bluuebunny/crossref_metadata_2025 huggingface dataset:
Born in 1953: The story about a post-war Swedish cohort, and a longitudinal research project
Authors: Stenberg Sten-Åke
Published: November 2018

At the beginning of the 1960s, Swedish researchers started a sociological study of all children born in Stockholm in 1953, Project Metropolitan. This book describes the project’s at times dramatic history, where issues of personal integrity and the role of social sciences were heavily debated. These discussions were fueled by the rapid and far-reaching digitalization in society at large and also within social sciences. As such, Project Metropolitan came to symbolize the benefits and potential risks related to an expanding body of research based on large groups of individuals and multiple register data sources.

At the outset, the project’s founders sought to answer the following question: “Why do some get on better in life than others?” One of the main aims of the project was to study the long-term impact of conditions in childhood. The book therefore also includes an updated presentation of the main findings, as they have been conveyed in over 160 publications to date. These publications cover a wide array of topics and phenomena such as social mobility and education, substance abuse and crime, health and ill-health, peer influences and family relations, and adult lives of adopted children.

Today Project Metropolitan is known as the “Stockholm Birth Cohort Multigenerational Study (SBC Multigen)” and is still in full vigor. From its original group of 15,000 children, the study has become multi-generational by adding data about their parents, siblings, children, nieces and nephews. As they approach their late 60s, it will also be possible to follow these “children” into retirement and old-age.

In the concluding chapter the author discusses some of the challenges contemporary social research is facing. What are the current threats to academic freedom and what opportunities do the unique data registers in countries like Sweden provide?
Transimperial History - Connectivity, Cooperation and Competition
Authors: Hedinger Daniel , Heέ Nadin
Published: November 2018

Transimperial History – Connectivity, Cooperation and Competition

This Forum article argues that a turn in empire history is needed, one which we label «transimperial». Whereas national history has been transnationalized in recent decades, the history of empires has, by and large, remained nationalized. Since transnational history, global history, postcolonial studies and new imperial history all offer an abundance of tools to tear down imperial borders and deconstruct nationalized narratives, the moment seems to have come for a shift, namely for what we call a transimperial approach to imperial history. We seek to show how such an approach makes it possible to dynamize and decentralize the history of empires both on the level of empirical research and historiographical narratives. By including marginalized empires we offer a way to overcome British centrism of empire studies. On the methodological level, this contribution seeks to discuss imperial competition, cooperation and connectivity not as separate phenomena but as entangled processes. The point is not to analytically isolate cooperation or competition but to shed light on how they reinforced each other and how connectivity plays into this. The article shows that a key to establishing a transimperial approach is to consider time and space together by focusing on the transformative aspect of competition, cooperation and connectivity in spaces in-between empires. In this article, we highlight transimperial histories avant la lettre, on which such an approach can rely. Finally, we discuss how this approach helps challenge essentializing master narratives in empire studies, be it the one in which the British Empire serves as a model for other empires or the one where the Japanese empire is seen as a mimicry of European imperialism.
Análise comparativa do nível de dependência funcional de idosos submetidos a artroplastia de quadril: estudo transversal
Authors: Silva Jefferson Carlos Araujo , Cavalcante Tamires Barradas , Santos Neusa Macchado Cabral dos , Nascimento Rosane Karine Gonçalves , Costa Ana Clara Lopes Freitas da , Miranda Jeferson Santos
Published: November 2018

INTRODUÇÃO: A Artoplastia de Quadril (AQ) é um procedimento cirúrgico realizado em casos de fratura de colo do fêmur (FF) e osteoartrose de quadril (OQ), e é responsável por causar danos funcionais aumentando o nível de dependência funcional do idivíduo idoso. OBJETIVO: analisar o nível de dependênciaonentre idosos que foram submetidos a AQ. MÉTODOS: indivíduos idosos internados na enfermaria traumato-ortopédica do Hospital Universitário da Universidade Federal do Maranhão (HU-UFMA) foram avaliados quanto ao seu nível de dependência funcional através da Medida de Independência Funcional (MIF) e quanto ao nível de dor por meio da Escala Visual Analógica (EVA), tanto no pré quanto no pós-operatório de AQ. Os voluntários foram divididos em grupo A, com diagnóstico de (OQ), e grupo B, com diagnóstico de (FF). O teste t não pareado foi utilizado para comparar os resultados no pré e pós-operatório, adotando-se nível de significância p<0,05. RESULTADOS: um total de 46 idosos compuseram a amostra, 17 (37%) do sexo masculino e 29 (63%) do sexo feminino. O grupo A apresentou menor nível de dependência funcional no pré-operatório em comparação aos sujeitos do grupo B, porém, a avaliação da dor revelou índices maiores para o grupo A no pré-operatório. A análise comparativa dos resultados da EVA no pré e pós-operatório se mostrou estatisticamente significante para ambos os grupos. Os resultados da MIF para o grupo A não foram estatisticamente significantes, para o grupo B, porém, os domínios autocuidados, mobilidade, locomoção e total apresentaram valores estatisticamente significantes. CONCLUSÃO: O grupo A apresentou maiores médias na EVA no pré-operatório e menor nível de dependência funcional pela MIF em comparação ao grupo B, este apresentou as maiores médias de idade e maior presença de co-morbidades.
Influência dos requisitos cinéticos funcionais e desfechos de saúde na mobilidade funcional de idosos
Authors: Nascimento da Silva Luan , Dayanne Alves Ribeiro Mara , Brito Oliveira Sabrynna , Silva Jefferson Carlos Araujo
Published: November 2018

INTRODUÇÃO: A mobilidade funcional é um fator determinante para promover a independência do idoso, com influência na saúde física e mental. Os testes para avaliar a capacidade funcional de idosos devem ser direcionados a simularem as atividades de vida diárias de locomoção. OBJETIVO: Verificar a influência de requisitos cinéticos funcionais e desfechos da saúde sobre a mobilidade funcional de idosos em uma unidade básica de saúde. MATERIAIS E MÉTODOS: O estudo foi realizado com 88 idosos, que foram submetidos a testes funcionais para avaliação da mobilidade funcional, equilíbrio estático e força muscular de membros inferiores. Além disso foi aplicada uma escala de depressão e coletada variáveis relacionadas a saúde do idoso. RESULTADOS: Os requisitos cinéticos funcionais e a sintomatologia depressiva também foram correlacionadas à capacidade de locomoção, todavia a força muscular (correlação de Spearman = 0,52, p=0,000) exibiu uma maior influência na mobilidade funcional. As variáveis que tiveram associação com uma pior mobilidade funcional foram: histórico de quedas (p=0,001), diabetes (p=0,008) e hipertensão (p=0,015). CONCLUSÃO: Nos idosos avaliados, a força muscular dos membros inferiores apresenta maior influência sobre a mobilidade funcional. Ser hipertenso, diabético e/ou já ter caído pode influenciar o desempenho funcional de locomoção.
Treinamento neuromuscular aquático com ênfase proprioceptiva: influência na potência mecânica muscular e na altura de salto
Authors: Wutzke Maria Luiza Serradourada , Bertolini Gladson Ricardo Flor , Carvalho Alberito Rodrigo de
Published: November 2018

INTRODUÇÃO: Tarefas motoras treinadas em ambiente aquático parecem potencializar o sistema proprioceptivo. Porém, é necessário investigar o efeito do meio aquático no desempenho neuromuscular de atletas. OBJETIVO: Avaliar o efeito de uma intervenção por exercícios neuromusculares funcionais aquáticos, com ênfase no sistema sensorial proprioceptivo, nas variáveis altura do salto e potência muscular, tendo a acuidade proprioceptiva como covariável. METODOLOGIA: Amostra composta por 14 homens universitários praticantes de futsal e dividida em grupo controle (GC/n=7) e grupo intervenção (GI/n=7). As variáveis potência mecânica muscular e altura do salto foram avaliadas por meio do teste de salto vertical de 60 segundos. A acuidade proprioceptiva foi avaliada pelo senso de posição articular e pela cinestesia quantificados pelo teste de percepção de movimentos passivos lentos (Tpassivo) e pelo teste de senso de posição articular (Tativo). As variáveis de desfecho foram mensuradas em dois momentos: antes e após a intervenção. A intervenção aquática foi aplicada durante seis semanas com três sessões em cada semana. RESULTADOS: Não houve efeito de grupo e nem do momento da avaliação na altura do salto, sendo que o GC alcançou altura de salto de 19,9±0,8 cm em comparação com o GI chegando a altura de 20,3±1,4 cm.  Na potência mecânica muscular não houve efeito do momento, mas houve efeito do grupo, em que o GC apresentou potência de 366,2±17,6 W, enquanto GI apresentou 332,0±21,2 W, sendo menor que o GC. Nem o Tativo e nem o Tpassivo influenciaram a altura de salto e a potência mecânica muscular. CONCLUSÃO: A intervenção de exercícios neuromusculares aquáticos funcionais, com ênfase na propriocepção não afetou nem a potência muscular nem a altura do salto, este resultado não foi influenciado pela acuidade proprioceptiva.
SOP PyroMark Assay Design Software v1
Authors: Mahmud Nadiya
Published: November 2018

Objective To design PCR and sequencing primers for methylated DNA using the PyroMark Assay Design 2.0 Software. Recording and Reporting of Results Results should be noted in the protocol below by pasting it into a new page in the Customer Reports section to form part of the final report, which should ultimately be exported as a PDF and stored within the relevant project folder on Apocrita before emailing to the customer. File exports should be labelled with the iLabs number and exported to the relevant project folder on Apocrita. Related Procedures Assay design modules Genotyping (SNP), Allele Quantification (AQ) , Sequence Analysis (SQA) and Methylation Analysis (CpG)
Fluorescence aggregation imaging v1
Authors: Ding Serena
Published: November 2018

For imaging aggregation behaviour of 40 young adult C. elegans on agar using the Twinnie TwinCam system. Worms are synchronised by bleaching and refeeding for 72 hours, and then 40 young adult hermaphrodites are transferred by glass pipette onto a 35 mm regular NGM plate for imaging for 1 hour at 9 fps.
A mathematical model of spatial transmission of vector-borne disease
Authors: Govorukhin V.N. , Zagrebneva A.D. , Kartashev V.V.
Published: November 2018

A mathematical model of the propagation of vector-borne diseases in a two-species population of a carrier and reservoir of the disease is proposed and studied.
The model is based on the mechanism of dirofilariosis propagation. The model is formulated as a system of four partial differential equations. As variables of
the model, densities of two population divided by the number of healthy and infected ones were chosen. The simplest case of a spatially homogeneous distribution
of populations was studied, stationary regimes were found, and their stability conditions were obtained. It is shown that a sufficiently intensive application
of all possible preventive arrangements (extermination of the vectors of the disease, treatment of infected individuals, prevention of contact with the vector
of the disease) leads to the stability of a stationary regime with no disease. A scheme for numerical analysis of a full mathematical model that takes into account
the spatial inhomogeneity of population distribution is proposed. In the computational experiment, various strategies for the application of insecticides in space
have been studied. As a result, the following recommendations on the use of insecticides for the prevention of vector-borne diseases are formulated: the most
effective is the localized use of insecticides; treatment should be carried out near the source of reproduction of the vectors of the disease, creating a barrier
between the source and reservoir of the pathogen; for each amount of insecticide there is an optimal size of the processing area.
The Application of a Distributed Model of Active Media for the Analysis of Urban Ecosystems Development
Authors: Sidorova A.E. , Levashova N.T. , Semina A.E. , Melnikovа А.А.
Published: November 2018

A model of spatiotemporal self-organization of urban ecosystems as a superposition of conjugate active media that takes into account inhomogeneities of anthropogenic and natural
factors is proposed. The type of ecosystems under assumption is characterized by a high rate of population growth and density due to the concentration of residential, industrial,
commercial and other objects, as well as communication media. These conditions reduce the "buffer capacity" of natural subsystems and increase the nonlinearity and consequently
the instability of system processes within the boundaries of urban ecosystems. The model is based on the system of FitzHugh-Nagumo equations, modified by the authors so to take
into account inhomogeneities of anthropogenic (activator) and natural (inhibitor) factors. The validity of the application of an equation of this type is determined by the relative
simplicity of the system analysis of two equations of the "activator-inhibitor" type. The previously published analytical studies of a system of equations of this type made
it possible to create on its basis an adequate model for urban ecosystems development. The numerical solution of the system in the two-dimensional case was carried out in
a rectangular region. On the boundaries of the domain the homogeneous Neumann conditions were given, the initial distribution was assumed to be known. The solution was carried
out by the method of evolutionary factorization. The iterative process continued until complete stationing. The developed model is used for analysis and forecasting the development
of the territory of New Moscow. The arrays of values of the control parameters of the model, which were subsequently taken into account in numerical implementation, were obtained
on the basis of the aerial survey data and maps of the studied territories translated into digital form using the C++ authoring application, which allows to create text files
with image-based data. The code was created in the OpenCL environment and implemented using AMD FIREPRO graphics processors. Graphical interpretation was carried out
using the "Serfer" program.
THE BIOLOGICAL ACTIVITY OF PLANT-DERIVED ANTI-HER2 RECOMBINANT ANTIBODIES
Authors: Kosorukov V. S. , Kosobokova E. N. , Pinyugina M. V. , Sevostyanova M. A. , Scherbakov A. I. , Andronova N. V. , Solomko E. Sh. , Sheshukova E. V. , Treschalina E. M. , Dorokhov Yu. L.
Published: November 2018

Pharmaceuticals derived from plants, have become one of the leading commercial directions in modern biotechnology. The benefits that offer these technologies, cannot be matched with any other modern technology for producing drugs from recombinant proteins. Main advantages of plant technologies for production of proteins are easy scalability, efficiency, bio-safety, ease of cultivation and collection of biological material. This approach promises to be the most perspective for production of a wide range of drug substances and vaccines. In current investigation we have analyzed in vitro and in vivo biological activity of plant-derived anti-HER2 recombinant antibodies - phytotrastuzumab. Phytotrastuzumab and trastuzumab have similar activity in grows suppression of breast cancer cells overexpressing HER2 in-vitro and were active in suppression of xenografted tumors SK-BR-3 in-vivo.
STRUCTURE AND FUNCTIONS OF MAIN APOPTOSIS RECEPTORS AND LIGANDS
Authors: Misyurin V. A.
Published: November 2018

Apoptosis can be triggered from external signals. Several homologous receptors transmit apoptotic signals from outside into the cell. For successful activation of apoptosis receptors should interact with their ligands. For example, FAS receptor must bind with FAS-ligand, TNFR1 with TNFα, TRAIL-R1 and TRAIL-R2 with TRAIL, DR3 - with TL1A, respectively. In majority of cases ligands should be anchoring in the cell membrane to perform their functions. FAS and TNFR1 receptors trigger apoptosis only when they are internalized into the cell’s cytoplasm. If FAS and TNFR1 are not internalized, then anti-apoptotic program won’t start. In contrast, TRAIL-R1, TRAIL-R2 and DR3 aren’t internalized during apoptotic signal transduction. Other receptors, TNFR2, TRAIL-R3 and TRAIL-R4 start an anti-apoptotic program. The apoptotic signal starts when DISC complex is formed on the inner side of the cell membrane. FADD, procaspase-8 and intracellular domain of receptor form together DISC complex. If the DISC complex wasn’t formed, signal is transmitted by the NFкB-way via MAP-kinase cascade. In such conditions anti-apoptotic program starts. A variety of receptors and ligands provides for multiple biological functions. For example, receptor-mediated apoptosis takes a part in elimination of infected or transformed cells, regulation of inflammation, modulation of ontogenesis, hematopoiesis and antibody production.
DEVELOPMENT OF LYOPHILIZED LIPOSOMAL PHARMACEUTICAL DOSAGE FORM CIFELIN
Authors: Lantsova A. V. , Kotova E. A. , Sanarova E. V. , Poloskova A. P. , Baryshnikova M. A. , Oborotova N. A.
Published: November 2018

His study objective has been to develop optimal composition of Cifelin sterically stabilized liposomal formulation. The substance of Cifelin synthesized in chemical synthesis laboratory FSBNI «N.N. Blokhin RCRC». All used excipients and reagents conform to the standard documentation. Method of obtaining liposomes includes: a method of obtaining Cifelin multilamellar and unilamellar liposomes dispersions. Liposomal dispersion has been lyophilized on freeze-dryer Edwards Minifast DO.2. Liposomes size has been measured by light diffusion dynamic spectrums copy on Nicomp 380 Submicron Particle Sizer. Quantitative measurement has been conducted by spectrometry in ultraviolet area. Crystals of unenclosed into lipid bilayer Cifelin have been separated by filtration through filter with pore diameter of 0,22 μm. Lipids peroxidation has been estimated by concentration of oxidation final product - MDA. MTT-test has been used to estimate Cifelin LF cytotoxic activity in vitro. In this study the optimum molar ratio of components has been found for liposomal membrane composed of phosphatidylcholine, cholesterol and DSPE-PEG-2000. Composition with lipids molar ratio 165 : 8 : 1 and “lipid: Cifelin” ratio 12 : 1 has been chosen as optimal by entrapment efficiency and appearance, encapsulated API value in this composition has been 98±1 %, liposomal size has been 136±12 nm. On cell line SKOV-3 and Jurkat in vitro cytotoxic effect of Cifelin liposomal drug form has been highly increased. As a result of the study drug product “Cifelin lyophilized liposomal for injections 17 mg” has been developed.
Liposomes as target delivery of antitumor drugs
Authors: Raikov A. O. , Hashem A. . , Baryshnikova M. A.
Published: November 2018

Target delivery of antitumor drugs to cancer cells seems to be the very promising way of cancer therapy. The study on the application of immunoliposomes as nanocontainers for anticancer drugs started in the 90-ies. Immunoliposomal drug formulations of antitumor preparations have some advantages over traditional forms of drugs: lipid capsule reduces toxicity of drug due to the selective delivery to tumor and improves its bioavailability. However, despite these benefits, at present immunoliposomal drugs application is limited in the clinic. This review discusses current research status in field of development immunoliposomes and the possible targets for anticancer immuno-liposomes.
E-CADHERIN EXPRESSION DOWNREGULATION ELEVATES TUMOROGENIC POTENTIAL OF HUMAN COLON CANCER CELL LINE HCT116 VIA INCREASE IN CANCER STEM CELLS AMOUNT
Authors: Farmakovskaya M. D. , Khromova N. V. , Kopnin B. P. , Kopnin P. B.
Published: November 2018

Introduction. E-cadherin aberrant expression or complete loss is common for a number of human malignant neoplasms, and can be a launching mechanism of an epithelial-mesenchymal transition. Passing through epithelial-mesenchymal transition could in turn promote to the acquisition of so called cancer stem cell phenotype by the transformed cells. The objective of the present study is to reveal the influence of E-cadherin expression level on the amount of cancer stem cells in human colon cancer cell line HCT116. Materials and methods. We have created cell sublines with E-cadherin up- and downregulation and assessed the percentage of cancer stem cells using tumor formation assay, clonogenic assay; we also evaluated profile of cell pluripotency markers. Results and conclusion. We have shown that the proportion of cancer stem cells in human colon adenocarcinoma cell line HCT116 depends on the E-cadherin expression level. E-cadherin expression downregulation results in elevated expression of pluripotency genes and in the increase of proportion of cancer stem cells via activation of Wnt/ß-signalling pathway. E-cadherin upregulation has a reverse effect and decreases the amount of HCT116 cancer stem cells. Thus, E-cadherin expression restoration seems prospective in colorectal anticancer therapy.
ADVANCED METHODS OF EXPERIMENTAL CANCER IMMUNOTHERAPY BASED ON THE DELAYED-TYPE HYPERSENSITIVITY
Authors: Karaseva V. I. , Osipova T. V. , Bukreev Yu. M.
Published: November 2018

Introduction. Among the variety forms of inflammation, many of which contribute to the growth of tumors, classical inflammation reaction - delayed type hypersensitivity is able to eliminate. Artificially induced intratumoral it can be used successfully in immunotherapy. As the level of antitumor immunity correlates with the intensity of the reaction, we used the results of our preliminary research, which helped to increase the level of delayed type hypersensitivity several times. 0ur earlier experiments indicated a paradoxical mechanism of bi-directional control of delayed type hypersensitivity reactions at various stages by antigens class IIMHC I-A-molecules, expressed on the surface of antigen-presenting cells. This fact must be strictly taken into account when designing schemes of immunotherapy. The purpose of the research is development of effective methods for experimental immunotherapy on the basis of delayed type hypersensitivity with the use of means and methods of its regulation. Materials and methods. The above-described phenomenon was used in the development of 2 methods experimental immunotherapy of carcinoma Lewis in mice BDF1. Delayed type hypersensitivity to laboratory antigen ovalbumin induced intratumoral and stimulated point based bi-directional development of reaction or aspirin in the induction stage (indirectly increasing the expression of I-A-anti-gens), or (overpowering her) nicotinamide in the effector phase of the reaction. Results. It is shown that delayed type hypersensitivity to ovalbumin induced intratumoral and stimulated by aspirin or nicotinamide, provides inhibition of tumor growth at 81.5 % and 86.5 % compared with the control, respectively. Conclusion. It is demonstrated 2 ways of experimental immunotherapy of tumors based on delayed type hypersensitivity, with strict regard to bi-directional control reaction by I-a-antigens. According to the literature in a number of agents capable of altering the expression of I-A-molecules, in addition to aspirin and nicotinamide are a well known, widely used in the clinic drugs. The irregularity of bi-directional development of delayed type hypersensitivity during their appointment subsequently leads not only to the weak therapeutic effect, but may cause increased tumor growth. Probably this is the reason for the observed unpredictability in immunotherapy. Obviously, to develop appropriate treatment regimens need careful, targeted intervention in the specific protective immune response in accordance with its molecular mechanism of regulation. In summary, the results presented here can be the basis for the testing of these methodological approaches in the clinic.
FEATURES OF THE TECHNOLOGY OF LIPOSOMAL FORMULATION OF A ANALOGUE HYPOTHALAMIC HORMONE SOMATOSTATIN
Authors: Sanarova E. V. , Xi Zhang , Dmitrieva M. V. , Lantsova A. V. , Orlova O. L. , Polozkova A. P. , Oborotova N. A. , Krasnyuk I. I.
Published: November 2018

Background. In connection with the prospect of the use of an analog of the hypothalamic hormone somatostatin synthesized by the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin Russian Cancer Research Center» and showed a high anti-tumor activity as a drug arises a need to establish an optimal technology of its receipt. In preliminary studies in a modelformulation for an analog of the hypothalamic hormone somatostatin selected liposome technological process of which has a series of specific steps comprising. Objective. Development of technology for obtaining liposomal formulation hypothalamic hormone somatostatin analogue. Materials and methods. Liposomes analog of the hypothalamic hormone somatostatin obtained by method Bengema in modification for hydrophobic substances. To reduce the diameter of the liposome are used methods extrusion, homogenization and ultrasonic. Analysis of the size of the liposomes was performed by correlation spectroscopy light scattering using nanosizer. The pH of the liposomal dispersion was determined by potentiometry. The quantitative content of the drug substance was determined by spectrophotometry using a standard sample with X (282 ± 3) nm and an alcoholic solution of empty liposomes as a reference solution. Amount of incorporated drug was calculated as the ratio of the concentration of drug in the liposome dispersion after filtration to the concentration of drug in the dispersion after preparation. Results and Conclusion. The hydrophobic nature of the substance causes an analog of the hypothalamic hormone somatostatin technological features of obtaining liposomal formulation. Since the step of forming a film of the lipid substance is dissolved in an organic solvent together with lipids, film is hydrated by a solution of cryoprotectant. Grinding liposomes an analog of the hypothalamic hormone somatostatin appropriate to be carried out using homogenization or extrusion methods, due to the high efficiency of these methods, the preservation stability of the liposomes and a high percentage of inclusion an analog of the hypothalamic hormone somatostatin, included in the liposomal bilayer. At the stage of separating the non-inclusion of substance an analog of the hypothalamic hormone somatostatin due to the insolubility of the substance in the water, you can use the filtering method, without the need for complicated procedures gel filtration, dialysis, etc. Furthermore the process of separating a substance not included can be combined with the sterilization of the liposome dispersion by selecting a particular filter material.
THERAPIES TARGETING CANCER STEM CELLS OF THE TUMOR: THE ONE AND ONLY HOPE
Authors: Vartanian A. A. , Baryshnikov K. A.
Published: November 2018

The basic problem in cancer treatment remains the identification of cells responsible for maintaining the whole population of cells in a tumor. For decades it has been considered that all transformed cells within a tumor have carcinogenic potential with unlimited proliferation capacity and metastases formation. At present, the concept of cancer stem cell was introduced indicating that tumor evolves from a small population of long-live and slow proliferating cells. These cells have the capacity to initiate the tumor formation in immunodeficient animals. Among their properties, resistance to standard oncology treatments leads to treatment failure and cancer recurrence. The management and eradication of different types cancer is completely depended on removal of this cell population. Current review presents basic information about cancer stem cell, particularly, the initiation of tumor, the peculiar properties of cancer stem cell, the role of cancer stem cell in metastasis formation and discusses therapeutic strategies targeted cancer stem cell.
The involvement of autophagy in melanoma vasculogenic mimicry
Authors: Vartanian A. A. , Burova O. S. , Ulasov I. V. , Baryshnikova M. A.
Published: November 2018

Introduction. Autophagy, a catabolic process of protein and organelle recycling by transferring defective cytoplasm and organelles into double-membraned vesicles to degrade and regenerate materials, plays a critical role in maintaining energy homeostasis. Autophagy also protects against stress and infection, participates at the development of autoimmune disease. In recent years, the existence of alternative blood circulation system in tumors, vasculogenic mimicry (VM), which can partially compensate the lack of nutrients and oxygen under the hypoxic conditions, has been described. Objective. To elucidate the relationship between autophagy and VM. Materials and methods. In this study we used 2D- and 3D-culturing of melanoma cells derived from surgical species of patients with disseminated melanoma, electrophoresis and western blot, knockdown of the genes by using small interfering RNA (siRNA), flow cytometry, fluorescence microscopy. Results. We detected the basal level autophagy by examining the expression of autophagy-specific protein (LC-3B) by flow cytometry and cellular immunofluorescence staining by monodancylcadaverine. Both assays are the markers of autophagy late stage. Here we show that the level of autophagy in melanoma cells mel P, participated in capillary-like structures (CLS) formation in matrigel, was considerably higher than in mel Me cells which do not involve in VM. To explore the function of autophagy in the ability of melanoma cells to form CLS 3-methyladenine (3-MA) or chloroquine - inhibitors of initiation and terminal stage of autophagy - were used. Both inhibitors reduced the ability of melanoma cells to engage in VM. The data obtained were confirmed by siRNA-mediated gene silencing of BECN1 involved in the initiation of autophagy and ATG5 gene which is considered to be a marker of late stage of autophagy. Knockdown of BECN1 or ATG5 in mel P melanoma cells reduced the level of protein Beclin-1 and Atg5 about 70-75 %, and suppressed CLS formation in matrigel. Melanoma cells with the ATG5 gene knockdown changed the shape but maintained the ability to migrate and recognize each other, the formation of CLS was not observed. Low molecular weight VM inhibitor LCS-1269, significantly reduced the basic level of autophagy. Conclusion. Our data indicate that autophagy participates in CLS formation, and inhibition of autophagy suppresses CLS formation. We suggest that autophagy plays a dual role in the survival and development of tumors: autophagy helps cancer cells against environment stress and provides a temporary survival pathway by promoting energy regeneration, autophagy also promotes VM formation which supplies nutrients and oxygen to less vascularized area of tumor.
Synthesis and investigation of modified gastrin fragments
Authors: Sushinina L. P. , Smirnova A. P. , Ustinkina S. V. , Smirnova L. I. , Sidorova T. A. , Kiseleva M. P. , Borisova L. M. , Shprakh Z. S.
Published: November 2018

Background. The purpose of this investigation is the search of new compounds with high selectivity of antitumor action on the tumor of the gastrointestinal tract (GIT) in the series of analogues of the peptide hormone gastrin. Objective: synthesis of 2 analogues of gastrin, 1 of which contains the cytotoxic group, the study of their cytotoxic and antitumor activity. Materials and methods. Synthesis of peptides was carried out by classical methods of peptide chemistry. Cytotoxic activity was studied on the cell culture НСТ116. Antitumor activity of analogues of gastrin were studied on transplanted tumors of the GIT of mice AKATOL and AKATON. Results. Two analogues of gastrin (octapeptide) were synthesized, 1 of which contains a cytotoxic group. Analogue containing cytotoxic group revealed the cytotoxic activity. Antitumor activity of two analogues of gastrin were studied on transplanted tumors of the GIT of mice AKATOL and AKATON. The cytotoxic and non-cytotoxic analogues of gastrin showed antitumor activity only on AKATON. Inhibition of tumor growth is 74 and 84 %, respectively. Conclusions. The therapeutic effect of two analogues of gastrin on adenocarcinome AKATON, probably, is associated with the expression of gastrin receptors ССК2 in this tumor.
In silico and in vitro research of potential antineoplastic amino acid derivatives of indolocarbazol glycosides properties
Authors: Apryshko G. N. , Zhukova O. S. , Fetisova L. V. , Vlasenkova N. K. , Pugacheva R. B. , Goryunova O. V.
Published: November 2018

Objective: to evaluate the prospects of the glycosides of indolocarbazole containing amino acid residues as potential antitumor compounds. Materials and methods. For 32 compounds by structural formulas using the methods of chemoinformatics, a number of molecular descriptors and the probability of manifestation of various types of biological activity were calculated, the cytotoxic activity was evaluated in vitro by methylthiazole tetrazolium (MTT) assay using five human tumor cell lines. Results. For the studied amino acid derivatives of glycosides of indolocarbazole, a high probability of antitumor activity with a low probability of cytotoxic activity in vitro is predicted by computer method. Low cytotoxic activity was confirmed in the MTT test on 5 cell lines. Computer methods were used to predict the mechanisms of possible antitumor activity and to calculate a number of molecular descriptors that are important for the qualification of substances as potential drugs. Conclusion. It is expedient to study the antitumor activity of amino-acid derivatives of glycosides of indolocarbazole in experiments on animals with transplanted tumors.
Mathematical modeling of the stage of freezing in technology of lyophilized drugs
Authors: Blynskaya E. V. , Tishkov S. V. , Alekseyev K. V. , Minaev S. V.
Published: November 2018

The purposeof this work is to demonstrate the existing possibilities and methodology of mathematical modeling of the freezing phase in the technology of lyophilization of vials filled with a solution containing a pharmaceutical substance and auxiliary substances. The freezing process is crucial for the subsequent stages of primary sublimation and the drying stage. So it is at the stage of freezing that ice crystals are formed and a certain microstructure forming the pores for subsequent stages and influencing the speed of all stages in the future. The developed methods allow estimating the kinetics of cooling, freezing, calculating the sizes of ice crystals and determining the permeability of the sublimation layer. Of course, for these calculations it is necessary to know the conditions and values of the variables, calculated and measured during the pilot freezing. However, modeling allows to reduce the time of development and optimization of the process, increases the speed of transfer of the technological process to other equipment. In this review, formulas are analyzed, the thermal conductivity equations for each cooling zone, equations for estimating the crystal size and pore size in the dried layer, and calculating the permeability of the sublimated layer. The article draws conclusions about the perspective of modeling methods for the freezing phase, examines the equations used in modeling and demonstrates the model of supercooling, crystal formation and other mass and heat exchange processes during the cooling and freezing stage. The calculations presented in this paper are confirmed by references to experimental data and have great practical value.
Crosstalk between autophagy and iron in melanoma progression
Authors: Vartanian A. A. , Burova O. S. , Khochenkova Yu. A. , Baryshnikova M. A.
Published: November 2018

Introduction.Autophagy, a catabolic process of protein and organelle recycling by transferring defective cytoplasm and organelles into double-membraned vesicles to degrade and regenerate materials, plays a critical role in maintaining energy homeostasis. Inefficiency chemo-and radiotherapy is largely associated with the activation of autophagy. Among the metals needed by the living organism, iron occupies a special place. The rapid growth of malignant tumors requires much more iron than the metabolism of normal cells.

Objective.To elucidate the relationship between autophagy and iron in melanoma progression.

Materials and methods.In this study we used 2D- and 3D-culturing of melanoma cells with high expression of CD71 (mel P and mel Z) and low expression of CD71 (mel Gus and mel Ibr), flow cytometry and fluorescence microscopy.

Results.The uptake of iron in cancer cells occurs through translocation of the complex of transferrin/receptor (CD71) in the cytoplasm with subsequent dissociation of iron from the complex. Chelation of iron by deferroxamine in melanoma cells mel P and mel Z reduced the level of autophagy about 2-fold. In the presence of an iron donor ferrum ammonium citrate the level of autophagy increased 2.5- fold. The same correlation was observed in melanoma cells with low expression of CD71. Chelation of iron in melanoma cells with high CD71 expression blocked the formation of capillary-like structures. In the presence of an iron donor the formation of capillary-like structures was also not observed. The same correlation was observed in melanoma cells with low expression of CD71. There was an increase in CD105 expression about 50 ± 5 % and 800 ± 50 % under the condition of iron chelation in melanoma cells with high and low expression of CD71, respectively. Quite unexpectably, iron donor also increased expression of CD105 about 35 ± 4 % and 300 ± 3 % in melanoma cells with high and low expression of CD71, respectively

Conclusions.The activation of autophagy promotes the survival of tumor cells by triggering a number of metabolic functions with the participation of iron.
Protection of intellectual property in N.N. Blokhin National Medical Research Center of Oncology in 2017
Authors: Tarasova O. I. , Ryzhovа A. A. , Kubasovа I. Yu. , Golubtsova N. V. , Grivtsova L. Yu.
Published: November 2018

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Aprendizaje situado en el diseño de entornos virtuales de aprendizaje: una experiencia de aprendizaje entre pares en una comunidad de práctica
Authors: Hevia Artime Isabel , Fueyo Gutiérrez Aquilina
Published: November 2018

El artículo analiza el potencial del aprendizaje situado entre pares en el contexto de una experiencia formativa con 155 estudiantes universitarios. Por un lado, se cuenta con un grupo de estudiantes de 4º curso del Grado de Pedagogía que diseñan y ponen en marcha seis cursos MOOC. Por otro, está un grupo de estudiantes de 1º curso que se matriculan en uno de esos MOOC y tienen como tarea la evaluación del diseño pedagógico de los mismos. A través de esta experiencia, se busca conocer qué beneficios reportan este tipo de experiencias tanto para el alumnado que enseña como para el que recibe la formación acerca de su campo profesional. Para ello, la recogida de información se realiza a través de la observación participante, el análisis documental y cuestionarios. Los resultados sugieren que, a través de esta modalidad de aprendizaje situado entre pares, los estudiantes desarrollan un aprendizaje de más profundidad evidenciándose indicadores del desarrollo de competencias profesionales de gran interés, entre las que destacan las relacionadas con el pensamiento reflexivo y las vinculadas al desempeño profesional y las competencias digitales
Acceso, uso y actitud de la tecnología en las escuelas de Educación Primaria
Authors: Céspedes Ventura Raúl , Ballesta Pagán Javier
Published: November 2018

La Sociedad de la Información demanda competencias específicas a sus actuales y futuros ciudadanos, entre ellas, la competencia digital. La tecnología debe estar presente en las aulas, pero la toma de decisiones, respecto a cómo hacer que esa presencia sea efectiva, no es tarea fácil, necesitando estudios que identifiquen indicadores y evalúen el estado de dicha integración, señalando lo que funciona bien y lo que se debe mejorar. Este estudio consta de dos etapas, una encuesta y un grupo de discusión. La Encuesta Escolar: Educación y TIC en la Región de Murcia se realizó en 2015 en la Universidad de Murcia con el objetivo de definir la situación de la integración de la tecnología en los centros escolares de la etapa de Educación Primaria. La encuesta se aplicó a todos los centros de la Región de Murcia encuestando tanto a directores como a tutores y realizándose íntegramente online. En este artículo se presentan los principales resultados y conclusiones de la encuesta, así como recomendaciones para administradores educativos de cualquier.
The optimal structure of lotto games
Authors: Gulley Orrin David
Published: November 2018

Operators of state-owned lottery games generally attempt to set the parameters of the game(s) to maximize revenue to the state. This paper discusses the state of the literature on how to set the parameters of a lotto game so as to accomplish this objective.
Plantaciones de árboles madereros con usos militares en Extremadura: el sesmo de Caparrosa en Valencia de Alcántara (Cáceres), un proyecto de Diego de Bordick
Authors: Diez González Mª del Carmen
Published: November 2018

El vivero de Caparrosa, ideado por el ingeniero Diego Bordik en 1725, fue un intento de replantación forestal para reparar las fortificaciones de la frontera luso-extremeña, muy dañadas por las repetidas guerras de los siglos XVII y XVIII. El estudio presenta tres planos con todas las referencias al estado de situación del terreno elegido, su trasformación en vivero y el plano correspondiente a la vivienda del guarda de la plantación. Constituye la primera referencia de este tipo de trabajos planteado por ingenieros militares en Extremadura y la primera noticia de una empresa ideada por Bordik fuera de los planes de fortificación en la región. El militar acomete el plan siguiendo las pautas del jardín clásico francés con claras referencias a Le Nôtre y Dezailler d’Argenville. No existen sin embargo datos que avalen su ejecución.
Evolución histórica de la ley de uso y promoción del bable/asturiano en la enseñanza secundaria: orígenes, debates jurídicos, educación y perspectivas de futuro/Historical evolution of the Asturians use and promotion law in the secondary education: origins, legal debates, Education and future prospects
Authors: García Benito Manuel Germán
Published: November 2018

Este artículo reflexiona sobre la implantación del asturiano (o bable) en el sistema educativo regional desde una perspectiva plural. El proceso se inició a mediados de la década de los ochenta, sin embargo, la aprobación de ley de promoción y uso del bable/asturiano fue el hecho más destacado. Esta ley ha permitido normalizar la enseñanza de la lengua vernácula, así como regular cuestiones importantísimas: titulaciones, formación del profesorado, voluntariedad del aprendizaje, etc. El número de estudiantes, profesores y centros relacionados con el asturiano ha aumentado en todo este tiempo, aunque ahora se encuentra estancado. La lengua asturiana aparece recogida como asignatura de libre configuración autonómica en los currículos educativos de secundaria y bachillerato. Su aprendizaje es voluntario y actualmente cuenta con buenos recursos didácticos, así como actividades específicas destinadas para facilitar su estudio. El plan piloto experimental de promoción del uso del asturiano utiliza el idioma regional como lengua vehicular, sin embargo, el empleo del bable sigue siendo minoritario en nuestro sistema educativo, lo que condiciona la supervivencia de la lengua a medio y largo plazo.
Reseña biográfica de Alberto Marcos Vallaure
Authors: Álvarez Pulgar Francisco Javier , Bastida Ibáñez Fernando
Published: November 2018

Reseña biográfica de Alberto Marcos Vallaure
Construction and Teaching Reform of Electrics and Electronics Ex-perimental Teaching Demonstration Center
Authors: Pelen Fathi , Bellamy Michell
Published: November 2018

Experimental teaching is the main means to improve students 'practical ability and independent innovation ability, and open laboratory is the most basic teaching and scientific research environment for cultivating innovative ability and compound talents[1,2]. In order to meet the needs of high-quality talents in our country, the Electrotechnics and electronics experimental teaching demonstration center has broken the traditional closed teaching system and learning methods, and has carried out open-ended experiments in order to cultivate students'independent learning ability and innovative spirit, improve students' enthusiasm of integrating theory with practice, and solve class-hour conflicts and time-consuming problems. Disadvantages such as fixed and idle experimental resources.
A clinical study of gastric outlet obstruction
Authors: K. Ashwin , Visruja R. Lakshmi
Published: November 2018

Background: Gastric outlet obstruction (GOO) is a diagnostic and therapeutic challenge in developing countries to a Surgeon. Gastric outlet obstruction, a clinical condition impeding emptying of stomach mechanically, can be due to varied etiology. This study was taken up to know the etiological factors and management.Methods: This was a descriptive prospective study done at Madurai Medical College for a period of 2 years from September 2009 to August 2011. A set of inclusion and exclusion criteria were defined and followed. Upper gastro-intestinal endoscopy (OGD) was done in all cases while Barium meal study was done in few cases to make the diagnosis. Relevant operative procedure was done, and patients were managed post operatively.Results: Cicatrised Duodenal ulcer (DU) was the commonest cause followed by Carcinoma Pyloric antrum (Ca PA). Majority of the patients were males (67.5%) with male to female ratio of 2.07:1. Vomiting was one of the major presenting symptoms in all the patients.Conclusions: Cicatrised DU was the commonest cause for GOO in present study. Present study highlights the increasing incidence of Ca PA. This could be due to better management of DU at an early stage.
Attachment of a pressure gradient chamber to existing lumbar theco-peritoneal shunt in a patient with pseudotumor cerebri with low pressure headaches, a novel procedure: a case report
Authors: Bhati Aditendraditya S. , Tyagi Aarjun , Tyagi Sudheer K.
Published: November 2018

Pesudotumor cerebri is a syndrome which causes intracranial hypertension with no associated mass lesion. It is managed both medically as well as surgically. Cerebral spinal fluid diversion using theco-peritoneal shunt is commonly performed to decrease intracranial tension. We present a case of a middle age lady who had severe low pressure headaches following theco-peritoneal shunt for pesudotumor cerebri. She was managed by attaching pressure gradient chamber to the pre-existing theco-peritoneal shunt. Patient had marked improvement in headache, which gradually subsided. Attaching pressure gradient chamber to the pre-existing theco-peritoneal shunt helps to improve low pressures headaches in pseudotumor cerebri. It is an alternative procedure considering other extensive surgical options.