Comparative Analysis of Nanoscale Ultrasound Contrast Agents

Current ultrasound contrast agents utilize microbubbles as a blood pooling agent, but the size inhibits access to small capillaries. The development of nanoscale ultrasound contrast agents can enter small capillaries of tissues and aid in the detection of diseased states. However, current nano-formulations are flushed from the body over a short period of time. We developed a nanoscale ultrasound contrast agent with increased circulation time to allow for better detection of diseased states in the microvasculature of the body. Characterization (zeta potential, size, echogenicity and stability) and pharmacokinetic analysis were conducted on three nanoscale formulations: 1) Liquid based Bovine Serum Albumin (BSA)- Perfluropentane (PFP), 2) Gas based Lipid -L61 Pluronic, and 3) Gas based L61-Pluronic with Polyethylene Glycol (PEG). Characterization was conducted using Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA). Echogenicity testing was performed using ultrasound imaging (Vevo2100) in vitro with a tissue phantom. The concentration, frequency response, and bubble stability were evaluated. The BSA-PFP, L61, and PEG L61 formulations had mean sizes of approximately 300 nm, 250 nm, and 330 nm respectively (n = 6). Images taken on the high frequency ultrasound system revealed that the L61 nanobubbles had higher signal intensity. Stability of the different formulations was measured over 2 hours. Nanobubble intensities decreased overtime, except the BSA-PFP bubbles, most likely due to being liquid-derived. Future in vivo studies will be conducted for circulation times in an animal model. Utilization of these formulations could lead to targeting of proteins in the body through modified nanobubble formulations

Tissue Clearing as a Mechanism to Identify Changes in Fibronectin Structure During Breast Cancer Metastasis

With metastasis accounting for approximately 90% of breast cancer deaths and an alarming number of over 300,000 new breast cancer cases to be diagnosed by the end of 2018, there is growing need to understand the process of breast cancer. Changes in the extracellular matrix (ECM) of the tumor microenvironment play an essential role in this deadly tumor progression. Specifically, the glycoprotein fibronectin (FN), has been identified to be up-regulated in patients with worse clinical outcomes. During tumor progression fibronectin undergoes conformational changes that aid in metastatic dissemination. In order to analyze the dynamic changes in FN expression and evaluate architectural changes within the metastatic niche, electrophoretic tissue clearing was used to image changes in whole murine lungs that have undergone breast cancer metastasis. The X-CLARITY tissue clearing system utilizes electrophoresis which removes the lipid compounds from tissues to make them optically transparent. Coupling this with the c-PRESTO immuno-labelling technique and confocal light microscopy allows imaging of FN expression and structure in whole murine organs. In this study, a tissue clearing, and staining protocol was developed and used to visualize the 3D FN structure in whole murine lungs. Future studies will evaluate changes in FN expression and structure over time during cancer progression. This would contribute to on-going research on the development of more effective breast cancer drugs that aim to combat metastasis

Effects of Stroma on ER+ Breast Cancer Cell Metastasis

Breast cancer is one of the most wide-spread diseases among women in America. If the cancer is local, it is easily controlled by surgical resection. However, if the cancer cells metastasize, patient survival is significantly reduced. 70% of breast cancers can be targeted through estrogen receptors (ER) on the membrane, with compounds such as tamoxifen. However, tamoxifen shows unreliable outcomes on different patients and it is believed that the ineffectiveness of tamoxifen is related to the epithetical-mesenchymal transition (EMT) of cancer cells. To address this problem, we are designing a system that stimulates metastasis activation with the aim of incorporating the results in target identification for drugs. To mimic the cellular microenvironment in both 3D and 2D, scaffold and plate seeding of T47D cell line, an ER+ breast cancer cell line, and human mammary fibroblast (HMF) has been utilized. To understand the activation state of secondary metastasis and identify the presence of drug-targeted receptors, IHC staining has been used. Only co-cultured samples of T47D and HMF in 3D showed EMT. The morphology of both cells, when kept isolated from each other, did not change, but epithelial markers appeared at the cytoplasm instead of the membrane after 7-days of co-culture. Our results suggest that communication of breast cancer cells with fibroblasts in 3D initiates secondary metastasis. We hypothesize that the EMT leads to loss of estrogen receptors and reduce medicines efficacy

Creating a Mammary Duct Model to Study the Effects of Cancer Heterogeneity on Tumor Metastasis

During tumor progression, the process of clonal evolution gives rise to a variety of cell subpopulations that cause differential sensitivity to drugs and give rise to cell populations with the ability to metastasize, there are many mouse models available that can be used to study tumor progression and metastasis. However, there is a lack of models to study the effect of tumor heterogeneity using human cancers. Xenograft based systems require the use of immunodeficient mice, which limits the use of the model to evaluate microenvironmental factors involved in metastatic dissemination. Humanized mouse models with established human immune systems have been developed. However the high cost, and deficiencies in the immune system limit their clinical utility. One way to combat these issues is through tissue-engineered models. A mammary duct model was created to study the effects of breast cancer cell heterogeneity on metastasis. A 3D printed mold was fabricated to create a lumen, representative of the hollow mammary duct using type I collagen. After lining the interior of the lumen with Matrigel to mimic the basement membrane, normal human epithelial cells (HMLEs) were seeded into the lumen. Future studies will use this physiologically relevant tissue model to systematically evaluate microenvironmental factors that drive human breast tumor initiation, progression, and metastasis. This model can further be used to study the effect of cancerous oncogenes that are activated by the presence of a common cancer drug, such as doxycycline, as well as systematically investigate the role of the tumor microenvironment on tumor progression

La publicidad registral y su implicancia en el tráfico inmobiliario

Publicación a texto completo no autorizada por el autorEl documento digital no refiere asesorPretende demostrar las múltiples interpretaciones que tiene el artículo 2012 del Código Civil y las normas afines, en detrimento de la última persona que debe salir afectada por estas dubitaciones normativas: el ciudadano común y corriente. Se busca no solo reparar en los muchos conflictos que genera el hecho de no tener una norma clara sobre la materia, sino contribuir a su solución mediante una modificación al Código Civil que tome partido por una de las concepciones de la publicidad registral.Tesi

With the Apocalypse at the Threshold. The Glorification of the Holy Family for Gonzalo Carrasco

Gonzalo Carrasco proyectó en La glorificación de la Sagrada  Familia los deseos de expedita ejecución del ideal ambicionado,  frente a las agudas disyuntivas entre el mundo secular y el  catolicismo. A través de los mensajes cifrados en dicha obra, el  pintor jesuita orquestó un alegato a favor de la conservación de un orden preestablecido, donde Cristo y su Iglesia continuasen como  regidores del cielo y la tierra.Gonzalo Carrasco reflected at La glorificación de la Sagrada Familia the expeditious execution of the coveted ideal, face acute dilemmas between the secular world and catholicism. Through the encrypted messages in this work, the jesuit painter orchestrated a plea for the preservation of a predetermined order, which Christ and his Church would continue as rulers of heaven and earth

The Effect of Additives on the Behavior of Phase Sensitive In Situ Forming Implants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113738/1/jps24558.pd

Agronomic Potential and Nutritive Value of Promising \u3ci\u3eLeucaena\u3c/i\u3e Species in the Yucatan Peninsula

Two experiments were carried out in order to evaluate the agronomic potential, the nutritive value and the tolerance to psyllid (Heteropsilla cubana) of nine Leucaena species. A randomized block design with four repetitions was used. There were significant (P\u3c 0.01) differences on dry matter production (i.e. leaf and twigs yield ). L. collinsii showed the most promising result, which could be related to its high psyllid tolerance. In a second experiment, the preference indices of Leucaena species was assessed with sixteen male pelibuey sheep in a cafeteria trial. There were significant (P\u3c 0.0001) differences among Leucaena species. L. esculenta paniculata was the species most preferred . There was no relationship between chemical composition (i.e. ADF, NDF, and polyphenols) and preference and psyllid tolerance

Three-Dimensional Microfluidic Tumor Vascular Model for Investigating Breast Cancer Metastasis

Metastasis is one of the primary reasons for the high mortality rates in female patients diagnosed with breast cancer. It involves the migration of cancer cells into the circulatory system allowing for the dissemination of cancer cells in distal tissues. Understanding the major processes that occur in cells and tissues during metastasis can help improve currently existing therapeutic methods. In order to understand such mechanisms, developing physiologically relevant tissue models is crucial. Advancements in microfluidics have led to the fabrication of 3D culture models with shear stress gradients and flow control that can recapitulate aspects of the tumor microenvironment in vitro. However, most of these 3D culture models were fabricated using photolithography techniques performed in a clean room, which requires extensive training and can be cost prohibitive. Other studies have used more accessible techniques such as mold casting to construct a vessel-like microchannel. The main drawback of this method is that it limits the usage of high magnification objective lenses. Here, we propose a simple, high-fidelity and cost-effective approach in fabricating in vitro tissue platforms using a 3D printer that is optimal for live-cell imaging. To demonstrate proof-of-concept, we imaged endothelial and fibroblast cells cultured inside the 3D microfluidic collagen hydrogel, which was compared with the control group cultured in the 2D platform. The integrity of the microchannel fabricated inside the collagen hydrogel was imaged by using confocal reflectance microscopy. This feature has broader implications to bioengineered tissue fabrication and should be further explored in depth in the future

The impact of veterinary medicine and animal husbandry on the biophysical characteristics of soils in neotropical agroecosystems

Los agroecosistemas neotropicales son áreas importantes en el escenario mundial en términos de producción ganadera. Por lo tanto, una buena conservación de sus suelos es crucial para garantizar la inocuidad de los alimentos y reducir el impacto de los procesos de degradación de la tierra. La conservación de los suelos neotropicales utilizados para las actividades agropecuarias podría obtenerse utilizando la medicina veterinaria y adoptando nuevos sistemas de pastoreo en los últimos decenios. Se realizó una amplia revisión bibliográfica que ilustra las cuestiones actuales de los agroecosistemas neotropicales, la importancia de sus propiedades del suelo, destacando el papel que desempeñan los escarabajos peloteros dentro de la edafofauna, y los efectos de las prácticas antiparasitarias más comunes, así como algunas alternativas naturales. Por último, presentamos los sistemas de pastoreo adoptados comúnmente y cómo están afectando a las propiedades del suelo y al bienestar de los animales. La conversión de bosques en tierras agrícolas y de pastoreo está alterando la calidad bioquímica de los suelos. Además, el uso de la ivermectina está reduciendo peligrosamente la cantidad total de escarabajos peloteros que son un elemento clave en los procesos de reciclaje de nutrientes. La aplicación de nuevos sistemas de pastoreo (por ejemplo, Voisin, Savory) está fragmentando progresivamente el hábitat de muchas especies. No obstante, también hay algunos beneficios en este tipo de prácticas y se están probando algunas alternativas naturales a los antihelmínticos.The neotropical agroecosystems are important areas in the global scene in terms of livestock production. Therefore, a good conservation of their soils is crucial in order to both guarantee food safety and reduce the impact of land degradation processes. Conservation of neotropical soils used for farming activities could be obtained using veterinary medicine and adopting new grazing systems in the last decades. A wide bibliographical review was carried out which illustrates current issues in neotropical agroecosystems, the importance of their soil properties highlighting the role played by dung beetles within the edaphofauna, and the effects of the most common anti-parasitic practices as well as some natural alternatives. Finally, we present commonly adopted grazing systems and how they are affecting soil properties and animal welfare. The conversion of forest into agricultural and pasture land is altering the biochemical quality of soils. Furthermore, the use of ivermectin is dangerously reducing the total amount of dung beetles that are a key element in nutrient recycling processes. The implementation of new grazing systems (e.g., Voisin, Savory) is progressively fragmenting the habitat of many species. Nevertheless, there are also some benefits in this kind of practices and some natural alternatives to anthelmintics are being tested.• Comisión Europea, IRSES FP7. Proyecto de investigación EcoDrypeerReviewe