Theoretical Investigation of Totally Asymmetric Exclusion Processes on Lattices with Junctions

Totally asymmetric simple exclusion processes on lattices with junctions, where particles interact with hard-core exclusion and move on parallel lattice branches that at the junction combine into a single lattice segment, are investigated. A simple approximate theory, that treats the correlations around the junction position in a mean-field fashion, is developed in order to calculate stationary particle currents, density profiles and a phase diagram. It is shown that there are three possible stationary phases depending on the state of each of the lattice branch. At first-order phase boundaries, where the density correlations are important, a modified phenomenological domain-wall theory, that accounts for correlations, is introduced. Extensive Monte Carlo computer simulations are performed to investigate the system, and it is found that they are in excellent agreement with theoretical predictions.Comment: 16 pages, 7 figure

Spontaneous Symmetry Breaking in Two-Channel Asymmetric Exclusion Processes with Narrow Entrances

Multi-particle non-equilibrium dynamics in two-channel asymmetric exclusion processes with narrow entrances is investigated theoretically. Particles move on two parallel lattices in opposite directions without changing them, while the channels are coupled only at the boundaries. A particle cannot enter the corresponding lane if the exit site of the other lane is occupied. Stationary phase diagrams, particle currents and densities are calculated in a mean-field approximation. It is shown that there are four stationary phases in the system, with two of them exhibiting spontaneous symmetry breaking phenomena. Extensive Monte Carlo computer simulations confirm qualitatively our predictions, although the phase boundaries and stationary properties deviate from the mean-field results. Computer simulations indicate that several dynamic and phase properties of the system have a strong size dependency, and one of the stationary phases predicted by the mean-field theory disappears in the thermodynamic limit.Comment: 13 page

Two-Channel Totally Asymmetric Simple Exclusion Processes

Totally asymmetric simple exclusion processes, consisting of two coupled parallel lattice chains with particles interacting with hard-core exclusion and moving along the channels and between them, are considered. In the limit of strong coupling between the channels, the particle currents, density profiles and a phase diagram are calculated exactly by mapping the system into an effective one-channel totally asymmetric exclusion model. For intermediate couplings, a simple approximate theory, that describes the particle dynamics in vertical clusters of two corresponding parallel sites exactly and neglects the correlations between different vertical clusters, is developed. It is found that, similarly to the case of one-channel totally asymmetric simple exclusion processes, there are three stationary state phases, although the phase boundaries and stationary properties strongly depend on inter-channel coupling. An extensive computer Monte Carlo simulations fully support the theoretical predictions.Comment: 13 pages, 10 figure

Differential Expression of CHL1 Gene during Development of Major Human Cancers

CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis.We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (>40% of cases)--in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression.Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer

Multifunctional Oxidized Dextran as a Matrix for Stabilization of Octahedral Molybdenum and Tungsten Iodide Clusters in Aqueous Media

Due to their high abundance, polymeric character, and chemical tunability, polysaccharides are perfect candidates for the stabilization of photoactive nanoscale objects, which are of great interest in modern science but can be unstable in aqueous media. In this work, we have demonstrated the relevance of oxidized dextran polysaccharide, obtained via a simple reaction with H2O2, towards the stabilization of photoactive octahedral molybdenum and tungsten iodide cluster complexes [M6I8}(DMSO)6](NO3)4 in aqueous and culture media. The cluster-containing materials were obtained by co-precipitation of the starting reagents in DMSO solution. According to the data obtained, the amount and ratio of functional carbonyl and carboxylic groups as well as the molecular weight of oxidized dextran strongly affect the extent of stabilization, i.e., high loading of aldehyde groups and high molecular weight increase the stability, while acidic groups have some negative impact on the stability. The most stable material based on the tungsten cluster complex exhibited low dark and moderate photoinduced cytotoxicity, which together with high cellular uptake makes these polymers promising for the fields of bioimaging and PDT

The Periventricular Nucleus as a Brain Center Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis

Since the 1980s, the concept of dopamine-rich brain centers as clusters of only dopaminergic neurons has been fundamentally revised. It has been shown that, in addition to dopaminergic neurons, most of these centers contain neurons expressing one of the enzymes of dopamine synthesis: tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). We have obtained convincing evidence that in rats, the hypothalamic periventricular nucleus (PeVN) is one of the largest dopamine-rich centers, containing dopaminergic and monoenzymatic neurons. Indeed, using double immunostaining for TH and AADC, the PeVN was shown to contain almost three thousand dopaminergic and monoenzymatic neurons. According to high-performance liquid chromatography, PeVN contains L-DOPA and dopamine, which, apparently, are synthesized in monoenzymatic TH neurons and bienzymatic neurons, respectively. According to confocal microscopy, neurons (cell bodies, fibers), which were immunopositive only to TH, only to AADC, or both, are in close topographic relationships with each other and with the 3rd ventricle. These data suggest the mutual regulation of the neurons, as well as the delivery of dopamine and L-DOPA to the third ventricle, which is confirmed by their detection in the cerebrospinal fluid. Thus, evidence has been obtained that PeVN is one of the largest dopamine-rich centers of the brain, containing dopaminergic and monoenzymatic neurons

Clinical Experience of High Frequency and Low Frequency TENS in Treatment of Diabetic Neuropathic Pain in Russia

Background: Transcutaneous electrical nerve stimulation (TENS) is presently one of the main methods of treatment for neuropathic pain in type II diabetes mellitus. The discussion about which TENS frequency is more effective in the treatment of neuropathic pain has been ongoing for many years. Despite this, the response of different aspects of neuropathic pain to various TENS modalities has not been sufficiently studied. Aim: To analyze changes in characteristics of neuropathic pain depending on the frequency of TENS. Materials and methods: Seventy-five Russian diabetic patients with painful distal axonal neuropathy were enrolled in the study. Patients were assigned to three groups: in the HF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + high-frequency TENS (HF); in the LF TENS group, 25 patients received standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin) + low-frequency TENS (LF); in the control group, 25 patients underwent just standard drug therapy (Alpha-lipoic acid, Pentoxifylline, Vitamin B12, Gabapentin). Pain intensity was calculated before and after treatment with visual analogue scale (VAS), McGill pain questionnaire (MPQ), Douleur Neuropathique 4 Questions (DN4) and Pain Drawing. Results: TENS increased the therapeutic effect of standard drug therapy, in the treatment of neuropathic pain, by 65.9% and prolonged its efficacy by 31% for up to 6 months after treatment. HF TENS had a more pronounced analgesic effect than LF TENS based on VAS (34.7%), sensory (57.6%) MPQ dimensions and DN4 (21%). Affective MPQ dimension with the use of LF TENS was lower than HF TENS by 34.7% immediately after treatment, by 47.3% after 2 months and by 34.8% after 6 months of the follow-up period. Conclusion: There are significant differences between HF and LF TENS based on pain assessment using various pain scales. This reflects the distinctive effects of different TENS modalities on different aspects of neuropathic pain

Opyt primeneniya Lantusa (glargin) u detey i podrostkov s sakharnym diabetom 1 tipa v klinicheskoy praktike

Цель. Оценить эффективность применения инсулина Лантус (гларгин) по динамике НвА1с как показателя долговременного контроля гликемии, динамику изменения доз болюсного и базального (Лантус) инсулина у пациентов, страдающих СД1, с разной длительностью и уровнем НвА1с на протяжении 1 года с контролем описанных параметров исходно, через 3 и 12 мес от начала применения. Материалы и методы. В исследование длительностью 1 год было включено 67 детей, страдающих СД1, с разной длительностью заболевания. Обследованные дети были разделены на 3 группы: 1- я группа ? впервые выявленный СД1 (ВВСД1), 2- я группа ? дети с текущим СД1 и уровнем НвА1с ниже 10%, 3- я группа ? дети с текущим СД1 и уровнем НвА1с более 10% на момент начала терапии Лантусом (Гларгином). Детям с СД1 с различными сроками заболевания используемый ранее в качестве базиса NPH-инсулин (Протафан НМ, Хумулин NPH, Инсуман Базал) был заменен на инсулин гларгин (Лантус). Коррекция дозы инсулина осуществлялась в зависимости от показателей гликемии в стационаре при начальной госпитализации, далее ? в условиях домашнего самоконтроля под наблюдением эндокринолога по месту жительства. Качество компенсации углеводного обмена оценивали по величине НвА1с. Результаты. В 1-й группе степень компенсации углеводного обмена через 3 мес лечения достоверно улучшилась по сравнению с исходным, уровень НвА1с снизился достоверно с 13,8+0,4 до 7,5+0,3%. У детей 2-й группы через 3 мес выявлено достоверное снижение уровня НвА1с (с 11,7+0,3 до 9,5+0,2%). У детей 3-й группы через 3 месяца выявлено достоверное снижение НвА1с с 8,6?0,3 до 8,0?0,3%. Выводы. Снижение уровня НвА1с, отсутствие тяжелых гипогликемий, а также возможность однократного в течение суток введения инсулина Лантус делает терапию этим препаратом особенно оправданным в педиатрической практике. Все пациенты, принимавшие участие в нашем исследовании, выразили удовлетворенность лечением при переводе на терапию инсулином Лантус, особенно отметив снижение количества ежедневных инъекций. Все дети, подростки и их родители выразили желание продолжить терапию инсулином Лантус. Полученные результаты согласуются с данными аналогичных исследований, проводившихся в РФ, США и Европе

Diagnostic value of islet autoantibody assays practised in Russia. 1. Classic immunofluorescence islet cell antibody assay, immunoradiometric glutamic acid decarboxylase antibody assay, and ELISA tyrosine phosphatase antibody and insulin antibody assays

Objective. To estimate performance characteristics and diagnostic value of immunofluorescent islet cell antibody (ICA) assay, immunoradiometric glutamic acid decarboxylase antibody (GADA) assay, and ELISA tyrosine phosphatase IA-2 antibody (IA-2A) and insulin antibody (IA) assays. Research Design and Methods. Antibodies were tested in 438 children and adolescents with newly diagnosed diabetes mellitus (DM) type 1, and in 891 subjects without DM type 1. ICA were determined by the classic indirect immunofluorescent method recommended by the Juvenile Diabetes Foundation International, GADA were determined with the Immunotech IRMA Anti-GAD kit, and IA-2A and IA were determined with Medizym Anti-IA2 and Orgentec Anti-Insulin ELISA kits, respectively. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the tests were estimated with contingency tables. Diagnostic accuracy was estimated from areas under receiver operating curves (AUC). Results. ICA test was of the greatest diagnostic value (Se=88%, Sp=96%, PPV=96%, NPV=94%, AUC=0,94), followed by IA-2A (Se=66%, Sp=98%, PPV=98%, NPV=59%, AUC=0,82) and GADA (Se=73%, Sp=84%, PPV=75%, NPV=83%, AUC=0,79). IA test exhibited a very low Se (4,3%) and lacked diagnostic accuracy (AUC=0,5). Conclusions. We recommend to use ICA, IA-2A and GADA tests surveyed in our study for diagnosis of DM type 1 and differential diagnosis of DM. We don’t recommend IA testing with an Orgentec Anti-Insulin ELISA kit for usage in clinical practice