Prognosis of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: statistically weighted syndrome analysis

PURPOSE: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. PATIENTS AND METHODS: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-2, IL-4, IL-6, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), GM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. RESULTS: Only one parameter gave significant differences at p < 0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5th-6th installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. CONCLUSION: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer.     

Discrete Semantics for Hybrid Automata

Many natural systems exhibit a hybrid behavior characterized by a set of continuous laws which are switched by discrete events. Such behaviors can be described in a very natural way by a class of automata called hybrid automata. Their evolution are represented by both dynamical systems on dense domains and discrete transitions. Once a real system is modeled in a such framework, one may want to analyze it by applying automatic techniques, such as Model Checking or Abstract Interpretation. Unfortunately, the discrete/continuous evolutions not only provide hybrid automata of great flexibility, but they are also at the root of many undecidability phenomena. This paper addresses issues regarding the decidability of the reachability problem for hybrid automata (i.e., “can the system reach a state a from a state b?”) by proposing an “inaccurate” semantics. In particular, after observing that dense sets are often abstractions of real world domains, we suggest, especially in the context of biological simulation, to avoid the ability of distinguishing between values whose distance is less than a fixed ε. On the ground of the above considerations, we propose a new semantics for first-order formulæ which guarantees the decidability of reachability. We conclude providing a paradigmatic biological example showing that the new semantics mimics the real world behavior better than the precise one.     

The morphological mechanism of the development of myosatellitocytes from the structural elements of the muscle fiber during increased functional activity of the skeletal muscles

Under increased muscular activity in some muscular fibers disintegration areas of myofibrillar apparatus has been revealed. Migration of myonuclei into these microregions starts the mechanism of their segregation due to plasmolemma produced from the reticulum sarcoplasmaticum and triad systems surface. After plasmolemma production in "sarcocytes" intensive development and differentiation of organellae occur. As a result of differentiation "sarcocytes" transform in to myosatellitocytes of type-2 and migrate under lamina externa muscular fibers. So, a hypothesis about formation of myogenic tissue's cellular phase from the myosymplastic one has been confirmed.     

Action of levorin on glucose transport in the rat small intestine

The technique of accumulating preparation of the mucosa and "turned out sac" was used to show that levorin, a polyenic antibiotic in a concentration of 10(-6) M, lowered the transport rate and accumulation of glucose by the epithelial cells of the rat thin intestine under conditions of oxygenation. Suppression of the glucose transport in the first stages resulted in partial inhibition of the transmembrane transfer. It is suggested that levorin suppression of the glucose transport through the erythrocyte apical membrane in the thin intestine is associated with a decrease in the electrochemical gradient of Na+.     

Stability of the polyribosomes of Blakeslea trispora Thaxter during normal translation, its stimulation and inhibition

beta-Ionone is found to stimulate considerably carotinoids synthesis in Blakeslea trispora. The stabilization of carotene-synthesizing ability of B. trispora in the presence of beta-ionine under prolonged incubation time is observed. Stabilization of polyribosomes in the presence of beta-ionine is observed when studying polyribosome content in B. trispora. A hypothesis is expressed on the existence of biochemical "receptors" as a linkage between synthesized protein and destroying mRNA.     

Determination of fibrin and fibrinogen split products by their anticoagulant activity

A new diagnostic method to determine fibrinogen and fibrin splitting products is based on the fact that high-molecular fragments acting as specific inhibitors of fibrin self-assembly compose these products. Fibrinogen and fibrin splitting products are detected and determined quantitatively by prolongation of coagulation time in the test with the standard monomeric fibrin. The number of units of anticoagulating activity in the studied urine are the results of the determinations. Sensitivity of the method if necessary may be increased by adding of a certain amount of the fibrinogen and fibrin splitting products to the test that makes a favourable background for the action of the products. The method is rather sensitive, reliable and simple. It may be used in ordinary clinical laboratories. The method proved to be quite satisfactory when testing renal diseases at the clinic. It is of great significance for early detection of the transplanted kidney rejection. The new method is compared with the known immunological method which consist in determination of the inhibitory effect of the fibrinogen and fibrin splitting products on agglutination of erythrocytes of specific antibodies; the erythrocytes being subjected to "tanning" and "loading" with fibrinogen. A satisfactory correlation is found between the results of two methods.     

Inclusion dynamics hybrid automata

Hybrid systems are dynamical systems with the ability to describe mixed discrete-continuous evolution of a wide range of systems. Consequently, at first glance, hybrid systems appear powerful but recalcitrant, neither yielding to analysis and reasoning through a purely continuous-time modeling as with systems of differential equations, nor open to inferential processes commonly used for discrete state-transition systems such as finite state automata. A convenient and popular model, called hybrid automata, was introduced to model them and has spurred much interest on its tractability as a tool for inference and model checking in a general setting. Intuitively, a hybrid automaton is simply a “finite-state” automaton with each state augmented by continuous variables, which evolve according to a set of well-defined continuous laws, each specified separately for each state. This article investigates both the notion of hybrid automaton and the model checking problem over such a structure. In particular, it relates first-order theories and analysis results on multivalued maps and reduces the bounded reachability problem for hybrid automata whose continuous laws are expressed by inclusions (x′f(x,t)) to a decidability problem for first-order formulæ over the reals. Furthermore, the paper introduces a class of hybrid automata for which the reachability problem can be decided and shows that the problem of deciding whether a hybrid automaton belongs to this class can be again decided using first-order formulæ over the reals. Despite the fact that the bisimulation quotient for this class of hybrid automata can be infinite, we show that our techniques permit effective model checking for a nontrivial fragment of CTL.     

Effect of Pasteurization and Retort Processing on Spectral Characteristics,Morphological, Thermal,Physico‐Mechanical,Barrier and Optical Properties of Nylon‐Based Food Packaging Materials

The effect of pasteurization and retort processing on spectral, morphological, thermal, physico‐mechanical, barrier and optical properties of three different packaging materials viz., PP/N6/PP, PET/N6/cPP and SiO_x‐PET/N6/cPP were studied. These packaging materials were packed with distilled water, which acted as a food simulant. Subsequently, these pouches were subjected to different thermal processing conditions such as pasteurization and retort processing. Both the processing techniques found to have retained the mechanical properties of all packaging materials. Water vapour transmission rate (WVTR) and oxygen transmission rate (OTR) of nylon‐based combinations were increased after processing. Gloss found to decrease invariably irrespective of the material and increases with the severity of the treatment. XRD diffractogram shows changes in crystal structure as a result of thermal processing, and SEM analysis shows the crystal fragmentation. Absorption of water by the amide group of nylon 6 was observed, which could be a reason for the increase in OTR and WVTR. Copyright © 2014 John Wiley & Sons, Ltd.     

Assessment of intradialysis calcium mass balance by a single pool variable‐volume calcium kinetic model

Introduction: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single‐pool variable‐volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. Methods: Thirty‐four patients on thrice‐weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end‐dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. Findings: The difference between predicted and measured values was 0.02 mmol/L (range ?0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD ?0.84 ± 1.33 mmol, range ?5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. Discussion: The proposed single pool variable‐volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.     

PolyMorph: Increasing the Spelling Efficiency of P300 by Selection Matrix PolyMorphism and Sentence-Based Predictions

One application of the P300 brain electric signal is sentence spelling, which enables subjects who have lost control of their motor pathways to communicate by selecting characters in a matrix containing all alphabet symbols. This technology still suffers from both low communication/high error rates. A P300 speller, named PolyMorph, which jointly introduces the selection matrix polymorphism (reducing the matrix size by removing useless symbols) and sentence-based predictions (which forecast words on the basis of language statistics) is presented. This is accomplished by using a custom dynamic knowledge-base, tailored to the subject lexicon, and updated in real time with the selections of the subject. The effectiveness of the presented speller is measured in vivo and in silico. The results suggest that the use of PolyMorph increases the number of spelt characters per time unit and reduces the error rate.