Cricetulus , Humanos , Ligantes , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Receptores Adrenérgicos alfa 2/química , Receptores Adrenérgicos alfa 2/genética , Alinhamento de Sequência , Transfecção
16.
Heredity (Edinb) ; 106(5): 741-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20823904

RESUMO

Few continuous, long-term studies have measured the intensity and variability of natural selection within a framework of clear adaptive hypotheses. In the snail Theba pisana, the proportion of effectively unbanded shells is higher in exposed habitats than in adjacent acacia thickets, which has been explained by microclimatic selection. Comparisons across an ecotone for 34 consecutive years determined the combined effects on morph frequencies of habitat and changes in weather conditions during summer. The long-term average (±s.e.) frequency of effectively unbanded shells was 0.577±0.011 in the open habitat when compared with 0.353±0.005 in the acacia. The persistent association of shell banding with habitat accounted for 34% of the variation in morph frequencies. Differences among years were also large, representing 23% of the variation. Higher proportions of effectively unbanded snails were associated with hotter, sunnier summers. Thus, temporal variation supports the hypothesis of microclimatic selection, consistent with the spatial association with habitat. Based on observed rates of change, the mean annual selection on this polymorphism was about 0.13, but with a large variance: s was as high as 0.5, but 0.05 in about 40% of the years. The large variance and frequent reversals in direction of selection indicate a potential for rapid genetic change, but with little net change in morph frequencies over three decades, highlighting the value of long-term continuous studies of populations facing natural environmental variation.


Assuntos
Clima , Ecossistema , Pigmentação/genética , Seleção Genética , Caramujos/genética , Animais , Caramujos/fisiologia , Austrália Ocidental
17.
Thromb Haemost ; 103(2): 387-97, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20126829

RESUMO

Interaction of blood platelets with vascular collagen is an initiating event in haemostasis and thrombus formation. Based on molecular modelling of human integrin alpha2I domain and cell-based screening assays we have developed sulfonamide derivatives, a mechanistically novel class of molecules. These molecules show antiplatelet efficacy by selectively inhibiting alpha2beta1 integrin-mediated collagen binding. One sulfonamide derivative, named BTT-3016, showed inhibitory capacity in several assessments of human platelet interaction with collagen. It inhibited about 90% of the aggregation of gel-filtered magnesium-supplemented platelets and 70% of aggregation in PPACK-anticoagulated platelet-rich plasma when stimulated with collagen but not with ADP. The antiplatelet activity of BTT-3016 was dependent on alpha2beta1 integrin, since in collagen binding test BTT-3016 had no effect on the platelets derived from alpha2 integrin null mice. When tested in an in vivo model in mice, BTT-3016 clearly reduced thrombus formation on the vessel wall after vascular injury. Furthermore, BTT-3016 prolonged tail-bleeding time in a manner comparable to aspirin. We show that new alpha2beta1 inhibitors exert collagen-specific antiplatelet activity and regulate thrombus growth in vivo without compromising primary haemostasis more than aspirin. We suggest that the alpha2beta1 inhibiting strategy could be further developed for the prevention and treatment of arterial thrombosis.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Integrina alfa2beta1/antagonistas & inibidores , Inibidores da Agregação Plaquetária/farmacologia , Sulfonamidas/farmacologia , Trombose/prevenção & controle , Animais , Aspirina/farmacologia , Tempo de Sangramento , Colágeno/metabolismo , Avaliação Pré-Clínica de Medicamentos , Fibrinolíticos , Hemostasia/efeitos dos fármacos , Camundongos , Inibidores da Agregação Plaquetária/química , Ligação Proteica/efeitos dos fármacos , Sulfonamidas/química , Sulfonamidas/uso terapêutico , Trombose/tratamento farmacológico
18.
Opt Lett ; 35(3): 354-6, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20125719

RESUMO

What we believe to be the first demonstration of isotope-specific detection of a low-Z and low density object shielded by a high-Z and high-density material using monoenergetic gamma rays is reported. The isotope-specific detection of LiH shielded by Pb and Al is accomplished using the nuclear resonance fluorescence line of L7i at 478 keV. Resonant photons are produced via laser-based Compton scattering. The detection techniques are general, and the confidence level obtained is shown to be superior to that yielded by conventional x-ray and gamma-ray techniques in these situations.

19.
J Small Anim Pract ; 50(9): 498-502, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19769672
20.
Int J Body Compos Res ; 7(3): 99-107, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20686636

RESUMO

OBJECTIVE: To validate the use of quantitative magnetic resonance (QMR) to measure fat and lean mass in conscious rats. METHODS: Fifty Osborne-Mendel rats (249-770 g) were scanned using the Echo Medical 2 MHz body composition analyzer. Each rat was scanned under six settings (three acquisition times, with and without determination of total water). Precision was determined by the calculated coefficient of variation (CV) of three consecutive scans. Accuracy was determined by comparing the first scan to chemical carcass analysis and analyzed by paired t-tests and least-squares regression analyses. Twenty-five rats were used in the validation study, and 25 in the cross-validation study. RESULTS: The precision for fat, lean and water at all settings was <1%. QMR significantly overestimated fat (~5%; P<0.0001), and underestimated both lean (~12.5%; P<0.0001) and total water (~5.5%; P<0.0001). All QMR measures were significantly correlated with carcass measures (r(2)>0.99; P<0.0001). Using prediction equations from the validation study with the cross-validation rats, there were no significant differences between QMR fat and carcass fat at any setting (P>0.400). For four of the six QMR settings, there were no significant differences between QMR and carcass lean (P>0.05). For total water, all QMR settings were significantly different than carcass (P<0.05), but only by ~1%. CONCLUSIONS: QMR showed excellent precision for the determination of fat, lean and water. Despite overestimating fat and underestimating lean and water, all were highly related to carcass values. When tested in the cross-validation group, QMR fat could be accurately predicted at all settings; however, lean mass (two settings) and water were still slightly different (less than 1%).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...