Generation of Transfer Functions with Stochastic Search Techniques

This paper presents a novel approach to assist the user in exploring appropriate transfer functions for the visualization of volumetric datasets. The search for a transfer function is treated as a parameter optimization problem and addressed with stochastic search techniques. Starting from an initial population of (random or pre-defined) transfer functions, the evolution of the stochastic algorithms is controlled by either direct user selection of intermediate images or automatic fitness evaluation using user-specified objective functions. This approach essentially shields the user from the complex and tedious "trial and error" approach, and demonstrates effective and convenient generation of transfer functions.Engineering and Applied Science

Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Purpose: This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods: Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results: Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion: In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS

CO observations of water-maser post-AGB stars and detection of a high-velocity outflow in IRAS 15452-5459

Many aspects of the evolutionary phase in which Asymptotic Giant Branch stars (AGB stars) are in transition to become Planetary Nebulae (PNe) are still poorly understood. An important question is how the circumstellar envelopes of AGB stars switch from spherical symmetry to the axially symmetric structures frequently observed in PNe. In many cases there is clear evidence that the shaping of the circumstellar envelopes of PNe is linked to the formation of jets/collimated winds and their interaction with the remnant AGB envelope. Because of the short evolutionary time, objects in this phase are rare, but their identification provides valuable probes for testing evolutionary models. We have observed (sub)millimeter CO rotational transitions with the APEX telescope in a small sample of stars hosting high-velocity OH and water masers. These targets are supposed to have recently left the AGB, as indicated by the presence of winds traced by masers, with velocities larger than observed during that phase. We have carried out observations of several CO lines, ranging from J=2-1 up to J=7-6. In IRAS 15452-5459 we detect a fast molecular outflow in the central region of the nebula and estimate a mass-loss rate between 1.2x10^{-4} Msun yr^{-1} (assuming optically thin emission) and 4.9x10^{-4} Msun yr^{-1} (optically thick emission). We model the SED of this target taking advantage of our continuum measurement at 345 GHz to constrain the emission at long wavelengths. For a distance of 2.5 kpc, we estimate a luminosity of 8000 Lsun and a dust mass of 0.01 Msun. Through the flux in the [CII] line (158 um), we calculate a total mass of about 12 Msun for the circumstellar envelope, but the line is likely affected by interstellar contamination.Comment: 12 pages, 9 figures, accepted for publication on A&

Modulating attentional load affects numerosity estimation: evidence against a pre-attentive subitizing mechanism

Traditionally, the visual enumeration of a small number of items (1 to about 4), referred to as subitizing, has been thought of as a parallel and pre-attentive process and functionally different from the serial attentive enumeration of larger numerosities. We tested this hypothesis by employing a dual task paradigm that systematically manipulated the attentional resources available to an enumeration task. Enumeration accuracy for small numerosities was severely decreased as more attentional resources were taken away from the numerical task, challenging the traditionally held notion of subitizing as a pre-attentive, capacity-independent process. Judgement of larger numerosities was also affected by dual task conditions and attentional load. These results challenge the proposal that small numerosities are enumerated by a mechanism separate from large numerosities and support the idea of a single, attention-demanding enumeration mechanism

Adrenergic and mesenchymal signatures are identifiable in cell-free DNA and correlate with metastatic disease burden in children with neuroblastoma

Background: Cell-free DNA (cfDNA) profiles of 5-hydroxymethylcytosine (5-hmC), an epigenetic marker of open chromatin and active gene expression, are correlated with metastatic disease burden in patients with neuroblastoma. Neuroblastoma tumors are comprised of adrenergic (ADRN) and mesenchymal (MES) cells, and the relative abundance of each in tumor biopsies has prognostic implications. We hypothesized that ADRN and MES-specific signatures could be quantified in cfDNA 5-hmC profiles and would augment the detection of metastatic burden in patients with neuroblastoma. Methods: We previously performed an integrative analysis to identify ADRN and MES-specific genes (n = 373 and n = 159, respectively). Purified DNA from cell lines was serial diluted with healthy donor cfDNA. Using Gene Set Variation Analysis (GSVA), ADRN and MES signatures were optimized. We then quantified signature scores, and our prior neuroblastoma signature, in cfDNA from 84 samples from 46 high-risk patients including 21 patients with serial samples. Results: Samples from patients with higher metastatic burden had increased GSVA scores for both ADRN and MES gene signatures (p Conclusions: While it is feasible to identify ADRN and MES signatures using 5-hmC profiles of cfDNA from neuroblastoma patients and correlate these signatures to metastatic burden, additional data are needed to determine the optimal strategies for clinical implementation. Prospective evaluation in larger cohorts is ongoing.</p

Expression of HIV transgene aggravates kidney injury in diabetic mice

With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wild-type mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease

Parton energy loss limits and shadowing in Drell-Yan dimuon production

A precise measurement of the ratios of the Drell-Yan cross section per nucleon for an 800 GeV/c proton beam incident on Be, Fe and W targets is reported. The behavior of the Drell-Yan ratios at small target parton momentum fraction is well described by an existing fit to the shadowing observed in deep-inelastic scattering. The cross section ratios as a function of the incident parton momentum fraction set tight limits on the energy loss of quarks passing through a cold nucleus

Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss

Melanomas driven by loss of the NF1 tumor suppressor have a high risk of treatment failure and effective therapies have not been developed. Here we show that loss-of-function mutations of nf1 and pten result in aggressive melanomas in zebrafish, representing the first animal model of NF1-mutant melanomas harboring PTEN loss. MEK or PI3K inhibitors show little activity when given alone due to cross-talk between the pathways, and high toxicity when given together. The mTOR inhibitors, sirolimus, everolimus, and temsirolimus, were the most active single agents tested, potently induced tumor-suppressive autophagy, but not apoptosis. Because addition of the BCL2 inhibitor venetoclax resulted in compensatory upregulation of MCL1, we established a three-drug combination composed of sirolimus, venetoclax, and the MCL1 inhibitor S63845. This well-tolerated drug combination potently and synergistically induces apoptosis in both zebrafish and human NF1/PTEN-deficient melanoma cells, providing preclinical evidence justifying an early-stage clinical trial in patients with NF1/PTEN-deficient melanoma