Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells

Cancer cells rely mostly on glycolysis to meet their energetic demands, producing large amounts of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). The role of MCTs in the survival of colorectal cancer (CRC) cells is scarce and poorly understood. In this study, we aimed to better understand this issue and exploit these transporters as novel therapeutic targets alone or in combination with the CRC classical chemotherapeutic drug 5-Fluorouracil. For that purpose, we characterized the effects of MCT activity inhibition in normal and CRC derived cell lines and assessed the effect of MCT inhibition in combination with 5-FU. Here, we demonstrated that MCT inhibition using CHC (a-cyano-4-hydroxycinnamic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and quercetin decreased cell viability, disrupted the glycolytic phenotype, inhibited proliferation and enhanced cell death in CRC cells. These results were confirmed by specific inhibition of MCT1/4 by RNA interference. Notably, we showed that 5-FU cytotoxicity was potentiated by lactate transport inhibition in CRC cells, either by activity inhibition or expression silencing. These findings provide novel evidence for the pivotal role of MCTs in CRC maintenance and survival, as well as for the use of these transporters as potential new therapeutic targets in combination with CRC conventional therapy.

Targeting lactate transport suppresses in vivo breast tumour growth.

BACKGROUND Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. RESULTS The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. CONCLUSIONS This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

A review of sustainable approaches in transport infrastructure geotechnics

Transportation geotechnics associated with constructing and maintaining properly functioning transportation infrastructure is a very resource intensive activity. Large amounts of materials and natural resources are required, consuming proportionately large amounts of energy and fuel. Thus, the implementation of the principles of sustainability is important to reduce energy consumption, carbon footprint, greenhouse gas emissions, and to increase material reuse/recycling, for example. This paper focusses on some issues and activities relevant to sustainable earthwork construction aimed at minimising the use of energy and the production of CO2 while improving the in-situ ground to enable its use as a foundation without the consumption of large amounts of primary aggregate as additional foundation layers. The use of recycled materials is discussed, including steel slag and tyre bales, alongside a conceptual framework for evaluating the utility of applications for recycled materials in transportation infrastructure.

Particle transport in fouling caused by kaolin-water suspensions on copper tubes

Particulate fouling tests were carried out using kaolin-water suspensions flowing through an annular heat exchanger with a copper inner tube. The flow rate was changed from test to test, but the fluid temperature and pH, as well as the particle concentration, were maintained constant. In the lower range of fluid velocities (<0.5 m/s), the deposition process seemed to be controlled by mass transfer. The corresponding experimental transport fluxes were compared to the predictions obtained with several models, showing that diffusion governed particle transport. The absolute values of the mass transfer fluxes and their dependences on the Reynolds number were satisfactorily predicted by some of the models.

Estación Astronómica Polar J. L. Sersic

- El grupo IATE del Observatorio Astronómico Córdoba está desarrollando un proyecto observacional en el antártico, desde 1989, denominado ASTROLABEL. Las observaciones se realizan en Base Antártica Belgrano, a 78º S y 34º W, siendo el sitio más adecuado según la prospección hecha en las bases argentinas de actividad permanente. - Se pretende determinar cualitativamente la aptitud de la atmósfera polar para realizar observaciones astronómicas en el rango visible del espectro. Las especiales cirscunstancias de la región, como lo son su prolongado período de oscuridad invernal, la inexistencia de contaminación atmosférica y lumínica y los bajos niveles de humedad relativa, han despertado el interés de los investigadores. - Las tareas se desarrollan en convenio con el Instituto Antártico Argentino (IAA). Objetivos Se pretende determinar cualitativa y cuantitativamente las condiciones del cielo del lugar, para la ejecución de trabajos astronómicos de interés. (...) La disponibilidad de muchas horas de observación continuada hace posible el monitoreo de estrellas con una frecuencia de varias veces al día, lo que permitirá obtener su curva de luminosidad completa, sin interrumpir las observaciones por la salida del sol. Esta situación es la que permitirá la observación de Eta Carina, estrella que presenta bruscos y sorprendentes cambios en su luminosidad. Similar es el caso de las estrellas variables R Corona Borealis con cambios esporádicos, aunque de bajo valor en su brillo. Estas observaciones demandan de un monitoreo constante y con una frecuencia de al menos dos o tres veces diarias. Se pretende obtener una conclusión sobre la transparencia en el UV, cuando se produce la apertura de la depresión de ozono, para lo cual se obtendrá una correlación entre las mediciones de los índices de esa banda y las mediciones de ozono hechas en el lugar con medidores Brewer y EVA. También se tomarán datos con radiómetro de sol durante el verano.

Computer integrated testing for the transport refrigeration systems industry.

This is a study of a state of the art implementation of a new computer integrated testing (CIT) facility within a company that designs and manufactures transport refrigeration systems. The aim was to use state of the art hardware, software and planning procedures in the design and implementation of three CIT systems. Typical CIT system components include data acquisition (DAQ) equipment, application and analysis software, communication devices, computer-based instrumentation and computer technology. It is shown that the introduction of computer technology into the area of testing can have a major effect on such issues as efficiency, flexibility, data accuracy, test quality, data integrity and much more. Findings reaffirm how the overall area of computer integration continues to benefit any organisation, but with more recent advances in computer technology, communication methods and software capabilities, less expensive more sophisticated test solutions are now possible. This allows more organisations to benefit from the many advantages associated with CIT. Examples of computer integration test set-ups and the benefits associated with computer integration have been discussed.

Polar S810 como recurso alternativo ao eletrocardiograma no teste de exercício de 4 segundos

FUNDAMENTO: O teste de exercício de 4 segundos (T4s) avalia o tônus vagal cardíaco durante o transiente inicial da frequência cardíaca (FC), em exercício dinâmico súbito, por meio da identificação do índice vagal cardíaco (IVC) obtido a partir do eletrocardiograma (ECG). OBJETIVO: Testar a utilização do monitor de frequência cardíaca (MFC) Polar S810 como recurso alternativo ao ECG na aplicação do T4s. MÉTODOS: Neste trabalho, 49 indivíduos do sexo masculino (25 ± 20 anos, 176 ± 12 cm, 74 ± 6 kg) realizaram o T4s. Os intervalos RR foram registrados simultaneamente por ECG e MFC. Calcularam-se média e desvio padrão do último intervalo RR do período pré-exercício ou o primeiro do período de exercício, aquele que for mais longo (RRB), do mais curto intervalo RR do período de exercício (RRC) e do IVC obtidos por ECG e MFC. Utilizou-se o teste t de Student para amostras dependentes (p < 0,05) para testar a significância das diferenças entre as médias. Para identificar a concordância entre o ECG e o MFC, utilizou-se a regressão linear, com cálculo do coeficiente de correlação de Pearson e a estratégia proposta por Bland e Altman. RESULTADOS: A regressão linear apresentou r² de 0,9999 para o RRB, 0,9997 para o RRC e 0,9996 para o IVC. A estratégia de Bland e Altman apresentou desvio padrão de 0,92 ms para o RRB, 0,86 ms para o RRC e 0,002 para o IVC. CONCLUSÃO: O MFC Polar S810 se mostrou eficiente na aplicação do T4s quando comparado ao ECG.

Electrokinetic flow and transport in porous media : experimental methods, numerical analysis, and applications

Electrokinetic transport, electrochromatography, electroosmotic flow, electrophoresis, concentration polarization, fixed beds, monoliths, dynamic NMR microscopy, quantitative confocal laser scanning microscopy, mathematical modelling, numerical analysis

Flow and transport in electrochromatography

Analyte retention, analyte transport, axial dispersion, adsorption, charge-selectivity, concentration polarization, confocal laser scanning microscopy, donnan-exclusion, electrical double layer; electrochromatography; electrohydrodynamics, electrokinetic instability, electroosmosis; electroosmotic flow; electroosmotic mobility, electroosmotic perfusion, electrophoresis, hierarchical porous media, hydrodynamic flow, induced-charge electroosmosis, ion-permselectivity, ion-permselective transport, monolith, nonequilibrium electrical double layer, nonequilibrium electrokinetic effects, nonlinear electroosmosis, plate height, plate number, porous media, pore-scale dispersion, refractive index matching, space charge effects, sphere packing, quantitative imaging, wall effect, zeta-potential

Sojabohnenprotein P34 : Aufreinigung, Verdauung und epithelialer Transport im enteralen Zellkulturmodell

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2008

Einfluss des Hitzeschockproteins Hsc70 und des Raf Kinase Inhibitor Proteins RKIP auf den zellulären Transport und die Aktivität des [my]-Opioidrezeptors

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2008

Growth of semi-polar GaN on high index silicon (11h) substrates by metal organic vapor phase epitaxy

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2014

Comparison of Contemporary Protocols for High-speed Data Transport via 10 Gbps WAN Connections

This work is dedicated to comparison of open source as well as proprietary transport protocols for highspeed data transmission via IP networks. The contemporary common TCP needs significant improvement since it was developed as general-purpose transport protocol and firstly introduced four decades ago. In nowadays networks, TCP fits not all communication needs that society has. Caused of it another transport protocols have been developed and successfully used for e.g. Big Data movement. In scope of this research the following protocols have been investigated for its efficiency on 10Gbps links: UDT, RBUDP, MTP and RWTP. The protocols were tested under different impairments such as Round Trip Time up to 400 ms and packet losses up to 2%. Investigated parameters are the data rate under different conditions of the network, the CPU load by sender andreceiver during the experiments, size of feedback data, CPU usage per Gbps and the amount of feedback data per GiByte of effectively transmitted data. The best performance and fair resources consumption was observed by RWTP. From the opensource projects, the best behavior is showed by RBUDP.

Analysis study of the axial transport and heat transfer of a flighted rotary drum operated at optimum loading

Magdeburg, Univ., Fak. für Verfahrens- und Systemtechnik, Diss., 2015