Three-dimensional laser Doppler anemometer measurements of a jet in a crossflow

A three-dimensional laser Doppler anemometer (3D-LDA) was used in a wind tunnel to measure a jet in a crossflow. Measurements were made in the vicinity of a 5-cm-diam jet which issued normally into a 10.65 m/sec wind tunnel crossflow; the velocity ratio Vjet/Vinf was 8. Detailed lateral surveys were made at two elevations (z = cm and 2 cm); both elevations were within the region affected by the boundary layer on the plate. The results are believed to provide reliable velocity field information in the boundary layer of the jet in a crossflow. Turbulence information also is available and believed to be roughly correct, although it may be subject to broadening effects for the lower values of turbulence. A weak vortex pair was observed in the wake at the plate surface. This structure existed in the boundary layer and built confidence because the 3D-LDA was, indeed, able to resolve fine detail in the wake. The capabilities of the 3D-LDA not only allow the making of the velocity surveys, but can be utilized to follow mean streamlines in the flow

New hydroxamates triterpenes as activators of HIF. Therapeutic implications

El factor inducible por hipoxia (HIF) se estabiliza durante los procesos inflamatorios asociados a un gran número de patologías, produciendo cambios en la expresión génica con un profundo impacto en el microambiente tisular, así como en la evolución de la enfermedad. Aunque los mecanismos que inician la estabilización de HIF dependen de diferentes factores, todos ellos convergen en las proteínas prolil-hidroxilasas (PHDs) que lo hidroxilan promoviendo su ubiquitinación y degradación. Actualmente, el desarrollo farmacológico de moléculas que funcionen como inhibidores de las PHDs estabilizando la expresión de HIF está en auge para el tratamiento de enfermedades fibróticas, inflamatorias y neurodegenerativas como son la Enfermedad Inflamatoria Intestinal (EII), la Enfermedad de Huntington (EH) y el Traumatismo Craneal Inducido (TCI). En esta tesis, hemos estudiado la eficacia de la molécula VCE-005.1, un derivado hidroxamato del ácido betulínico con carácter hipoximimético, en distintas enfermedades que pueden beneficiarse de esta modulación. Para ello, se llevaron a cabo aproximaciones tanto in vitro como in vivo, además de estudiar su perfil farmacológico. Los ensayos in vitro nos permitieron determinar el mecanismo de acción del compuesto, así como desvelar las posibles patologías en las que sería interesante su uso. Concretamente, se determinó que el compuesto VCE-005.1 modifica la actividad de la PHD2 por medio de la modulación de la proteína fosfatasa 2A (PP2A)/B55α, afectando así a la estabilidad de HIF-1α. En experimentos llevados a cabo en fibroblastos, el compuesto indujo la retracción de colágeno, y en células Caco-2 evitó la pérdida de resistencia eléctrica transepitelial (TEER) inducida por citocinas proinflamatorias. Además, en células estriatales con una forma mutada de la huntingtina, el compuesto indujo la expresión de genes dependientes de HIF y protegió contra la citotoxicidad inducida por 3-NP. Finalmente, también se demostró en células microvasculares cerebrales que el VCE-005.1 aumenta la expresión de genes dependientes de HIF con carácter protector. Además, el compuesto también indujo la angiogénesis en células endoteliales vasculares y en un modelo de ratón basado en implantes de matrigel. Los ensayos in vivo llevados a cabo en modelos animales nos permitieron determinar de una manera más preclínica los efectos que el compuesto VCE-005.1 era capaz de llevar a cabo. Primero, en dos modelos murinos de EII demostramos que el tratamiento oral con VCE- 005.1 previno la inflamación y la fibrosis del colon por medio de una mejora en la integridad de la barrera epitelial. Segundo, en un modelo de ratón de neurodegeneración estriatal usado como aproximación a la EH, se mostró que el compuesto mejoró los síntomas clínicos, previno la pérdida neuronal, disminuyó la astrogliosis reactiva, la activación microglial y los marcadores proinflamatorios y mejoró las defensas antioxidantes en el cerebro. Tercero, en un modelo de TCI el compuesto VCE-005.1 mejoró los síntomas clínicos y promovió una mejora de la barrera hematoencefálica, que se tradujo en una menor infiltración y en una mejora de la expresión de mediadores inflamatorios y marcadores de daño de la BHE. Por último, el compuesto VCE-005.1 mostró una biodisponibilidad oral prometedora, una buena penetrabilidad cerebral y carece de efectos genotóxicos y cardiotóxicos. Tomados en conjunto, nuestros resultados muestran la capacidad del compuesto VCE- 005.1 para activar la ruta PP2A/B55α/PHD2/HIF-1α, y proporcionan evidencias de que el tratamiento oral alivia la inflamación del colon y la fibrosis asociada a la colitis. Además, el tratamiento intraperitoneal mejora la neuroinflamación asociada a enfermedades neurodegenerativas como son la EH y el TCI, identificando la mejora de la integridad de la barrera intestinal y hematoencefálica como posible mecanismo de acción y proporcionando así, una base sólida para estudios clínicos adicionales.Hypoxia-inducible factor (HIF) stabilizes during inflammatory processes associated with a large number of pathologies, producing changes in gene expression with a profound impact on the tissue microenvironment, as well as on the evolution of the disease. Although the mechanisms that initiate the stabilization of HIF depend on different factors, all of them converge on the prolyl-hydroxylases proteins (PHDs) that hydroxylate it, promoting its ubiquitination and degradation. Currently, the pharmacological development of small molecules used as inhibitors of PHD to stabilize the expression of HIF is experiencing a great increase for the treatment of fibrotic, inflammatory and neurodegenerative diseases such as Inflammatory Bowel Disease (IBD), Huntington's Disease (HD) and Traumatic Brain Injury (TBI). In this thesis, we have studied the efficacy of the molecule VCE-005.1, a hydroxamate derivative of the betulinic acid with a hypoximimetic feature, in different diseases that can benefit from this modulation. For this, in vitro and in vivo approaches were carried out, in addition to studying its pharmacological profile. The in vitro experiments allowed us to determine the mechanism of action of the compound, as well as to reveal the possible pathologies in which its use would be interesting. Specifically, it was determined that the compound VCE-005.1 modifies the activity of PHD2 through the modulation of protein phosphatase 2A (PP2A)/B55α, thus affecting the stability of HIF-1α. In experiments carried out in fibroblasts, the compound induced collagen retraction, and in Caco-2 cells it prevented the loss of transepithelial electrical resistance (TEER) induced by pro-inflammatory cytokines. Furthermore, in striatal cells with a mutated form of huntingtin, the compound induced the expression of HIF-dependent genes and protected against 3-NP-induced cytotoxicity. Finally, it was also demonstrated in brain microvascular cells that VCE-005.1 increases the expression of protective HIF-dependent genes. Furthermore, the compound also induced angiogenesis in vascular endothelial cells and in a mouse model based on matrigel. In vivo experiments carried out in animal models allowed us to determine in a more preclinical way the effects that the compound VCE-005.1 would be able to carry out. First, in two murine IBD models we demonstrated that oral VCE-005.1 treatment prevented inflammation and fibrosis of the colon by improving the integrity of the epithelial barrier. Second, in a mouse model of striatal neurodegeneration used as an approximation to HD, the compound was shown to improve clinical symptoms, prevent neuronal loss, decrease reactive astrogliosis, microglial activation, and pro-inflammatory markers, and improve antioxidant defenses in the brain. Third, in a TBI model, compound VCE-005.1 improved clinical symptoms and promoted the improvement of the blood-brain barrier, which resulted in less infiltration and improved expression of inflammatory mediators and damage markers of BBB. Lastly, compound VCE-005.1 showed promising oral bioavailability, good brain penetrability, and lacks genotoxic and cardiotoxic effects. Taken together, our results show the ability of compound VCE-005.1 to activate the PP2A/B55α/PHD2/HIF-1α pathway and provide evidence that oral treatment alleviates colon inflammation and fibrosis associated with colitis. In addition, intraperitoneal treatment improves the neuroinflammation associated with neurodegenerative diseases such as HD and TBI, identifying the improvement of the integrity of the intestinal and blood-brain barrier as a possible mechanism of action and thus providing a solid basis for additional clinical studies

Report FSW: 005.1 Faculty Salary Report

Trends in average salaries--comparisons with consumer price index using 1970-71 as the base year

Точечные активные измерительные рамочные антенны в диапазоне частот 5 Гц … 30 МГц

The results of development of dot loop-aerias for measurement of magnetic fields are submitted. The areas of application are determined.Представлены результаты разработки точечных активных антенн для измерения магнитных полей. Определены области применения

Точечные активные измерительные рамочные антенны

The results of development of dot fissile antennas for measurement of magnetic fields are submitted. The areas of application are determined.Представлены результаты разработки точечных активных антенн для измерения магнитных полей. Определены области их применения

Варианты антикоагуляции при продолженной заместительной почечной терапии в кардиохирургии

При ретроспективном анализе 86 историй болезни определялись параметры безопасности проведения цитратной антикоагуляции при проведении продленной почечнозаместительной терапии у пациентов после кардиохирургических вмешательств. Изучали клинико-биохимические показатели и параметры гемостаза, оценивали частоту возникновения кровотечений и дренажные потери. Показано отсутствие значимых различий с гепариновой антикоагуляцией. Отмечено повышение маркеров печеночной недостаточности к 48 ч процедуры, а также значимо меньшие объемы дренажных потерь при цитратной антикоагуляции. Сделано заключение о безопасности и эффективности цитратной антикоагуляции при высоком риске кровотечений в послеоперационном периоде, с ограничениемвозможно- сти применения при полиорганной недостаточности.The safe parameters for citrate anticoagulation during the continuous renal replacement therapy in patients after cardiac surgery were determined in retrospective analysis of 86 clinical cases. The clinical and biochemical variables and hemostasis parameters were investigated, bleeding occurrence and drainage losses were evaluated. The absence of significant differences with heparin anticoagulation were noted. The increase of liver failure markers within 48 h of undergoing procedure were detected, the drainage losses volume were significantly less during citrate anticoagulation. In conclusion, the safety and efficacy of citrate anticoagulation in patients at high risk of bleeding in the postoperative period were detected, but with limited clinical usage in case of multiple organ dysfunction

On the Enhancement of the Reconstruction Accuracy obtained with a Multi-Source/Multi-Illumination Inverse Scattering Technique

This paper explores the possibility of enhancing the available information content of scattered data by means of an innovative Multi-Source strategy. The approach exploits the scattering interactions between scatterer and probing source when the investigation domain is illuminated by different (in terms of radiation patterns) illuminations. The results of a set of representative numerical simulations are shown to point out the potentialities of the inversion strategy

Лапароскопические операции у больных с тяжелой сочетанной травмой и тупой травмой живота

In this article we analyzed our experience of treatment of 822 patients with polytrauma and abdominal blunt trauma. The aim of this study was to evaluate the possible benefits of the routine diagnostic laparoscopy and laparoscopic operations performed in case of abdominal trauma. After general examination, labtests, X-ray, USS and CT and diagnosis of trauma, 622 patients were performed videolaparoscopic examinations. In 152 (24.6%) cases we found trauma of the liver complicated with bleeding. We performed the laparoscopic operation in 152 (53.9%) patients of 282 liver trauma cases. In 51 cases of thoracic trauma with haemothorax we performed videothoracoscopies with coagulation of intercostal vessels. We also analyzed indications to laparoscopy in case of trauma and came to conclusion that laparoscopy is a useful tool to avoid an unnecessary laparotomy in stable patients with abdominal trauma. Bleeding from minor injuries of the liver or the spleen can be controlled through the laparoscopy. Laparoscopic operations in patients with mixed trauma and abdominal blunt trauma decrease mortality and number of postoperative complications. Future developments in minimally invasive surgery will allow a wider usage of laparoscopy for diagnosis and treatment of abdominal trauma.Проанализирован опыт лечения 822 пациентов с политравмой и тупой травмой живота. Целью данной работы было оценить возможные преимущества стандартной диагностической лапароскопии и лапароскопических операций, выполненных у пациентов с травмой живота. После общего обследования, лабораторных тестов, рентгенографии, УЗИ и КТ-диагностики травмы у 622 пациентов выполняли диагностическую лапароскопию. В 152 (24,6 %) случаях обнаружили травму печени, осложненную кровотечением. Во всех этих случаях (53,4 % от общего числа — 282 пациентов, которым проводили лапароскопию) выполняли лапароскопические операции. В 51 случае травмы грудной клетки, осложненной гемотораксом, выполнили видеоторакоскопии с коагуляцией межреберных сосудов. Также проанализированы показания к лапароскопии в случаях травмы. Сделан вывод, что при травме живота лапароскопия позволяет избежать ненужных лапаротомий у гемодинамически стабильных пациентов. Кровотечения из небольших повреждений печени и (или) селезенки могут быть проконтролированы лапароскопически. У пациентов с политравмой и тупой травмой живота лапароскопические операции значительно снижают летальность и количество постоперационных осложнений