RESUMO
On-chip demagnetization refrigeration has recently emerged as a powerful tool for reaching microkelvin electron temperatures in nanoscale structures. The relative importance of cooling on-chip and off-chip components and the thermal subsystem dynamics are yet to be analyzed. We study a Coulomb blockade thermometer with on-chip copper refrigerant both experimentally and numerically, showing that dynamics in this device are captured by a first-principles model. Our work shows how to simulate thermal dynamics in devices down to microkelvin temperatures, and outlines a recipe for a low-investment platform for quantum technologies and fundamental nanoscience in this novel temperature range.
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The Republic of the Marshall Islands (RMI) has been affected by marine pollution from militarization and urbanization. To address concerns raised by the Marshall Islands Marine Resources Authority, this study examined concentrations of dissolved contaminants in reef and pelagic fishes in the RMI and assessed potential associated risks. Metals, organochlorine pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) were examined in reef and pelagic fishes from six atolls: Kwajalein, Majuro, Jaluit, Utirik, Rongelap, and Wotje. Clear trophic patterns emerged for metals. Total arsenic was highest in higher trophic level reef fishes, particularly in the camouflage grouper (Epinephelus polyphekadion) (>100 µg g-1 total As), but inorganic arsenic was negligible in higher trophic levels and showed an inverse trend with the highest percentages present in parrotfishes and herbivores. Copper and mercury were elevated in higher trophic level reef and pelagic fishes, respectively, and the maximum mercury concentrations (6.45 µg g-1 in Gymnosarda unicolor) were among the highest reported in the Pacific. Conversely, cadmium and lead were highest in lower trophic levels, like surgeonfishes and parrotfishes. PCBs were more clearly linked to locations and were highest at two atolls with military history (Kwajalein and Jaluit) (>U.S. EPA Screening Value of 2.5 ppb). PAHs were ubiquitous across taxa (detected in 97% of samples), but the highest concentrations were in lower trophic levels. Organochlorine pesticides were detected at very low concentrations that do not likely pose a risk. We compare concentrations to established thresholds for human health and find that - for specific locations and species - contaminant concentrations may pose a risk to fish and other marine taxa, as well as human consumers. This study provides baseline information that aids the development of marine conservation and public health recommendations and addresses a data gap that persists for marine pollution throughout the Pacific Islands.
Assuntos
Arsênio , Bass , Hidrocarbonetos Clorados , Mercúrio , Praguicidas , Bifenilos Policlorados , Poluentes Químicos da Água , Animais , Humanos , Bifenilos Policlorados/análise , Arsênio/análise , Hidrocarbonetos Clorados/análise , Peixes , Mercúrio/análise , Metais , Praguicidas/análise , Micronésia , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
In quantizing magnetic fields, graphene superlattices exhibit a complex fractal spectrum often referred to as the Hofstadter butterfly. It can be viewed as a collection of Landau levels that arise from quantization of Brown-Zak minibands recurring at rational (p/q) fractions of the magnetic flux quantum per superlattice unit cell. Here we show that, in graphene-on-boron-nitride superlattices, Brown-Zak fermions can exhibit mobilities above 106 cm2 V-1 s-1 and the mean free path exceeding several micrometers. The exceptional quality of our devices allows us to show that Brown-Zak minibands are 4q times degenerate and all the degeneracies (spin, valley and mini-valley) can be lifted by exchange interactions below 1 K. We also found negative bend resistance at 1/q fractions for electrical probes placed as far as several micrometers apart. The latter observation highlights the fact that Brown-Zak fermions are Bloch quasiparticles propagating in high fields along straight trajectories, just like electrons in zero field.
RESUMO
As childhood obesity increases, it is becoming important to understand the complications of obesity in children and develop novel biomarkers. Evidence indicates that microRNAs (miRNA) are dys-regulated in obesity and may serve as sensitive and specific circulating biomarkers. Non-alcoholic fatty liver disease (NAFLD) is a complication of obesity that ultimately requires a liver biopsy to determine disease severity. While studies have been conducted in adults, no study to date has examined circulating miRNAs in children with obesity and NAFLD. The goal of this study was to evaluate a panel of selected circulating miRNAs in obese children compared to healthy controls. We present here an analysis of a pre-selected panel of 20 candidate miRNAs in obese children compared to healthy controls. The miRNAs were chosen based on having been previously reported to be involved in NAFLD. We found that 16 out of 20 miRNAs tested were elevated at least twofold in children with obesity compared to controls. miR-122 and miR-199a showed the greatest increase in children with obesity versus controls. Both also had a high area under the curve when receiver-operator curves were plotted. Several circulating miRNAs correlated with body mass index (BMI) or serum transaminases. This study provides initial evidence that circulating miRNAs can be measured in the paediatric population and provides several diagnostic candidates increased in children with obesity that may be relevant to NAFLD.
Assuntos
MicroRNAs/sangue , Obesidade Infantil/sangue , Adolescente , Biomarcadores , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade Infantil/complicaçõesRESUMO
An energy gap can be opened in the spectrum of graphene reaching values as large as 0.2 eV in the case of bilayers. However, such gaps rarely lead to the highly insulating state expected at low temperatures. This long-standing puzzle is usually explained by charge inhomogeneity. Here we revisit the issue by investigating proximity-induced superconductivity in gapped graphene and comparing normal-state measurements in the Hall bar and Corbino geometries. We find that the supercurrent at the charge neutrality point in gapped graphene propagates along narrow channels near the edges. This observation is corroborated by using the edgeless Corbino geometry in which case resistivity at the neutrality point increases exponentially with increasing the gap, as expected for an ordinary semiconductor. In contrast, resistivity in the Hall bar geometry saturates to values of about a few resistance quanta. We attribute the metallic-like edge conductance to a nontrivial topology of gapped Dirac spectra.
RESUMO
The Escherichia coli aadA gene product, which confers resistance to spectinomycin and streptomycin, has been widely used as a dominant selectable marker for chloroplast transformation of Chlamydomonas and tobacco. An aadA transformation cassette was adapted for expression in Euglena gracilis chloroplasts by replacing the Chlamydomonas promoter and 3' untranslated region (UTR) with the E. gracilis psbA promoter and 3' UTR. Transgenic DNA was introduced into E. gracilis chloroplasts by biolistic transformation. Streptomycin- and spectinomycin-resistant colonies were obtained, which screened positively for the presence of the transforming vector by PCR amplification. Although integration of the transforming DNA into the chloroplast genome was not detected, transforming DNA was stably maintained in the chloroplast as an episomal element during continuous selection on antibiotics. The aadA cassette was also inserted into a transformation vector which contained the independently expressed psbK operon from either E. gracilis or a closely related species, E. stellata. The psbK operon contained at least two group III introns and a group III twintron, was highly expressed, and was only 1.5 kb in length. In transgenic E. gracilis chloroplasts, a truncated E. stellata psbK operon was transcribed, and the resultant pre-mRNA was accurately spliced. This system should allow the first direct analysis of group II and group III intron-splicing mechanisms. In addition, it could prove useful in the study of many other Euglena transcription and processing events.
Assuntos
Cloroplastos/genética , Euglena gracilis/genética , Transformação Genética , Animais , Chlamydomonas/genética , Clonagem Molecular , Euglena gracilis/efeitos dos fármacos , Íntrons , Modelos Genéticos , Estrutura Molecular , Óperon , Reação em Cadeia da Polimerase , Splicing de RNA , RNA Mensageiro/genética , TransgenesRESUMO
A novel mixed operon has been identified in the photosynthetic protist E. gracilis. The genes for psbK, ycf12, psaM, and trnR are co-transcribed. The resulting tetracistronic transcripts are processed through endonucleolytic cleavage of the intergenic spacers and intron splicing to form three mature monocistronic mRNAs and a tRNA. A group III twintron and a group III intron are located in psbK. Another group III intron is found in ycf12. The psbK operon has been cloned by PCR amplification from nine related Euglenoid species. In each species, the gene order and content of the psbK operon is conserved. The psbK operons contain phylogenetically conserved eubacterial promoter, translational, and 3' processing elements. Intron content varies significantly from species to species. Based on a comparison of the intron content with the results of phylogenetic analysis, group III intron evolution within the Euglenoid lineage is much more complex than previously believed.
Assuntos
Proteínas de Algas , Cloroplastos/genética , Euglena/genética , Íntrons , Óperon/genética , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Complexo de Proteína do Fotossistema II , Proteínas de Plantas/metabolismo , Proteínas de Protozoários , Animais , Sequência de Bases , Northern Blotting , Clonagem Molecular , DNA Complementar/metabolismo , Evolução Molecular , Éxons , Genoma , Modelos Genéticos , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , RNA Mensageiro/metabolismo , RNA de Transferência/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
The serotonin transporter (5-HTT) gene is a candidate gene in alcohol dependence because serotonin reuptake inhibitors (SRIs) can alleviate alcohol withdrawal. Studies of the 5-HTT gene in alcohol dependence have not resulted in a consensus. Recent studies have examined the transcriptionally active promoter polymorphism, a 44-bp deletion resulting in short (S) or long (L) alleles. In this study, 131 alcohol-dependent patients of Northern and Western European descent were genotyped. Seventy of these patients were diagnosed with alcohol dependence without comorbid disorders. Sixty-one patients were diagnosed with alcohol dependence comorbid with Tourette syndrome (alcoholic-TS). We found an excess of the S allele in alcohol-dependent patients (47%) compared with 125 ethnically matched controls (39%). A similar trend was found in 150 ethnically matched TS patients without alcohol dependence comorbidity (51%). However, the statistical significance of this trend in the data was not present after Bonferroni correction. The data presented suggests a trend toward increased frequency of the S promoter allele in alcohol-dependent, alcoholic-TS and TS patients.
Assuntos
Alcoolismo/genética , Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Polimorfismo Genético , Adulto , Alcoolismo/complicações , Alelos , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Proteínas da Membrana Plasmática de Transporte de Serotonina , Síndrome de Tourette/complicações , Síndrome de Tourette/genéticaRESUMO
BACKGROUND: In the rat model of forebrain ischemia, long-term dexamethasone treatment is reported to cause hyperglycemia and worsen postischemic functional and histologic injury. This effect was assumed to result from glucose enhancement of intraischemic lactic acidosis within the brain. Short-term insulin therapy restored normoglycemia but did not return histologic injury completely to baseline values. Using a nonischemic rat model, the current study attempted to identify a metabolic basis for such outcome data. METHODS: Fifty-eight halothane-anesthetized (1.3% inspired) Sprague-Dawley rats were assigned randomly to be administered either no treatment (N = 18) or 2 mg/kg intraperitoneal dexamethasone (N = 40). The latter were administered dexamethasone 3 h before the study only (N = 8) or for 3 h before the study plus daily for 1 day (N = 8), 2 days (N = 8), or 4 days (N = 16). Of the rats treated with dexamethasone for 4 days, one half (N = 8) were administered an insulin-containing saline infusion subsequently to restore normoglycemia short-term. All other rats (N = 50) were administered an infusion of saline without insulin. Plasma glucose was quantified, and brains were excised after in situ freezing. Brain glucose and glycogen concentrations were measured using enzymatic fluorometric analyses. RESULTS: After 4 days of dexamethasone treatment, plasma glucose was 159% greater than in rats administered placebo (i.e., 22.01 +/- 4.66 vs. 8.51 +/- 1.65 micromol/ml; mean +/- SD; P < 0.0001). Brain glucose concentrations increased parallel to plasma glucose. An insulin infusion for 27 +/- 5 min restored normoglycemia but resulted in a brain-to-plasma glucose ratio that was 32% greater than baseline values (P < 0.01). Neither dexamethasone nor the combination of dexamethasone plus insulin affected brain glycogen concentrations. CONCLUSIONS: In a nonischemic rat model, dexamethasone alone had no independent effect on the brain-to-plasma glucose ratio. However, short-term insulin therapy caused a dysequilibrium between plasma and brain glucose, resulting in an underestimation of brain glucose concentrations when normoglycemia was restored. The dysequilibrium likely was caused by the rapid rate of glucose reduction. The magnitude of the effect may account for the failure of insulin to reverse dexamethasone enhancement of neurologic injury completely in a previous report that used the rat model of forebrain ischemia.
Assuntos
Encéfalo/metabolismo , Dexametasona/toxicidade , Glucocorticoides/toxicidade , Glucose/metabolismo , Glicogênio/metabolismo , Hiperglicemia/metabolismo , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Encéfalo/efeitos dos fármacos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The dopamine transporter (DAT) provides major regulation of the synaptic levels of dopamine and is a principal target of psychostimulant drugs. Associations between DAT gene polymorphisms and human disorders with possible links to dopaminergic neurotransmission, including attention-deficit/hyperactivity disorder (ADHD) and consequences of cocaine and alcohol administration, have been reported. We now report approximately 60000 bp of genomic sequence containing the entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons and several introns and analyze these amplification products by single-stranded sequence conformation (SSCP) and/or direct sequencing. These results define silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and 15. Rare conservative mutations are identified in amino acids encoded by DAT exons 2 and 8. Analyses of the common nucleotide variants and the previously reported VNTR in the non-coding region of exon 15 define the pattern of linkage disequilibrium across the DAT locus. These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are consistent with substantial evolutionary conservation of the DAT protein sequence. They suggest that gene variants that alter levels of DAT expression provide the best current candidate mechanism for reported associations between DAT gene markers, ADHD and other more tentatively associated neuropsychiatric disorders.
Assuntos
Alcoolismo/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas de Transporte/genética , Glicoproteínas de Membrana , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Transtornos Relacionados ao Uso de Substâncias/genética , Síndrome de Tourette/genética , Adolescente , Sequência de Bases , Criança , Sequência Conservada , Proteínas da Membrana Plasmática de Transporte de Dopamina , Éxons , Variação Genética , Humanos , Íntrons , Desequilíbrio de Ligação , Repetições Minissatélites , Polimorfismo Conformacional de Fita SimplesRESUMO
The Trail Making Test (TMT) is one of the most frequently used measures in clinical neuropsychology. Data obtained from the TMT practice times were analyzed to determine their utility in predicting success and failure on the full version of the test and to allow establishment of criteria by which to judge administration or discontinuation of the full test. Results indicated that TMT practice times were useful in predicting successful completion of Part A and B of the TMT. Tables are provided which describe the classification accuracy of various TMT practice times. These tables allow clinicians to select a practice-time cutoff and then use the cutoff as a heuristic to assist in the decision to administer the remainder of that particular part of the TMT or discontinue the test. A 20-s cutoff resulted in optimal prediction of successful completion (< 180 s) of TMT Part A. A cutoff of 30 s optimally predicted successful completion (< 300 s) of TMT Part B.
Assuntos
Encefalopatias/psicologia , Transtornos Mentais/psicologia , Prática Psicológica , Teste de Sequência Alfanumérica , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Psicometria , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
The need for low cost, noninvasive procedures for aiding in the diagnosis and understanding of Alzheimer's Disease (AD) has led to theories and procedures examining the role of olfactory disorders because of the finding that the brains of AD patients invariably exhibit neuropathology in the hippocampus and entorhinal cortex. This loss correlates with the increase in the number of plaques and tangles and with the severity of dementia. Considered together, these findings suggest that brain structures closely related to the olfactory system demonstrate significant histopathology in AD. A comprehensive review of the literature pertaining to olfaction in persons with AD revealed that the olfactory identification ability of patients with memory disorders is impaired relative to controls. Consistency is lacking, however, when olfactory detection thresholds are investigated. Also, there is inconsistency in regards to severity of illness and olfactory function. In addition to differentiating AD patients from normals, the olfactory paradigm has shown some limited usefulness in differentiating AD patients from some other demented patients.
Assuntos
Doença de Alzheimer , Transtornos do Olfato/etiologia , Transtornos da Percepção/etiologia , Olfato/fisiologia , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Demência/complicações , Demência/fisiopatologia , Discriminação Psicológica/fisiologia , Avaliação Geriátrica , Humanos , Testes Neuropsicológicos , Transtornos do Olfato/fisiopatologia , Condutos Olfatórios/fisiologia , Transtornos da Percepção/fisiopatologia , Limiar Sensorial/fisiologia , Índice de Gravidade de DoençaRESUMO
The fourth intron of the Euglena gracilis chloroplast photosystem II gene, psbCi4, is a 1,605-bp twintron composed of two group III introns and a coding locus for a 458-aa polypeptide, mat1, located in the internal intron. psbCi4 homologs have been identified in seven euglenoids, including E. myxocylindracea, E. viridis, E. deses, E. pisciformis, Cryptoglena pigra, Eutreptia sp., and Lepocinclis beutschlii. All of the species examined contain both the group III twintron and the mat1 locus, revealing a more widespread occurrence of group III introns than previously known. The L. beutschlii mat1 locus is interrupted by two novel mini-group II introns of 224 and 258 nt, the smallest group II introns yet identified. Reverse transcriptase polymerase chain reaction analysis confirmed the splicing boundaries of the external and internal E. myxocylindracea, E. viridis, and E. deses introns as well as the novel L. beutschlii mat1 introns. As determined by comparative phylogenetic analysis, group III introns contain a structural homolog of group II intron domain VI. The mat1 loci encode peptide motifs characteristic of group II intron maturases. A group III intron-encoded protein whose predicted sequence is similar to group II intron-encoded maturases and a bona fide domain VI within group III introns are compelling evidence for a common ancestor of group II and group III introns.
Assuntos
DNA de Cloroplastos/genética , DNA de Protozoário/genética , Euglênidos/genética , Evolução Molecular , Homologia de Genes , Genes de Plantas/genética , Genes de Protozoários/genética , Íntrons/genética , Nucleotidiltransferases/genética , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Complexo de Proteína do Fotossistema II , Proteínas de Plantas/genética , Proteínas de Protozoários/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA de Cloroplastos/química , DNA de Protozoário/química , Euglênidos/classificação , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Filogenia , Splicing de RNA , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da EspécieRESUMO
Eleven patients with Yersinia enterocolitica infections were identified in the Upper Valley of New Hampshire and Vermont during October and November of 1995. Three children presented with an appendicitis-like picture. Two underwent appendectomy, one of whom was the outbreak's index case. Both appendectomy patients presented with lower abdominal pain, fever, vomiting, and a right lower quadrant mass associated with leukocytosis. Both had terminal ileitis, and in both, cultures of peritoneal fluid and a mesenteric lymph node grew Y. enterocolitica. Even during an outbreak there is no consistently reliable nonoperative way to separate a sporadic case of appendicitis from one whose appendicitis-like symptoms are due to Yersinia. In addition, a small percentage of Yersinia patients will present with true appendicitis as a complication of their disease.
Assuntos
Surtos de Doenças , Enterocolite/microbiologia , Yersiniose/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Microbiologia de Alimentos , Humanos , Lactente , New Hampshire/epidemiologia , Vermont/epidemiologia , Yersiniose/diagnósticoRESUMO
A series of 2,4,6-trisubstituted-5-nitropyrimidines have been prepared and evaluated for inhibition of proliferation of L1210 and H.Ep.2 cells in vitro. The most potent compound was 6-(dibromomethyl)-2-methoxy-4-morpholino-5-nitropyrimidine (11) (L1210, IC50 = 0.32 microM; H.Ep.2, IC50 = 1.6 microM). Of the 6-substituents incorporated, only CHBr2, CH2Br, and CHO were compatible with antiproliferative activity, while a wider variety of 4-substituents were tolerated. At concentrations near the IC50 for antiproliferative activity, a delayed resumption of cell proliferation in L1210 cultures indicated that the activity of the compounds was short-lived and suggested they might act by an alkylation mechanism.
Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Nucleosídeos de Purina/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Ribonucleosídeos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antivirais/síntese química , Antivirais/química , Divisão Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Nucleosídeos de Purina/síntese química , Nucleosídeos de Purina/química , Pirimidinas/química , Ribonucleosídeos/síntese química , Ribonucleosídeos/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Studies of the phylogeny and chloroplast intron content of selected Euglena species have led to insights in our understanding of the timing of intron acquisition. In the current study, two new twintrons, found in E. gracilis, have been characterized by the analysis of partially spliced pre-mRNAs. Intron 1 of atpE is a 463-nt group-II intron interrupted by a second group-II intron 320 nt long. Intron 1 of psbD is also a group-II twintron with external and internal introns of 635 nt and 463 nt, respectively. The two introns composing the psbD twintron, as well as six additional group-II introns found in the E. gracilispsbD gene, are not present in several basally branching Euglena species, including E. myxocylindracea, E. stellata and E. viridis. The distribution of psbD introns in Euglena is consistent with a late evolutionary acquisition of group-II introns in this lineage.
Assuntos
Cloroplastos/genética , Euglena gracilis/genética , Euglena/genética , Íntrons , Animais , Mapeamento Cromossômico , Clonagem Molecular , DNA Complementar/análise , DNA Complementar/genética , Eletroforese em Gel de Ágar , Estrutura Molecular , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Complexo de Proteína do Fotossistema II , Filogenia , Reação em Cadeia da Polimerase , Splicing de RNA , RNA Mensageiro/genéticaRESUMO
82 of the 155 chloroplast introns in Euglena gracilis have been categorized as group II introns. Because they are shorter and more divergent than group II introns from other organisms, the assignment of these Euglena introns to the group II class has been questioned. In the current study, two homologs of E. gracilis petB intron 1 and four homologs of psbC intron 2 have been isolated from related species and characterized. Based on a comparative sequence analysis of intron homologs, the intron core and four of the six helical domains present in the canonical group II intron structural model are conserved in E. gracilis petB intron 1 and psbC intron 2 and all of their homologs. Distal portions of domain I, which are involved in most of the tertiary interactions, are less well conserved than the central core.
Assuntos
Cloroplastos/genética , Euglena/genética , Íntrons , Complexo de Proteína do Fotossistema II , Animais , Sequência de Bases , Sequência Conservada , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Proteínas de Plantas/genética , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido NucleicoRESUMO
This report describes the preparation and characterization of two polymorphic forms of RG 12525, a leukotriene D4 (LTD4) antagonist. Polymorph I is prepared by recrystallization from methanol or titration of the sodium salt of RG 12525 with citric acid. Polymorph II is prepared by recrystallization from methanol or titration of the ammonium salt of RG 12525 with citric acid. The polymorphic system is enantiotropic, with pure form I melting at 154 degrees C, 3 deg less than the melting temperature of form II. Form I is thermodynamically more stable than form II at room temperature. These polymorphic forms are differentiated using microscopy, differential scanning calorimetry (DSC), infrared spectroscopy (IR), and powder X-ray diffraction (XRD) analysis. Solubility properties from 31 to 72 degrees C were determined to be similar for both forms. The calculated solubilities at 25 degrees C are 7.6 and 9.8 microM for forms I and II, respectively. The free energy change from form II to form I at 25 degrees C is -0.15 kcal/mol. Thermodynamic properties of the system are summarized using a schematic free energy diagram.