Dynamic Set Intersection

Consider the problem of maintaining a family $F$ of dynamic sets subject to insertions, deletions, and set-intersection reporting queries: given $S,S'\in F$, report every member of $S\cap S'$ in any order. We show that in the word RAM model, where $w$ is the word size, given a cap $d$ on the maximum size of any set, we can support set intersection queries in $O(\frac{d}{w/\log^2 w})$ expected time, and updates in $O(\log w)$ expected time. Using this algorithm we can list all $t$ triangles of a graph $G=(V,E)$ in $O(m+\frac{m\alpha}{w/\log^2 w} +t)$ expected time, where $m=|E|$ and $\alpha$ is the arboricity of $G$. This improves a 30-year old triangle enumeration algorithm of Chiba and Nishizeki running in $O(m \alpha)$ time. We provide an incremental data structure on $F$ that supports intersection {\em witness} queries, where we only need to find {\em one} $e\in S\cap S'$. Both queries and insertions take O\paren{\sqrt \frac{N}{w/\log^2 w}} expected time, where $N=\sum_{S\in F} |S|$. Finally, we provide time/space tradeoffs for the fully dynamic set intersection reporting problem. Using $M$ words of space, each update costs $O(\sqrt {M \log N})$ expected time, each reporting query costs $O(\frac{N\sqrt{\log N}}{\sqrt M}\sqrt{op+1})$ expected time where $op$ is the size of the output, and each witness query costs $O(\frac{N\sqrt{\log N}}{\sqrt M} + \log N)$ expected time.Comment: Accepted to WADS 201

An IP-10 (CXCL10)-derived peptide inhibits angiogenesis

Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the α-helical domain residues 77-98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis. © 2012 Yates-Binder et al

On staying grounded and avoiding Quixotic dead ends

The 15 articles in this special issue on The Representation of Concepts illustrate the rich variety of theoretical positions and supporting research that characterize the area. Although much agreement exists among contributors, much disagreement exists as well, especially about the roles of grounding and abstraction in conceptual processing. I first review theoretical approaches raised in these articles that I believe are Quixotic dead ends, namely, approaches that are principled and inspired but likely to fail. In the process, I review various theories of amodal symbols, their distortions of grounded theories, and fallacies in the evidence used to support them. Incorporating further contributions across articles, I then sketch a theoretical approach that I believe is likely to be successful, which includes grounding, abstraction, flexibility, explaining classic conceptual phenomena, and making contact with real-world situations. This account further proposes that (1) a key element of grounding is neural reuse, (2) abstraction takes the forms of multimodal compression, distilled abstraction, and distributed linguistic representation (but not amodal symbols), and (3) flexible context-dependent representations are a hallmark of conceptual processing

The effect of prior walking on coronary heart disease risk markers in South Asian and European men.

Purpose: Heart disease risk is elevated in South Asians possibly due to impaired postprandial metabolism. Running has been shown to induce greater reductions in postprandial lipaemia in South Asian than European men but the effect of walking in South Asians is unknown. Methods: Fifteen South Asian and 14 White European men aged 19-30 years completed two, 2-d trials in a randomised crossover design. On day 1, participants rested (control) or walked for 60 min at approximately 50% maximum oxygen uptake (exercise). On day 2, participants rested and consumed two high fat meals over a 9h period during which 14 venous blood samples were collected. Results: South Asians exhibited higher postprandial triacylglycerol (geometric mean (95% confidence interval) 2.29(1.82 to 2.89) vs. 1.54(1.21 to 1.96) mmol·L-1·hr-1), glucose (5.49(5.21 to 5.79) vs. 5.05(4.78 to 5.33) mmol·L-1·hr-1), insulin (32.9(25.7 to 42.1) vs. 18.3(14.2 to 23.7) µU·mL-1·hr-1) and interleukin-6 (2.44(1.61 to 3.67) vs. 1.04(0.68 to 1.59) pg·mL-1·hr-1) than Europeans (all ES ≥ 0.72, P≤0.03). Between-group differences in triacylglycerol, glucose and insulin were not significant after controlling for age and percentage body fat. Walking reduced postprandial triacylglycerol (1.79(1.52 to 2.12) vs. 1.97(1.67 to 2.33) mmol·L-1·hr-1) and insulin (21.0(17.0 to 26.0) vs. 28.7(23.2 to 35.4) µU·mL-1·hr-1) (all ES ≥ 0.23. P≤0.01), but group differences were not significant. Conclusions: Healthy South Asians exhibited impaired postprandial metabolism compared with White Europeans, but these differences were diminished after controlling for potential confounders. The small-moderate reduction in postprandial triacylglycerol and insulin after brisk walking was not different between the ethnicities

SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation

Synchronization of mitochondrial and cytoplasmic translation rates is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translational uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, compensating mechanisms in mitochondrial translation remain elusive. Here we show that the malignant long non-coding RNA (lncRNA) SAMMSON promotes a balanced increase in ribosomal RNA (rRNA) maturation and protein synthesis in the cytosol and mitochondria by modulating the localization of CARF, an RNA-binding protein that sequesters the exo-ribonuclease XRN2 in the nucleoplasm, which under normal circumstances limits nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favoring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. These data highlight how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth

Canonical wnt signaling activity in early stages of chick lung development

Wnt signaling pathway is an essential player during vertebrate embryonic development which has been associated with several developmental processes such as gastrulation, body axis formation and morphogenesis of numerous organs, namely the lung. Wnt proteins act through specific transmembrane receptors, which activate intracellular pathways that regulate cellular processes such as cell proliferation, differentiation and death. Morphogenesis of the fetal lung depends on epithelial-mesenchymal interactions that are governed by several growth and transcription factors that regulate cell proliferation, fate, migration and differentiation. This process is controlled by different signaling pathways such as FGF, Shh and Wnt among others. Wnt signaling is recognized as a key molecular player in mammalian pulmonary development but little is known about its function in avian lung development. The present work characterizes, for the first time, the expression pattern of several Wnt signaling members, such as wnt-1, wnt-2b, wnt-3a, wnt-5a, wnt-7b, wnt-8b, wnt-9a, lrp5, lrp6, sfrp1, dkk1, β-catenin and axin2 at early stages of chick lung development. In general, their expression is similar to their mammalian counterparts. By assessing protein expression levels of active/total β-catenin and phospho-LRP6/LRP6 it is revealed that canonical Wnt signaling is active in this embryonic tissue. In vitro inhibition studies were performed in order to evaluate the function of Wnt signaling pathway in lung branching. Lung explants treated with canonical Wnt signaling inhibitors (FH535 and PK115-584) presented an impairment of secondary branch formation after 48 h of culture along with a decrease in axin2 expression levels. Branching analysis confirmed this inhibition. Wnt-FGF crosstalk assessment revealed that this interaction is preserved in the chick lung. This study demonstrates that Wnt signaling is crucial for precise chick lung branching and further supports the avian lung as a good model for branching studies since it recapitulates early mammalian pulmonary development.Rute S. Moura was supported by a grant of ON.2 SR&TD Integrated Program (N-01-01-0124-01-07), ref: UMINHO/BPD/31/2013. The funders had no role in study design, data collection and analysis

Moving carbon between spheres, the potential oxalate-carbonate pathway of Brosimum alicastrum Sw.; Moraceae.

Aims The Oxalate-Carbonate Pathway (OCP) is a biogeochemical process that transfers atmospheric CO2 into the geologic reservoir as CaCO3; however, until now all investigations on this process have focused on species with limited food benefits. This study evaluates a potential OCP associated with Brosimum alicastrum, a Neotropical species with agroforestry potential (ca. 70–200 kg-nuts yr−1), in the calcareous soils of Haiti and Mexico. Methods / results Enzymatic analysis demonstrated significant concentrations of calcium oxalate (5.97 % D.W.) were associated with B. alicastrum tissue in all sample sites. The presence of oxalotrophism was also confirmed with microbiological analyses in both countries. High concentrations of total calcium (>7 g kg−1) and lithogenic carbonate obscured the localised alkalinisation and identification of secondary carbonate associated with the OCP at most sample sites, except Ma Rouge, Haiti. Soils adjacent to subjects in Ma Rouge demonstrated an increase in pH (0.63) and CaCO3 concentration (5.9 %) that, when coupled with root-like secondary carbonate deposits in Mexico, implies that the OCP does also occur in calcareous soils. Conclusions Therefore this study confirms that the OCP also occurs in calcareous soils, adjacent to B. alicastrum, and could play a fundamental and un-accounted role in the global calcium-carbon coupled cycle

A multiple timepoint pre-post evaluation of a ‘sexual respect’ dvd to improve competence in discussing sex with patients with disability

Sexual problems are common after chronic illnesses and disability, yet research indicates that this is a neglected area in healthcare services. Evaluation studies provide evidence of the effectiveness of education in enhancing professionals’ knowledge, skills, and comfort in addressing patients’ sexual concerns. However, there are limited evaluations aimed at improving ability to discuss sexuality when working with people with disabilities. The overall aim of this study was to evaluate a ‘Sexual Respect’ DVD as an intervention to improve competence in addressing ‘sexuality and disability’. A mixed methods design was used with both quantitative and qualitative components. Nursing students’ self-report ratings of knowledge, confidence, comfort and willingness (to discuss sexuality) levels were collected across four time points: baseline, pre-intervention, post-intervention, and follow-up. Data were analysed using one-way repeated measures ANOVAs with post hoc comparisons. Open-ended qualitative comments relating to the barriers and facilitators to discussing sexuality were analysed using content analysis and subsequent frequency analysis. Reported barriers included lack of knowledge about sex¬uality and disability issues, the patient’s level of disability, and waiting for the patient to raise sexuality issues first. Facilitators included education/training, written information, and if the patient raised it first. Overall, the DVD intervention had a significant and positive impact on nursing students’ self-reported knowledge, confidence, comfort and willingness levels. The findings are discussed in relation to the PLISSIT model, which emphasises the importance of a proactive approach to addressing sexuality issues

A Natural Combination Extract of Viscum album L. Containing Both Triterpene Acids and Lectins Is Highly Effective against AML In Vivo

Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML

Ontology-based end-user visual query formulation: Why, what, who, how, and which?

Value creation in an organisation is a time-sensitive and data-intensive process, yet it is often delayed and bounded by the reliance on IT experts extracting data for domain experts. Hence, there is a need for providing people who are not professional developers with the flexibility to pose relatively complex and ad hoc queries in an easy and intuitive way. In this respect, visual methods for query formulation undertake the challenge of making querying independent of users’ technical skills and the knowledge of the underlying textual query language and the structure of data. An ontology is more promising than the logical schema of the underlying data for guiding users in formulating queries, since it provides a richer vocabulary closer to the users’ understanding. However, on the one hand, today the most of world’s enterprise data reside in relational databases rather than triple stores, and on the other, visual query formulation has become more compelling due to ever-increasing data size and complexity—known as Big Data. This article presents and argues for ontology-based visual query formulation for end-users; discusses its feasibility in terms of ontology-based data access, which virtualises legacy relational databases as RDF, and the dimensions of Big Data; presents key conceptual aspects and dimensions, challenges, and requirements; and reviews, categorises, and discusses notable approaches and systems