The implementation of a charge-sensitive amplifier (CSA) based on the МН2ХА030 array chip (AC) with an adjustable conversion factor for processing signals of silicone photomultipliers (SPM) is ...considered. The developed CSA, named ADPreampl3, contains a fast and slow signal circuit (SC). The fast SC includes a transresistive amplifier-shaper with a base-level adjustment circuit, and a slow SC includes an CSA, a shaper, and a base-level restorer (BLR) circuit. The main advantage of ADPreampl3 amplifier when used in multichannel integrated circuits is the minimum number of elements used, due to the use of the same stages to perform different functions. To correctly simulate the operation of ADPreampl3, taking into account the features of the input signal source, a simplified electrical equivalent circuit of the SPM, applicable to both circuit simulation and measurements, is proposed. Circuit simulation of ADPreampl3 using the proposed equivalent circuit of SPM with a supply voltage of ±3 V, made possible to establish that: fast SC is characterized by the bandwidth up to 60 MHz and allows adjusting the base level in the range from -0.1 V to 0.2 V. Thus, it is possible to compensate the technological variation of the output voltage of the fast SC or set the required switching threshold of the comparator connected to the output of the fast SC; slow SC allows you to adjust the base level in the range from -1 V to 1 V and smoothly change the amplitude of the output signal, including phase inversion, when the control voltage changes from -1 V to 1 V; the BLR circuit provides a constant shape of the output voltage pulse with a DC input current of ADPreampl3, varying in the range of ±190 μA, and a negligible change of the base level at ±20% of the resistance variation of integrated resistors. ADPreampl3 amplifier enables the transition to the ``sleep'' mode with a decrease in current consumption up to 10 μA, maintains operability at an absorbed dose of gamma radiation up to 500 krad and the effect of the integral neutron fluence up to 1013 n/cm2 and can be used in multi-channel signal processing chips of SPM.
The use of dual-gate field-effect transistors located on the base matrix crystal MH2XA031, controlled by a
p–n
junction needed to reduce the input current of operational amplifiers is studied. ...Typical circuits of operational amplifiers, containing: source repeaters connected to the inputs of the operational amplifier on complementary bipolar transistors; input differential stage on
p
-JFET with a “current mirror” load on
n–p–n
-transistors; input differential in the form of a “folded cascode” on a
p
-JFET are analyzed. To minimize the input current, it is re commended to use bootstrapped feedback to keep the drain-to-source voltage of the input JFETs low, independent of the input common-mode voltage, and to connect only the top gate of the dual-gate JFET to the op-amp input. The electrical circuits for MH2XA031 elements and the results of circuit simulation of the developed amplifiers, called OAmp10J, OAmp11.1, OAmp11.2, are presented. Accounting the established features of the input stages and operating modes of active elements in circuit design will allow to create an operational amplifier with the required combination of basic parameters.
Aim
. Investigation of the influence of canceroembryonic antigen (CEA) on the immune cells in patients with breast tumors.
Materials and methods
. Peripheral blood of 67 patients with invasive ductal ...carcinoma (n = 44), fibroadenoma (n = 12) and breast pre-cancer (n = 11). In the supernatants of the blood cells cytokine production induced by CEA was determined by ELISA.
Results.
It was found that CEA stimulated production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFα, G-CSF, GM-CSF and the protein MCP-1 by blood immune cells in patients with fibroadenoma compared with groups of patients with invasive ductal carcinoma and precancerous lesions. Stimulation index of CEA on cytokine production by immunocompetent cells in patients in these groups was lower than in groups of patients with fibroadenoma due to initially high levels of spontaneous cytokine production.
Results.
In patients with fibroadenoma CEA was found to stimulate the production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFa, G-CSF, GM-CSF and MCP-1 compared with groups of patients with invasive ductal carcinoma and precancerous conditions. Indexes of the influence of CEA on cytokine production by immunocompetent cells in these groups was lower than in the fibroadenoma due to initially high spontaneous production of cytokines.
Conclusion.
Evident spontaneous cytokine-producing function of immunocompetent blood cells was revealed in patients with invasive ductal carcinoma and precancerous conditions compared to patients with fibroadenoma. The differences between the indices of CEA influence on cytokine production in patients with malignant, benign and precancerous conditions can serve as a basis for the development of methods of differential diagnosis of breast tumors.
It is known that a relationship exists between patient’s age and pathogenesis of malignant tumors associated with ability of tumor and its microenvironment to secrete cytokines that may play an ...important role in carcinogenesis. The aim of present study was a comparative analysis of cytokine production by peripheral blood cells and tumor samples when exposed to polyclonal activators (PA) in patients of different age groups with invasive ductal carcinoma. Peripheral blood samples of 54 women with invasive ductal carcinoma were under study. The patients were divided into the following groups: I, 40-60 years old; II, 61 year and older. Metastases into lymph nodes were revealed at the moment of study in 13 patients (42%) from group I. By contrast, only 3 of 23 (10%) patients with metastases were revealed in group II. Fisher’s ratio test showed significant differences between occurrence of metastases in lymph nodes, and patient age (p = 0.034). In both groups of patients, there was an increase of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ra, G-CSF, GM-CSF and VEGF concentrations in tumor supernates and its microenvironment, when compared with the production of cytokines by blood cells, thus indicating to high functional activity of tumor together with its microenvironment. Effect of PA led to increase of IL-2, IL-10, IL-17, IL-1β, IL-1ra, TNFα and IFNγ concentrations in blood cells supernatant which suggested their high ability to produce cytokines. In the group of patients who were 40-60 years old, the stimulatory index of PA (SIPA) for IFNγ production was several times higher than similar index in patients aged 61 years or more. Increase of SIPA for all cytokines in blood cells supernates, in comparison to SIPA of tumor supernates, could be explained by initially high levels of spontaneous cytokine production by the tumor and its microenvironment that are able to promote tumor growth. Therefore, effect of PA upon tumor tissue was not so expressed as its effect upon immunocompetent blood cells. Both tumor and microenvironment maintained high ability of IL-18 production, thus confirming its important role in carcinogenesis. In summary, these findings suggest that circulating immunocompetent cells may serve as an additional factor providing tumor progression, due to their high ability to secrete cytokines.
Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The ...analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide). Levels of cytokines and growth factors (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A) and MCP-1 (monocyte chemoattractant protein-1) in tumor supernatants were determined by an ELISA. Expression of VEGF-A was analyzed in tumor biopsy specimens by immunohistochemical analysis. In the IDC supernatants, the concentrations of IL-17, IL-18, and IFN-γ were higher and the concentrations of IL-10 and MCP-1 were lower in comparison with the FA supernatants. We observed negative correlations between the macrophage infiltration and VEGF-A concentration in the IDC supernatants (r = −0.508; P = 0.011) and between VEGF-A expression and the IDC vascularization degree (r = −0.423, P = 0.039). Spontaneous expression of VEGF-A in samples of IDC significantly exceeded the VEGF-A expression in FA. There was no difference between IDC and FA in VEGF-A expression after treatment with the polyclonal activators. Our results indicate that greater malignancy may have a paradoxical effect that is controlled by cytokines and characterized by weakening of tumor angiogenesis during overproduction of VEGF-A. These findings point to complex mechanisms of positive and negative regulation of tumor angiogenesis by cytokines that are produced by the tumor and by cells in its microenvironment, whose cytokine profiles may change at different stages of tumor progression.
The aim of the study was to investigate a relationship between cytokine-producing reserve of invasive ductal cancer cells and its microenvironment, and cytokine-producing reserve of immunocompetent ...blood cells (IBC), as well as with histopathological and immunohistochemical characteristics of breast cancer. Using ELISA method we investigated the spontaneous and stimulated with polyclonal activators (PA) cytokine-producing reserve of IBC and biopsy specimens from invasive ductal cancer (adenocarcinoma) in 34 women. Appropriate values were expressed by the Influence Index of polyclonal activators (IIPA) upon cytokine production (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF-A, MCP-1). In tumor biopsies, we studied expression of VEGF-A, estrogen receptor, progesteron receptor and pro-proliferation marker Ki-67 by means of immunohistochemical method. Activation values of blood IBC in most cases, except of IL-18, IL-1β and MCP-1, were higher than appropriate effects upon cytokine production by tumor tisuues. Meanwhile, the IIPA activation index upon IL-18 (a proinflammatory and prooncogene cytokine) production by tumor cells and its microenvironment proved to be elevated, as compared to appropriate IIPA by the blood IBC. Statistical studies showed a direct correlation between IIPA and cytokine production in tumor supernates, IIPA of VEGF-A expression in tumor tissue, with pathohistological parameters and expression of estrogen and progesterone receptors and Ki-67 proliferation marker. A high positive correlation was obtained between IIPA TNFα production by the tumor tissue, and degree of tumor vascularization.We have revealed a negative correlation between IIPA for IL-6, MCP-1 and Ki-67 marker of cell proliferation. A direct correlation was found between IIPA values for IL-1ra/IL-1β production ratios in blood cells, and IIPA for VEGF-A expression in adenocarcinoma tissues, thus indicating to probable connections between IL-1ra production by IBC and VEGF-A expression. We have discerned several intersecting, diverging, and even circle-closed correlative chains of correlation, e.g.: VEGF-A (immunohistochemical marker of IIPA expression) – IL-10 and IL-8 (IIPA for supernate products); MCP-1, IL-6, and IL-10 (IIPA for supernate products)– VEGF-A (immunohistochemical indicator of expression for IIPA). The results of this study suggest a relationship between cytokine-producing reserves of the tumor identified by appropriate PA correlations with the processes occurring in malignant tumors, as assessed by histopathological and immunohistochemical parameters. The data are indicative for some complex mechanisms mediated by cytokines which provide invasive growth of malignant tumor.
Presented below are the results of the measurements of temperature of simulators of front-end electronic boards (62 pcs), heat sinks for electronic units, housing of the ROC chamber, and the pad ...plane of the TPC detector for the MPD facility to be operated at the NICA collider. The measurements were conducted for two coolant temperatures. Data of computer simulations, which are in good agreement with the measurements, are also presented. The results reported will be used to develop and optimize cooling and thermal stabilization systems for ROC chambers and front-end electronics.
Dependence of cytokine pattern in the tumor supernatant obtained after cultivation of biopsy samples–on the patients’ age was evaluated among patients with invasive ductal carcinoma of the breast. An ...increase in VEGF and IL-6 production in a group of younger patients was observed. An increase only in interferon γ concentration was revealed in the supernatants of the tumor after addition of polyclonal activators to the culture medium. This result indicates likely secretion of interferon γ in younger patients. The relation among the production of angiogenic factors by tumor cells, age of the patients, and presence or absence of lymph node metastases shows that in such studies, patients have to be stratified by age.
Abstract
The process of evaporation of sessile water droplets on a heated substrate was experimentally studied. A droplet evaporation is a fundamental phase change process which requires thorough ...consideration in various conditions. In this work we investigated the evaporation of water droplets on the smooth copper substrate with a circle groove made on its surface, which helped to keep the sessile droplet stable. Thus, the contact area of the evaporating droplet with the substrate remained constant, while the contact angle varied over a wide range. The experiment was conducted with a help of Krüss DSA100.
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