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Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Linfócitos T CD8-Positivos/metabolismo , Feminino , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Exposição à Radiação , Luz SolarRESUMO
The Zebrafish Model Organism Database (ZFIN; zfin.org) serves as the central repository for genetic and genomic data produced using zebrafish (Danio rerio). Data in ZFIN are either manually curated from peer-reviewed publications or submitted directly to ZFIN from various data repositories. Data types currently supported include mutants, transgenic lines, DNA constructs, gene expression, phenotypes, antibodies, morpholinos, TALENs, CRISPRs, disease models, movies, and images. The rapidly changing methods of genomic science have increased the production of data that cannot readily be represented in standard journal publications. These large data sets require web-based presentation. As the central repository for zebrafish research data, it has become increasingly important for ZFIN to provide the zebrafish research community with support for their data sets and guidance on what is required to submit these data to ZFIN. Regardless of their volume, all data that are submitted for inclusion in ZFIN must include a minimum set of information that describes the data. The aim of this chapter is to identify data types that fit into the current ZFIN database and explain how to provide those data in the optimal format for integration. We identify the required and optional data elements, define jargon, and present tools and templates that can help with the acquisition and organization of data as they are being prepared for submission to ZFIN. This information will also appear in the ZFIN wiki, where it will be updated as our services evolve over time.
Assuntos
Bases de Dados Genéticas , Genômica/métodos , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Genoma/genética , Morfolinos/genética , MutaçãoRESUMO
AIMS: The renal pelvis shows spontaneous rhythmic contractile activity. We assessed to what extent this activity depends on renal innervation and studied the role of connexins in pelvic contractions. METHODS: Rats underwent unilateral renal denervation or renal transplantation. Renal pelvic pressure and diuresis were measured in vivo. Spontaneous and agonist-induced contractions of isolated renal pelves were investigated by wire myography. Rat and human renal pelvic connexin mRNA abundances and connexin localization were studied by real-time PCR and immunofluorescence respectively. RESULTS: Renal denervation or transplantation increased renal pelvic pressure in vivo by about 60 and 150%, respectively, but did not significantly affect pelvic contraction frequency. Under in vitro conditions, isolated pelvic preparations from innervated or denervated kidneys showed spontaneous contractions. Pelves from denervated kidneys showed about 50% higher contraction frequencies than pelves from innervated kidneys, whereas contraction force was similar in pelves from denervated and innervated kidneys. There was no denervation-induced supersensitivity to noradrenaline or endothelin-1. Renal denervation did not increase pelvic connexin37, 40, 43 or 45 mRNA abundances. Gap junction blockade had no effect on spontaneous pelvic contractile activity. CONCLUSIONS: The denervation-induced effect on pelvic pressure may be the consequence of the enhanced diuresis. The mechanisms underlying the denervation-induced effects on pelvic contraction frequency remain unknown. Our data rule out a major role for two important candidates, by showing that renal denervation neither induced supersensitivity to contractile agonists nor increased connexin mRNA abundance in the pelvic wall.
Assuntos
Conexinas/biossíntese , Pelve Renal/fisiologia , Rim/inervação , Contração Muscular/fisiologia , Animais , Denervação , Eletromiografia , Imunofluorescência , Humanos , Rim/metabolismo , Masculino , Músculo Liso/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD). H4R antagonists have already been tested in several animal models of AD, but these studies have yielded conflicting results. MATERIAL AND METHODS: The development of ovalbumin-induced AD-like skin lesions was analysed in H4R(-/-) mice and in H4R antagonist (JNJ28307474)-treated mice. RESULTS: H4R(-/-) mice showed a clear amelioration of the skin lesions, with a diminished influx of inflammatory cells and a reduced epidermal hyperproliferation at lesional skin sites. H4R(-/-) mice had a reduced amount of ovalbumin-specific IgE, a reduced number of splenocytes and lymph node cells with a decreased number of CD4+ T cells. The H4R modulated the cytokine secretion of CD4+ T cells and splenocytes and altered the cellular profile in the lymph nodes. The anti-inflammatory effect could only partially be mimicked by JNJ28307474 and only when the H4R antagonist was given during sensitization and challenge and not when JNJ28307474 was only given during the provocation phase of the allergic reaction. CONCLUSION: The H4R modulates inflammation in a chronic allergic dermatitis setting. However, results of this study indicate that it is necessary to block the H4R during ontogeny and development of the allergic inflammation.
Assuntos
Dermatite Atópica/etiologia , Dermatite Atópica/patologia , Receptores Acoplados a Proteínas G/deficiência , Receptores Histamínicos/deficiência , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Citocinas/biossíntese , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Feminino , Imunoglobulina E/imunologia , Linfonodos/imunologia , Linfonodos/metabolismo , Camundongos , Camundongos Knockout , Ovalbumina/efeitos adversos , Piperidinas/farmacologia , Piridinas/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Receptores Histamínicos/genética , Receptores Histamínicos H4 , Pele/imunologia , Pele/metabolismo , Pele/patologiaRESUMO
BACKGROUND: The aim of this study was to investigate the influence of etching time with 15% hydrochloric acid (HCl) on the enamel surface destruction by studying the resulting roughness and erosion depth. METHODS: The vestibular surfaces of 12 extracted, caries free human incisors were divided into four quadrants, and each quadrant was etched with 15% HCl for different numbers of etching cycles (1×2, 2×2, 3×2 and 4×2 min). Surface roughness and erosion depth were measured quantitatively with optical profilometry, and the surface morphology was imaged with scanning electron microscopy (SEM). RESULTS: After two minutes of 15% HCl application a median enamel substance loss of 34.02 µm was observed. Lengthening of etching time (2×2, 3×2 and 4×2 min) resulted in significantly increase in erosion depth to each additionally, between 13.28 -15.16 µm (p < 0.05) ending up in a total median enamel surface loss of 77 µm. Regarding surface roughness no significant (p > 0.05) difference was found between unetched enamel and the etched enamel surfaces. CONCLUSION: Repeated 15% HCl conditioning of the enamel surface increases the depth of the etched surface erosion. However, the total erosion depth is rather shallow and therefore negligible.
Assuntos
Condicionamento Ácido do Dente/efeitos adversos , Esmalte Dentário/efeitos dos fármacos , Ácido Clorídrico/efeitos adversos , Condicionamento Ácido do Dente/métodos , Humanos , Ácido Clorídrico/uso terapêutico , Incisivo , Microscopia Eletrônica de Varredura , Propriedades de SuperfícieRESUMO
BACKGROUND: In spite of a decline in mortality due to asthma in Germany various studies point towards deficits in asthma care. Our investigation should collect data about ambulatory care from the view of statutory health insured patients (SHI), who participate in the disease management program asthma (DMP-P) or do not (NP). Primary question was, if there is a difference between asthma control. Secondary questions referred to process parameters. METHODS: The postal inquiry was conducted in 2010 with 8000 randomly selected members of a SHI company with asthma (4000 DMP-P and 4000 NP). The descriptive evaluation of categorical items was performed with cross-tables. The absolute risk reduction (ARR) and 97.5â %-confidence interval (CI; multiple level 5â %) was used to evaluate the primary question. Secondary questions were analysed by ARR and 95â %-CI. RESULTS: The response rate of the questionnaire accounted for 31.1â % (2565). 49.2â % of all respondents lived with an uncontrolled asthma with no differences between DMP-P and NP (ARR -2.7â %, 97.5â %-CI -7.9â -2.4â %). Results did not alter after adjustment for sex and age. The secondary questions revealed significant differences (DMP-P vs. NP) in participation in asthma trainings 50.6 vs. 32.3â %, use of a peak-flow-meter 49.3 vs. 25.3â % and asthma action plan within reach 21.7 vs. 11.0â %. CONCLUSION: Half of all respondents lives selfreported - even in the DMP-group - with an uncontrolled asthma. Process parameters showed better results in the DMP-group.âIt can be considered, that the DMP has its desired effect on patient-centered care, but does not lead to a better therapeutic outcome. Explanations can only be assumed: insufficient impact of the process parameters on the outcome, patient behavior, that minimizes a possible effect, or selection effects, if patients, who were more sick and at the same time more motivated, were mainly included in the DMP. These aspects should be addressed in studies with a prospective design.
Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Asma/epidemiologia , Asma/terapia , Programas Nacionais de Saúde/estatística & dados numéricos , Autocuidado/estatística & dados numéricos , Revisão da Utilização de Recursos de Saúde , Adulto , Idoso , Asma/diagnóstico , Feminino , Alemanha/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: Award of the degree MD has special relevance in Germany since the underlying research project can be started during the qualification for admission to doctoral training. This leads to a large number of thesis projects with a not always sufficiently pronounced enthusiasm and thus poor chances of success. Accordingly a case control study was undertaken in the Department of Human Medicine, Witten/Herdecke University to investigate reported drop-outs of thesis projects. MATERIAL AND METHOD: In autumn 2012 all students in the clinical phases of human medicine education were surveyed using a self-conceived questionnaire on previously initiated or terminated thesis projects, "terminated" is defined as the unsuccessful ending of a project after working for at least 3 months. Individually reported thesis terminations were evaluated using defined items in a 4-stage Likert scale regarding thesis plan and project, subsequently, graduate students who successfully completed a project received the same questionnaire. The items possibly corresponding to process determinants were averaged to a total of 7 dimensions prior to the analysis; the resulting scores were normalised in value ranges 0.0 to 1.0 (1.0 = optimal project situation) whereby individual items could be included in several scores. By means of 5 items a primary endpoint from the faculty's perspective on "compliance with formal procedures" was aggregated; by means of a two-sided Wilcoxon test at the 5â% level students with unsuccessful and successful courses were compared along the corresponding scores. RESULTS: 181 of 276 students from 7 study semesters participated in the screening; details of 17 terminations and 23 currently successful courses could be evaluated in the case control study. For significant differences (p < 0.001) between unsuccessful and successful courses in the primary endpoint, median scores of 0.17 (0.07-0.50) versus 0.73 (0.53-0.83) were estimated. CONCLUSION: There were differences between unsuccessful and (as yet) successful courses, especially with regard to the aspects "compliance with formal procedures". Thus a recommendation can be derived in the sense of a stricter and, if necessary, sanctioning demand for formal procedures such as early reporting of thesis projects to the responsible committees. A weakness is the low number of evaluable self-reported drop-outs as well as the overall moderate response rate.
Assuntos
Dissertações Acadêmicas como Assunto , Educação Médica , Evasão Escolar , Estudos de Casos e Controles , Comportamento Cooperativo , Currículo , Alemanha , Humanos , Inquéritos e QuestionáriosRESUMO
UNLABELLED: BACKGROUND AND AIM OF THE INVESTIGATION: Deep oscillation refers to an electromechanical therapy method in which electrostatic attraction and friction, produced by the use of a hand-held applicator, create resonance vibrations in treated tissue. In a pilot clinical trial the impact of deep oscillation has been examined in relation to the physiological parameters of wound healing on postoperative wounds. MATERIAL AND METHODS: Following osteosynthesis operations (extremities and spinal column), 40 patients were stratified by operation localisation and randomised into two samples (intervention [n = 20], control [n = 20]). Aside from primary care of the operation wound, finding-oriented deep oscillation was applied for at least one week following the operation in the intervention sample. The intra-individual reduction in postoperative pain occurrence between day 2 and day 7 of the postsurgical period was quantified by means of a visual analogue scale (VAS) serving as primary clinical end point from the patient's point of view. Confirmatory analysis of this primary endpoint was based on a two-sample Wilcoxon test at the 5â% level of significance. RESULTS: According to VAS pain occurrence declined in the intervention group from day 2 to day 7 in the postoperative period by a median of 3 points (P) (quartile range -4-0.25 P) and a mean of -2.3 P, the control group remained (almost) unaltered with a median difference of 0 P (-2-0 P) and a mean difference of -0.85 P; the treatment groups differed significantly in the postoperative profile of VAS-based pain sensation (Wilcoxon p = 0.006). None of the secondary endpoints showed any locally significant sample differences. DISCUSSION: These results demonstrate a significant pain-alleviating effect of deep oscillation. However, the exact physiological effects underpinning the impact of deep oscillation are still not completely understood.
Assuntos
Autoavaliação Diagnóstica , Terapia por Estimulação Elétrica/métodos , Massagem/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Cicatrização , Adulto , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/etiologia , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
Pyrimidinones are part of the (6-4) photolesions which may be formed from two pyrimidine bases adjacent on a DNA strand. In relation to the secondary photochemistry of the (6-4) lesion, i.e. its transformation into a Dewar valence isomer, photophysical and photochemical properties of 1-methyl-2(1H)-pyrimidinone (1MP) in water, acetonitrile, methanol, and 1,4-dioxane are reported here. As deduced from steady state fluorescence and femtosecond transient absorption spectroscopy the S1 lifetime of 1MP is strongly affected by the solvent. The lifetimes range from 400 ps for water to 40 ps for 1,4-dioxane. Internal conversion (IC) and intersystem crossing (ISC) contribute to the S1 decay. The solvent effect on the IC rate constant is more pronounced than on the ISC constant. The quantum yields for the consumption of 1MP (values for nitrogen purged solvents) are large for methanol (0.35) and 1,4-dioxane (0.24) and small for acetonitrile (0.02) and water (0.003). Hydrogen abstraction from the solvent by the triplet state of 1MP may rationalize this.
Assuntos
Pirimidinonas/química , Acetonitrilas/química , Dioxanos/química , Isomerismo , Cinética , Luz , Metanol/química , Modelos Moleculares , Fotoquímica , Solventes/química , Água/químicaRESUMO
BACKGROUND: In 2010, 19.3% of German inhabitants were either first or second generation immigrants. Language barriers can potentially impair quality of care of this heterogenous group of patients. It has not yet been studied how pediatricians practicing in Germany experience and cope with language barriers. METHODS: We conducted a written survey among participants of the 105th annual meeting of the German Society of Pediatrics in 2009. The questionnaire was newly developed and consisted of 39 items and 3 open questions. Frequency distribution and cross tables were used for descriptive analysis of categorical data. RESULTS: 229 participants returned the questionnaire (40% in inpatient care, 33% in private practice, 26% in public outpatient services). 75% of participants are confronted with language barriers regularly. The most widespread strategy to overcome barriers is using bilingual colleagues, employees or patient family members as interpreters. The opportunity to access professional interpreters depends on the care setting (22% [inpatient care] vs. 5% [private practice] vs. 28% [public outpatient service]). 91% claim that the expenditure of time to organize professional interpreting services is high. CONCLUSION: The results of the pilot project suggest that the possibilities to overcome language barriers largely depend on the care setting. A high amount of organizational work and vague financing currently limit the use of professional interpreting services. However, health politics and science increasingly demand their use.
Assuntos
Barreiras de Comunicação , Emigrantes e Imigrantes , Idioma , Pediatria , Criança , Estudos Transversais , Coleta de Dados , Alemanha , Humanos , Multilinguismo , Projetos Piloto , Inquéritos e Questionários , TraduçãoRESUMO
The first hypothesis free genome wide association study on cognition recently revealed the thus far unknown association of a single nucleotide polymorphism (SNP) of the KIBRA gene with episodic memory in healthy young and middle aged volunteers. Here, we report the first independent replication of this finding in an in-depth characterized sample of healthy elderly subjects. The effectsizes of the respective KIBRA SNP on memory even exceed those of the initial report. In parallel to the first study, the effect is restricted to hippocampus-related episodic memory without effects on frontal lobe function. The impact of KIBRA on memory is most likely of high relevance in elderly subjects as it is in young.
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Cognição/fisiologia , Memória/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Feminino , Variação Genética/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Mutação/genética , FosfoproteínasRESUMO
On the basis of octanol solubility data (log S(o)) for 218 structurally diverse solid chemicals it was shown that the exclusive consideration of melting points did not provide satisfactory results in the quantitative prediction of this parameter (s = 0.92). The application of HYBOT physicochemical descriptors separately (s = 0.94) and together with melting points (s = 0.70) in the framework of a common regression model also was not successful, although contributions of volume-related and H-bond terms to solubility in octanol were identified. It was proposed that the main reason for such behaviour was the different crystal lattice interaction of different classes of chemicals. Successful calculations of the solubility in octanol of chemicals of interest were performed on the basis of the experimental solubility of structurally/physicochemically/numerically similar nearest neighbours with consideration of their difference in physicochemical parameters (molecular polarisability, H-bond acceptor and donor factors (s = 0.66)) and of these descriptors together with melting point differences (s = 0.38). Good results were obtained for all compounds having nearest neighbours with sufficient similarity, expressed by Tanimoto indexes, and by distances in the scaled 3D descriptor space. Obviously the success of this approach depends on the size of the database.
Assuntos
1-Octanol/química , Modelos Químicos , Relação Quantitativa Estrutura-Atividade , Análise de Regressão , Solubilidade , Temperatura de TransiçãoRESUMO
QSPR analyses of a data set containing experimental partition coefficients in the three systems octanol-water, water-gas, and octanol-gas for 98 chemicals have shown that it is possible to calculate any partition coefficient in the system 'gas phase/octanol/water' by three different approaches: (1) from experimental partition coefficients obtained in the corresponding two other subsystems. However, in many cases these data may not be available. Therefore, a solution may be approached (2), a traditional QSPR analysis based on e.g. HYBOT descriptors (hydrogen bond acceptor and donor factors, SigmaCa and SigmaCd, together with polarisability alpha, a steric bulk effect descriptor) and supplemented with substructural indicator variables. (3) A very promising approach which is a combination of the similarity concept and QSPR based on HYBOT descriptors. In this approach observed partition coefficients of structurally nearest neighbours of a compound-of-interest are used. In addition, contributions arising from differences in alpha, SigmaCa, and SigmaCd values between the compound-of-interest and its nearest neighbour(s), respectively, are considered. In this investigation highly significant relationships were obtained by approaches (1) and (3) for the octanol/gas phase partition coefficient (log Log).
Assuntos
1-Octanol/química , Ar , Compostos Orgânicos/química , Água/química , Gases/química , Relação Quantitativa Estrutura-Atividade , Software , Solubilidade , Solventes/químicaRESUMO
QSPR analyses of the solubility in water of 558 vapors, 786 liquids and 2045 solid organic neutral chemicals and drugs are presented. Simultaneous consideration of H-bond acceptor and donor factors leads to a good description of the solubility of vapors and liquids. A volume-related term was found to have an essential negative contribution to the solubility of liquids. Consideration of polarizability, H-bond acceptor and donor factors and indicators for a few functional groups, as well as the experimental solubility values of structurally nearest neighbors yielded good correlations for liquids. The application of Yalkowsky's "General Solubility Equation" to 1063 solid chemicals and drugs resulted in a correlation of experimental vs calculated log S values with only modest statistical criteria. Two approaches to derive predictive models for solubility of solid chemicals and drugs were tested. The first approach was based on the QSPR for liquids together with indicator variables for different functional groups. Furthermore, a calculation of enthalpies for intermolecular complexes in crystal lattices, based on new H-bond potentials, was carried out for the better consideration of essential solubility- decreasing effects in the solid state, as compared with the liquid state. The second approach was based on a combination of similarity considerations and traditional QSPR. Both approaches lead to high quality predictions with average absolute errors on the level of experimental log S determination.
Assuntos
Compostos Orgânicos/química , Preparações Farmacêuticas/química , Software , Solubilidade , Desenho de Fármacos , Gases/química , Transição de Fase , Valor Preditivo dos Testes , Relação Quantitativa Estrutura-Atividade , Volatilização , Água/químicaRESUMO
Traditionally, the in vitro activity of antibacterial agents is characterized by their minimal inhibitory concentrations. However, these endpoints are, by nature, discrete and do not provide information on time-dependent killing of the bacteria during the incubation period. Nevertheless, the pharmacodynamic characteristics of antibacterial agents are almost always defined by correlating a static endpoint describing the antibacterial activity of an agent with the pharmacokinetics, describing the time-dependent fluctuation of drug concentrations. This approach is basically a contradiction in itself. Therefore, it would be more logical to correlate pharmacokinetics to in vitro parameters describing the time- and concentration-dependent antibacterial action of an agent. Thus, experimental methods and mathematical models quantifying the decrease in growth rate of a bacterial population due to the action of an antibacterial agent as a function of time and drug concentration have been applied to quantitate their pharmacodynamics. The effect of nine antibacterial agents representing drug classes of penicillins, cephalosporins, penems, macrolides, and fluoroquinolones were mathematically analyzed by using three different but related models. The kill rate, maximal kill, the 50%-effective concentration (EC50), the Hill coefficient, and concentrations and times needed to obtain a 1,000-fold decrease of the initial number of viable counts were calculated. Both the phenotypic description of the time-kill curves and these five parameters mirror the bacteriostatic or bactericidal activity of all nine agents studied as a function of time and concentration. Therefore, it would be more logical to correlate a parameter quantifying the kinetics of antibacterial in vitro activity with the pharmacokinetics of the drug, thus, replacing static endpoints like minimal inhibitory concentrations.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Fluoroquinolonas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Macrolídeos/farmacologia , beta-Lactamas/farmacologia , Relação Dose-Resposta a Droga , Fluoroquinolonas/farmacocinética , Macrolídeos/farmacocinética , Testes de Sensibilidade Microbiana , Modelos Biológicos , Infecções Respiratórias/microbiologia , beta-Lactamas/farmacocinéticaRESUMO
Lipopolysaccharides (LPSs, endotoxins) are the major amphiphilic constituents of the outer leaflet of the outer membrane of Gram-negative bacteria. They are known to activate the complement cascade to form lytic membrane pores. Here, we study the influence of the fluidity of the acyl chains of LPSs and lipid As on the formation of lytic pores. To this end, we have performed electrical measurements on asymmetric planar endotoxin/phospholipid bilayers as a reconstitution model of the outer membrane using two deep rough mutant LPSs (from Escherichia coli strains WBB01 and WBB25) and two lipid As (from E. coli WBB25 and Rhodobacter sphaeroides). The two LPSs and the two lipid As each differ in their acylation pattern which is correlated with the fluidity. The addition of human serum to the endotoxin side of the bilayers led to the formation of membrane pores, and pore formation correlated in each case with acyl chain fluidity, i.e. time required for the first lytic pore to be formed was shorter for the more fluid endotoxin. Furthermore, in the case of LPSs, the activation rate was higher for the more fluid membrane and the respective bacteria had a higher susceptibility to the growth inhibitory action of serum.
Assuntos
Ativação do Complemento/efeitos dos fármacos , Proteínas do Sistema Complemento/imunologia , Endotoxinas/farmacologia , Lipídeo A/farmacologia , Acilação , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/imunologia , Condutividade Elétrica , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/imunologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/imunologia , Humanos , Bicamadas Lipídicas/imunologia , Fluidez de Membrana , Rhodobacter sphaeroides/crescimento & desenvolvimento , Rhodobacter sphaeroides/imunologiaRESUMO
We describe a sequence of low-level operations to isolate and classify brain tissue within T1-weighted magnetic resonance images (MRI). Our method first removes nonbrain tissue using a combination of anisotropic diffusion filtering, edge detection, and mathematical morphology. We compensate for image nonuniformities due to magnetic field inhomogeneities by fitting a tricubic B-spline gain field to local estimates of the image nonuniformity spaced throughout the MRI volume. The local estimates are computed by fitting a partial volume tissue measurement model to histograms of neighborhoods about each estimate point. The measurement model uses mean tissue intensity and noise variance values computed from the global image and a multiplicative bias parameter that is estimated for each region during the histogram fit. Voxels in the intensity-normalized image are then classified into six tissue types using a maximum a posteriori classifier. This classifier combines the partial volume tissue measurement model with a Gibbs prior that models the spatial properties of the brain. We validate each stage of our algorithm on real and phantom data. Using data from the 20 normal MRI brain data sets of the Internet Brain Segmentation Repository, our method achieved average kappa indices of kappa = 0.746 +/- 0.114 for gray matter (GM) and kappa = 0.798 +/- 0.089 for white matter (WM) compared to expert labeled data. Our method achieved average kappa indices kappa = 0.893 +/- 0.041 for GM and kappa = 0.928 +/- 0.039 for WM compared to the ground truth labeling on 12 volumes from the Montreal Neurological Institute's BrainWeb phantom.
Assuntos
Encéfalo/anatomia & histologia , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Adulto , Algoritmos , Anisotropia , Mapeamento Encefálico , Líquido Cefalorraquidiano/fisiologia , Difusão , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/classificação , Computação Matemática , Imagens de Fantasmas , Valores de ReferênciaRESUMO
The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.
Assuntos
Algoritmos , Encéfalo/anatomia & histologia , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Computação Matemática , Artefatos , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Valores de ReferênciaRESUMO
A classical quantitative structure-activity relationship (Hansch) study and artificial neural networks (ANNs) have been applied to a training set of 32 substituted phenylpiperazines with affinity for 5-HT(1A) and alpha(1)-adrenergic receptors, to evaluate the structural requirements that are responsible for 5-HT(1A)/alpha(1) selectivity. The resulting models provide a significant correlation of electronic, steric, and hydrophobic parameters with the biological affinities. Although the derived linear Hansch correlations give good statistics and acceptable predictions, the introduction of nonlinear relationships in the analysis gives more solid models and more accurate predictions. In the ANN models on the basis of the obtained 3D plots, the 5-HT(1A) affinity has a nonlinear dependence on F, V(o), V(m), and pi(o), although the nonlinear relationship is not far from a planar one. The alpha(1)-adrenergic receptor affinity has a clear nonlinear dependence on F, V(o), V(m), pi(o), and pi(m). A comparison of both analyses gives an additional understanding for 5-HT(1A)/alpha(1) selectivity: (a) high F values increase the binding affinity for 5-HT(1A) receptors and decrease the affinity for alpha(1) sites; (b) the hydrophobicity at the meta-position has only influence for the alpha(1)-adrenergic receptor; (c) the meta-position seems to be implicated in the 5-HT(1A)/alpha(1) selectivity. While the 5-HT(1A) receptor is able to accommodate bulky substituents in the region of its active site, the steric requirements of the alpha(1)-adrenergic receptor at this position are more restricted. This information was used for the design of the new ligand EF-7412 (33) (5-HT(1A): K(i exptl) = 27 nM, alpha(1): K(i exptl) > 1000 nM; 5-HT(1A): K(i pred) (ANN) = 36 nM, alpha(1): K(i pred ANN) = 2745 nM) which was characterized as an antagonist in vivo in pre- and postsynaptic 5-HT(1A)R sites. Computational simulations of the complex between EF-7412 (33) and a 3D model of the transmembrane domain of the 5-HT(1A) receptor allowed us to define the molecular details of the ligand-receptor interaction that includes: (i) the ionic interaction between the protonated amine of the ligand and Asp 3.32; (ii) the hydrogen bonds between the m-NHSO(2)Et group of the ligand and Asn 7.39; and the hydrogen bonds between the hydantoin moiety of the ligand and (iii) Thr 3.37, (iv) Ser 5.42, and (v) Thr 5.43. These QSAR and ANN results in combination with computational simulations of ligand recognition will be useful for the design of potent selective 5-HT(1A) ligands.