A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors

A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput "omics" approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumors

Identification of a Profile of Neutrophil-Derived Granule Proteins in the Surface of Gold Nanoparticles after Their Interaction with Human Breast Cancer Sera

It is well known that the interaction of a nanomaterial with a biological fluid leads to the formation of a protein corona (PC) surrounding the nanomaterial. Using standard blood analyses, alterations in protein patterns are difficult to detect. PC acts as a "nano-concentrator" of serum proteins with affinity for nanoparticles' surface. Consequently, characterization of PC could allow detection of otherwise undetectable changes in protein concentration at an early stage of a disease, such as breast cancer (BC). Here, we employed gold nanoparticles (AuNPsdiameter: 10.02 +/- 0.91 nm) as an enrichment platform to analyze the human serum proteome of BC patients (n = 42) and healthy controls (n = 42). Importantly, the analysis of the PC formed around AuNPs after their interaction with serum samples of BC patients showed a profile of proteins that could differentiate breast cancer patients from healthy controls. These proteins developed a significant role in the immune and/or innate immune system, some of them being neutrophil-derived granule proteins. The analysis of the PC also revealed serum proteome alterations at the subtype level

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics

Artefactos para iluminación natural integrados a la arquitectura. Estrategias de optimización de las condiciones lumínicas en la envolvente de un taller de la FADU - UBA

Se presentan aquí los resultados del trabajo realizado en el marco del Seminario NuevaTec Diseño de Artefactos para Iluminación Natural, dictado por la D.I. Andrea Pattini. El objetivo del trabajo es integrar a un hecho arquitectónico existente un dispositivo que permita mejorar las condiciones de iluminación natural dentro de los locales. El desarrollo del estudio comprende el relevamiento de las condiciones existentes, la propuesta de dos dispositivos, un estante de luz sencillo y un captador con un funcionamiento semejante a un lumiducto horizontal, su verificación mediante ensayos con maquetas en el Cielo Artificial y el Heliodón y las conclusiones del trabajo realizado, que comprenden una comparación entre la situación existente y los dispositivos ensayados.This paper presents the results of a study realized in a NuevaTec Seminar Design of Devices for Natural Lighting,. The objective of the study is to integrate a technological device in architecture, to improve daylight into the building. The stages followed are the analysis of actual conditions, the design of two devices, a light shelf and a light collector; and simulations in the artificial sky and the helidon of the CIHE. The conclusion includes a comparative evaluation between the actual conditions and the performance of the devices.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

最大値原理に関連する諸課題

学位の種別:課程博士University of Tokyo(東京大学

Propiedades Físicas e Hidráulicas de Perlita en Cultivos de Rosas y sus Variaciones Temporales

Fil: Martínez, Daniel A. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Física; Argentina.Fil: Landiini, Ana M. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Svartz, Héctor. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Vence, Lilia. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Bottini, Lucila. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Bottini, Lucila. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Mascarini, Libertad. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Orden, Susana. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Fil: Vilella, Fernando. Universidad de Buenos Aires. Facultad de Agronomía; Argentina.Physical and hydraulic properties of perlite used as unique substrate in a greenhouse cut roses (Rosa hybrida L.) culture and their dependence on time were investigated. Samples of, perlite with 0,28 and 39 months of use, extracted from the rhizosphere, were analyzed. Bulk density (DA), real density of intact particles (DRI) real density of pulverized particles (DRP), particle size distribution, air capacity (CA), available water (AFD), unavailable water (AR) and effective porosity (PE) were determined. Non-saturated hydraulic conductivity (Kns) was obtained using the Mualem van Genuchten model. It was found cracking of particles with diameters greater than 2 mm and an increment of the fraction between 1 mm and 2 mm after 28 and 39 months of use. No significant alteration of particles with diameters smaller than 0,5 mm was found. Values of PE and CA increased with time of use, while values of AFD, AR showed no variation. The increment of PE with time of use could be explained as a consequence of particle breakdown due to roots, or tiny particle drift from the rhizosphere. Accordingly with the increment of CA, a diminution in one order of magnitude of Kns after 39 months of use was found.Se evaluaron las características físicas e hidráulicas de la perlita usada como sustrato único, en un cultivo bajo cubierta de rosas (Rosa hybrida L.) para corte, observando su comportamiento durante el cultivo. Se evaluaron muestras de perlita con 0, 28 y 39 meses de uso extraídas de la zona radicular del cultivo. Se determinaron la densidad aparente (DA), densidad real de las partículas intactas (DRI), densidad real de las partículas pulverizadas (DRP), distribución de tamaño de partícula, capacidad de aire (CA), agua fácilmente disponible (AF), agua de reserva (AR), porosidad efectiva (PE). La conductividad hidráulica no saturada (Kns) se obtuvo a partir del modelo de Mualem-van Genuchten. La perlita registró en el tiempo, rotura de los granos superiores a 2 mm, observándose un incremento de la fracción comprendida entre 1 mm y 2 mm, no habiendo modificaciones significativas en partículas inferiores a 0,5 mm. Se observó un aumento de la PE, y de la CA mientras que los valores de AF, AR se mantuvieron aproximadamente constantes. El aumento de PE podría explicarse como resultado de la inserción de las raíces y el arrastre de las partículas finas fuera de la zona radicular. En cambio, de forma consistente con el aumento de la CA, Kns experimentó una disminución en un orden de magnitud luego de 39 meses

Multifaceted role of BTLA in the control of CD8+ T cell fate after antigen encounter

Purpose: Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown an overall clinical response rate 40%–50% in metastatic melanoma patients. BTLA (B-and-T lymphocyte associated) expression on transferred CD8+ TILs was associated with better clinical outcome. The suppressive function of the ITIM and ITSM motifs of BTLA is well described. Here, we sought to determine the functional characteristics of the CD8+BTLA+TIL subset and define the contribution of the Grb2 motif of BTLA in T-cell costimulation. Experimental Design: We determined the functional role and downstream signal of BTLA in both human CD8+ TILs and mouse CD8+ T cells. Functional assays were used including single-cell analysis, reverse-phase protein array (RPPA), antigen-specific vaccination models with adoptively transferred TCR-transgenic T cells as well as patient-derived xenograft (PDX) model using immunodeficient NOD-scid IL2Rgammanull (NSG) tumor-bearing mice treated with autologous TILs. Results: CD8+BTLA? TILs could not control tumor growth in vivo as well as their BTLA+ counterpart and antigen-specific CD8+BTLA? T cells had impaired recall response to a vaccine. However, CD8+BTLA+ TILs displayed improved survival following the killing of a tumor target and heightened “serial killing” capacity. Using mutants of BTLA signaling motifs, we uncovered a costimulatory function mediated by Grb2 through enhancing the secretion of IL-2 and the activation of Src after TCR stimulation. Conclusions: Our data portrays BTLA as a molecule with the singular ability to provide both costimulatory and coinhibitory signals to activated CD8+ T cells, resulting in extended survival, improved tumor control, and the development of a functional recall response. Clin Cancer Res; 23(20); 6151–64. ©2017 AACR

Improved personalized survival prediction of patients with diffuse large B-cell Lymphoma using gene expression profiling

BACKGROUND: Thirty to forty percent of patients with Diffuse Large B-cell Lymphoma (DLBCL) have an adverse clinical evolution. The increased understanding of DLBCL biology has shed light on the clinical evolution of this pathology, leading to the discovery of prognostic factors based on gene expression data, genomic rearrangements and mutational subgroups. Nevertheless, additional efforts are needed in order to enable survival predictions at the patient level. In this study we investigated new machine learning-based models of survival using transcriptomic and clinical data. METHODS: Gene expression profiling (GEP) of in 2 different publicly available retrospective DLBCL cohorts were analyzed. Cox regression and unsupervised clustering were performed in order to identify probes associated with overall survival on the largest cohort. Random forests were created to model survival using combinations of GEP data, COO classification and clinical information. Cross-validation was used to compare model results in the training set, and Harrel's concordance index (c-index) was used to assess model's predictability. Results were validated in an independent test set. RESULTS: Two hundred thirty-three and sixty-four patients were included in the training and test set, respectively. Initially we derived and validated a 4-gene expression clusterization that was independently associated with lower survival in 20% of patients. This pattern included the following genes: TNFRSF9, BIRC3, BCL2L1 and G3BP2. Thereafter, we applied machine-learning models to predict survival. A set of 102 genes was highly predictive of disease outcome, outperforming available clinical information and COO classification. The final best model integrated clinical information, COO classification, 4-gene-based clusterization and the expression levels of 50 individual genes (training set c-index, 0.8404, test set c-index, 0.7942). CONCLUSION: Our results indicate that DLBCL survival models based on the application of machine learning algorithms to gene expression and clinical data can largely outperform other important prognostic variables such as disease stage and COO. Head-to-head comparisons with other risk stratification models are needed to compare its usefulness

Population dynamics and identification of efficient strains of Azospirillum in maize ecosystems of Bihar (India)

Information on inoculum load and diversity of native microbial community is an important prerequisite for crop management of microbial origin. Azospirillum has a proven role in benefiting the maize (Zea mays) crop in terms of nutrient (nitrogen) supply as well as plant growth enhancement. Bihar state has highest average national maize productivity although fertilizer consumption is minimum, indicating richness of Azospirillum both in terms of population and diversity in soils. An experiment was planned to generate basic information on Azospirillum population variation in maize soils under different agricultural practices and soil types of Bihar, to identify suitable agricultural practices supporting the target microorganism and efficient Azospirillum strain(s). No tillage, growing traditional maize cultivar, land use history (diara soil having history of maize cultivation), soil organic carbon (>1%) and intercrop with oat supported prevalence of Azospirillum in maize rhizosphere. Native Azospirillum population varied from 1 million to 1 billion/g soil under diverse agricultural practices and soil types. Such richness, however, does not necessarily mean that artificial inoculation of Azospirillum is not required in Bihar soils as 92% of Azospirillum isolates (50 isolates) were poor in nitrogen-fixing ability and 88% were poor on IAA production. Efficient strains of Azospirillum based on growth (three), acetylene reduction assay (three), IAA production (three), broad range of pH (two) and temperature tolerance were identified. The findings suggested that maize crop in Bihar should be inoculated in universal mode rather than site-specific mode

Is race medically relevant? A qualitative study of physicians' attitudes about the role of race in treatment decision-making

<p>Abstract</p> <p>Background</p> <p>The role of patient race in medical decision-making is heavily debated. While some evidence suggests that patient race can be used by physicians to predict disease risk and determine drug therapy, other studies document bias and stereotyping by physicians based on patient race. It is critical, then, to explore physicians' attitudes regarding the medical relevance of patient race.</p> <p>Methods</p> <p>We conducted a qualitative study in the United States using ten focus groups of physicians stratified by self-identified race (black or white) and led by race-concordant moderators. Physicians were presented with a medical vignette about a patient (whose race was unknown) with Type 2 diabetes and untreated hypertension, who was also a current smoker. Participants were first asked to discuss what medical information they would need to treat the patient. Then physicians were asked to explicitly discuss the importance of race to the hypothetical patient's treatment. To identify common themes, codes, key words and physician demographics were compiled into a comprehensive table that allowed for examination of similarities and differences by physician race. Common themes were identified using the software package NVivo (QSR International, v7).</p> <p>Results</p> <p>Forty self-identified black and 50 self-identified white physicians participated in the study. All physicians - regardless of their own race - believed that medical history, family history, and weight were important for making treatment decisions for the patient. However, black and white physicians reported differences in their views about the relevance of race. Several black physicians indicated that patient race is a central factor for choosing treatment options such as aggressive therapies, patient medication and understanding disease risk. Moreover, many black physicians considered patient race important to understand the patient's views, such as alternative medicine preferences and cultural beliefs about illness. However, few white physicians explicitly indicated that the patient's race was important over-and-above medical history. Instead, white physicians reported that the patient should be treated aggressively regardless of race.</p> <p>Conclusions</p> <p>This investigation adds to our understanding about how physicians in the United States consider race when treating patients, and sheds light on issues physicians face when deciding the importance of race in medical decision-making.</p