Morphoproteomic profiling of the mammalian target of rapamycin (mTOR) signaling pathway in desmoplastic small round cell tumor (EWS/WT1), Ewing's sarcoma (EWS/FLI1) and Wilms' tumor(WT1).

BackgroundDesmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies.MethodologyThis pilot study assessed patients with DSRCT, Wilms' tumor and Ewing's sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls.Principal findingsIn DSRCT the PI3K/Akt/mTOR pathway is constitutively activated by p-Akt (Ser 473) expression in the nuclear compartment of the tumor cells and p-mTOR phosphorylated on Ser 2448, suggesting mTORC2 (rictor+mTOR) as the dominant form. Ewing's sarcoma had upregulated p-Akt and p-mTOR, predominantly mTORC2. In Wilm's tumor, the mTOR pathway is also activated with most tumor cells moderately expressing p-mTOR (Ser 2448) in plasmalemmal and cytoplasmic compartments. This coincides with the constitutive activation of one of the downstream effectors of the mTORC1 signaling pathway, namely p-p70S6K (Thr 389). There was constitutive activation of the Ras/Raf/ERK pathway p-ERK 1/2 (Thr202/Tyr204) expression in the Wilms tumor and metastatic Ewing's sarcoma, but not in the DSRCT.ConclusionMORPHOPROTEOMIC TUMOR ANALYSES REVEALED CONSTITUTIVE ACTIVATION OF THE MTOR PATHWAY AS EVIDENCED BY: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic assessments of these tumors are warranted

Bismuth-Based Nano- and Microparticles in X-Ray Contrast, Radiation Therapy, and Radiation Shielding Applications

Bismuth has gained attention in preclinical research because of its ability to attenuate X-rays and high biocompatibility, which make it an excellent element for use in a biomedical agent or in radiation shielding. Developments in the synthesis of elemental bismuth nano- and microparticles, their X-radiation interactions, and their biological interactions will be reviewed in this chapter. The chapter will pay special focus to emerging medical applications of elemental bismuth nano- and microparticles, including the possibility of targeted molecular X-ray imaging, photo-thermal and X-radiation dose enhancing therapies for cancer treatment, and the construction of flexible radiation shielding materials and X-ray opaque devices

Piloting a Community of Student Data Consultants that Supports and Enhances Research Data Services

Research ecosystems within university environments are continuously evolving and requiring more resources and domain specialists to assist with the data lifecycle. Typically, academic researchers and professionals are overcommitted, making it challenging to be up-to-date on recent developments in best practices of data management, curation, transformation, analysis, and visualization. Recently, research groups, university core centers, and Libraries are revitalizing these services to fill in the gaps to aid researchers in finding new tools and approaches to make their work more impactful, sustainable, and replicable. In this paper, we report on a student consultation program built within the University Libraries, that takes an innovative, student-centered approach to meeting the research data needs in a university environment while also providing students with experiential learning opportunities. This student program, DataBridge, trains students to work in multi-disciplinary teams and as student consultants to assist faculty, staff, and students with their real-world, data-intensive research challenges. Centering DataBridge in the Libraries allows students the unique opportunity to work across all disciplines, on problems and in domains that some students may not interact with during their college careers. To encourage students from multiple disciplines to participate, we developed a scaffolded curriculum that allows students from any discipline and skill level to quickly develop the essential data science skill sets and begin contributing their own unique perspectives and specializations to the research consultations. These students, mentored by Informatics faculty in the Libraries, provide research support that can ultimately impact the entire research process. Through our pilot phase, we have found that DataBridge enhances the utilization and openness of data created through research, extends the reach and impact of the work beyond the researcher’s specialized community, and creates a network of student “data champions” across the University who see the value in working with the Library. Here, we describe the evolution of the DataBridge program and outline its unique role in both training the data stewards of the future with regard to FAIR data practices, and in contributing significant value to research projects at Virginia Tech. Ultimately, this work highlights the need for innovative, strategic programs that encourage and enable real-world experience of data curation, data analysis, and data publication for current researchers, all while training the next generation of researchers in these best practices. [This paper is a conference pre-print presented at IDCC 2020 after lightweight peer review.

Exploring the role of pain as an early predictor of category 2 pressure ulcers: a prospective cohort study

Objective To explore pressure area related pain as a predictor of category ≥2 pressure ulcer (PU) development. Design Multicentre prospective cohort study. Setting UK hospital and community settings. Participants inclusion Consenting acutely ill patients aged ≥18 years, defined as high risk (Braden bedfast/chairfast AND completely immobile/very limited mobility; pressure area related pain or; category 1 PU). Exclusion Patients too unwell, unable to report pain, 2 or more category ≥2 PUs. Follow-up Twice weekly for 30 days. Primary and secondary outcome measures Development and time to development of one or more category ≥2 PUs. Results Of 3819 screened, 1266 were eligible, 634 patients were recruited, 32 lost to follow-up, providing a 602 analysis population. 152 (25.2%) developed one or more category ≥2 PUs. 464 (77.1%) patients reported pressure area related pain on a healthy, altered or category 1 skin site of whom 130 (28.0%) developed a category ≥2 PU compared with 22 (15.9%) of those without pain. Full stepwise variable selection was used throughout the analyses. (1) Multivariable logistic regression model to assess 9 a priori factors: presence of category 1 PU (OR=3.25, 95% CI (2.17 to 4.86), p<0.0001), alterations to intact skin (OR=1.98, 95% CI (1.30 to 3.00), p=0.0014), pressure area related pain (OR=1.56, 95% CI (0.93 to 2.63), p=0.0931). (2) Multivariable logistic regression model to account for overdispersion: presence of category 1 PU (OR=3.20, 95% CI (2.11 to 4.85), p<0.0001), alterations to intact skin (OR=1.90, 95% CI (1.24 to 2.91), p=0.0032), pressure area related pain (OR=1.85, 95% CI (1.07 to 3.20), p=0.0271), pre-existing category 2 PU (OR=2.09, 95% CI (1.35 to 3.23), p=0.0009), presence of chronic wound (OR=1.66, 95% CI (1.06 to 2.62), p=0.0277), Braden activity (p=0.0476). (3) Accelerated failure time model: presence of category 1 PU (AF=2.32, 95% CI (1.73 to 3.12), p<0.0001), pressure area related pain (AF=2.28, 95% CI (1.59 to 3.27), p<0.0001). (4) 2-level random-intercept logistic regression model: skin status which comprised 2 levels (versus healthy skin); alterations to intact skin (OR=4.65, 95% CI (3.01 to 7.18), p<0.0001), presence of category 1 PU (OR=17.30, 95% CI (11.09 to 27.00), p<0.0001) and pressure area related pain (OR=2.25, 95% CI (1.53 to 3.29), p<0.0001). Conclusions This is the first study to assess pain as a predictor of category ≥2 PU development. In all 4 models, pain emerged as a risk factor associated with an increased probability of category ≥2 PU development

Aerobic Method for the Synthesis of Nearly Size-Monodisperse Bismuth Nanoparticles from a Redox Non-Innocent Precursor

Herein, we report an aerobic synthesis method to produce bismuth nanoparticles (Bi NPs) with average diameters in the range 40-80 nm using commercially available bismuth triiodide (BiI3) as starting material; the method uses only readily available chemicals and conventional laboratory equipment. Furthermore, size data from replicates of the synthesis under standard reaction conditions indicate that this method is highly reproducible in achieving Bi NP populations with low standard deviations in the mean diameters. We also investigated the mechanism of the reaction, which we determined results from the reduction of a soluble alkylammonium iodobismuthate precursor species formed in situ. Under appropriate concentration conditions of iodobismuthate anion, we demonstrate that burst nucleation of Bi NPs results from reduction of Bi3+ by the coordinated, redox non-innocent iodide ligands when a threshold temperature is exceeded. Finally, we demonstrate phase transfer and silica coating of the Bi NPs, which results in stable aqueous colloids with retention of size, morphology, and colloidal stability. The resultant, high atomic number, hydrophilic Bi NPs prepared using this synthesis method have potential for application in emerging X-ray contrast and X-ray therapeutic applications

Investigating planet formation in circumstellar disks: CARMA observations of RY Tau and DG Tau

(Abridged) We present CARMA observations of the thermal dust emission from the circumstellar disks around the young stars RYTau and DGTau at wavelengths of 1.3mm and 2.8mm. The angular resolution of the maps is as high as 0.15arcsec, or 20AU at the distance of the Taurus cloud, which is a factor of 2 higher than has been achieved to date at these wavelengths. The unprecedented detail of the resulting disk images enables us to address three important questions related to the formation of planets. (1) What is the radial distribution of the circumstellar dust? (2) Does the dust emission show any indication of gaps that might signify the presence of (proto-)planets? (3) Do the dust properties depend on the orbital radius? We find that modeling the disk surface density in terms of either a classical power law or the similarity solution for viscous disk evolution, reproduces the observations well. The 1.3mm image from RYTau shows two peaks separated by 0.2arcsec with a decline in the dust emission toward the stellar position, which is significant at about 2-4sigma. For both RYTau and DGTau, the dust emission at radii larger than 15 AU displays no significant deviation from an unperturbed viscous disk model. In particular, no radial gaps in the dust distribution are detected. Under reasonable assumptions, we exclude the presence of planets more massive than 5 Jupiter masses orbiting either star at distances between about 10 and 60 AU. The radial variation of the dust opacity slope, beta, was investigated by comparing the 1.3mm and 2.8mm observations. We find mean values of beta of 0.5 and 0.7 for DGTau and RYTau respectively. Variations in beta are smaller than 0.7 between 20 and 70 AU. These results confirm that the circumstellar dust throughout these disks differs significantly from dust in the interstellar medium.Comment: ApJ in press

airbrush spray coating of amorphous titanium dioxide for inverted polymer solar cells

One of the main topics of organic photovoltaics manufacturing is the need for simple, low cost, and large area compatible techniques. Solution-based processes are the best candidates to achieve this aim. Among these, airbrush spray coating has successfully applied to deposit both active and PEDOT layers of bulk-heterojunction solar cells. However, this technique is not yet sufficiently studied for interfacial layers (electron and hole transporting layers or optical spacers). In this paper, we show that amorphous titanium dioxide ( ) films, obtained with an airbrush from a solution of titanium (IV) isopropoxide diluted in isopropanol, are successfully deposited on glass and PET substrates. Good surface covering results from the coalescence of droplets after optimizing the spray coating system. Simple inverted polymer solar cells are fabricated using as electron transporting layer obtaining encouraging electrical performances ( % on glass/FTO and 0.7% on PET/ITO substrates)

Timescales of spike-train correlation for neural oscillators with common drive

We examine the effect of the phase-resetting curve (PRC) on the transfer of correlated input signals into correlated output spikes in a class of neural models receiving noisy, super-threshold stimulation. We use linear response theory to approximate the spike correlation coefficient in terms of moments of the associated exit time problem, and contrast the results for Type I vs. Type II models and across the different timescales over which spike correlations can be assessed. We find that, on long timescales, Type I oscillators transfer correlations much more efficiently than Type II oscillators. On short timescales this trend reverses, with the relative efficiency switching at a timescale that depends on the mean and standard deviation of input currents. This switch occurs over timescales that could be exploited by downstream circuits

Photometric Variability in Kepler Target Stars: The Sun Among Stars -- A First Look

The Kepler mission provides an exciting opportunity to study the lightcurves of stars with unprecedented precision and continuity of coverage. This is the first look at a large sample of stars with photometric data of a quality that has heretofore been only available for our Sun. It provides the first opportunity to compare the irradiance variations of our Sun to a large cohort of stars ranging from vary similar to rather different stellar properties, at a wide variety of ages. Although Kepler data is in an early phase of maturity, and we only analyze the first month of coverage, it is sufficient to garner the first meaningful measurements of our Sun's variability in the context of a large cohort of main sequence stars in the solar neighborhood. We find that nearly half of the full sample is more active than the active Sun, although most of them are not more than twice as active. The active fraction is closer to a third for the stars most similar to the Sun, and rises to well more than half for stars cooler than mid K spectral types.Comment: 13 pages, 4 figures, accepted to ApJ Letter