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1.
Phys Med Biol ; 69(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38843809

RESUMO

Objective. Image reconstruction is a fundamental step in magnetic particle imaging (MPI). One of the main challenges is the fact that the reconstructions are computationally intensive and time-consuming, so choosing an algorithm presents a compromise between accuracy and execution time, which depends on the application. This work proposes a method that provides both fast and accurate image reconstructions.Approach. Image reconstruction algorithms were implemented to be executed in parallel ingraphics processing units(GPUs) using the CUDA framework. The calculation of the model-based MPI calibration matrix was also implemented in GPU to allow both fast and flexible reconstructions.Main results. The parallel algorithms were able to accelerate the reconstructions by up to about6,100times in comparison to the serial Kaczmarz algorithm executed in the CPU, allowing for real-time applications. Reconstructions using the OpenMPIData dataset validated the proposed algorithms and demonstrated that they are able to provide both fast and accurate reconstructions. The calculation of the calibration matrix was accelerated by up to about 37 times.Significance. The parallel algorithms proposed in this work can provide single-frame MPI reconstructions in real time, with frame rates greater than 100 frames per second. The parallel calculation of the calibration matrix can be combined with the parallel reconstruction to deliver images in less time than the serial Kaczmarz reconstruction, potentially eliminating the need of storing the calibration matrix in the main memory, and providing the flexibility of redefining scanning and reconstruction parameters during execution.


Assuntos
Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Gráficos por Computador , Fatores de Tempo , Imagem Molecular/métodos , Calibragem
2.
R Soc Open Sci ; 10(12): 230241, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38094264

RESUMO

Research on stingless bee products has increased in recent years, and of particular interest is propolis because of its biological activities such as antioxidant and antimicrobial. However, there is paucity of information regarding intra-hive variations in the biochemical composition and biofunctional properties of this propolis. In this study, we investigated the phytochemicals and radical scavenging activity (RSA) of Meliponula ferruginea propolis from 10 wooden hives (n = 49). The samples were collected from five different locations comprising the entrance, involucrum, pillars, pots and sealant. Principal component analysis showed that there is an intra-hive variation in phytochemical content and RSA. Phenolic content constituted the highest phytochemical content in all the locations. The sealant and entrance had the highest amounts of phytochemicals compared to the involucrum, pillars and pots. Further analysis of propolis extracts by gas chromatography-mass spectrometry revealed occurrence of different compounds such as monoterpenoids, hydrocarbons, triterpenoids and alkaloids. Hydrocarbons were common in all parts while monoterpenes and triterpenes were present in the entrance. The findings of our study indicates that there is an intra-hive variation in propolis of M. ferruginea and hence this information will provide further insight into better understanding of stingless bee propolis.

3.
Sci Rep ; 13(1): 15762, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737290

RESUMO

Advances in instrumentation and tracer materials are still required to enable sensitive, accurate, and localized in situ 3D temperature monitoring by magnetic particle imaging (MPI). We have developed a high-resolution magnetic particle imaging instrument and implemented a low-noise multi-harmonic lock-in detection method to observe and quantify temperature variations in iron oxide nanoparticle tracers using the harmonic ratio method for determining temperature. Using isolated harmonics for MPI and temperature imaging revealed an apparent dependence of imaging resolution on harmonic number. Thus, we present experimental and simulation studies to quantify the imaging resolution dependence on temperature and harmonic number, and directly validate the fundamental origin of MPI imaging resolution on harmonic number based on the concept of a harmonic point-spread-function.

4.
PLoS One ; 18(5): e0282974, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37167260

RESUMO

White melon (Cucumeropsis mannii Naudin), is among common and yet underutilized oil seed crop within the West African region, does not have sufficient information specific to its nutrient composition for foreign consumers. To supplement existing information, therefore, we investigated the nutritional profile of defatted and full-fat flour, alongside physicochemical breakdown and storage performance of soxhlet-extracted oil from two white melon (C. mannii) seed varieties found in Southeast Nigeria. Nutritional profile involved the determinations of proximate composition, minerals, vitamins, functional properties as well as amino acid profile. Physicochemical breakdown involved the determinations of fatty acid profile, lipid breakdown parameters, as well as associated physical attributes. Results showed defatting of flours increased the protein (69.04%), carbohydrates (16.26%), crude fiber (2.68%), ash (11.9%), mineral (Na ranging from 223.92-246.99 mg/100g), and vitamin contents (Vit B1 ranging from 0.453-0.712 mg/100g). Total amino acid differed slightly when comparing miniature (30.36 g/100g) and large (22.36 g/100g) seeds. Soxhlet-extracted oil possessed low thiobarbituric acid, acid, and peroxide values (0.030 and 0.038 mg MDA/kg, 1.08 and 1.27 mg KOH/g, and 2.95 and 3,94 mEqO2/kg, for large and miniature seeds respectively), and peak linoleic acid (5 and 6.45 mg/ml, for miniature and large seeds respectively). During storage, the thiobarbituric acid and peroxide values of soxhlet-extracted oil increased yet within acceptable limits.


Assuntos
Cucurbitaceae , Farinha , Farinha/análise , Nigéria , Sementes/química , Minerais/análise , Ácidos Graxos/análise , Vitaminas/análise , Aminoácidos/análise , Óleos de Plantas/química
5.
ACS Appl Mater Interfaces ; 15(10): 13439-13448, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36877093

RESUMO

Temperature is a fundamental physical quantity important to the physical and biological sciences. Measurement of temperature within an optically inaccessible three-dimensional (3D) volume at microscale resolution is currently limited. Thermal magnetic particle imaging (T-MPI), a temperature variant of magnetic particle imaging (MPI), hopes to solve this deficiency. For this thermometry technique, magnetic nano-objects (MNOs) with strong temperature-dependent magnetization (thermosensitivity) around the temperature of interest are required; here, we focus between 200 K and 310 K. We demonstrate that thermosensitivity can be amplified in MNOs consisting of ferrimagnetic (FiM) iron oxide (ferrite) and antiferromagnetic (AFM) cobalt oxide (CoO) through interface effects. The FiM/AFM MNOs are characterized by X-ray diffraction (XRD), (scanning) transmission electron microscopy (STEM/TEM), dynamic light scattering (DLS), and Raman spectroscopy. Thermosensitivity is evaluated and quantified by temperature-dependent magnetic measurements. The FiM/AFM exchange coupling is confirmed by field-cooled (FC) hysteresis loops measured at 100 K. Magnetic particle spectroscopy (MPS) measurements were performed at room temperature to evaluate the MNOs MPI response. This initial study shows that FiM/AFM interfacial magnetic coupling is a viable method to increase thermosensitivity in MNOs for T-MPI.

6.
Appl Phys Lett ; 120(1)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36590240

RESUMO

Characterization of the magnetization dynamics of single-domain magnetic nanoparticles (MNPs) is important for magnetic particle imaging (MPI), magnetic resonance imaging (MRI), and emerging medical diagnostic/therapeutic technologies. Depending on particle size and temperature, nanoparticle magnetization relaxation time constants span from nanoseconds to seconds. In solution, relaxation occurs via coupled Brownian and Néel relaxation mechanisms. Even though their coexistence complicates analysis, the presence of two timescales presents opportunities for more direct control of magnetization behavior if the two processes can be understood, isolated, and tuned. Using high frequency coils and sample temperature tunability, we demonstrate unambiguous determination of the specific relaxation processes for iron oxide nanoparticles using both time and frequency domain techniques. Furthermore, we study the evolution of the fast dynamics at ≈ 10 nanosecond timescales, for magnetic field amplitudes relevant to MPI.

7.
Opt Eng ; 60(3)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475608

RESUMO

We have constructed, calibrated, and tested a cryogenic low-background infrared radiometer for both spectral radiance and irradiance measurements over the 4 µm to 20 µm wavelength range. The primary purpose of the Missile Defense Transfer Radiometer (MDXR) is to measure absolute irradiance or radiance from cryogenic infrared test chamber sources using a photoconductive Si:As Blocked Impurity Band (BIB) detector and a set of spectral filters. The MDXR also includes an absolute cryogenic radiometer (ACR) and a Fourier transform spectrometer (FTS). For irradiance measurements, the ACR is used to provide the primary power scale for the BIB detector in conjunction with spectral filters, while the FTS/BIB configuration derives its scale from an internal blackbody source. The two measurement scales show agreement for the irradiance of highly collimated (< 1 mrad) infrared beams from 10-13 W/µm/cm2 to 10-8 W/µm/cm2 within the combined relative uncertainties of 2.6 % (coverage factor k = 1.) We have also calibrated the radiometer for radiance measurements by using a large cavity fluid bath blackbody that overfills the spatial and angular extent of the radiometer entrance pupil. The radiometric calibration uncertainty analysis of the radiometer as well as its maintenance and stability are discussed.

8.
Front Chem ; 8: 583926, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330372

RESUMO

The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10-3 M and 1.1 × 10-3 M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10-3 M, 5.7 × 10-4 M, and 6.5 × 10-4 M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10-4 M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10-3 M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10-4 M) was most active against A. niger.

9.
J Appl Phys ; 128(22)2020.
Artigo em Inglês | MEDLINE | ID: mdl-34121764

RESUMO

Magnetic nanoparticle (MNP) thermometry based on magnetic particle spectroscopy (MPS) is explored as a potential approach for realizing in-situ temperature measurement of 3D objects. MNP thermometry relies on the nonlinear magnetization response to an AC drive field. This nonlinear response has functional dependence on frequency and temperature, governed by the complex magnetization dynamics of MNPs suspended in solution. In this work, we introduce our approach for accurate and precise AC magnetization measurements using actively stabilized drive fields ranging from DC to 10 kHz. To isolate the harmonic response of MNPs from the drive field, we also perform active cancellation to reach drive field suppression up to 120 dB. Active stabilization and cancellation are utilized for real-time, sensitive measurements of AC magnetization of commercial samples, with stability on the timescale of hours. Initial results for MNP thermometry are demonstrated using this technique, and we achieved a total temperature uncertainty of 410 mK and 170 mK at 100 ms and 10 s integration time, respectively.

10.
J Neurovirol ; 26(1): 118-120, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31286440

RESUMO

A 71-year-old man presented with sudden onset, generalized tonic-clonic seizures and altered mental status. Initial brain magnetic resonance imaging was normal but a brain FDG-PET scan showed hypermetabolism in the left ventral striatum and septal area. Initial cerebrospinal fluid (CSF) examination showed mildly elevated protein but herpes simplex virus (HSV) polymerase chain reaction (PCR) was negative. A repeat CSF examination performed 9 days later showed a positive HSV PCR. Histopathological and immunohistochemical examination of autopsy specimen confirmed the presence of CD45+ lymphocytes and HSV antigen, suggesting the presence of both inflammation and viral infection corresponding to PET abnormality.


Assuntos
Encefalite por Herpes Simples/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Septo do Cérebro/diagnóstico por imagem , Estriado Ventral/diagnóstico por imagem , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Encefalite por Herpes Simples/tratamento farmacológico , Evolução Fatal , Fluordesoxiglucose F18 , Humanos , Masculino , Compostos Radiofarmacêuticos , Septo do Cérebro/metabolismo , Estriado Ventral/metabolismo
11.
J Neurovirol ; 26(1): 121, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31515701

RESUMO

The word "hypermetabolism" needs to be replaced by "hypometabolism" at only ONE place and NOT throughout the article.So the correction could be stated as:"In the case description section, the sentence "A repeat dedicatedbrain FDG-PET scan performed on day 9, under burst suppression,showed diffuse hypermetabolism with persistent relativehypermetabolism in the left ventral striatum and septalarea (Fig. 1b)."should read as"A repeat dedicatedbrain FDG-PET scan performed on day 9, under burst suppression,showed diffuse hypometabolism with persistent relativehypermetabolism in the left ventral striatum and septalarea (Fig. 1b)." At all other places, the word hypermetabolism is appropriate.

12.
J Hematol Oncol ; 6(1): 81, 2013 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-24283202

RESUMO

BACKGROUND: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. METHODS: Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. RESULTS: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. CONCLUSIONS: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.


Assuntos
Plaquetas/patologia , Mielofibrose Primária/sangue , Mielofibrose Primária/tratamento farmacológico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Janus Quinases/antagonistas & inibidores , Masculino , Nitrilas , Contagem de Plaquetas , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Resultado do Tratamento
13.
Bull Environ Contam Toxicol ; 90(3): 314-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23229305

RESUMO

The effects of uptake of metals (iron, zinc, cadmium and chromium) by juvenile snail Limicolaria aurora fed edible mushroom Pleurotus spp from 3 contaminated farm sites and a laboratory grown species (control) respectively were investigated. The 120 snails were fed in plastic snaileries for 4 weeks in the laboratory. Control site was risk free. Metal uptake was low and bioaccumulation in L. aurora tissue was below FAO/WHO standard of 1 mg/kg for chromium and cadmium. Snails were considered safe for consumption.


Assuntos
Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Metais Pesados/análise , Pleurotus/química , Caramujos/metabolismo , Ração Animal , Animais , Cádmio/análise , Cádmio/farmacocinética , Cromo/análise , Cromo/farmacocinética , Poluentes Ambientais/farmacocinética , Cadeia Alimentar , Ferro/análise , Ferro/farmacocinética , Metais Pesados/farmacocinética , Nigéria , Caramujos/química , Zinco/análise , Zinco/farmacocinética
14.
AANA J ; 80(4 Suppl): S17-24, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23248826

RESUMO

Perioperatively, insulin to treat hyperglycemia is administered judiciously to minimize the risk of hypoglycemia. In patients with diabetes in whom preoperative blood glucose levels are on the low end of normal, hypoglycemia risk may be underestimated. This retrospective study enrolled subjects with presenting preoperative blood glucose values in these ranges: 70 to 89 mg/dL (low normal group) and above 249 mg/dL (hyperglycemia-treated group). These groups were compared for subsequent perioperative hypoglycemia development. Subjects in the low normal group (n = 308) were older (P < .001), had increased incidence of renal disease (P = .02), and more prevalent beta-blocker use (P = .02) than the hyperglycemia-treated subjects (n = 279). Accounting for differences between groups, the incidence of perioperative blood glucose levels below 70 mg/dL was greater in the low normal group than the hyperglycemia-treated group (17.2% vs 3.6%, P < .001). Of subjects whose blood glucose levels fell below 70 mg/dL, blood glucose levels dropped below 50 mg/dL in 40% of hyperglycemia-treated subjects and 4% of low normal subjects. Perioperative hypoglycemia was likelier to develop in patients with diabetes who presented preoperatively with low normal blood glucose values than in patients treated with insulin for presenting hyperglycemia.


Assuntos
Glicemia/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/epidemiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Insulina/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Incidência , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Retrospectivos , Fatores de Risco
15.
J Clin Anesth ; 24(8): 610-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23122972

RESUMO

STUDY OBJECTIVE: To evaluate three evening insulin glargine dosing strategies for achievement of target (100-179 mg/dL; 5.5 - 9.8 mmol/L) and widened (80-249 mg/dL; 4.4 - 13.7 mmol/L) preoperative fasting blood glucose (FBG) ranges on the day of surgery. DESIGN: Prospective, randomized, open trial. SETTING: Preoperative units at two sites of a suburban hospital system. PATIENTS: 401 adult, ASA physical status 3 and 4 patients with type 1 and type 2 diabetes, undergoing elective noncardiac surgery. INTERVENTIONS: Patients were divided into two groups according to absence of daily rapid-acting/short-acting insulin (insulin glargine-only group) or presence of daily rapid-acting/short-acting insulin (insulin glargine plus bolus group). Subjects were then randomized to three evening insulin glargine dosing strategies: (a) take 80% of usual dose, (b) call physician for dose, or (c) refer to dosing table, based on self-reported usual FBG and insulin regimen. In the prehospital setting, patients administered the instructed insulin glargine dose on the evening before surgery. MEASUREMENTS: Venous blood glucose values were recorded in the preoperative holding area on the day of surgery. MAIN RESULTS: No significant differences in target preoperative FBG achievement were detected among strategies in the insulin glargine-only group (n = 174) or the insulin glargine plus bolus group (n = 227). In widened preoperative FBG achievement, no significant difference was noted among strategies in the insulin glargine-only group. In the insulin glargine plus bolus group, fewer subjects following the dosing table had FBG > 249 mg/dL (> 13.7 mmol/L; P = 0.031). CONCLUSIONS: Target preoperative FBG achievement was similar among strategies in both insulin glargine groups. An insulin glargine adjustment strategy based on usual glycemic control may better prevent severe preoperative hyperglycemia in patients receiving basal/bolus regimens.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Idoso , Glicemia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina Glargina , Insulina de Ação Prolongada/administração & dosagem , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos
16.
Bioelectrochemistry ; 80(1): 17-25, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20471920

RESUMO

(111) silicon surfaces can be controlled down to atomic level and offer a remarkable starting point for elaborating nanostructures. Hydrogenated surfaces are obtained by oxide dissolution in hydrofluoric acid or ammonium fluoride solution. Organic species are grafted onto the hydrogenated surface by a hydrosilylation reaction, providing a robust covalent Si-C bonding. Finally, probe molecules can be anchored to the organic end group, paving the way to the elaboration of sensors. Fluorescence detection is hampered by the high refractive index of silicon. However, improved sensitivity is obtained by replacing the bulk silicon substrate by a thin layer of amorphous silicon deposited on a reflector. The development of a novel hybrid SPR interface by the deposition of an amorphous silicon-carbon alloy is also presented. Such an interface allows the subsequent linking of stable organic monolayers through Si-C bonds for a plasmonic detection. On the other hand, the semiconducting properties of silicon can be used to implement field-effect label-free detection. However, the electrostatic interaction between adsorbed species may lead to a spreading of the adsorption isotherms, which should not be overlooked in practical operating conditions of the sensor. Atomically flat silicon surfaces may allow for measuring recognition interactions with local-probe microscopy.


Assuntos
Técnicas Biossensoriais/métodos , Silício/química , Ligas/química , Compostos de Amônio , Técnicas Biossensoriais/instrumentação , Carbono/química , Fluoretos/química , Ácido Fluorídrico/química , Hidrogênio/química , Óxidos/química , Compostos de Amônio Quaternário/química , Espectrometria de Fluorescência/métodos , Eletricidade Estática , Ressonância de Plasmônio de Superfície/instrumentação , Ressonância de Plasmônio de Superfície/métodos , Propriedades de Superfície
18.
Biosens Bioelectron ; 25(4): 952-5, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19781934

RESUMO

We have designed a new architecture of fluorescent microarrays based on a thin layer of hydrogenated amorphous silicon-carbon alloy (a-Si(0.85)C(0.15):H) deposited on an aluminium-on-glass back reflector. These substrates are modified with an organic monolayer anchored through Si-C bonds and terminated with carboxyl groups, allowing for the covalent immobilization of biological probes. The fluorescence yield is maximized by optimization of the a-Si(0.85)C(0.15):H layer thickness. This approach is assessed for DNA recognition, demonstrating an increase in sensitivity by over one order of magnitude as compared to commercial slides, and the possibility of following in situ the molecular recognition event (hybridization). The immobilization chemistry provides these substrates with a superior chemical stability toward ageing or long-term exposure to physiological buffers, which allows for many successive hybridization/dehybridization cycles without measurable changes in performance.


Assuntos
Carbono/química , DNA/análise , DNA/genética , Hidrogênio/química , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Silício/química , Espectrometria de Fluorescência/instrumentação , Ligas/química , Desenho de Equipamento , Análise de Falha de Equipamento , Reutilização de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
J Neurophysiol ; 100(4): 1770-99, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18650310

RESUMO

A large body of data suggests that the pontine respiratory group (PRG) is involved in respiratory phase-switching and the reconfiguration of the brain stem respiratory network. However, connectivity between the PRG and ventral respiratory column (VRC) in computational models has been largely ad hoc. We developed a network model with PRG-VRC connectivity inferred from coordinated in vivo experiments. Neurons were modeled in the "integrate-and-fire" style; some neurons had pacemaker properties derived from the model of Breen et al. We recapitulated earlier modeling results, including reproduction of activity profiles of different respiratory neurons and motor outputs, and their changes under different conditions (vagotomy, pontine lesions, etc.). The model also reproduced characteristic changes in neuronal and motor patterns observed in vivo during fictive cough and during hypoxia in non-rapid eye movement sleep. Our simulations suggested possible mechanisms for respiratory pattern reorganization during these behaviors. The model predicted that network- and pacemaker-generated rhythms could be co-expressed during the transition from gasping to eupnea, producing a combined "burst-ramp" pattern of phrenic discharges. To test this prediction, phrenic activity and multiple single neuron spike trains were monitored in vagotomized, decerebrate, immobilized, thoracotomized, and artificially ventilated cats during hypoxia and recovery. In most experiments, phrenic discharge patterns during recovery from hypoxia were similar to those predicted by the model. We conclude that under certain conditions, e.g., during recovery from severe brain hypoxia, components of a distributed network activity present during eupnea can be co-expressed with gasp patterns generated by a distinct, functionally "simplified" mechanism.


Assuntos
Bulbo/fisiologia , Rede Nervosa/fisiologia , Redes Neurais de Computação , Ponte/fisiologia , Animais , Tronco Encefálico/fisiologia , Gatos , Simulação por Computador , Tosse/fisiopatologia , Retroalimentação , Hipóxia/fisiopatologia , Bulbo/citologia , Modelos Neurológicos , Movimento/fisiologia , Neurônios/fisiologia , Ponte/citologia , Reflexo/fisiologia , Mecânica Respiratória/fisiologia , Sono/fisiologia , Software
20.
Lancet ; 371(9610): 395-403, 2008 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-18242413

RESUMO

BACKGROUND: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. METHODS: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count > or =50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. FINDINGS: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.7], p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0.8 (0.4) weeks for those given placebo (0.2 [0.1] weeks vs 1.3 [0.8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. INTERPRETATION: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.


Assuntos
Proteínas de Transporte/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Receptores Fc/uso terapêutico , Adulto , Idoso , Proteínas de Transporte/administração & dosagem , Proteínas de Transporte/efeitos adversos , Doença Crônica/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/imunologia , Receptores Fc/administração & dosagem , Proteínas Recombinantes de Fusão , Esplenectomia , Trombopoetina , Resultado do Tratamento
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