Biomarker phenotyping drives clinical management in axillary sentinel node: A retrospective study on women with primary breast cancer in 2002

The current study examined if cancer biomarker phenotyping could predict the clinical/pathological status of axillary nodes in women with primary breast cancer. Primary breast cancers from 2002 were analyzed for tumor size, estrogen receptor (ER), progesterone receptor (PgR), Ki.67MIB expression and Her2/neu amplification. Relationships between the clinical and pathological status of the axilla and the biological subtypes classification were analyzed using univariate, multivariate and regression tree analysis. A total of 65% of women with axillary nodes clinically involved had complete axillary node dissection (ALND) while 705 women with clinically negative axillary underwent sentinel lymph node biopsy (SLNB), 18.5% of the latter had at least one pathologically SLNB involved node. Multivariate analysis revealed that the Luminal A subtype was significantly associated (OR 0.62; P<10-9) with clinical negative axilla while HER2pos/not Luminal was associated with clinical positivity (OR 1.71; P<0.01). No significant association between biological subtypes and SLNB status was demonstrated. Regression tree analysis revealed that subgroups with significantly different probability of SLNB status were separated according to tumor size and PgR values. In conclusion, the current study demonstrated that biomarker breast cancer phenotyping is significantly associated with clinical status of axillary nodes but not with pathological involvement of nodes at SLNB. Regression tree analysis could represent a valid attempt to individualize some patients subgroups candidate to different surgical axilla approaches

ISA-TAB-Nano: A Specification for Sharing Nanomaterial Research Data in Spreadsheet-based Format

BACKGROUND AND MOTIVATION: The high-throughput genomics communities have been successfully using standardized spreadsheet-based formats to capture and share data within labs and among public repositories. The nanomedicine community has yet to adopt similar standards to share the diverse and multi-dimensional types of data (including metadata) pertaining to the description and characterization of nanomaterials. Owing to the lack of standardization in representing and sharing nanomaterial data, most of the data currently shared via publications and data resources are incomplete, poorly-integrated, and not suitable for meaningful interpretation and re-use of the data. Specifically, in its current state, data cannot be effectively utilized for the development of predictive models that will inform the rational design of nanomaterials. RESULTS: We have developed a specification called ISA-TAB-Nano, which comprises four spreadsheet-based file formats for representing and integrating various types of nanomaterial data. Three file formats (Investigation, Study, and Assay files) have been adapted from the established ISA-TAB specification; while the Material file format was developed de novo to more readily describe the complexity of nanomaterials and associated small molecules. In this paper, we have discussed the main features of each file format and how to use them for sharing nanomaterial descriptions and assay metadata. CONCLUSION: The ISA-TAB-Nano file formats provide a general and flexible framework to record and integrate nanomaterial descriptions, assay data (metadata and endpoint measurements) and protocol information. Like ISA-TAB, ISA-TAB-Nano supports the use of ontology terms to promote standardized descriptions and to facilitate search and integration of the data. The ISA-TAB-Nano specification has been submitted as an ASTM work item to obtain community feedback and to provide a nanotechnology data-sharing standard for public development and adoption

EXPLORING ANTICORRELATIONS AND LIGHT ELEMENT VARIATIONS IN NORTHERN GLOBULAR CLUSTERS OBSERVED BY THE APOGEE SURVEY

We investigate the light-element behavior of red giant stars in northern globular clusters (GCs) observed by the SDSS-III Apache Point Observatory Galactic Evolution Experiment. We derive abundances of 9 elements (Fe, C, N, O, Mg, Al, Si, Ca, and Ti) for 428 red giant stars in 10 GCs. The intrinsic abundance range relative to measurement errors is examined, and the well-known C–N and Mg–Al anticorrelations are explored using an extreme-deconvolution code for the first time in a consistent way. We find that Mg and Al drive the population membership in most clusters, except in M107 and M71, the two most metal-rich clusters in our study, where the grouping is most sensitive to N. We also find a diversity in the abundance distributions, with some clusters exhibiting clear abundance bimodalities (for example M3 and M53) while others show extended distributions. The spread of Al abundances increases significantly as cluster average metallicity decreases as previously found by other works, which we take as evidence that low metallicity, intermediate mass AGB polluters were more common in the more metal-poor clusters. The statistically significant correlation of [Al/Fe] with [Si/Fe] in M15 suggests that 28Si leakage has occurred in this cluster. We also present C, N, and O abundances for stars cooler than 4500 K and examine the behavior of A(C+N+O) in each cluster as a function of temperature and [Al/Fe]. The scatter of A(C+N +O) is close to its estimated uncertainty in all clusters and independent of stellar temperature. A(C+N+O) exhibits small correlations and anticorrelations with [Al/Fe] in M3 and M13, but we cannot be certain about these relations given the size of our abundance uncertainties. Star-to-star variations of a-element (Si, Ca, Ti) abundances are comparable to our estimated errors in all clusters

Pulsating White Dwarf Stars and Precision Asteroseismology

Galactic history is written in the white dwarf stars. Their surface properties hint at interiors composed of matter under extreme conditions. In the forty years since their discovery, pulsating white dwarf stars have moved from side-show curiosities to center stage as important tools for unraveling the deep mysteries of the Universe. Innovative observational techniques and theoretical modeling tools have breathed life into precision asteroseismology. We are just learning to use this powerful tool, confronting theoretical models with observed frequencies and their time rate-of-change. With this tool, we calibrate white dwarf cosmochronology; we explore equations of state; we measure stellar masses, rotation rates, and nuclear reaction rates; we explore the physics of interior crystallization; we study the structure of the progenitors of Type Ia supernovae, and we test models of dark matter. The white dwarf pulsations are at once the heartbeat of galactic history and a window into unexplored and exotic physics.Comment: 70 pages, 11 figures, to be published in Annual Review of Astronomy and Astrophysics 200

ISA-TAB-Nano: A Specification for Sharing Nanomaterial Research Data in Spreadsheet-based Format

Background and motivation: The high-throughput genomics communities have been successfully using standardized spreadsheet-based formats to capture and share data within labs and among public repositories. The nanomedicine community has yet to adopt similar standards to share the diverse and multi-dimensional types of data (including metadata) pertaining to the description and characterization of nanomaterials. Owing to the lack of standardization in representing and sharing nanomaterial data, most of the data currently shared via publications and data resources are incomplete, poorly-integrated, and not suitable for meaningful interpretation and re-use of the data. Specifically, in its current state, data cannot be effectively utilized for the development of predictive models that will inform the rational design of nanomaterials. Results: We have developed a specification called ISA-TAB-Nano, which comprises four spreadsheet-based file formats for representing and integrating various types of nanomaterial data. Three file formats (Investigation, Study, and Assay files) have been adapted from the established ISA-TAB specification; while the Material file format was developed de novo to more readily describe the complexity of nanomaterials and associated small molecules. In this paper, we have discussed the main features of each file format and how to use them for sharing nanomaterial descriptions and assay metadata. Conclusion: The ISA-TAB-Nano file formats provide a general and flexible framework to record and integrate nanomaterial descriptions, assay data (metadata and endpoint measurements) and protocol information. Like ISA-TAB, ISA-TAB-Nano supports the use of ontology terms to promote standardized descriptions and to facilitate search and integration of the data. The ISA-TAB-Nano specification has been submitted as an ASTM work item to obtain community feedback and to provide a nanotechnology data-sharing standard for public development and adoption

The role of thrombospondins in wound healing, ischemia, and the foreign body reaction

Thrombospondin (TSP) 1 and TSP2 have been implicated in the regulation of several processes during tissue repair. Due to their matricellular nature, these proteins are thought to modulate cell-matrix interactions through a variety of mechanisms specific to the spatio-temporal context of their expression. Most notably, TSP1 and TSP2 appear to play distinct, non-overlapping roles in the healing of skin wounds. In contrast, both proteins have been implicated as regulators of ischemia-induced angiogenesis. Moreover, TSP2 has been shown to be a critical regulator of angiogenesis in the foreign body response (FBR). In this review, we discuss the role of TSPs in tissue repair and examine the mechanistic data regarding the ability of the thrombospondins to modulate cell-matrix interactions in this context

LRP-1 Promotes Cancer Cell Invasion by Supporting ERK and Inhibiting JNK Signaling Pathways

Background: The low-density lipoprotein receptor-related protein-1 (LRP-1) is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. Methodology/Principal Findings: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. Conclusions: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion

Gelation of waxy crude oils by ultrasonic and dynamic mechanical analysis

A novel technique, based on low intensity ultrasonic wave propagation, has been applied to investigate the gelation of a waxy crude oil, caused by the crystallization of paraffin fractions as the temperature reduces below a threshold value, called WAT (wax appearance temperature). Because this phenomenon significantly affects the rheological behavior of crude oils, the knowledge of the conditions under which it occurs, during oil storage and/or transportation, is a topical issue in the oil industry. In this work, an ultrasonic equipment has been set up, able to propagate longitudinal waves in the MHz range and to display in real time the behavior of ultrasonic velocity and attenuation when the crude oil sample is subjected to heating and cooling cycles. When the ultrasonic probes alternatively rotate as parallel plates of a conventional rheometer, low intensity longitudinal waves (in the megahertz range), and shear oscillations (in the hertz range) are simultaneously applied on the sample, thus widely broadening the frequency range of investigation. On cooling, the crystallization of paraffin fractions and the consequent formation of a network structure in the oil matrix are responsible of the development and growth of the crude oil elastic response, which becomes dominant over the viscous response. This process can be reliably detected by dynamic mechanical analysis and by ultrasonic analysis through the increase of the storage modulus G′ and longitudinal velocity, respectively. The growth and further association between wax crystals causes a dissipation of acoustic energy, which is indicated by the increase of the wave attenuation. The combination of rheological and ultrasonic methods has provided a better insight both on the gel transition of crude oils and the viscoelastic behavior of gelled samples. The ultrasonic wave propagation has demonstrated to be a powerful tool for monitoring the sol–gel transition in waxy crude oils. Finally, the effect of ultrasonic waves with different intensity on the gel build-up has been also evaluated. A reduction of the gel strength with increasing wave intensity has been observed and the recovery of elastic response after removing ultrasonic irradiation has been monitored

Inertia Estimation of Equivalent Areas by a PMU-Based Approach Following Perturbations

This paper investigates the problem of inertia estimation of power system equivalent areas by a PMU-based approach. Assuming measurements available on the borders of the area, a reduced model is built based on the data acquired during a perturbation. An iterative method is proposed to calculate the parameters of an equivalent generator, and in particular its inertia. The dynamic behavior of the equivalents are compared with the behavior of the Center of Inertia (COI) of each area, and the equivalent inertia is estimated using a Least Squares approach. Results obtained for a 11-bus, 4 generators test-system are presented and discussed

Oral amino acid supplementation improves age-induced sarcopenia in elderly rats

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