Principle Of Negative Feedback Research Articles

The Role of Decreased Expression of Glucocorticoid Receptors in the Development of Itsenko-Cushing Syndrome

Background: Itsenko-Cushing syndrome is caused by unregulated excessive cortisol incretion by the adrenal cortex. The causes of increased stimulation of cortisol incretion by the adrenal cortex, leading to hyperplasia and tumors (adenoma and cancer) of the adrenal cortex, as well as to adenoma of the pituitary gland itself, remain unclear to date. Materials and Methods: 6 patients with adrenal Itsenko-Cushing syndrome with adrenal cortex adenoma were under observation. The age of the patients ranged from 24 to 87 years. The patients underwent removal of the adrenal gland on the affected side. The control group consisted of 6 individuals who underwent surgical treatment of varicocele and hernias of various localization. In patients of the main group and control group, with their consent, a small fragment of skin from the edge of the surgical wound was taken for examination, which were fixed in a 10% formalin solution. Results: The presence of adrenal Itsenko-Cushing syndrome in patients of the main group was confirmed by laboratory and instrumental studies, as well as characteristic clinical manifestations. The average Histochemical score of the expression of glucocorticoid receptors (GR) of the skin in patients of the main group with Itsenko-Cushing adrenal syndrome was 2.7 times less than the same value in the control group. Conclusions: A decrease in the formation or absence of glucocorticoid receptors (congenital or acquired) blocks the negative feedback of cortisol suppression of corticoliberin production by the hypothalamus and ACTH-pituitary gland. The resulting excessive incretion of corticoliberin becomes the main link in pathogenesis of pituitary adenoma formation, and an excessive incretion of ACTH leads to the formation of cortical hyperplasia and tumors (adenomas, cancers) of the adrenal cortex. Unregulated excessive cortisol production by hyperplastic adrenal tissues or benign/malignant adrenal tumors leads to overcoming resistance to glucocorticoids and, according to the principle of negative feedback, suppresses the production of corticoliberin by the hypothalamus and ACTH-pituitary gland. As a result, the pituitary form of Itsenko-Cushing syndrome turns into an adrenal form with an unregulated increase in cortisol levels and a decrease in ACTH levels. Transfusion of the mononuclear fraction of peripheral blood obtained from healthy donors, which allows the pluripotent stem cells contained in it to partially replace the altered cells of all tissues of patients, is a promising method of treating patients with Itsenko-Cushing syndrome due to a hereditary decrease in the expression of glucocorticoid receptors.

TECHNOSPHERE: PHILOSOPHICAL CONCEPTS, DEVELOPMENT TRENDS AND PRACTICAL CHALLENGES

The global technological environment, which mediates the interaction of mankind with the biosphere, carries technogenic and environmental hazards and serious anthropological and social risks. Today there is a tendency in which every improvement of the technogenic system ultimately increases its negative impact on nature on the principle of negative feedback. In such a situation, an objective assessment of the technosphere’s characteristics is necessary for timely harmonization in the relationship “Human – Natural Environment”.
 The purpose of the article is to conceptualize ideas about the technogenic path of human development and to introduce the concept of “ecological technosphere” as a new stage of coevolutionary relations between nature and technogenic civilization.
 The research is carried out within the framework of the concept of post-classical science, a structural and functional approach, postphenomenology, actor-network theory.
 In the article, based on the concepts of “technique”, “technology”, “technocenosis”, “technological environment”, an ontological analysis of the concept of “technosphere” is proposed, its essential characteristics and risky scenarios of development are highlighted.
 The article was carried out within the framework of the project “Socio-ecological monitoring of the technical environment of the region: a socio-cultural approach” (RFBR Grant 20-311-90060 Graduate students)

Wagner's Furious Host

Wagner's Furious Host

A SQUID-Based Picovoltmeter for Quantum Resistors

We present a sensitive voltage amplifier suited for measurements of source impedances in the k $$\Omega$$ range at dilution refrigerator temperatures. The circuit is based on a commercial dc SQUID, an impedance matching transformer, and it works on the principle of negative feedback. At 10 mK, the amplifier contribution to the noise is only 17 $$\text{pV/}\sqrt{\text{ Hz }}$$ , which is negligible in comparison with the fluctuations of the thermal voltage of a 3.25 k $$\Omega$$ metallic source resistor. Various circuit parameters of the amplifier are discussed.

DAFS-25k impact on cattle’s thyroid hormonal status

The paper studies the impact of selenium organic preparation DAFS-25k on thyroid capacity in pregnant cows. A stud farm which the work is done in is a biogeochemical province distinguished by a sharp deficit of selenium and iodine in the diet. DAFS-25k had been implanted into the animals subcutaneously during 1 month 30 days before the predicted calving. A sterile 0.6 % DAFS-25k oil solution was used in doses containing 2 mg/cow/day, 6 mg/cow/day and 12 mg/cow/day. It was found that the cows’ diet is deficient in iodine and selenium by 63 and 82 % respectively. Daily use of selenium in DAFS-25k in the dose range causes a decrease in the concentration of free thyroxine due to deiodination activating by selenium dependent deiodinases of the first and second types. Consequently, there is a progressive increase in the blood content of total triiodothyronine in all experimental animals as relating to the background values. In this case, the concentration of thyroid-stimulating hormone decreases in blood serum by the 30th day according to the principle of negative feedback. In control animals, an increase in the serum concentration of thyroid-stimulating hormone reached the point 1.8 by the 30th day, total triiodothyronine increased by 14 and 19 % by the 21st day and the 30th day respectively, while the concentration of free thyroxine was reduced by 19 % by the 30th day. The use of selenium in the setting of iodine deficiency leads to aggravation of iodine deficiency.

The Influence of Phytoplankton Primary Production on the Cycle of Biogenic Elements in the Coastal Waters off Sevastopol, Black Sea

The phytoplankton primary production and the biogenic elements content of the coastal waters off Sevastopol have been studied as a result of 2-year monitoring. It has been found that mineral phosphorus is a key factor of chemical limitation of the production processes. During primary production of organic matter, the habitat conditions for phytoplankton in the photic layer are in accordance with the Le Chatelier–Braun principle of negative feedback.

Development of the imitation model of the two-stage separation process of oil

In accordance with the law of preservation of the amount of substance, an imitation model for the process of two-stage oil separation has been developed. The creation of this model took into account the features of the operating mode of the horizontally placed separators B-1 and B-2 of the first and second stages of separation. The simulation mathematical model after the identification of parameters was investigated by a numerical method that takes into account the effect of perturbations on the separation process, which is a consequence of the action of a number of physical quantities from the environment on the object. Automated control systems that operate on the principle of negative feedback were used to stabilize the main technological parameters of oil separation. But since the deviation of the regulated quantities from their given values is small, this allowed linearizing the nonlinear model of the two-stage separation process. After studying the simulation model by a numerical method, it is established that the mathematical model of the installation of two-stage separation can be used for the synthesis of effective control systems of the two-stage separation process and the creation of mathematical models in terms of “input-output”. The obtained numerical and graphical result in the form of functional dependencies allows us to establish the relationship of technological parameters, in other words, the change of the value of the parameters at the second stage of separation will depend on the first one and vice versa. Thus, the applied aspect of using the obtained scientific result is the possibility of improving the typical technological process of oil separation.

Automation of a Single Cryogenic Rectification Column for the Production of Isotopes of the Light Elements

oxide imposes high requirements in terms of the stability of the circulating fl ow in the cryogenic column; this fl ow can change because of the instability of the external fl ow, the electric power of the heater, and heating insulation [2]. The result is, aside from degradation of the characteristics of separation, loss of column serviceability owing to the phenomenon of fl ooding/emptying. Control System. The measurement of automatic stabilization of the circulating fl ow G is based on the following principle (Fig. 1). For constant thermal power N of the evaporator and precise material balance of the external fl ows F = W + P, the circulating fl ow G remains unchanged. This means that the liquid mass fl ow G liq arriving in the evaporator 3 equals the outgoing gas fl ow G gas , the measured level H of the liquid phase 2 in collecting vessel 1 is unchanged, and the measured electric (thermal) power 4 N corresponds thermodynamically to the fl ow G. A change in the level H of the liquid phase in the collecting tank 1, for example, owing to errors in the operation of the controlled stabilizers 5–7, is restored by the automatic regulator RegG controlling the power N of the evaporator 3 to the correspondence H = H set . The new power N 1 corresponds to a different circulating fl ow G 1 [3]. The circulating fl ow is restored according to the principle of negative feedback by the regulator RegG. The regulator compares the instantaneous electric power N 1 (t) consumed by the evaporator 3 with the prescribed value N set , which corresponds to the nominal fl ow G nom , by changing the setting signal W set (t) to the controlled stabilizer 7 of the waste fl ow until N(t) = N set [2]. A particularity of the control of the circulating fl ow is the time delay �≤ of the regulatory action W; this delay is due to the transport delay of the motion of the liquid phase along the column to the evaporator of the column’s still. For industrial-height columns, the delay �≤ can be thousands of seconds. For delay �≤ in the circuit controlling the circulating fl ow, which is much greater than the regulation time in the system controlling the level H, a structural solution, called the Smith predictor [4, 5], must be used. This makes it possible to take the delay factor outside the control circuit with negative feedback, so that the transient process at the exit will manifest after a delay time �≤ . Then the system controlling the circulating fl ow has the form shown in Fig. 2, where W RegH (p), W RegG (p), W te.h , W col (p), and k W are the transfer functions of the automatic regulators of the level H, circulating fl ow G, thermoelectric heater, collecting tank, waste W regulator, respectively, and the transfer function of the Smith predictor assumes the form: W s.p (p)= N s.p (p) W(p) =W o (p)[1�exp(�� p)], where

Tropical cyclone, as powerful natural self-oscillatory systems, and wind-energetic a way of struggle against it—The analysis of a cyclone from a position of the theory of vibrations

It is considered three phases of development of a tropical cyclone: the origin, the steady-state regime and the termination, coinciding with three phases of self-oscillatory process: oscillation buid-up, dynamic balance and failure of self-oscillations. The rough size of energy of a cyclone, as column of air rotating with high speed, at initial and final stages of development and comparison of the received sizes with nuclear and hydrogen bombs is calculated. The model of the electronic oscillator with negative active conductivity by the numerical solution of the equation of the Van-der-Pol is analyzed. Formal coincidence of transient in this model with increase of capacity of vortical air formation, that allows to make mnemonic model of a cyclone in the form of volume self-oscillatory system is shown. The numerical solution of the made equations allows to construct schedules of dynamic process for each of particles of the investigated environment. The general recipe on restraint of development of a cyclone by compulsory entering into it of attenuation is given. Realization of this recipe by means of group of platforms with powerful wind-electrogenerator and the fans and uses of a principle of negative feedback is shown. The results of laboratory experiment confirming idea, taken as a principle struggle against an arising air whirlwind, by transformation of a laminar stream in chaotic, turbulent are resulted. For fuller check offered a wind-energetic method of struggle against a cyclone carrying out of more scale experiment is necessary.

Stabilization of a multimode He–Ne laser: A vivid demonstration of thermal feedback

A thermal stabilization technique for multimode He–Ne laser tubes is demonstrated. Intensity stability of ∼1% is achieved, where the intensity of the unstabilized laser varied by more than a factor of 5. The system provides both a dramatic demonstration of the principle of negative feedback and a stimulating introduction to basic electronics, laser physics, and solid state physics. It is simple enough to be constructed as an undergraduate laboratory project.

Feedback regulators in normal and tumour tissues

Regulation of cell behaviour and population size is presumed to be not unlike classical regulation in non-biological systems, i.e. it is controlled by the cybernetic principle of negative feedback whereby the performance of progenitor cells depends inversely on a signal from their product, the size of which is proportional to the mass of the product. This signal may be inhibitory, acting directly on the progenitor cells. Alternatively, it may operate via an indirect and integrated inhibitor/stimulator feedback loop in which the one influences the production of the other. Illustrations taken from the various phases of haemopoietic development show the operation of these loops. Haemopoietic stem cells are under the direct influence of both inhibitor and stimulator but it is a feedback signal from the stem cell population that dictates the production of the one rather than the other. A second inhibitor acting at the stem cell level is a low molecular weight tetrapeptide which blocks the entry of cells into DNA synthesis, thus protecting them during a regimen of treatment with an S-phase cytotoxic drug. Proliferation of the maturing cells is also inhibited by feedback products of their fully mature descendants. Here, the effect is one of cell cycle modulation, whereas in the stem cell population the inhibitor and stimulator effect an on/off switch. Attempts to characterize the molecules involved have been limited. A series of tri- to pentapeptides has been described for haemopoietic or epithelial cell inhibitors. A common feature of several is a pGlu-Glu end though whether this has any significance is not known. In tumours it has been shown that some ascites are self-limiting and treatment of small tumours with cell-free fluid from a mature growth blocks their further growth. It appears that many tumour cells produce the feedback signals characteristic of their normal counterparts but are themselves less sensitive to it. The same is true of transforming growth factor-beta which is produced and detected by virtually all cell types. In this case, the factor, inhibiting in most cases, is produced in inactive form and achieves its target specificity by a localized capacity to activate it. Some tumours, while responding to exogenous active TGF-beta are incapable of activating the latent molecule. It is concluded that the differential sensitivity of normal and neoplastic tissues to physiological feedback regulators is a potentially exploitable property in cancer therapy.

Feedback in action-the mechanism of the iris

Homeostasis, i.e. the tendency of biological organisms to maintain a stable state, is always based on the principle of negative feedback in one way or another. The feedback process behind the stabilisation can generally be considered as taking place in two steps: first, the perception and second, the adjustment. An example of this is the mechanism of the iris of the eye: the intensity of the light reaching the retina is passed to the brain (first step) and from there signals are sent to the muscles which control the aperture of the iris diaphragm (second step). In both processes a time delay can occur, so it takes some time for the iris diaphragm to accommodate to a changed light intensity. Two demonstration experiments are described. The first one allows a demonstration of the general principle of positive and negative feed-back and the influence of time delays in feedback circuits. In the second one the principle of negative feedback is elucidated with a model of the iris of the eye.

On mechanisms of depression in pathways of presynaptic inhibition

We investigated inhibition of the N1-component of the spinal cord dorsal potential (CDP) evoked by experimental stimulation of the n. peroneus in spinal cats. Stimulation was carried out following two conditioning stimuli administered at different time intervals to the same or different cutaneous nerves. The interval between the last conditioning stimulus and the experimental one remained constant (20 msec). It is demonstrated that there is no dependence between weakening of inhibitory action of the second conditioning stimulus and inhibition of the dorsal horn interneurons excited by it that generate the N1-component of the CDP. It is hypothesized that mechanisms which act on the principle of negative feedback are present in the vincinity of the synaptic junctions of cutaneous afferent fibers with neurons of the substantia gelationsa, and that these mechanisms restrict the development of presynaptic inhibition during inflow of a series of afferent impulses into the cord.

A complementary driver with a subnanosecond rise time

A circuit specifically designed as a complementary driver for a high- speed scaling circuit is described. This circuit incorporates the principle of time-delayed negative feedback by using a passive delay line in the feedback path. The delay line provides optimum positioning of the bias voltage at the base of the nondriven transistor in a current-mode pair.

Studies on the mechanisms of resistance to hypoxia a review

The review summarises results of experimental research in Russia.The ultimate response mechanism of the hypoxic stimulus appears to reside in the cell itself and is activated by the direct action of nervous stimulation on the tissues involved and/or various hormonal regulatory systems.The adaptive mechanism in the cell to hypoxia involves a change in the cellular metabolism mediated by various enzymatic alterations. These cellular alterations,according to the principle of negative feedback, readjust the control of the nervous input from the lower and higher regulatory centers to a level corresponding to the changed environmental stimulus. Therefore, a new level in the coordination of the functional systems is established and the organism's general resistance is enhanced to hypoxia, the ultimate stimulus.

A Negative-Feedback Linear-Pulse Amplifier

A linear pulse amplifier is described which utilizes the principle of negative feedback. The amplifier is substantially unaffected by changes in supply voltages and provides either positive or negative output pulses with practically exact linearity and little backwave. The circuit components are easily obtainable and of moderate cost. A mechanical design is suggested which minimizes the labor of construction.