Совершенствование организационной культуры в образовательной организации на примере МАОУ СОШ № 3

Проблема исследования заключается в необходимости совершенствования организационной культуры МАОУ СОШ № 3.Целью выпускной квалификационной работы является анализ организационной культуры МАОУ СОШ № 3 и ее совершенствование. Объект исследования: организационная культура образовательного учреждения. Предмет исследования: совершенствование организационной культуры образовательной организации МАОУ СОШ № 3.Структура работы. Работа состоит из введения, двух глав, списка использованных источников

Assessment of the genetic risks of a metallic alloy used in medical implants

The use of artificial implants provides a palliative or permanent solution for individuals who have lost some bodily function through disease, an accident or natural wear. This functional loss can be compensated for by the use of medical devices produced from special biomaterials. Titanium alloy (Ti-6Al-4V) is a well-established primary metallic biomaterial for orthopedic implants, but the toxicity of the chemical components of this alloy has become an issue of concern. In this work, we used the MTT assay and micronucleus assay to examine the cytotoxicity and genotoxicity, respectively, of an extract obtained from this alloy. The MTT assay indicated that the mitochondrial activity and cell viability of CHO-K1 cells were unaffected by exposure to the extract. However, the micronucleus assay revealed DNA damage and an increase in micronucleus frequency at all of the concentrations tested. These results show that ions released from Ti-6Al-4V alloy can cause DNA and nuclear damage and reinforce the importance of assessing the safety of metallic medical devices constructed from biomaterials

Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

Resistance to the CCR5 Inhibitor 5P12-RANTES Requires a Difficult Evolution from CCR5 to CXCR4 Coreceptor Use

Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC) or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16–18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a “resistant” variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching

Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response

Human lymphocyte antigen (HLA)-restricted CD8+ cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs

The Effects of Mild Hypothermia on Coagulation Tests and Haemodynamic Variables in Anaesthetized Rabbits

Objective: Hypothermia has been associated with coagulation defects. The purpose of this experimen-tal study was to investigate the effect of mild hypothermia on clinically used coagulation tests and on haemodynamic variables. Methods: Νine New Zealand rabbits were subjected to mild core hypothermia by administration of general anaesthesia and exposure to room temperature of 22°C for 60 minutes. Blood samples were obtained at normothermia and mild hypothermia for measurement of prothrombin time, activated partial thromboplastin time, fibrinogen levels, platelet count and haemoglobin concentration. Hypo-thermic values were compared to the normothermic values. Additionally, the progressive temperature drop and haemodynamic changes (blood pressure, heart rate) were recorded. Results: Core temperature decreased significantly over time changing from 39.4 ± 0.27 to 36.6 ± 0.28°C (p = 0.0001). Prothrombin time and activated partial thromboplastin time decreased at hypothermia, but the changes were not statistically significant (p = 0.203 and p = 0.109, respectively). Platelet count, fibrinogen levels and haemoglobin concentration decreased significantly (p = 0.0001, p = 0.03 and p = 0.027) but remained within normal limits. Mean arterial pressure and heart rate declined significantly over time (p = 0.0001 and p = 0.0001, respectively). Conclusion: The results of this study suggest that short term mild hypothermia may affect the coagulation mechanism to a clinically nonsignificant extent, while haemodynamic responses are significantly suppressed. Keywords: Coagulation tests, haemodynamics, mild hypothermia "Efectos de la Hipotermia Leve sobre las Pruebas de Coagulación y las Variables Hemodinámicas en Conejos Anestesiados" RESUMEN Objetivo: La hipotermia ha sido asociada con defectos de coagulación. El propósito de este estudio experimental fue investigar el efecto de la hipotermia leve sobre las pruebas de coagulación de uso clínico, así como sobre las variables hemodinámicas. Métodos: Nueve conejos de Nueva Zelanda fueron sometidos a hipotermia central leve mediante la administración de anestesia general y exposición a una temperatura ambiente de 22°C durante 60 minutos. Se obtuvieron muestras de sangre en condiciones de normotermia e hipotermia leve para medir el tiempo de protrombina, el tiempo de tromboplastina parcial activada, los niveles de fibrinó-geno, el conteo de plaquetas, y la concentración de hemoglobina. Se compararon los valores hipo-térmicos con los valores normotérmicos. Además, se registraron la caída progresiva de la temperatura y los cambios hemodinámicos (presión sanguínea, frecuencia cardíaca). Resultados: La temperatura corporal central disminuyó significativamente con el tiempo, cambiando de 39.4 ± 0.27 a 36.6 ± 0.28°C (p = 0.0001). El tiempo de protrombina y el tiempo de tromboplastina parcial activado disminuyeron en la hipotermia, pero los cambios no fueron estadísticamente signi-ficativos (p = 0.203 y p = 0.109, respectivamente). El conteo de plaquetas, los niveles de fibrinógeno y la concentración de la hemoglobina disminuyeron significativamente (p = 0.0001, p = 0.03 y p = 0.027) pero permanecieron dentro de los límites normales. La presión arterial promedio y la frecuencia cardíaca disminuyeron significativamente con el tiempo (p = 0.0001 y p = 0.0001, respectivamente). Conclusión: Los resultados de este estudio sugieren que la hipotermia leve a corto plazo puede afectar el mecanismo de la coagulación hasta un punto clínicamente no significativo, mientras que respuestas hemodinámicas se suprimen significativamente. Palabras claves: Pruebas de coagulación prueba, hemodinámica, hipotermia lev

The European Sero-Epidemiology Network 2 (ESEN2): standardization of assay results for hepatitis A virus (HAV) to enable comparisons of seroprevalence data across 15 countries

The European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0.90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe