•novel test and reference sample for calibration and characterization of scanning thermal microscopy (SThM) probes•integration of plasma etching of Pt and chemical-mechanical planarization (CMP) ...processing, enabled manufacturing a nanosize 100 nm thick Pt resistor on SiO2 with topography profile below 10 nm.•active test structure allows to minimize the influence of variable tip-sample thermal resistance during the scanning and to analyze actual performance of the SThM probe.
In this paper we describe the design, technology and application of a test and reference sample for calibration and characterization of scanning thermal microscopy (SThM) probes and systems. In our solution temperature field in thin film structure, which is being contacted with the thermal tip is controlled in the traceable manner. The developed technology, integrating plasma etching of Pt and chemical-mechanical planarization (CMP) processing, enabled manufacturing a nanosize 100 nm thick Pt resistor on SiO2 with topography profile below 10 nm.
Four-point setup makes it possible to generate and measure (in other words control) a defined temperature field of such a structure. The size of the thermally active structure is big enough to enable reliable SThM measurements and small enough to reduce the parasitic heat transport between the surface and the cantilever platform. The proposed solution enables measurement of the output signal of the scanning thermal microscope measurement system when the temperature of the reference sample is varied in the quantitative way. Furthermore, basing on the determined sensitivity the assessment of the resolution capabilities is possible.
•Novel type of piezoresistive SThM cantilevers that allow for quantitative spatial and thermal observations.•Integrated thermal probe (due to compact size) ideal for application in small AFM heads ...without optical beam deflection measurement.•LoFM scanning mode for thermal observation of the nanosize structures.•Characterization of the mechanical probe parameters and piezoresistive deflection sensor combined with calibration of the thermal tip response allowed for quantitative measurements of the thermal behavior of silicon nanoresistors. The technology described in this article made it possible to map temperature distribution on 200 nm wide nanowire biased with current 500 µA.
In this paper we present design and application of novel piezoresistive scanning thermal microscopy (SThM) probes. The proposed probe integrates a piezoresistive deflection sensor and thermally active, resistive nanosize tip. Manufacturing technology includes standard silicon MEMS/CMOS processing and sophisticated postprocessing using Focus Ion Beam milling. Authors also describe dedicated measurement technique in order to perform quantitative nanoscale thermal probing. Performance of the developed thermal probes is validated by test scans (topography and temperature distribution) of silicon nanoresistors supplied with current.
In this paper we present the design, technology and application of Si/Si3N4 micro calibration stage equipped with Pt microheaters. This 500nm thick MEMS structure with 4 independently controlled ...microheaters allows for precise control temperature dissipation and contact between surface and tip of cantilever. Localization on thin, low thermally conductive membrane minimizes the heat transfer to the bulk silicon. In order to increase mechanical stability of the structure, the membrane is supported by the tip. Structure stiffness is increased which allows for characterization of relatively stiff (30–70Nm−1) piezoresistive scanning thermal microscopy probes. The small size and spatial arrangement of independent heaters allows for the controlled heat flow in the membrane and measurements of the temperature distribution.
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•MEMS structure with 4 microheaters allows for precise control the temperature dissipation and SThM tip-membrane contact•Supporting tip increases the stiffness of the structure without drop of the membrane-chip thermal resistance•Not parasitic heating of the microscope head (in contrary to standard Pt-100 based structures)•Flexible platform for various experiments with locally controlled heat sources and temperature sensors
In the rheumatic diseases, the changes in the carbohydrate part of serum glycoproteins occur and these abnormalities can be monitored by serum level of total and free sialic acid. The aim of this ...study was to evaluate the total and free sialic acid level as a marker of inflammation activity (TSA) and the changes in glycosylation of blood glycoproteins (FSA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Studies were carried out in 50 patients with RA, 24 with SLE and 32 with SSc. TSA concentration was measured with an enzymatic, colorimetric method and FSA with a thiobarbituric method. The serum levels of TSA in RA and SLE patients were significantly increased compared to controls and in RA patients were higher than that in SSc patients. The mean serum level of FSA in RA patients was significantly higher, but in SSc patients significantly lower than that in the controls, and in RA patients was significantly higher than in SLE and in SSc patients. All acute-phase proteins were changed: Positive acute-phase proteins were elevated, and the negative protein was decreased. The positive acute-phase proteins positively correlated with the levels of TSA and FSA in RA and SSc patients. In SLE patients, TSA positively correlated with haptoglobin and α1-antitrypsin. In RA patients, there was the positive correlation of TSA and FSA with DAS 28. The changes in the serum levels of TSA and FSA in the course of rheumatic diseases could reflect the abnormalities in glycosylation/sialylation patterns of glycoproteins induced by acute-phase response.
Avaliar a relação entre os dois tipos de modificações pós‐translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos ...anticorpos no caso do antipeptídeo citrulinado cíclico (anti‐CCP).
O estudo foi feito em 50 pacientes com AR. A TDC foi medida com o teste imunonefelométrico N Latex CDT e os resultados foram apresentados em unidades absolutas e relativas. O anti‐CCP foi mensurado com o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico.
Dos pacientes com AR, 80% foram positivos para anti‐CCP, 70% para FR e 62% para ambos (anti‐CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti‐CCP positivos do que naqueles anti‐CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti‐CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti‐CCP. O percentual de TDC não se correlacionou com o anti‐CCP, mas seu nível absoluto se correlacionou com o anti‐CCP apenas em pacientes FR negativos e anti‐CCP negativos. A TDC não se correlacionou com o FR, somente com o anti‐CCP em pacientes anti‐CCP negativos. O anti‐CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti‐CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti‐CCP positivos.
Esses resultados sugerem que as alterações na TDC e as concentrações de anti‐CCP não estão associadas e indicam a independência dessas modificações pós‐translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.
The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate‐deficient transferrin (CDT) and citrullination by means of autoantibodies to cyclic citrullinated peptides (anti‐CCP).
The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti‐CCP were measured using the chemiluminescent method and rheumatoid factor (RF) by immunoturbidimetric method.
80% of RA patients were positive for anti‐CCP, 70% for RF and 62% for both, anti‐CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti‐CCP positive patients than that in anti‐CCP negative. CDT (absolute and relative concentration) did not correlate with anti‐CCP and RF. However, serum RF significantly correlated with anti‐CCP. %CDT did not correlate with anti‐CCP, but absolute level correlated with anti‐CCP only in anti‐CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti‐CCP in anti‐CCP negative patients. Anti‐CCP correlated with DAS 28 only in anti‐CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti‐CCP positive RA.
These results suggest that the changes in CDT and anti‐CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.
The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and ...citrullination by means of autoantibodies to cyclic citrullinated peptides.
The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method.
80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA.
These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.
O objetivo deste estudo foi avaliar a relação entre os dois tipos de modificações pós-translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos anticorpos no caso do antipeptídeo citrulinado cíclico (anti-CCP).
O estudo foi realizado em 50 pacientes com AR. A TDC foi medida utilizando o teste imunonefelométrico N Latex CDT, e os resultados foram apresentados em unidades absolutas e relativas. O anti-CCP foi mensurado usando o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico.
80% dos pacientes com AR foram positivos para anti-CCP, 70% para FR e 62% para ambos (anti-CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti-CCP positivos do que naqueles anti-CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti-CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti-CCP. O percentual de TDC não se correlacionou com o anti-CCP, mas seu nível absoluto se correlacionou com o anti-CCP apenas em pacientes FR negativos e anti-CCP negativos. A TDC não se correlacionou com o FR, somente com o anti-CCP em pacientes anti-CCP negativos. O anti-CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti-CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti-CCP positivos.
Estes resultados sugerem que as alterações na TDC e as concentrações de anti-CCP não estão associadas entre si e indicam a independência destas modificações pós-translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.
Lysosomal exoglycosidases participate in the destruction of the articular cartilage by cleaving glycoside bonds in glycoproteins and proteoglycans. The aim of the study was to determine the activity ...of exoglycosidases: hexosaminidase, -glucuronidase, -galactosidase, -mannosidase and -fucosidase in serum and synovial fluid of patients with Lyme and rheumatoid arthritis. The study group consisted of 10 patients with chronic Lyme arthritis (age 18 - 74 y), 13 with rheumatoid arthritis (age 32 - 70 y) and 10 with juvenile idiopathic arthritis (age 8 - 17 y). The control group consisted of 9 healthy volunteers (age 24 - 62 y). The activity of the exoglycosidases was determined with the p-nitrophenyl derivatives of sugars as substrates. A significant increase of the activity of all the exoglycosidases in serum and in synovial fluid of the patients with different forms of arthritis was found. The ratio of synovial fluid/serum activity of exoglycosidases was above 2.0 in LA but not in JIA and RA patients. As the main source of exoglycosidases in the joint is the synovial membrane, this result supports the appropriateness of therapeutic synovectomy in chronic Lyme arthritis with knee effusion. The serum activity of hexosaminidase may be used in monitoring the course of Lyme arthritis and the efficiency of treatment.
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