The Use of Flow Model Analysis (FMA) in the Case of Incomplete Mathematical Models

The main aim of the "System for Analyzing Mathematical Flow Models" (FMA system) described in this paper is to supply the decision-maker with a computerized tool for quantitative investigation of problem that can be described, at least partially, in terms of standard mathematical models of the Bow type. The FMA system permits the decision-maker to find states of the considered model that satisfy all introduced constraints, are close to the desirable structure, and are optimal with respect to single- or multiobjective evaluation

Analytical model of brittle destruction based on hypothesis of scale similarity

The size distribution of dust particles in nuclear fusion devices is close to the power function. A function of this kind can be the result of brittle destruction. From the similarity assumption it follows that the size distribution obeys the power law with the exponent between -4 and -1. The model of destruction has much in common with the fractal theory. The power exponent can be expressed in terms of the fractal dimension. Reasonable assumptions on the shape of fragments concretize the power exponent, and vice versa possible destruction laws can be inferred on the basis of measured size distributions.Comment: 10 pages, 3 figure

MOLDING SAND PREPARATION METHOD

FIELD: foundry.SUBSTANCE: method comprises steps of charging granular filler into mixer; at first charging one doze of filler and mixing it with binder till uniform distribution of binder on surface of grains of filler; adding second doze of filler and mixing it till uniform distribution of filler in the whole mass of molding sand. Invention provides shortened time period of distributing binder on surface of filler grains.EFFECT: enhanced strength of molding sand without increased consumption of binder.1 ex.Изобретение относится к литейному производству. Зернистый наполнитель загружают в смеситель по частям. Первую часть смешивают со связующим до равномерного распределения его по поверхности зерен наполнителя. Добавляют вторую часть наполнителя и перемешивают до равномерного распределения наполнителя в общей массе смеси. Снижается время распределения связующего по поверхности зерен наполнителя. Обеспечивается повышение прочности смеси без увеличения расхода связующего

AUTOIMMUNE ORIGIN OF SARCOIDOSIS: DETERMINATION OF SPECIFIC IMMUNE COMPLEXES IN PATIENTS WITH RESPIRATORY SARCOIDOSIS

The etiology of sarcoidosis is not completely understood. A hypothesis exists about the relationship between sarcoidosis and a complex of pathological autoimmune reactions that occur under the influence of triggering factors. In this study, specific immune complexes in the blood plasma of patients have been determined, which can indirectly reveal the causes of the disease.The study included 33 patients with lung sarcoidosis (I group), compared to 24 healthy donors who served as a control group (II group). The patients underwent standard examination. Their blood plasma was investigated by the dynamic light scattering method with addition of tuberculosis antigens (ESAT-6/SFP-10) and “lung healthy tissue extract”. Statistical analysis was performed using the Statistica 7.0 program. Test results were considered significant at p < 0.05.Аccording to the data obtained, addition of ESAT-6/SFP-10 to patient’s blood plasma almost did not lead to the formation of immune complexes in most samples. Meanwhile, development of such complexes after addition of “lung tissue extract” was revealed in all the patients. The immune complexes were not detected in any donor from control group after stimulation with both kinds of antigens (p < 0.01).The data on distinct formation of immune complexes with the addition of “lung healthy tissue extract” in patients with lung sarcoidosis may be considered an indirect evidence for occurrence of autoimmune reaction under the influence of some pathogenic factors. Absence of de novo immune complex formation after addition of tuberculosis antigens (ESAT-6/SFP-10) makes it unlikely any direct effects of tuberculosis bacteria upon development of sarcoidosis

Pharmacogenetic Modulation of Orexin Neurons Alters Sleep/Wakefulness States in Mice

Hypothalamic neurons expressing neuropeptide orexins are critically involved in the control of sleep and wakefulness. Although the activity of orexin neurons is thought to be influenced by various neuronal input as well as humoral factors, the direct consequences of changes in the activity of these neurons in an intact animal are largely unknown. We therefore examined the effects of orexin neuron-specific pharmacogenetic modulation in vivo by a new method called the Designer Receptors Exclusively Activated by Designer Drugs approach (DREADD). Using this system, we successfully activated and suppressed orexin neurons as measured by Fos staining. EEG and EMG recordings suggested that excitation of orexin neurons significantly increased the amount of time spent in wakefulness and decreased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep times. Inhibition of orexin neurons decreased wakefulness time and increased NREM sleep time. These findings clearly show that changes in the activity of orexin neurons can alter the behavioral state of animals and also validate this novel approach for manipulating neuronal activity in awake, freely-moving animals

DIAGNOSTIC VALUE OF SPECIFIC IMMUNE COMPLEXES IN DETECTION OF ACTIVE TUBERCULOSIS INFECTION

The diagnostic of tuberculosis infection, including the use of immunological methods, evolved significant changes. The introduction of new diagnostic tests allowed to improve the diagnosis of latent tuberculosis infection (LTI). However, the positive results of immunological tests in both tuberculosis patients and in those with LTI do not allow to divide these conditions, which requires the development and implementation of new diagnostic approaches.Materials and methods. A prospective study with a survey of two groups of patients was conducted: group I (n=50) - patients with verified pulmonary tuberculosis, MBT (+); group II (n =15) – subjects with LTI and control group – healthy subjects (n=14). The examination complex included clinical, radiological, bacteriological, immunological (Mantoux test with 2 TU, T-SPOT.TB, QFT and Diaskintest) methods. Immune complexes were determined in all patients and healthy individuals by the method of dynamic light scattering after the in vitro addition of specific antigens - peptides ESAT-6 and SFP-10.Results. The obtained data demonstrate the low informativeness of the clinical method in the diagnostic of pulmonary tuberculosis. In the presence of characteristic X-ray changes, bacteriological verification of tuberculosis was obtained only in 46% of cases. The use of various immunological tests allows to obtain positive test results in 84-90% of cases simultaneously with the 100% of the positive results in subjects with LTI. Determination of specific immune complexes by the method of dynamic light scattering allows to determine the activity of tuberculosis infection in 100 % of cases and to identify a high-risk group for the development of active tuberculosis in people with latent tuberculosis infection.Conclusions: the obtained data can be applied not only in the diagnosis of active tuberculosis in the absence of diagnosis verification, but also allow to identify a high-risk group for the development of the disease in people with latent tuberculosis infection

LV-pIN-KDEL: a novel lentiviral vector demonstrates the morphology, dynamics and continuity of the endoplasmic reticulum in live neurones

BACKGROUND The neuronal endoplasmic reticulum (ER) is an extensive, complex endomembrane system, containing Ca2+ pumps, and Ca2+ channels that permit it to act as a dynamic calcium store. Currently, there is controversy over the continuity of the ER in neurones, how this intersects with calcium signalling and the possibility of physical compartmentalisation. Unfortunately, available probes of ER structure such as vital dyes are limited by their membrane specificity. The introduction of ER-targeted GFP plasmids has been a considerable step forward, but these are difficult to express in neurones through conventional transfection approaches. To circumvent such problems we have engineered a novel ER-targeted GFP construct, termed pIN-KDEL, into a 3rd generation replication-defective, self-inactivating lentiviral vector system capable of mediating gene transduction in diverse dividing and post-mitotic mammalian cells, including neurones. RESULTS Following its expression in HEK293 (or COS-7) cells, LV-pIN-KDEL yielded a pattern of fluorescence that co-localised exclusively with the ER marker sec61beta but with no other major organelle. We found no evidence for cytotoxicity and only rarely inclusion body formation. To explore the utility of the probe in resolving the ER in live cells, HEK293 or COS-7 cells were transduced with LV-pIN-KDEL and, after 48 h, imaged directly at intervals from 1 min to several hours. LV-pIN-KDEL fluorescence revealed the endoplasmic reticulum as a tubular lattice structure whose morphology can change markedly within seconds. Although GFP can be phototoxic, the integrity of the cells and ER was retained for several weeks and even after light exposure for periods up to 24 h. Using LV-pIN-KDEL we have imaged the ER in diverse fixed neuronal cultures and, using real-time imaging, found evidence for extensive, dynamic remodelling of the neuronal ER in live hippocampal cultures, brain slices, explants and glia. Finally, through a Fluorescence Loss in Photobleaching (FLIP) approach, continuous irradiation at a single region of interest removed all the fluorescence of LV-pIN-KDEL-transduced nerve cells in explant cultures, thus, providing compelling evidence that in neurons the endoplasmic reticulum is not only dynamic but also continuous. CONCLUSION The lentiviral-based ER-targeted reporter, LV-pIN-KDEL, offers considerable advantages over present systems for defining the architecture of the ER, especially in primary cells such as neurones that are notoriously difficult to transfect. Images and continuous photobleaching experiments of LV-pIN-KDEL-transduced neurones demonstrate that the endoplasmic reticulum is a dynamic structure with a single continuous lumen. The introduction of LV-pIN-KDEL is anticipated to greatly facilitate a real-time visualisation of the structural plasticity and continuous nature of the neuronal ER in healthy and diseased brain tissue

MCT Expression and Lactate Influx/Efflux in Tanycytes Involved in Glia-Neuron Metabolic Interaction

Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes

Association of narcolepsy-cataplexy with HLA-DRB1 and DQB1 in Mexican patients: A relationship between HLA and gender is suggested

<p>Abstract</p> <p>Background</p> <p>Narcolepsy-cataplexy is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hallucinations and sleep paralysis. Its aetiology is unknown, but it is positively associated with the human leukocyte antigens (HLA) in all studied populations. The purpose of the present study was to investigate the association of HLA class II <it>DRB1</it>/<it>DQB1 </it>alleles with narcolepsy-cataplexy in Mexican Mestizo patients.</p> <p>Methods</p> <p>This is a case-control study of consecutive patients and ethnically matched controls. We included 32 patients diagnosed with typical narcolepsy-cataplexy, of the National Institute of Neurology, of the Institute of Psychiatry and at the Center of Narcolepsy at Stanford University. As healthy controls, 203 Mexican Mestizos were included. <it>DRB1 </it>alleles were identified using sequence based typing. A PCR-SSOP reverse dot blot was used for <it>DQB1 </it>typing. Allele frequency was calculated by direct counting and the significance of the differences was assessed using the Yates Chi square. Odds ratio and confidence intervals were evaluated.</p> <p>Results</p> <p>HLA-<it>DRB1</it>*1501 (OR = 8.2; pc < 0.0001) and <it>DQB1</it>*0602 (OR = 8.4; pc < 0.0001) were found positively associated with narcolepsy. When deleting <it>DQB1</it>*0602+ patients from the analysis, <it>DQB1</it>*0301 was also found increased (OR = 2.7; p = 0.035; pc = NS). <it>DQB1</it>*0602/<it>DQB1</it>*0301 genotype was present in 15.6% of the cases (OR = 11.5; p = 0.00035), conferring a high risk. <it>DRB1</it>*0407 (OR = 0.2; p = 0.016 pc = NS) and <it>DQB1</it>*0302(OR = 0.4; p = 0.017, pc = NS) were found decreased in the patients. The gender stratification analysis showed a higher risk in females carrying <it>DRB1</it>*1501 (OR = 15.8, pc < 0.0001) and <it>DQB1</it>*0602 (OR = 19.8, pc < 0.0001) than in males (OR = 5.0 for both alleles; p = 0.012, pc = NS for <it>DRB1 </it>& p = 0.0012, pc = 0.017 for <it>DQB1</it>). The susceptibility alleles found in Mexicans with narcolepsy are also present in Japanese and Caucasians; <it>DRB1</it>*04 linked protection has also been shown in Koreans. A stronger HLA association is suggested in females, in accordance with the sexual dimorphism claimed previously.</p> <p>Conclusion</p> <p>This knowledge may contribute to a better understanding of the disease pathogenesis in different populations. The evaluation of the risk to develop narcolepsy-cataplexy in carriers of the described alleles/genotypes may also be possible. A larger sample should be analysed in Mexican and in other Hispanic patients to confirm these results.</p