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

Algorithms in the Ultra-Wide Word Model

The effective use of parallel computing resources to speed up algorithms in current multi-core parallel architectures remains a difficult challenge, with ease of programming playing a key role in the eventual success of various parallel architectures. In this paper we consider an alternative view of parallelism in the form of an ultra-wide word processor. We introduce the Ultra-Wide Word architecture and model, an extension of the word-RAM model that allows for constant time operations on thousands of bits in parallel. Word parallelism as exploited by the word-RAM model does not suffer from the more difficult aspects of parallel programming, namely synchronization and concurrency. For the standard word-RAM algorithms, the speedups obtained are moderate, as they are limited by the word size. We argue that a large class of word-RAM algorithms can be implemented in the Ultra-Wide Word model, obtaining speedups comparable to multi-threaded computations while keeping the simplicity of programming of the sequential RAM model. We show that this is the case by describing implementations of Ultra-Wide Word algorithms for dynamic programming and string searching. In addition, we show that the Ultra-Wide Word model can be used to implement a nonstandard memory architecture, which enables the sidestepping of lower bounds of important data structure problems such as priority queues and dynamic prefix sums. While similar ideas about operating on large words have been mentioned before in the context of multimedia processors [Thorup 2003], it is only recently that an architecture like the one we propose has become feasible and that details can be worked out.Comment: 28 pages, 5 figures; minor change

A report on the health and social care listening event

The purpose of the Listening Event was to enable a wide range of people, including professionals working in statutory, voluntary and other organisations and members of the public, to ‘have a say’ about health and social care and what we as a University can do for and with these partners and the public. We particularly wanted to hear about key concerns of the University such as: • Strengthening community engagement and partnerships • Health and social care training we should be providing, for whom, and how this is delivered • Ideas relating to the University themes including media, use of space and buildings, human rights, social justice and security • Research topics we should be addressing However the main strength of the Listening Event approach is that topics for discussion are mostly led by participants who attend. On this occasion, the discussion topics were very much focused on the concerns of participants and lots of information and ideas were generated. The task now is for the event planning team to review the discussion notes and identify what can be addressed and how, in the short, medium and long term. This planning will be taking place over the Autumn in 2011, and any participants or readers of this report are more than welcome to get in touch to work with us or add their views. The purpose of this report is to record all discussion summaries for sharing amongst participants and others. It is important that participants especially get to read what others had said at the event. The report will lead to changes in University practices such as the content of some of our courses and new business ideas and relationships will also be explored. The event itself provided a useful means of public engagement that others may wish to adopt

Query Filtering with Low-Dimensional Local Embeddings

The concept of local pivoting is to partition a metric space so that each element in the space is associated with precisely one of a fixed set of reference objects or pivots. The idea is that each object of the data set is associated with the reference object that is best suited to filter that particular object if it is not relevant to a query, maximising the probability of excluding it from a search. The notion does not in itself lead to a scalable search mechanism, but instead gives a good chance of exclusion based on a tiny memory footprint and a fast calculation. It is therefore most useful in contexts where main memory is at a premium, or in conjunction with another, scalable, mechanism. In this paper we apply similar reasoning to metric spaces which possess the four-point property, which notably include Euclidean, Cosine, Triangular, Jensen-Shannon, and Quadratic Form. In this case, each element of the space can be associated with two reference objects, and a four-point lower-bound property is used instead of the simple triangle inequality. The probability of exclusion is strictly greater than with simple local pivoting; the space required per object and the calculation are again tiny in relative terms. We show that the resulting mechanism can be very effective. A consequence of using the four-point property is that, for m reference points, there arèarè m 2 ´ pivot pairs to choose from, giving a very good chance of a good selection being available from a small number of distance calculations. Finding the best pair has a quadratic cost with the number of references ; however, we provide experimental evidence that good heuristics exist. Finally, we show how the resulting mechanism can be integrated with a more scalable technique to provide a very significant performance improvement, for a very small overhead in build-time and memory cost. Keywords: metric search · extreme pivoting · supermetric space · four-point property · pivot based index 2 Chávez 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

Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin

Metastasis is a multi-step process wherein tumour cells detach from the primary mass, migrate through barrier matrices, gain access to conduits to disseminate, and subsequently survive and proliferate in an ectopic site. During the initial invasion stage, prostate carcinoma cells undergo epithelial–mesenchymal-like transition with gain of autocrine signalling and loss of E-cadherin, hallmarks that appear to enable invasion and dissemination. However, some metastases express E-cadherin, and we found close connections between prostate carcinoma cells and hepatocytes in a liver microtissue bioreactor. We hypothesise that phenotypic plasticity occurs late in prostate cancer progression at the site of ectopic seeding. Immunofluorescence staining for E-cadherin in co-cultures of hepatocytes and DU-145 prostate cancer cells revealed E-cadherin upregulation at peripheral sites of contact by day 2 of co-culture; E-cadherin expression also increased in PC-3 cells in co-culture. These carcinoma cells bound to hepatocytes in an E-cadherin-dependent manner. Although the signals by which the hepatocytes elicited E-cadherin expression remain undetermined, it appeared related to downregulation of epidermal growth factor receptor (EGFR) signalling. Inhibition of autocrine EGFR signalling increased E-cadherin expression and cell–cell heterotypic adhesion; further, expression of a downregulation-resistant EGFR variant prevented E-cadherin upregulation. These findings were supported by finding E-cadherin and catenins but not activated EGFR in human prostate metastases to the liver. We conclude that the term epithelial–mesenchymal transition only summarises the transient downregulation of E-cadherin for invasion with re-expression of E-cadherin being a physiological consequence of metastatic seeding

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Performance status score: do patients and their oncologists agree?

Oncologists traditionally assess their patients' ECOG performance status (PS), and few studies have evaluated the accuracy of these assessments. In this study, 101 patients attending a rapid access clinic at Papworth Hospital with a diagnosis of lung cancer were asked to assess their own ECOG PS score on a scale between 0 and 4. Patients' scores were compared to the PS assessment of them made by their oncologists. Of 98 patients with primary non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), weighted kappa statistics showed PS score agreement between patient and oncologist of 0.45. Both patient- and oncologist-assessed scores reflected survival duration (in NSCLC and SCLC) as well as disease stage (in NSCLC), with oncologist-assessed scores being only marginally more predictive of survival. There was no sex difference in patient assessment of PS scores, but oncologists scored female patients more pessimistically than males. This study showed that, with few exceptions, patients and oncologists assessed PS scores similarly. Although oncologists should continue to score PS objectively, it may benefit their clinical practice to involve their patients in these assessments