Impact of Tumor-Derived CCL2 on Macrophage Effector Function

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is produced by many different types of cells. In the current investigation, the effect of tumor-derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense-CCL2-expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor-derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor-associated macrophages. In addition, tumor-derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor-derived CCL2 does not directly influence macrophage-mediated antitumor activity

Beyond Worst-Case Analysis for Joins with Minesweeper

We describe a new algorithm, Minesweeper, that is able to satisfy stronger runtime guarantees than previous join algorithms (colloquially, `beyond worst-case guarantees') for data in indexed search trees. Our first contribution is developing a framework to measure this stronger notion of complexity, which we call {\it certificate complexity}, that extends notions of Barbay et al. and Demaine et al.; a certificate is a set of propositional formulae that certifies that the output is correct. This notion captures a natural class of join algorithms. In addition, the certificate allows us to define a strictly stronger notion of runtime complexity than traditional worst-case guarantees. Our second contribution is to develop a dichotomy theorem for the certificate-based notion of complexity. Roughly, we show that Minesweeper evaluates $\beta$-acyclic queries in time linear in the certificate plus the output size, while for any $\beta$-cyclic query there is some instance that takes superlinear time in the certificate (and for which the output is no larger than the certificate size). We also extend our certificate-complexity analysis to queries with bounded treewidth and the triangle query.Comment: [This is the full version of our PODS'2014 paper.

Accurate Ritz wavelengths of parity-forbidden [Fe II], [Ti II] and [Cr II] infrared lines of astrophysical interest

With new astronomical infrared spectrographs the demands of accurate atomic data in the infrared have increased. In this region there is a large amount of parity-forbidden lines, which are of importance in diagnostics of low-density astrophysical plasmas. We present improved, experimentally determined, energy levels for the lowest even LS terms of Fe II, Ti II and Cr II, along with accurate Ritz wavelengths for parity-forbidden transitions between and within these terms. Spectra of Fe II, Ti II and Cr II have been produced in a hollow cathode discharge lamp and acquired using high-resolution Fourier Transform (FT) spectrometry. The energy levels have been determined by using observed allowed ultraviolet transitions connecting the even terms with upper odd terms. Ritz wavelengths of parity-forbidden lines have then been determined. Energy levels of the four lowest Fe II terms (a$^{6}$D, a$^{4}$F, a$^{4}$D and a$^{4}$P) have been determined, resulting in 97 different parity-forbidden transitions with wavelengths between 0.74 and 87 micron. For Ti II the energy levels of the two lowest terms (a$^{4}$F and b$^{4}$F) have been determined, resulting in 24 different parity-forbidden transitions with wavelengths between 8.9 and 130 micron. Also for Cr II the energy levels of the two lowest terms (a$^{6}$S and a$^{6}$D) have been determined, in this case resulting in 12 different parity-forbidden transitions with wavelengths between 0.80 and 140 micron.Comment: Accepted for publication in A&A, 13 pages, 6 figures, 9 table

Answering Conjunctive Queries under Updates

We consider the task of enumerating and counting answers to $k$-ary conjunctive queries against relational databases that may be updated by inserting or deleting tuples. We exhibit a new notion of q-hierarchical conjunctive queries and show that these can be maintained efficiently in the following sense. During a linear time preprocessing phase, we can build a data structure that enables constant delay enumeration of the query results; and when the database is updated, we can update the data structure and restart the enumeration phase within constant time. For the special case of self-join free conjunctive queries we obtain a dichotomy: if a query is not q-hierarchical, then query enumeration with sublinear$^\ast$ delay and sublinear update time (and arbitrary preprocessing time) is impossible. For answering Boolean conjunctive queries and for the more general problem of counting the number of solutions of k-ary queries we obtain complete dichotomies: if the query's homomorphic core is q-hierarchical, then size of the the query result can be computed in linear time and maintained with constant update time. Otherwise, the size of the query result cannot be maintained with sublinear update time. All our lower bounds rely on the OMv-conjecture, a conjecture on the hardness of online matrix-vector multiplication that has recently emerged in the field of fine-grained complexity to characterise the hardness of dynamic problems. The lower bound for the counting problem additionally relies on the orthogonal vectors conjecture, which in turn is implied by the strong exponential time hypothesis. $^\ast)$ By sublinear we mean $O(n^{1-\varepsilon})$ for some $\varepsilon>0$, where $n$ is the size of the active domain of the current database

A continuous non-linear shadowing model of columnar growth

We propose the first continuous model with long range screening (shadowing) that described columnar growth in one space dimension, as observed in plasma sputter deposition. It is based on a new continuous partial derivative equation with non-linear diffusion and where the shadowing effects apply on all the different processes.Comment: Fast Track Communicatio

In-situ Analysis of Laminated Composite Materials by X-ray Micro-Computed Tomography and Digital Volume Correlation

The complex mechanical behaviour of composite materials, due to internal heterogeneity and multi-layered composition impose deeper studies. This paper presents an experimental investigation technique to perform volume kinematic measurements in composite materials. The association of X-ray micro-computed tomography acquisitions and Digital Volume Correlation (DVC) technique allows the measurement of displacements and deformations in the whole volume of composite specimen. To elaborate the latter, composite fibres and epoxy resin are associated with metallic particles to create contrast during X-ray acquisition. A specific in situ loading device is presented for three-point bending tests, which enables the visualization of transverse shear effects in composite structures

Real-world Experience With Sunitinib Treatment in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to Risk Score.

BACKGROUND: ADONIS is an ongoing observational study in 9 European countries, designed to evaluate treatment patterns/outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib and/or second-line axitinib post sunitinib. We present an evaluation of sunitinib efficacy by risk group, in the real-world setting examined in ADONIS. PATIENTS AND METHODS: Patients were enrolled at the start of first-line sunitinib treatment or second-line axitinib post sunitinib treatment. Evaluation of sunitinib efficacy was assessed by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center risk criteria. RESULTS: For all patients in this analysis (N = 467), the median progression-free survival was 23.8 months (95% confidence interval [CI], 16.5-28.5 months), 11.8 months (95% CI, 8.1-17.4 months), and 4.6 months (95% CI, 2.5-7.7 months) for IMDC favorable-, intermediate-, and poor-risk groups, respectively. The median overall survival was 97.1 months (95% CI, 46.3 months-not evaluable [NE]), 33.5 months (95% CI, 20.5-46.6 months), and 10.0 months (95% CI, 4.5-19.8 months) for the respective risk groups. Data on individual risk factors were available for a subgroup of patients, allowing analysis by intermediate risk by 1 versus 2 risk factors. When including this subgroup (n = 120), the median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 months (95% CI, 16.3 months-NE), 20.5 months (15.5 months-NE), and 15.1 months (4.1 months-NE), respectively. CONCLUSIONS: For patients overall and by risk-group stratification, survival estimates were aligned with previously published data. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration of outcome data from different sources is needed to confirm these observations

Php4 Is a Key Player for Iron Economy in Meiotic and Sporulating Cells

Meiosis is essential for sexually reproducing organisms, including the fission yeast Schizosaccharomyces pombe. In meiosis, chromosomes replicate once in a diploid precursor cell (zygote), and then segregate twice to generate four haploid meiotic products, named spores in yeast. In S. pombe, Php4 is responsible for the transcriptional repression capability of the heteromeric CCAAT-binding factor to negatively regulate genes encoding iron-using proteins under low-iron conditions. Here, we show that the CCAAT-regulatory subunit Php4 is required for normal progression of meiosis under iron-limiting conditions. Cells lacking Php4 exhibit a meiotic arrest at metaphase I. Microscopic analyses of cells expressing functional GFP-Php4 show that it colocalizes with chromosomal material at every stage of meiosis under low concentrations of iron. In contrast, GFP-Php4 fluorescence signal is lost when cells undergo meiosis under iron-replete conditions. Global gene expression analysis of meiotic cells using DNA microarrays identified 137 genes that are regulated in an iron- and Php4-dependent manner. Among them, 18 genes are expressed exclusively during meiosis and constitute new putative Php4 target genes, which include hry1+ and mug14+. Further analysis validates that Php4 is required for maximal and timely repression of hry1+ and mug14+ genes. Using a chromatin immunoprecipitation approach, we show that Php4 specifically associates with hry1+ and mug14+ promoters in vivo. Taken together, the results reveal that in iron-starved meiotic cells, Php4 is essential for completion of the meiotic program since it participates in global gene expression reprogramming to optimize the use of limited available iron