[Early and long-term outcomes of treatment in patients with medulloblastoma]. / Sravnitel'nyi analiz otdalennykh i neposredstvennykh rezul'tatov lecheniya patsientov s medulloblastomoi.

OBJECTIVE: To compare the modes of craniospinal irradiation (CSI) and to determine possible factors improving the outcome in patients with medulloblastoma. MATERIAL AND METHODS: The study included 92 patients with medulloblastoma who were treated at the Russian Research Radiology Center between 2008 and 2019. Mean age of patients was 12 years. Classical morphological variant of medulloblastoma prevailed (48.4%). After surgery, 78 patients underwent radiotherapy (CSI + full-volume «boost¼ on the tumor site). Standard risk patients received CSI in a reduced dose after tumor resection. Weekly modification of radiotherapy with vincristine was performed in 73 (79.3%) patients. RESULTS: We significantly (p<0.05) determined the total focal doses for CSI in patients with medulloblastoma. Total resection of posterior cranial fossa tumor improved relapse-free survival by several times. Complete CSI up to total dose of 36/54 Gy ensures the most positive effect compared to irradiation in reduced dose. CONCLUSION: Relapse-free survival significantly depends on total focal dose of CSI. Single focal dose, chemotherapeutic modification of radiotherapy and M-stage had no significant effect on relapse-free survival. Perhaps, this is due to small sample size.

Kramers' law for a bistable system with time-delayed noise.

We demonstrate that the classical Kramers' escape problem can be extended to describe a bistable system under the influence of noise consisting of the superposition of a white Gaussian noise with the same noise delayed by time tau . The distribution of times between two consecutive switches decays piecewise exponentially, and the switching rates for 0

Decomposition of conditional probability for high-order symbolic Markov chains.

The main goal of this paper is to develop an estimate for the conditional probability function of random stationary ergodic symbolic sequences with elements belonging to a finite alphabet. We elaborate on a decomposition procedure for the conditional probability function of sequences considered to be high-order Markov chains. We represent the conditional probability function as the sum of multilinear memory function monomials of different orders (from zero up to the chain order). This allows us to introduce a family of Markov chain models and to construct artificial sequences via a method of successive iterations, taking into account at each step increasingly high correlations among random elements. At weak correlations, the memory functions are uniquely expressed in terms of the high-order symbolic correlation functions. The proposed method fills the gap between two approaches, namely the likelihood estimation and the additive Markov chains. The obtained results may have applications for sequential approximation of artificial neural network training.

Entropy and long-range memory in random symbolic additive Markov chains.

The goal of this paper is to develop an estimate for the entropy of random symbolic sequences with elements belonging to a finite alphabet. As a plausible model, we use the high-order additive stationary ergodic Markov chain with long-range memory. Supposing that the correlations between random elements of the chain are weak, we express the conditional entropy of the sequence by means of the symbolic pair correlation function. We also examine an algorithm for estimating the conditional entropy of finite symbolic sequences. We show that the entropy contains two contributions, i.e., the correlation and the fluctuation. The obtained analytical results are used for numerical evaluation of the entropy of written English texts and DNA nucleotide sequences. The developed theory opens the way for constructing a more consistent and sophisticated approach to describe the systems with strong short-range and weak long-range memory.

Entropy of finite random binary sequences with weak long-range correlations.

We study the N-step binary stationary ergodic Markov chain and analyze its differential entropy. Supposing that the correlations are weak we express the conditional probability function of the chain through the pair correlation function and represent the entropy as a functional of the pair correlator. Since the model uses the two-point correlators instead of the block probability, it makes it possible to calculate the entropy of strings at much longer distances than using standard methods. A fluctuation contribution to the entropy due to finiteness of random chains is examined. This contribution can be of the same order as its regular part even at the relatively short lengths of subsequences. A self-similar structure of entropy with respect to the decimation transformations is revealed for some specific forms of the pair correlation function. Application of the theory to the DNA sequence of the R3 chromosome of Drosophila melanogaster is presented.

Entropy and long-range correlations in DNA sequences.

We analyze the structure of DNA molecules of different organisms by using the additive Markov chain approach. Transforming nucleotide sequences into binary strings, we perform statistical analysis of the corresponding "texts". We develop the theory of N-step additive binary stationary ergodic Markov chains and analyze their differential entropy. Supposing that the correlations are weak we express the conditional probability function of the chain by means of the pair correlation function and represent the entropy as a functional of the pair correlator. Since the model uses two point correlators instead of probability of block occurring, it makes possible to calculate the entropy of subsequences at much longer distances than with the use of the standard methods. We utilize the obtained analytical result for numerical evaluation of the entropy of coarse-grained DNA texts. We believe that the entropy study can be used for biological classification of living species.

Analytical solution for a class of network dynamics with mechanical and financial applications.

We show that for a certain class of dynamics at the nodes the response of a network of any topology to arbitrary inputs is defined in a simple way by its response to a monotone input. The nodes may have either a discrete or continuous set of states and there is no limit on the complexity of the network. The results provide both an efficient numerical method and the potential for accurate analytic approximation of the dynamics on such networks. As illustrative applications, we introduce a quasistatic mechanical model with objects interacting via frictional forces and a financial market model with avalanches and critical behavior that are generated by momentum trading strategies.

Iterative method for generating correlated binary sequences.

We propose an efficient iterative method for generating random correlated binary sequences with a prescribed correlation function. The method is based on consecutive linear modulations of an initially uncorrelated sequence into a correlated one. Each step of modulation increases the correlations until the desired level has been reached. The robustness and efficiency of the proposed algorithm are tested by generating sequences with inverse power-law correlations. The substantial increase in the strength of correlation in the iterative method with respect to single-step filtering generation is shown for all studied correlation functions. Our results can be used for design of disordered superlattices, waveguides, and surfaces with selective transport properties.

Green factories for biopharmaceuticals.

Plants and plant cells have been used to produce many diverse and valuable recombinant proteins, including subunit vaccines, antibodies and antibody fragments, hormones, blood products, cytokines and enzymes. Different plant species and platforms have been explored as production hosts, each with unique properties in terms of production timescales, environmental containment, scalability, downstream processing strategy and overall costs. Whole plants are suitable for the economical and safe production of recombinant proteins on a large scale, providing unique advantages for pharmaceutical proteins that are required in large amounts and normally too expensive for conventional manufacturing processes. Seed-based systems have additional advantages because they exploit the natural storage properties of seeds to facilitate batch processing and distribution. The stabilizing effect of seeds after harvest allows recombinant subunit vaccines and antibodies to be delivered via the mucosal route as they are better able to withstand the harsh microenvironment when protected by the plant matrix. Although the differences between plant and human N-glycans were initially thought to limit the therapeutic potential of plant-derived glycoproteins, several such products have now been tested in the clinic and in some cases the presence of plant glycans has been turned into an advantage because they improve the performance of the protein or confer unique characteristics. In this review we discuss recent case studies of recombinant pharmaceuticals produced in plants to demonstrate the versatility and unique advantages of molecular farming and the bottlenecks that remain to be addressed.

Excitability in a quantum dot semiconductor laser with optical injection.

We experimentally analyze the dynamics of a quantum dot semiconductor laser operating under optical injection. We observe the appearance of single- and double-pulse excitability at one boundary of the locking region. Theoretical considerations show that these pulses are related to a saddle-node bifurcation on a limit cycle as in the Adler equation. The double pulses are related to a period-doubling bifurcation and occur on the same homoclinic curve as the single pulses.

Analytical isoelectric focusing of apolipoprotein B of human plasma low-density lipoproteins in the presence of a nonionic and a zwitterionic detergent.

A method for the analytical isoelectric focusing of Nonidet-P40-delipidated apolipoprotein B of human plasma low-density lipoproteins has been developed. Isoelectric focusing was performed in the presence of the zwitterionic nondenaturing detergent Chaps, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate, and the nonionic surfactant Nonidet-P40, polyoxyethyleneglycol p-t-octylphenol with a mean of 9.0 ethylene oxide units per molecule. Low-density lipoprotein (LDL) apolipoprotein B (apo-B) entered 3.75% polyacrylamide gels without precipitation at the sites of sample application, permitting apoprotein recoveries of greater than 90% in the migrating bands. LDL apo-B exhibited 10 distinguishable bands with apparent isoelectric points of 7.34 (band 1), 7.27 (band 2), 7.16 (band 3), 7.02 (band 4), 6.88 (band 5), 6.70 (band 6), 6.61 (band 7), 6.48 (band 8), 6.40 (band 9), and 6.24 (band 10), respectively. Bands 3 and 4, 6 and 7, as well as 8 and 9 could be identified as major double bands. When the focused apo-B was run in a second dimension by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the same relative molecular weight of B-100 was obtained for all focused bands. After electrotransfer to nitrocellulose paper, all bands reacted with polyclonal anti-human LDL antibody. Furthermore, the detergent-solubilized apo-B retained the immunological properties of native low-density lipoproteins when tested by double immunodiffusion against polyvalent anti-human LDL sera.

[Do not forget: lead poisoning]. / Nicht vergessen: Bleivergiftung.

3 patients with lead intoxication are demonstrated. The analysis of porphyrins and porphyrin precursors led to the tentative diagnosis which was confirmed by the increased lead levels. The increased urinary excretion of porphyrins and of delta-aminolevulinic acid, the decreased activity of uroporphyrinogen synthase and the increased protoporphyrin content (absorption maximum 595 nm) in the red cells suggested the diagnosis before the lead values of the patients were known. Clinical signs of the patients included gastrointestinal and neurological symptoms. It is assumed that the lead intoxication in these patients was caused by occupational exposition.

Zero-length protein-nucleic acid crosslinking by radical-generating coordination complexes as a probe for analysis of protein-DNA interactions in vitro and in vivo.

Redox-active coordination complexes such as 1,10-phenanthroline-Cu(II) (OP-Cu) and bleomycin-Fe(III) are commonly used as "chemical nucleases" to introduce single-strand breaks in nucleic acids. Here we report that under certain conditions these complexes may crosslink proteins to nucleic acids. In vitro experiments suggest that proteins are crosslinked to DNA by a mechanism similar to dimethyl sulfate-induced crosslinking. Furthermore, we demonstrate that the OP-Cu complex can generate protein-DNA crosslinks in mammalian cells in vivo. By combining the OP-Cu crosslinking and a "protein shadow" hybridization assay we identify proteins interacting with DNA in isolated pea chloroplasts and show that this methodology can be applied to detect DNA-binding proteins on specific DNA sequences either in vitro or in vivo.