Assessing the Effects of Oxaliplatin on an In Vitro Three-Dimensional Human Colorectal Cancer Model

Colorectal cancer is the third most common cancer in the United States with a 5-year late-stage survival rate of only 14%. Due to the lack of translation between animal models and clinical trials as well as the inefficacy of many chemotherapeutics in initial clinical trials, researchers are turning to in vitro drug screening models in an effort to mimic the conditions in vivo. This research project aimed to validate an in vitro tumor culture model within a microfluidic device using a clinically relevant chemotherapy drug. The first experiment consisted of a cell density and drug concentration study to determine the correct cell density and oxaliplatin concentration combinations that would result in a spectrum of quantifiable effects on the tumor cells. This experiment was then converted from a monolayer cell culture on glass into a 2D culture on top of a fibrin extracellular matrix (ECM) to ensure that the cells would respond in a similar way to the drug in the presence of an ECM as they did in the first experiment. The third experiment involved SW620 cells cultured within the fibrin hydrogel to create a 3D tumor model that better mimics the growing conditions in vivo. The goal of this experiment was again to ensure that the cells would respond in the same way to the oxaliplatin treatments as the previous experiments when adding complexity to the model. The final experiment was then to convert this 3D experiment performed in chamber slides into a 3D culture within a microfluidic device with media and oxaliplatin treatments perfused through the chamber using a syringe pump. The purpose of this experiment was to assess whether tumor cells could grow and survive within a microfluidic device with interstitial flow as well as determining if they responded as expected to the oxaliplatin treatment. The first three experiments performed within chamber slides showed that tumor count and average tumor size decreased with increasing oxaliplatin concentrations as expected, which is comparable to the in vivo tumor response to the drug. The fourth experiment demonstrated that, although cells are able to grow within the microfluidic device, this model did not accurately replicate the in vivo condition and future work needs to be aimed at improving the design of the device as well as optimizing parameters within the experiment

Non-slip Prosthetic Surf Foot

The Surf Foot project was created to resolve the challenges faced by Dana Cummings, a former Marine and transtibial left leg amputee, while surfing. Dana is a competitive surfer who first picked up the sport after he lost his leg. He currently utilizes a carbon fiber prosthetic leg when surfing. However, this prosthetic is not ideal for Dana as he often slips while standing up on his surfboard. As such, Dana would like a new non-slip prosthetic leg so that he can further pursue his passion of competitive surfing. Our team, which consisted of four engineering students attending Cal Poly, San Luis Obispo, was sponsored by the QL+ organization. Over the course of three quarters, we worked to research, design, manufacture, and test a prototype that would meet Dana’s requirements. After several months of brainstorming and conceptualizing, we designed a prosthetic leg made from five main components. These components include two pieces of carbon fiber which together serve as a leg, two rubber components intended to serve as a non-slip sole for the prosthetic, and an adapter that would allow Dana to attach the prosthetic to the socket he uses when surfing. Unfortunately, due to the closure of on-campus facilities that resulted from the COVID-19 pandemic, our team was unable to complete the manufacturing and in-person testing of the prosthetic we designed. Instead, we compiled a list of in-depth instructions regarding the planned manufacturing process and testing of our design so that a future QL+ team could complete our project once campus facilities reopen. Although we were unable to produce a final product, our team is confident that our design will eliminate Dana’s problem of slipping while surfing, thus enabling him to further pursue surfing as a competitive sport

Assessing interactions, predicting function, and increasing degradation potential of a PAH-degrading bacterial consortium by effect of an inoculant strain

A natural phenanthrene-degrading consortium CON was inoculated with an exogenous strain Sphingobium sp. (ex Sp. paucimobilis) 20006FA yielding the consortium called I-CON, in order to study ecological interactions into the bacterial community. DGGE and proteomic profiles and analyses by HTS (High-Throughput Sequencing) technologies demonstrated inoculant establishment and changes on CON composition. Inoculation increased degradation efficiency in I-CON and prevented intermediate HNA accumulation. This could be explained not only by the inoculation, but also by enrichment in Achromobacter genus at expense of a decrease in Klebsiella genus. After inoculation, cooperation between Sphingobium and Achromobacter genera were improved, thereby, some competition could have been generated, and as a consequence, species in minor proportion (cheaters), as Inquilinus sp. and Luteibacter sp., were not detected. Sequences of Sphingobium (corresponding to the inoculated strain) did not vary. PICRUSt predicted a network with bacterial phylotypes connected with enzymes, showing functional redundancy in the phenanthrene pathway, with exception of the first enzymes biphenyl-2,3-diol 1,2-dioxygenase and protocatechuate 4,5-dioxygenase that were only encoded in Sphingobium sp. This is the first report where a natural consortium that has been characterized by HTS technologies is inoculated with an exogenous strain in order to study competitiveness and interactions.Fil: Macchi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Festa, Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Vega Vela, Nelson E.. Pontificia Universidad Javeriana; Colombia. Universidad de Bogotá Jorge Tadeo Lozano; ColombiaFil: Morelli, Irma Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Coppotelli, Bibiana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentin

Métodos Estatísticos mais Recorrentes nas Dissertações do Programa de Pós-graduação em Ciências Contábeis da FURB

O estudo buscou analisar os métodos estatísticos aplicados nas dissertações do programa de pós-graduação em ciências contábeis da Universidade Regional de Blumenau (FURB), no período de 2005 a 2009. A pesquisa de cunho descritivo foi realizada por meio de uma pesquisa documental e bibliográfica com abordagem quantitativa. A amostra compreendeu as 102 dissertações aprovadas e defendidas no programa de pós-graduação em ciências contábeis da FURB no período de 2005 a 2009. Os resultados demonstram que 43% das dissertações possuem natureza qualitativa e 69 dissertações pertencem à linha de Controle de Gestão. Nos recursos ilustrativos têm-se o predomínio de figuras, quadros e tabelas em 42% das dissertações analisadas, onde as hipóteses de pesquisa foram encontradas em 22 dissertações. Detectou-se uma evolução nos métodos estatísticos utilizados nos últimos anos, onde os mais recorrentes foram à análise multivariada dos dados (18%), inferências estatísticas (15%), regressão e correlação (10%). A evolução da utilização de ferramentas estatísticas nas dissertações confeccionadas no programa de pós-graduação em ciências contábeis nos últimos anos tem como intuito o incentivo as pesquisas quantitativas, pois os métodos estatísticos ajudam no desenvolvimento das pesquisas realizadas e contribuem para a interpretação dos fenômenos sociais investigados a fim de proporcionar uma evolução científica

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

Investigating the Therapeutic Potential of Soursop in Treating Hematologic Malignancies

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and resistance could be attributed to the survival of progenitor cells with stem-cell-like properties in the protective niches of the bone marrow. Our research suggests that the plant, soursop, may have potential in combating hematologic cancers by triggering apoptosis and potentially preventing drug resistance and relapse. Soursop, scientifically known as Annona muricata, is a plant that thrives in tropical and subtropical regions. Every component of the plant, including the leaves, fruit, seeds, and bark, exhibit preventative properties against a wide range of diseases. Our study focuses on examining the effectiveness and mode of action of an extract obtained from soursop leaves. We aim to determine its potential in exhibiting anti-cancer properties, specifically against AML and MM cell lines. Our findings reveal that the extract from soursop leaves has the ability to trigger apoptosis and reduce cell viability in HL-60 and MM.1S cells. Through our research, we have discovered the inhibition or downregulation of the JAK/STAT pathway

Trypanosomatid-caused conditions: State of the art of therapeutics and potential applications of lipid-based nanocarriers

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy–safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy–safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.Fil: Muraca, Giuliana Sabrina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Fávaro, Wagner J.. Universidade Estadual Do Campinas. Instituto de Biologia. Departamento de Biologia Estructural y Funcional.; BrasilFil: Durán, Nelson. Universidade Estadual Do Campinas. Instituto de Biologia. Departamento de Biologia Estructural y Funcional.; Brasil. Universidad Federal do Abc; BrasilFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Efficacy of Mcl-1 Inhibitors in Multiple Myeloma Cells Resistant to Bortezomib

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, which further rises to 81% during relapse. Thus, researchers are investigating the potential of Mcl-1 inhibitors as a viable treatment option for patients with MM, particularly those who have not responded to previous therapies. Proteasome inhibitor Bortezomib (BTZ) is commonly prescribed as the initial treatment for MM, but unfortunately, patients eventually develop resistance to it. For this study, we created cells that are resistant to BTZ in order to explore the potential mechanisms behind the development of resistance. These cells have been treated with BTZ over a period of 6 months. Regrettably, there are currently no Mcl-1 inhibitors that have been approved by the FDA. However, there are several agents, such as S63845, AZ5991, and VU661013, that are currently undergoing clinical trials. Interestingly, Mcl-1 inhibitors demonstrated effectiveness against sensitive cells but showed a decrease in efficacy against BTZ resistant cells. Our research indicates that cells resistant to BTZ require a higher concentration of Mcl-1 inhibitors in order to undergo cell death. This suggests that these resistant cells may possess a compensatory mechanism that stabilizes the Mcl-1 protein and alters the effectiveness of Mcl-1 inhibitors in treatment. It is worth noting that the anti-apoptotic Bcl-2 protein exhibits heightened expression in resistant cells, even when inhibitors are present. This observation may provide valuable insights into a potential resistance mechanism and calls for further investigation into the compensatory mechanisms that play a crucial role in drug resistance

Redes bayesianas aplicadas a la Ingeniería de Software

En ausencia de una medida acordada de la calidad del software, la densidad de defectos ha sido una medida comúnmente usada. En consecuencia ha habido numerosos intentos para construir modelos para la predicción del número de defectos residuales en el software. Las variables clave en dichos modelos son en general métricas de tamaño y complejidad o medidas derivadas del testing de la información y la codificación. Sin embargo estos enfoques presentan dificultades estadísticas y teóricas. El uso de redes de creencias bayesianas puede superar algunos de estos problemas, teniendo en cuenta los diversos factores implícitos en la prevención de defectos, detección y complejidad. La línea de investigación propuesta se centra en el uso de redes de creencias bayesianas aplicado al modelo de densidad de defectos proporcionando un nuevo enfoque para los procesos de modelización y de ingeniería de artefactos de software. La naturaleza dinámica de este modelo proporcionará una manera de simular diferentes hechos e identificar cursos óptimos de acción basados en el conocimiento incierto.Eje: Ingeniería de SoftwareRed de Universidades con Carreras en Informática (RedUNCI